Geriatric Anesthesiology - The Global Regional Anesthesia Website

Geriatric Anesthesiology 

Second Edition

Geriatric 

Anesthesiology 

Second Edition 

Jeffrey H. Silverstein 

G. Alec Rooke 

J.G. Reves 

Charles H. McLeskey 

Editors

Jeffrey H. Silverstein, MD 

Professor 

Department of Anesthesiology, Surgery, 

and Geriatrics and Adult Development 

Vice Chairman for Research 

Associate Dean for Research 

Mount Sinai School of Medicine 

New York, NY, USA 

J.G. Reves, MD 

Vice President for Medical Affairs 

Dean, College of Medicine 

Department of Anesthesiology/College 

of Medicine 

Medical University of South Carolina 

Charleston, SC, USA 

G. Alec Rooke, MD, PhD 

Professor 

Department of Anesthesiology 

University of Washington and the Veterans 

Affairs Puget Sound Health Care System 

Seattle, WA 

and 

Visiting Professor of Anesthesia, Critical 

Care, and Pain Medicine 

Harvard Medical School 

Beth Israel Deaconess Medical Center 

Boston, MA, USA 

Charles H. McLeskey, MD 

Salt Lake City, UT, USA 

Library of Congress Control Number: 2007926756 

ISBN: 978-0-387-72526-0 e-ISBN: 978-0-387-72527-7 

Printed on acid-free paper. 

© 2008 Springer Science+Business Media, LLC. 

All rights reserved. This work may not be translated or copied in whole or in part without the written 

permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 

10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection 

with any form of information storage and retrieval, electronic adaptation, computer software, or by 

similar or dissimilar methodology now known or hereafter developed is forbidden. 

The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are 

not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject 

to proprietary rights. 

While the advice and information in this book are believed to be true and accurate at the date of going 

to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any 

errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect 

to the material contained herein. 

9 8 7 6 5 4 3 2 1 

springer.com

To my Grandparents, Regina and David Silverstein and Blanche and Daniel 

Klein, MD. Their love and their sufferings provided endless opportunities and 

insights. I hope, and believe, they would have liked this result. 

—JHS 

To my Children, Douglas and Linnea. 

—GAR 

To Margaret Cathcart and her late Husband, Dr. John W. Cathcart. 

—JGR 

To my Parents, Marion and Hamilton McLeskey, who encouraged care and 

consideration for our elderly. 

—CHM

Preface to the Second Edition 

Do not go gentle into that good night, 

Old age should burn and rave at close of day; 

Rage, rage against the dying of the light. 

Dylan Thomas 

The goal of getting older is to age successfully. Unfortunately, the majority of our 

older patients will have acquired one or more chronic medical conditions as they 

age, and, even if a perfectly healthy older patient presents for surgery, that patient’s 

ability to handle physiologic stress will be diminished, including the stress of surgery. 

Nearly half of all surgical procedures involve patients older than age 65, and that 

percentage is likely to increase as the U.S. population ages. Thus, the perioperative 

care of the older patient represents one of the primary future frontiers of anesthetic 

practice. Even though perioperative mortality has diminished for the elderly, as well 

as for the population in general, the growing number of cases spotlights perioperative 

morbidity and mortality as an important issue for patients and health care 

systems alike. The vision set forward by the first edition (i.e., to apply the growing 

body of knowledge in this subspecialty area to the everyday practice of anesthesiology) 

remains the mission and vision of this second edition. The editors believe that 

the updated contents of this edition represent an important opportunity to consolidate 

and organize the information that has been acquired since 1997 and to apply 

that knowledge to the current practice of anesthesiology. 

Part I contains several new chapters on topics that may not always seem to be 

directly involved with anesthetic care, but are important to the future of medical 

and anesthesia care. An understanding of the aging process may lead to methods of 

slowing its progression, or at least of ameliorating some of its consequences, including 

the development of chronic disease. Most anesthesiology residency programs 

provide limited formal teaching of geriatric anesthesia. The editors believe the 

incorporation of relevant subspecialty material in the anesthesiology curriculum is 

needed to improve care for this patient population. The realities of reimbursement 

for services rendered to the older patient, either by Medicare or other payers, 

warrant the attention of all anesthesiologists who provide care for older patients. 

Ethics as applied to treatment of the older patient is also addressed. The medical 

management of this population is often complicated by issues such as patient goals 

that differ from physician expectations, physician “ageism,” patient cognitive impairment, 

and the physician’s failure to recognize the true risk of surgery and attendant 

recovery time. The last chapter of Part I reviews current knowledge and suggests 

research areas where the greatest impact on patient outcomes might be realized. 

Parts II and III review the physiology of aging and the basic anesthetic management 

of the geriatric patient, and Part IV examines selected surgical procedures 

vii

viii 

Preface to the Second Edition 

frequently performed in older patients. Not all of these chapters are specific to 

anesthetic management. Geriatric medicine is a broad field with many relevant 

topics. Wound healing is a perfect example. The reality is that anesthesiologists can 

likely have a positive impact on patient care by being better able to recognize conditions 

that may compromise skin when other medical professionals may fail to and, 

as a result, can improve protection of the skin, especially during long operating room 

cases. In contrast, polypharmacy and drug interactions, major topics in geriatric 

medicine, have direct relevance to anesthetic management. The cardiac surgery 

chapter is an example of how age affects outcomes after a specific type of surgical 

procedure. The unusual aspects of anesthetic management for cardiac surgery 

revolve mostly around the patient’s underlying disease status rather than there 

being anything specific to cardiac anesthesia in the older patient beyond the principles 

delineated in Parts II and III. 

For chapters similar to those in the first edition, an effort has been made to update 

content and incorporate studies that examine outcome. Such work helps us challenge 

conventional wisdom and sometimes test novel ideas that prove beneficial. 

Even the most casual reader of this textbook will recognize huge gaps in our present 

knowledge. It is not sufficient, for example, to take an understanding of the physiology 

of aging and draw conclusions regarding anesthetic management from that 

information. Oftentimes, however, we are forced to do just that when making anesthetic 

management decisions. The editors hope the future will provide better research 

and answers that advance the field of geriatric anesthesiology. 

The editors thank the many authors of this text. In addition to their hard work, 

they responded to entreaties for revisions and updates with admirable patience and 

promptness. Their contributions expand our knowledge and will improve the care 

of elderly patients. 

Lastly, the editors thank Stacy Hague and Elizabeth Corra from Springer. Without 

their vision and determination, this book would not exist. 




Charles H. McLeskey, MD

Preface to the First Edition 

Approximately 14% of the current U.S. population is 65 years of age or older. By 

the year 2020, it is predicted that 20% or 60,000,000 Americans will reach this milestone. 

Further, if today’s statistics continue unchanged, at least half of these individuals 

will undergo anesthesia and surgery, likely of increasing complexity, prior to 

their eventual demise. The geriatric patient population represents a huge and 

growing challenge for anesthesia providers the world over. 

My interest in the anesthetic management of geriatric patients was kindled 15 

years ago while on the faculty at Bowman Gray. One of our surgeons asked me to 

anesthetize his healthy 72-year-old father. All went well in the intraoperative and 

postoperative periods and he was discharged home in the customary time frame. 

However, my colleague later reported that he had observed subtle psychomotor 

changes in his father which persisted postoperatively for 7 weeks. It dawned on me 

that perhaps the geriatric patient is not simply an older adult, but rather, a truly 

different physiologic entity. What could explain the relatively commonly observed 

delayed postoperative return of normal mentation in the geriatric surgical patient? 

It is this and other unanswered questions regarding the anesthetic management of 

the elderly that stimulated the development of this text. 

Geriatric Anesthesiology is designed to be a comprehensive text that methodically 

addresses the aging process while emphasizing important clinical anesthetic considerations. 

The first two sections of the text define the demographics of our aging population 

and describe age-related physiologic changes that occur in each major organ 

system. The third section addresses the multitude of factors that contribute to a safe 

and successful anesthetic with suggested adjustments in technique that may improve 

anesthetic management of the elderly. Topics range from preoperative evaluation and 

risk assessment to the altered effects of various classes of drugs with further discussion 

regarding positioning, thermoregulation, perioperative monitoring, and postoperative 

recovery. In addition, issues such as management of pain syndromes, outpatient 

anesthesia, medicolegal implications, and even special CPR techniques in this age 

group are considered. The fourth section identifies the ten most commonly performed 

surgical procedures in the elderly, and for each, offers recommended anesthetic 

techniques. The text ends with an intriguing exploration into future research opportunities 

in the field, including molecular mechanisms of aging. 

Considerable energy has gone into the creation of this text. I am grateful for 

the significant efforts made by all the contributing authors and especially appreciate 

contributions made by the editors from Williams & Wilkins. The text would 

have been impossible to complete without the encouragement, dogged determination, 

and professionalism of Ms. Tanya Lazar and Mr. Carroll Cann. Tim Grayson 

was innovative and supportive during the original design and formulation of 

this project. 

ix

x 

Preface to the First Edition 

I am optimistic that this text will heighten the awareness of the very real clinical 

differences presented by the geriatric patient population. Perhaps by referring to 

appropriate sections in this text, anesthesia providers will be armed with a better 

understanding of the physiologic changes of aging and the recommended considerations 

and modifications of anesthetic technique, which we hope will contribute to 

an ever-improving outcome for the geriatric surgical patient population. 

Charles H. McLeskey, MD

Contents 

Preface to the Second Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Preface to the First Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

vii 

ix 

xiii 

Part I Introduction to Clinical Geriatrics 

1 The Practice of Geriatric Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 


2 Demographics and Economics of Geriatric Patient Care . . . . . . . . . . . . 15 

Maria F. Galati and Roger D. London 

3 Theories of Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 

Stanley Muravchick 

4 Ethical Management of the Elderly Patient . . . . . . . . . . . . . . . . . . . . . . . 38 

Paul J. Hoehner 

5 Teaching Geriatric Anesthesiology to Practitioners, Residents, 

and Medical Students . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 

Sheila J. Ellis 

6 Research Priorities in Geriatric Anesthesiology . . . . . . . . . . . . . . . . . . . 66 

Christopher J. Jankowski and David J. Cook 

Part II Cardinal Manifestations of Aging and Disease in the Elderly 

7 Alterations in Metabolic Functions and Electrolytes . . . . . . . . . . . . . . . 97 

Michael C. Lewis 

8 Perioperative Thermoregulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 

Daniel I. Sessler 

9 Postoperative Central Nervous System Dysfunction . . . . . . . . . . . . . . . . 123 

Deborah J. Culley, Terri G. Monk, and Gregory Crosby 

10 Alterations in Circulatory Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 

Thomas J. Ebert and G. Alec Rooke 

11 The Aging Respiratory System: Anesthetic Strategies to 

Minimize Perioperative Pulmonary Complications . . . . . . . . . . . . . . . . . 149 

Rodrigo Cartin-Ceba, Juraj Sprung, Ognjen Gajic, and 

David O. Warner 

xi

xii 

Contents 

12 Operative Debridements of Chronic Wounds . . . . . . . . . . . . . . . . . . . . . 165 

Andrew M. Hanflik, Michael S. Golinko, Melissa Doft, 

Charles Cain, Anna Flattau, and Harold Brem 

Part III Anesthetic Management of the Aged Surgical Candidate 

13 Preoperative Risk Stratification and Methods to Reduce Risk . . . . . . . 181 

Linda L. Liu and Jacqueline M. Leung 

14 Anesthetic Implications of Chronic Medications . . . . . . . . . . . . . . . . . . . 197 

Tamas A. Szabo and R. David Warters 

15 The Pharmacology of Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 

Steven L. Shafer and Pamela Flood 

16 Intravenous Hypnotic Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 

Matthew D. McEvoy and J.G. Reves 

17 Inhalational Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 

Gary R. Haynes 

18 Relaxants and Their Reversal Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266 

Cynthia A. Lien and Takahiro Suzuki 

19 Management of Regional Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278 

Bernadette Veering 

20 Fluid Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 

Jessica Miller, Lee A. Fleisher, and Jeffrey L. Carson 

21 Pain Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308 

Jack M. Berger 

22 Anesthesia Considerations for Geriatric Outpatients . . . . . . . . . . . . . . . 322 

Kathryn E. McGoldrick 

Part IV Anesthesia for Common Surgical Procedures in the Aged 

23 Sedation and Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 

Sheila R. Barnett 

24 Total Hip Replacement, Joint Replacement, and Hip Fracture . . . . . . 355 

Idit Matot and Shaul Beyth 

25 Transurethral Prostatectomy Syndrome and Other Complications 

of Urologic Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 

Daniel M. Gainsburg 

26 Thoracic Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378 

Steven M. Neustein and James B. Eisenkraft 

27 Cardiac Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390 

James H. Abernathy III 

28 Vascular Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398 

Leanne Groban and Sylvia Y. Dolinski 

29 Abdominal Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416 


Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429

Contributors 

James H. Abernathy, III, MD, MPH 

Assistant Professor 

Department of Anesthesia and 

Perioperative Medicine 



Sheila R. Barnett, MD 

Associate Professor 





Jack M. Berger, MD, PhD 

Clinical Professor 


Keck School of Medicine 

University of Southern California 

Los Angeles, CA, USA 

Shaul Beyth, MD, MSc 

Department of Orthopedic Surgery 

Hadassah Hebrew University Medical Center 

Jerusalem, Israel 

Harold Brem, MD 


Director, Wound Healing 

Department of Surgery—Wound Healing Program 

Columbia University Medical Center 


Charles Cain, MD, MBA 

Clinical Professor 




Jeffrey L. Carson, MD 

Richard C. Reynolds Professor of Medicine 

Chief 

Division of General Internal Medicine 

Department of Medicine 

UMDNJ—Robert Wood Johnson Medical School 

New Brunswick, NJ, USA 

Rodrigo Cartin-Ceba, MD 

Critical Care Medicine Fellow 

Department of Critical Care Service 

Mayo Clinic 

Rochester, MN, USA 

David J. Cook, MD 

Professor 


Mayo Clinic College of Medicine 


Gregory Crosby, MD 



Brigham and Women’s Hospital 



Deborah J. Culley, MD 



Brigham and Women’s Hospital 



Melissa Doft, MD 

Surgical Resident 

Department of Surgery 



xiii

xiv 

Contributors 

Sylvia Y. Dolinski, MD, FCCP 


Department of Anesthesiology and Critical Care 

Medical College of Wisconsin 

Milwaukee, WI, USA 

Thomas J. Ebert, MD, PhD 

Professor and Vice-Chair for Education 


Medical College of Wisconsin 

Milwaukee, WI, USA 

James B. Eisenkraft, MD 

Professor 




Sheila J. Ellis, MD 



University of Nebraska Medical Center 

Omaha, NE, USA 

Anna Flattau, MD 


Department of Surgery and Family 

Medicine—Wound Healing Program 



Lee A. Fleisher, MD 

Robert D. Dripps Professor 


Chair of Anesthesiology and Critical Care 

Hospital of the University of Pennsylvania 

Philadelphia, PA, USA 

Pamela Flood, MD 



Columbia University 


Daniel M. Gainsburg, MD 





Ognjen Gajic, MD, MSc, FCCP 


Department of Internal Medicine 



Maria F. Galati, MBA 

Vice Chair, Administration 




Michael S. Golinko, MD 

Post-Doctoral Research Scientist 

Department of Surgery—Wound Healing Program 



Leanne Groban, MD 



Wake Forest University School of Medicine 

Winston-Salem, NC, USA 

Andrew M. Hanflik, BS 

Medical Student 

Keck School of Medicine 

University of Southern California 

Los Angeles, CA, USA 

Gary R. Haynes, MD, PhD 

Professor 

Department of Anesthesia and Perioperative Medicine 



Paul J. Hoehner, MD, MA, FAHA 

Director 

Department of Cardiovascular and Thoracic 


Central Maine Heart Associates 

Central Maine Heart and Vascular Institute 

Lewiston, ME 

Harvey Fellow in Theology 

Ethics and Culture 

Department of Religious Studies 

University of Virginia Graduate School of Arts 

and Sciences 

Charlottesville, VA, USA 

Christopher J. Jankowski, MD 

Assistant Professor and Consultant 




Jacqueline M. Leung, MD, MPH 

Professor 

Department of Anesthesia and Perioperative Care 

University of California San Francisco 

San Francisco, CA, USA

Contributors 

xv 

Michael C. Lewis, MD 



Miller School of Medicine 

University of Miami 

Miami, FL, USA 

Cynthia A. Lien, MD 

Professor 


Weill Medical College of Cornell University 


Linda L. Liu, MD 


Department of Anesthesia and Perioperative Care 


San Francisco, CA, USA 

Roger D. London, MD, MBA 

Vice President and Medical Director 

Flagship Patient Advocates 


Idit Matot, MD 


Department of Anesthesiology and Critical 

Care Medicine 

Hadassah Hebrew University Medical Center 

Jerusalem, Israel 

Matthew D. McEvoy, MD 


Department of Anesthesia and 

Perioperative Medicine 



Kathryn E. McGoldrick, MD 

Professor and Chair 


New York Medical College 

Valhalla, NY, USA 

Charles H. McLeskey, MD 

Salt Lake City, UT, USA 

Jessica Miller, MD 

Fellow 

Department of Pediatric Anesthesiology and 

Critical Care 

Children’s Hospital of Philadelphia 


Terri G. Monk, MD 

Professor 


Duke University Health System 

Durham, NC, USA 

Stanley Muravchick, MD, PhD 

Professor 


Hospital of the University of Pennsylvania 


Steven M. Neustein, MD 






Vice President for Medical Affairs 

Dean, College of Medicine 

Department of Anesthesiology/College of Medicine 




Professor 


University of Washington and the Veterans Affairs 

Puget Sound Health Care System 

Seattle, WA 

Visiting Professor of Anesthesia, Critical Care, and 

Pain Medicine 




Daniel I. Sessler, MD 

Chair 

Department of Outcomes Research 

The Cleveland Clinic 

Cleveland, OH, USA 

Steven L. Shafer, MD 

Professor 

Department of Anesthesia 

Stanford University 

Palo Alto, CA 

Professor 

Department of Biopharmaceutical Sciences and 

Anesthesia 


San Francisco, CA, USA

xvi 

Contributors 


Professor 

Department of Anesthesiology, Surgery, 

and Geriatrics and Adult Development 

Vice Chairman for Research 

Associate Dean for Research 



Juraj Sprung, MD, PhD 

Professor 




Takahiro Suzuki, MD, PhD 



Nihon University Surugadai Hospital 

Tokyo, Japan 

Tamas A. Szabo, MD, PhD 



Ralph H. Johnson Veterans Administration 

Medical Center 


Bernadette Veering, MD, PhD 



Leiden University Medical Center 

Leiden, The Netherlands 

David O. Warner, MD 

Professor 




R. David Warters, MD 

Professor 


Ralph H. Johnson Veterans Administration 

Medical Center 

Charleston, SC, USA

Part I 

Introduction to Clinical Geriatrics

1 

The Practice of Geriatric Anesthesia 


The approach to and management of surgery and anesthesia 

in geriatric patients is different and frequently 

more complex than in younger patients. In caring for 

the elderly in the operating room, recovery room, and 

intensive care unit, the members of the perioperative 

medical team should be aware of the nature of aging 

physiology, the interaction of these alterations with 

pathologies, and the likelihood of multiple diagnoses 

and polypharmacy. The context of geriatric care encompasses 

multiple levels, stretching from primary care, 

through acute hospitalization, acute and subacute rehabilitation, 

nursing home care, and hopefully back to sufficient 

function to require additional primary care. By the 

nature of their practices, anesthesiologists and geriatricians 

have different approaches to patient care and the 

time frame over which such care occurs. In communicating 

with patients and geriatricians, one should understand 

that expectations for recovery are frequently different 

than in younger patients, marked by issues of maintenance 

of function and independence. There is an evolving 

understanding that specific approaches taken in the perioperative 

period have an impact that remains apparent 

months to years following surgery. Integrating care across 

this continuum can be difficult but invariably improves 

patient outcomes. 

Geriatric medical care has evolved from an empiric 

specialty in the 1950s and 1960s to a largely evidencebased 

practice today. An excellent short reference guide 

called Geriatrics at Your Fingertips is available in a 

small pocket edition as well as on the Internet 1 (http:// 

www.geriatricsatyourfingertips.org/). Perioperative geriatrics, 

however, is very much at the beginning of the 

process of developing sufficient primary data on which 

to base practice guidelines. There are few randomized 

controlled trials that provide class I evidence regard - 

ing perioperative care of the elderly, leaving the practitioner 

to extra polate data from literature that has 

accumulated on geriatric care in other contexts, from retrospective 

reviews, and from the nonoperative geriatric 

literature. 

This introductory chapter presents some of the common 

concepts of geriatrics and a general approach to caring 

for geriatric patients presenting for anesthesia and 

surgery. Virtually every chapter in this book elaborates 

on this foundation chapter. In approaching the elderly as 

patients, the anesthesiologist must understand that there 

is tremendous heterogeneity or variability in aging, both 

in the body as a whole as well as in individual systems. 

Thus, the alterations described in this and the following 

chapters are likely, on average, to be present in geriatric 

surgical patients. However, each individual patient will 

manifest these changes differently. The reader is encouraged 

to develop expertise and judgment and to identify 

those areas in need of improved approaches with the goal 

of developing an evidence-based practice for perioperative 

geriatrics. 

Demography 

As a result of nationwide improvements in health care, 

nutrition, education, and general living standards, the 

elderly account for an increasing percentage of the United 

States population (Figure 1-1). One in eight Americans 

were elderly (age 65 and older) in 1997. By 2030, according 

to the United States Bureau of the Census, one in five 

could be elderly. Between 2010 and 2030, as the baby 

boom generation reaches age 65, anesthesiologists will 

face a variety of challenges. The fastest-growing segment 

of the population is that aged 85 and older. 

The average life expectancy in the United States 

is almost 72 years for men and 79 years for women. 

However, those who reach the age of 65 can expect to 

live 17.4 more years; a life expectancy of 82.4 years. There 

are racial disparities in longevity. In the United States, 

white men who reach age 65 can expect to live 15.7 more 

3

4 J.H. Silverstein 

MILLIONS 

80 

60 

40 

Figure 1-1. Growth of the Elderly Population, 1900–2030. 

(Reprinted from He W, Sengupta M, Velkoff VA, DeBarros KA. 

U.S. Census Bureau. Current Population Reports, P23-209, 65+ 

in the United States: 2005. Washington, DC: U.S. Government 

Printing Office; 2005.) 

20 

0 

1900 1920 1940 1960 1980 2000 2020 

1910 1930 1950 1970 1990 2010 2030 

YEAR 

years whereas black men who reach 65 can expect to live 

13.6 more years. Women are generally longer lived 

than men; however, the racial discrepancy is similar, with 

19.4 and 17.6 additional years, respectively, of additional 

life expected for white and black women who reach 

age 65. 

In 2004, 7.9 million patients over the age of 65 underwent 

a surgical procedure. 2 The number of patients over 

the age of 65 years who undergo noncardiac surgery has 

been projected to increase to 14 million over the next 

three decades 3 with similar increases expected for cardiac 

surgery. Seventy years ago, surgery was considered a desperate 

measure for patients older than 50 years of age, 

who were thought to be incapable of sustaining the rigors 

of even an inguinal hernia repair. 4 Advances in anesthesia 

during the past century have allowed surgeons to develop 

an extraordinary array of procedures with excellent outcomes 

in an increasingly aged population. Recent estimates 

confirm that the amount of surgical activity in the 

aging population is increasing. 5 Bolstered by the evolving 

demographics noted above, anesthesiologists can expect 

an ever-increasing portion of their overall workload to 

involve geriatric patients. 

Definitions of Aging 

Aging is a process of gradual and spontaneous change 

resulting first in maturation and subsequently decline 

through middle and late life. Senescence is the process by 

which the capacity for growth, function, and capacity for 

cell division are lost over time, ultimately leading to 

death. Aging comprises both a positive component of 

development (e.g., wisdom and experience) along with 

the negative component of physiologic and often cognitive 

decline. 

Researchers and clinicians have found advantages in 

differentiating normal aging from age-related disease 

processes. Normal aging is those changes measured, on 

average, across the population. Some of these changes, 

for example, decrease in muscle mass, occur even in the 

well-conditioned, exercising elderly. In order to distinguish 

aging from disease, researchers have had to carefully 

screen patients for disease processes. This process 

has allowed gerontologists to determine that many longheld 

truisms concerning aging were not accurate. For 

example, it is now clear that aging per se does not involve 

neuronal loss in the brain, and cognitive decline is not an 

inevitable aspect of aging. Although it is evident to clinicians 

that diseases progressively accumulate in aging, 

many of these processes are no longer considered synonymous 

with increased age. That is not to suggest that 

aging is an innocent bystander, that is, that age-related 

disease accumulation could occur simply as a function 

of time. Lakatta and Levy, 6 in their studies of cardiac 

physiology, explained that age-related changes alter the 

substrate upon which disease processes evolve. In this 

conception, age affects the severity of disease manifestations 

for a given time at risk. 

In contrast to normal aging, Rowe and Kahn 7 de - 

scribed the idea of successful aging. In successful aging, 

the deleterious effects of senescence are minimized 

such that the individuals suffer few of the unwanted 

features of aging. These individuals are vibrant and active 

into late age, with limited impairment. The combi - 

nation of genetic and environmental status that leads to 

longevity is discussed in the chapter Theories of Aging 

(Chapter 3). The distinction between normal and successful 

aging highlights one of the principal phenomena in 

gerontology: that there is tremendous variability in aging 

between individuals of a given species. Although it is 

extremely convenient to categorize and even stereotype

1. The Practice of Geriatric Anesthesia 5 

patients by age, chronological age is a poor predictor of 

physiologic aging. 

Currently, morbidity, mortality, and recovery times 

for elderly patients undergoing surgery are substantially 

greater than those for younger patients. 8 (See also 

the section Surgical Outcomes and Functional Decline 

later in this chapter.) Age frequently alters the presentation 

of surgical illness. Symptoms of disease may be 

diminished, ignored, or inappropriately attributed to old 

age. Obtaining an accurate history can be challenging in 

the elderly. One of the results of the complexity of the 

patient population is an increased likelihood of preventable 

adverse events and consequences. 9 Thus, improving 

anesthetic care for geriatric patients represents the 

primary challenge of anesthesiology in the next few 

decades. 

Physiologic 

Reserves 

Available 

“The Precipice” 

Increasing Age 

Physiologic 

Reserves 

Already in Use 

Figure 1-2. Schematic of homeostenosis. This diagram shows 

that maintaining homeostasis is a dynamic process. The older 

person uses or consumes physiologic reserves just to maintain 

homeostasis, and therefore there are fewer reserves available 

for meeting new challenges. (Reprinted with permission from 

Taffet GE. Physiology of aging. In: Cassel CK, Leipzig R, Cohen 

HJ, Larson EB, Meier DE, eds. Geriatric Medicine: An Evidence-Based 

Approach. 4th ed. New York: Springer; 2003.) 

General Physiology of Aging 

A homeostatic system is an open system that maintains 

its structure and functions by means of a multiplicity of 

dynamic equilibriums rigorously controlled by interdependent 

regulatory mechanisms. 10 Such a system reacts 

to change through a series of modifications of equal size 

and opposite direction to those that created the disturbance. 

The goal of these modifications is to maintain the 

internal balances. The term homeostenosis has been used 

to describe the progressive constriction of homeostatic 

reserve capacity. Another common means of expressing 

this idea is that aging results in a progressive decrease in 

reserve capacity. Diminishing reserve capacity can be 

identified at a cellular, organ, system, or whole-body level. 

As an example, glomerular filtration rate (GFR) progressively 

decreases with aging, limiting the capacity to deal 

with any stress on this excretory mechanism, be that a 

fluid load or excretion of medications or other toxic substances. 

Once again, the variability associated with aging 

is a key modifier of the decrease in physiologic function. 

So, although in general GFR decreases 1 mL/year, 30% 

of participants in a large study that defined this change 

had no change in GFR whereas others showed much 

greater decrements. 11 The concept of reserve has also 

been used in describing cognitive function. 12 Taffet has 

expanded the general interpretation of the decrease in 

physiologic reserve to emphasize that the reserve capacity 

is not an otherwise invisible organ capacity but the 

available organ function that will be used to maximal 

capacity by the elderly to maintain homeostasis (Figure 

1-2). When the demands exceed the capacity of the organ 

or organism to respond, pathology ensues. This is ever 

more likely as aging decreases the capacity of any system 

to respond. The concept of organ reserve will be invoked 

in many chapters of this textbook. 

Frailty 

A term frequently applied to elderly patients is “frail.” 

One would expect the frail elderly to be at higher risk 

for functional decline following surgery. Unfortunately, 

much like Justice Potter Stewart’s 1964 definition of 

obscenity, most physicians can identify frailty when 

they see it, but a clinically relevant scientific definition 

has been elusive. Linda Fried and colleagues 13 have 

defined frailty, focusing primarily on muscle loss, or sarcopenia, 

as a clinical syndrome in which three or more 

of the following criteria are present: unintentional weight 

loss (10 lbs. in past year), self-reported exhaustion, 

weakness (grip strength), slow walking speed, and low 

physical activity. In the initial evaluation of the participants 

from the Cardiovascular Health Study (5317 men 

and women 65 years and older), the overall prevalence 

of frailty was 6.9%. 13 Frailty is perceived, in this context, 

as a cyclical decline that perpetuates itself (Figure 1-3). 

Frailty has been described as a form of predisability, 

which is distinct from functional impairment. 14 However, 

in the setting of sarcopenia, further muscle loss associated 

with surgical illness could be functionally disastrous. 

Indeed, Wolfe 15,16 has recently shown that the catabolic 

response to the stress of surgery and the subsequent loss 

of muscle mass is of even greater concern in the elderly. 

Frailty as a specific measure has not been prospectively 

characterized as a preoperative risk factor. The American 

Society of Anesthesiologists physical status score does 

not easily capture frailty, although clinicians may factor 

significant frailty into their assessment of a patient’s physical 

status. Current research efforts should help define the 

relevance of frailty in the assessment and management of 

elderly patients.


Neuroendocrine 

Dysregulation 

Anoreria 

of aging 

Total Energy Expenditure 

Chronic 

Undernutrition 

[Inadequate intake 

of protein and 

energy micronutrient 

deficiencies] 

Aging: 

Senescent 

musculoskeletal changes 

Negative Energy Balance 

Negative Nitrogen Balance 

Disease 

Weight Loss 

Loss of musele mass 

Sarcopenia 

Activity 

Walking 

Speed 

Disability 

Resting 

Metabolic 

Rate 

Strength 

& 

Power 

. 

VO 2 max 

Dependency 

Figure 1-3. Cycle of frailty hypothesized as consistent with 

demonstrated pairwise associations and clinical signs and 

symptoms of frailty. (Reprinted with permission from Fried 

LP, Tangen CM, Walston J, Newman AB, Hirsch C, 

Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie 

MA; Cardiovascular Health Study Collaborative Research 

Group. Frailty in older adults: evidence for a phenotype. J 

Gerontol A Biol Sci Med Sci. 2001 Mar; 56(3):M146–56.) 

Surgical Outcomes and 

Functional Decline 

Traditional surgical outcomes include morbidity and 

mortality within a defined period following a procedure, 

frequently 30 days. Data from the Veterans Administrations 

National Surgical Quality Improvement Program 

(NSQIP) provides the most current insight into surgical 

outcomes for elderly patients. Hamel et al. 17 reported on 

26,648 patients aged ≥80 (median age 82) and 568,263 

patients 80 (Table 1-1). Mortality was low 

(80 had one or more complications, and the presence of 

a complication increased mortality from 4% to 26%. 

Respiratory and urinary tract complications were the 

most common. 

For the mid- to late-life patient, symptoms and disability 

are the principal outcomes of most disease processes. 

They may become the focus of protracted care. In 

order to conceptualize disability in a format that supports 

medical and survey research, Verbrugge and Jette 18 elucidated 

The Disablement Process. The pathway to disability 

(Figure 1-4) begins with a disease or pathology. 

Impairments occur at the organ-system level and are dysfunctional 

and structural abnormalities in specific body 

systems, such as cardiovascular or neurologic. Functional 

limitations subsequently occur at the organism, or entire 

Table 1-1. Thirty-day mortality for operations. 

80 years 

General surgery 4.3 11.4 

Vascular surgery 4.1 9.4 

Thoracic surgery 6.3 13.5 

Urologic surgery 0.7 1.9 

Neurosurgery 2.4 8.6 

Otolaryngological surgery 2.5 8.8 

Orthopedic surgery 1.2 8.3 

Source: Hamel et al. 17 

Note: Median age for the 80 = 82 years.


Pathology 

Diagnoses of 

disease, injury, 

congenital 

condition 

Impairments 

Dysfunction and 

structural 

abnormalities in 

specific body 

systems, i.e., 

cardiovascular 

The Disablement Process 

Main Pathway 

Functional Limitations 

Restriction in basic 

physical and mental 

actions: ambulate, stoop, 

produce intelligible 

speech 

Disability 

Difficulty doing 

activities of daily 

life, job, 

household 

management, etc. 

Figure 1-4. The disablement process: main pathway. (Adapted with permission from Verbrugge and Jette. 18 ) 

being, level and comprise restrictions in basic physical 

and mental abilities such as ambulation, reaching, bending, 

and communicating intelligibly. Disability occurs when 

there is an insurmountable gap between an individual 

and environmental demands such that their expected 

social role is compromised. Intra-individual (e.g., age, 

socioeconomic status) and extra-individual (e.g., acute 

medical events, preventive interventions) factors can 

influence the Disablement Process in either direction. 

These factors may be preexisting or new occurrences. 

The goals of therapy for a geriatric patient are frequently 

motivated by a desire to avoid disability and 

preserve or perhaps improve functional status. The 

most common measures of functional status are called 

activities of daily living (ADL) and instrumental activities 

of daily living (IADL) 19 (Tables 1-2 and 1-3). ADLs 

are those basic activities fundamental to self-care whereas 

IADLs are those functions necessary to live independently. 

ADLs and IADLs are subjective reported measures. 

In a research context, it is common to include 

objective measures of function to assess strength, time to 

perform specific activities, or distance covered in a fixed 

period of time. Measurement of cognitive function by 

neuropsychologic tests is analogous to measures of physical 

function. In general medical patients, there has been 

extensive research regarding both the basis for functional 

decline as well as approaches to improving outcomes in 

elderly patients hospitalized for acute illness. Many of the 

published clinical trials studied variations of the comprehensive 

geriatric assessment, described below. 

The disablement process model is the theoretical basis 

for a model of elements that influence functional 

recovery after elective major surgery (Figure 1-5). There 

are two types of preexisting factors or determinants: 

1) variable elements of function that may be modifiable 

or amenable to interventions; 2) relatively fixed elements 

in the context of daily living, which shape function 

and the roles of the variable elements, but may not be 

feasible targets for improving recovery. Variable elements 

are a comprehensive array of psychosocial, behavioral, 

and preoperative biomedical factors that can influence 

the evolution of function directly or indirectly through 

their influences on, and/or interaction with, other determinants. 

These elements are potentially amendable to 

intervention prior to an elective surgical procedure. 

Fixed elements are a separate constellation of contextual 

factors of daily living in which determinants and functional 

evolution interact and unfold. Anesthesia incorporates 

pharmacologic techniques to eliminate pain and 

the stress response attendant to surgical procedures. 

Within the acute event, there are surgical options (e.g., 

laparoscopic procedures) that may decrease the stress of 

the surgical procedure as well as the potential for anesthetic 

choices that may impact the trajectory of recovery. 

The model is qualitatively similar to a model for acute 

medical illness developed by Palmer et al. 20 and provides 

a framework for the identification of potential interventions 

to enhance postoperative recovery, prevent disability, 

and prolong independence in elders undergoing 

surgery. 

The impact of surgery on functional outcomes in elderly 

patients has been most clearly described by Lawrence 

et al. 21 in their report on a prospective cohort of 372 patients, 

60 years or older, undergoing abdominal surgery by surgeons 

in private practice and two university-affiliated 

hospitals in the San Antonio area. The participants were 

assessed preoperatively and postoperatively at 1, 3, and 6 

weeks, 3 and 6 months, using self-report and performancebased 

measures ADL, IADL, the Medical Outcomes Study 

Short Form-36 (SF-36) Physical Component and Mental


Table 1-2. Activities of daily living. In each category, circle the item that most closely describes the person’s highest level of 

functioning and record the score assigned to that level (either 1 or 0) in the blank at the beginning of the category. 

A. Toilet _______ 

1. Care for self at toilet completely; no incontinence 1 

2. Needs to be reminded, or needs help in cleaning self, or has rare (weekly at most) accidents 0 

3. Soiling or wetting while asleep more than once a week 0 

4. Soiling or wetting while awake more than once a week 0 

5. No control of bowels or bladder 0 

B. Feeding _______ 

1. Eats without assistance 1 

2. Eats with minor assistance at meal times and/or helps with special preparation of food, or in cleaning up after meals 0 

3. Feeds self with moderate assistance and is untidy 0 

4. Requires extensive assistance for all meals 0 

5. Does not feed self at all and resists efforts of others to feed him or her 0 

C. Dressing _______ 

1. Dresses, undresses, and selects clothes from own wardrobe 1 

2. Dresses and undresses self with minor assistance 0 

3. Needs moderate assistance in dressing and selection of clothes 0 

4. Needs major assistance in dressing but cooperates with efforts of others to help 0 

5. Completely unable to dress self and resists efforts of others to help 0 

D. Grooming (neatness, hair, nails, hands, face, clothing) _______ 

1. Always neatly dressed and well-groomed without assistance 1 

2. Grooms self adequately with occasional minor assistance, e.g., with shaving 0 

3. Needs moderate and regular assistance or supervision with grooming 0 

4. Needs total grooming care but can remain well-groomed after help from others 0 

5. Actively negates all efforts of others to maintain grooming 0 

E. Physical ambulation _______ 

1. Goes about grounds or city 1 

2. Ambulates within residence or about one-block distance 0 

3. Ambulates with assistance of (check one) a ( ) another person, b ( ) railing, c ( ) cane, d ( ) walker, e ( ) wheelchair 0 

1. ________ Gets in and out without help. 

2. ________ Needs help getting in and out 

4. Sits unsupported in chair or wheelchair but cannot propel self without help 0 

5. Bedridden more than half the time 0 

F. Bathing _______ 

1. Bathes self (tub, shower, sponge bath) without help 1 

2. Bathes self with help getting in and out of tub 0 

3. Washes face and hands only but cannot bathe rest of body 0 

4. Does not wash self but is cooperative with those who bathe him or her 0 

5. Does not try to wash self and resists efforts to keep him or her clean 0 

Source: Lawton and Brody. 19 

Scoring interpretation: For ADLs, the total score ranges from 0 to 6. In some categories, only the highest level of function receives a 1; in others, 

two or more levels have scores of 1 because each describes competence at some minimal level of function. These screens are useful for indicating 

specifically how a person is performing at the present time. When they are also used over time, they serve as documentation of a person’s functional 

improvement or deterioration. 

Component Scales (PCS, MCS), Geriatric Depression 

Scale (GDS), Folstein Mini-Mental State Exam (MMSE), 

timed walk, functional reach, and hand-grip strength. The 

mean recovery times were: MMSE, 3 weeks; timed walk, 6 

weeks; ADL, SF-36 PCS, and functional reach, 3 months; 

and IADL, 6 months (Figure 1-6). Mean grip strength did 

not return to preoperative status by 6 months. This result, 

that most functional recovery takes 3 to 6 months or longer, 

provides an indication of the impact that surgery makes on 

an elderly population. It should be noted that this cohort 

was accumulated before the popularity of laparoscopic 

procedures, so the stress of surgery and the recovery period 

may now be, on average, shorter. 

In preparing a patient for surgery, informing him or her 

regarding the prolonged time that it will take to recover 

to preoperative status or better can be extremely important. 

Patients who understand that recovery is a prolonged 

process are less likely to become discouraged and 

more likely to continue prolonged efforts to regain 

strength and endurance. 

Approach to the Patient 

Although a variety of investigations in elderly patients 

have explored specific issues in geriatric care, a comprehensive 

evidence-based approach to the perioperative 

care of the elderly is not available in 2007. Therefore, the 

current approach is based on the few studies that have 

addressed these issues directly, extrapolation from studies


Table 1-3. Instrument (independent) activities of daily living. In each category, circle the item that most closely describes the person’s 

highest level of functioning and record the score assigned to that level (either 1 or 0) in the blank at the beginning of the category. 

A. Ability to use telephone _______ 

1. Operates telephone on own initiative; looks up and dials numbers 1 

2. Dials a few well-known numbers 1 

3. Answers telephone but does not dial 1 

4. Does not use telephone at all 0 

B. Shopping _______ 

1. Takes care of all shopping needs independently 1 

2. Shops independently for small purchases 0 

3. Needs to be accompanied on any shopping trip 0 

4. Completely unable to shop 0 

C. Food preparation _______ 

1. Plans, prepares, and serves adequate meals independently 1 

2. Prepares adequate meals if supplied with ingredients 0 

3. Heats and serves prepared meals or prepares meals but does not maintain adequate diet 0 

4. Needs to have meals prepared and served 0 

D. Housekeeping _______ 

1. Maintains house alone or with occasional assistance (e.g., domestic help for heavy work) 1 

2. Performs light daily tasks such as dishwashing, bedmaking 1 

3. Performs light daily tasks but cannot maintain acceptable level of cleanliness 1 

4. Needs help with all home maintenance tasks 1 

5. Does not participate in any housekeeping tasks 0 

E. Laundry _______ 

1. Does personal laundry completely 1 

2. Launders small items; rinses socks, stockings, etc. 1 

3. All laundry must be done by others 0 

F. Mode of transportation _______ 

1. Travels independently on public transportation or drives own car 1 

2. Arranges own travel via taxi but does not otherwise use public transportation 1 

3. Travels on public transportation when assisted or accompanied by another 1 

4. Travel limited to taxi or automobile with assistance of another 0 

5. Does not travel at all 0 

G. Responsibility for own medications _______ 

1. Is responsible for taking medication in correct dosages at correct time 1 

2. Takes responsibility if medication is prepared in advance in separate dosages 0 

3. Is not capable of dispensing own medication 0 

H. Ability to handle finances _______ 

1. Manages financial matters independently (budgets, writes checks, pays rent and bills, goes to bank); collects and keeps 1 

track of income 

2. Manages day-to-day purchases but needs help with banking, major purchases, etc. 1 

3. Incapable of handling money 0 

Source: Lawton and Brody. 19 Copyright by the Gerontological Society of America. 

Scoring interpretation: For IADLs, from 0 to 8. In some categories, only the highest level of function receives a 1; in others, two or more levels 

have scores of 1 because each describes competence at some minimal level of function. These screens are useful for indicating specifically how a 

person is performing at the present time. When they are also used over time, they serve as documentation of a person’s functional improvement 

or deterioration. 

that provide some insight into the broader care of elderly 

surgical patients, and some general suggestions derived 

from the experience of the author and his colleagues. 

Stanley Muravchik nicely delineated the approach to 

the preanesthetic assessment of the elderly by specifying 

an organ-based vertical approach, as opposed to the horizontal 

approach of traditional diagnostic medicine (Figure 

1-7). The specific age-related changes to major organ 

systems as well as the interaction between aging and 

disease processes are each covered in individual chapters 

in this book. For each organ system, the anesthesiologists 

should determine the functional status and attempt to 

assess the reserve capacity. In some cases, reserve 

capacity can be directly tested, as in a cardiac stress test. 

Many systems, particularly many of the homeostatic 

mechanisms of concern in the elderly, e.g., the autonomic 

nervous system, immune system, or even thermoregulatory 

control, remain difficult to assess. Neither baseline 

function nor reserve capacity have easily administered 

tests with reliable results for these systems. Maintenance 

of intraoperative normothermia can be a challenging goal 

in some elderly patients, although it is difficult to predict 

which will be particularly resistant. 22 (See Chapter 8.) The 

clinician should be attempting to distinguish age-related 

changes from disease, acknowledging that there are 

important interactions between the two, and that it can


Figure 1-5. This model, developed by 

Valerie Lawrence, MD, from the University 

of Texas Medical Center at San 

Antonio, Texas, and Jeffrey H. Silverstein, 

MD, from the Mount Sinai School 

of Medicine in New York, divides preoperative 

elements into those that are 

potentially variable and those that are 

not amenable to preoperative alteration. 

An important aspect is the management 

of the acute event. The combination 

of these factors determines the functional 

outcomes of patients undergoing 

surgery. 

be difficult to determine what is aging and what is actual 

disease. 

In addition to a focus on senescent physiology of standard 

organ systems, proper evaluation in elderly patients 

requires attention to areas that are not frequently evaluated 

in younger patients (Table 1-4). Sometimes it is difficult 

to imagine an anesthesiologist evaluating a patient’s 

pressure points for early skin breakdown or specifically 

asking a patient about incontinence. The thrust of this 

chapter is that someone on the perioperative team must 

be cognizant of these issues. The team taking care of the 

patient has to have both the acute event and the recovery 

period as their focus of cooperation. 

The skin and musculoskeletal system can undergo tremendous 

alterations. Up to 10% of elderly patients 

develop serious skin breakdown during prolonged operations 

in which pressure is exerted over debilitated areas. 23 

Patients with severe arthritis, other limitations of range of 

motion, or prosthetic joints should, to the extent possible, 

be positioned on an operating room table in a position 

they find comfortable before the induction of anesthesia. 

This avoids severe strain on ligaments and joints that can 

be severely painful in the postoperative period. 

The elderly take a large percentage of the medications 

prescribed in the United States. Patients frequently 

consume multiple medications. The management of these 

medications is frequently chaotic. The patient may present 

a bag full of prescription bottles and is not totally sure 

which one they take, or, somewhat more likely, convey a 

few of the many medications that they have been prescribed. 

Many of these medications have interactions 

with drugs used by anesthesiologists in the perioperative 

period. These issues are presented in some detail in 

Chapter 14. 

Acquiring information can be challenging and may 

involve discussion with not only the patient, but also their 

immediate caregiver as well as reference to previous 

medical records. A comprehensive approach to caring for 

the geriatric surgical patient may assign some of the 

assessment goals to the geriatrician, anesthesiologist, or 

surgeon. Additional time should be scheduled to accomplish 

an appropriate preoperative assessment. The area 

in which the preoperative assessment is conducted should 

be relatively quiet and well lit. 

Hearing loss is a common complaint and should be 

generally understood by the anesthesiologist. Presbyacusia 

generally involves impaired sensitivity, particularly to 

higher pitched sounds, a derangement in loudness perception, 

impaired sound localization, and a decrease in timerelated 

processing tasks. The summary behavior is 

frequently expressed as “I can hear you, but I can’t understand 

you.” The examiner can maximize the potential for 

communicating effectively with the patient by placing 

themselves 3–6 feet away, directly facing the patient. Use 

deliberate, clear speech at a somewhat slower (not comically 

or sarcastically) rate. The general tendency to speak 

louder needs to be tempered by the realization that shouted 

speech is often perceived as distorted by the elderly who 

are hard of hearing. Hearing aid technology has expanded 

dramatically and includes a variety of both external and 

surgically implantable technologies. 24 In general, patients 

should always be interviewed with their hearing aids in


Mean 

Summary 

Score 

7 

8 

9 

10 

11 

21 

Mean 

Change 

Score 

Percent Not Recovered 

Total Number Assessed 

Activities of Daily Living Instrumental Activities of Daily Living SF36 Physical Component 

0 

1 

2 

3 

4 

Pre 

Op 

* 

1 

Wk 

60% 

345 

* 

3 

Wk 

– 

372 

26% 

328 

* 

6 

Wk 

17% 

321 

3 

Mo 

14% 

293 

6 

Mo 

9% 

290 

Mean 

Summary 

Score 

8 

10 

12 

14 

16 

18 

24 

Mean 

Change 

Score 



1 

3 

5 

7 

9 

Pre 

Op 

* 

1 

Wk 

92% 

345 

* 

3 

Wk 

– 

372 

76% 

328 

* 

6 

Wk 

55% 

321 

* 

3 

Mo 

34% 

293 

6 

Mo 

19% 

290 

Mean 

Summary 

Score 

100 

45 

40 

35 

30 

25 

0 

Mean 

Change 

Score 



10 

5 

0 

–5 

–10 

* 

Pre 1 3 

Op Wk Wk 

– –– 56% 

372 327 

* 

6 

Wk 

36% 

320 

* 

3 

Mo 

19% 

292 

* 

6 

Mo 

16% 

289 

Mean 

Summary 

Score 

100 

60 10 

55 

50 

45 

0 

Mean 

Change 

Score 



SF36 Mental Component 

5 

0 

–5 

Pre 

Op 

– 

372 

1 

Wk 

–– 

3 

Wk 

30% 

327 

* 

6 

Wk 

27% 

320 

* 

3 

Mo 

19% 

292 

* 

6 

Mo 

17% 

289 

Mean 

Summary 

Score 

5 

6 

7 

8 

9 

10 

30 

Mean 

Change 

Score 



Geriatric Depression Scale 

–3 

–2 

–1 

0 

1 

2 

Pre 

Op 

1 

Wk 

46% 

339 

3 

Wk 

– 

366 

40% 

323 

* 

6 

Wk 

31% 

317 

* 

3 

Mo 

30% 

289 

* 

6 

Mo 

25% 

286 

30 

28 

Mean 

Summary 

Score 

27 

26 

Mean 

Change 

Score 



1.0 

0.5 

0 

–0.5 

Folstein MMSE 

* 

–1 

Pre 1 3 

Op Wk 

– 

372 

44% 

342 

Wk 

31% 

326 

* 

6 

Wk 

23% 

320 

3 

Mo 

32% 

291 

6 

Mo 

27% 

288 

Mean 

Seconds 

12 

14 

16 

18 

20 

22 

24 

Mean 

Change 

Score 



–4 

–2 

10 

0 

2 

4 

6 

8 

Pre 

Op 

Timed Up and Go Functional Reach Grip Strength 

* 

1 

Wk 

84% 

317 

* 

60% 

301 

3 

Wk 

– 

341 

* 

6 

Wk 

41% 

294 

* * 

3 

Mo 

35% 

268 

6 

Mo 

37% 

265 

Mean 

Number of 

inches 

12 

11 0 

Mean 

Change 

10 Score –1 

9 

8 



–2 

–3 

Pre 

Op 

* 

1 

Wk 

75% 

295 

* 

3 

Wk 

– 

323 

61% 

278 

* 

6 

Wk 

62% 

276 

3 

Mo 

54% 

250 

6 

Mo 

58% 

248 

Mean 

Kilograms 

of 

Pressure 

29 

28 

27 

26 

25 

24 

23 

Mean 

Change 

Score 



1 

1 

–1 

–2 

–3 

Pre 

Op 

* 

1 

Wk 

68% 

323 

* 

68% 

309 

3 

Wk 

– 

354 

* 

6 

Wk 

63% 

301 

* 

3 

Mo 

61% 

271 

6 

Mo 

52% 

258 

Figure 1-6. Functional recovery after major abdominal operation. Recovery is 

shown as mean individual change from preoperative baseline and 95% confidence 

intervals, with worsened function below a zero line representing preoperative status; 

a score of −1 indicates a one-point worsening relative to the preoperative baseline. 

An additional “shadow” y-axis is shown for orientation to mean summary or total 

scores. Asterisks indicate statistically significant differences from preoperative baseline, 

adjusted for multiple comparisons. MMSE, Mini-Mental State Exam; SF36, 

Medical Outcomes Study Short Form-36. (Reprinted with permission from Lawrence 

et al. 21 )


place, and, barring an operation in which the ear is within 

the sterile operative field, hearing aids can be left in during 

surgery. Modern hearing aids do not pose a risk to the 

patient associated with the use of electrocautery and, if not 

within the primary electrical path, are not at risk for 

damage from electrocautery units. Having the hearing aid 

in place assists communication during emergence and in 

the postanesthesia care unit. 

Loss of visual acuity is also common in the elderly. Visual 

acuity is included in a number of geriatric-care paradigms, 

including those that approach the prevention of perioperative 

delirium by means of making visual orientation easier. 

Cataracts can be particularly problematic. Before major 

surgery that is truly elective and schedulable, such as a 

total hip replacement, serious thought should be given to 

correcting the patient’s vision if they have bilateral dense 

cataracts. Although less likely to have major impact, given 

the opportunity, a visit to an eye doctor to maximize visual 

acuity, perhaps through a change in correction, may be 

beneficial to the patient. The patient may be better able to 

read and utilize rehabilitation aids. 

A particularly important issue in perioperative geriatrics 

is the role of the geriatrician. In the 1980s, geriatricians 

began evaluating a concept generally referred to as 

comprehensive geriatric assessment (CGA). CGA is a 

multidimensional, interdisciplinary, diagnostic process to 

identify care needs, plan care, and improve outcomes of 

frail older people. 25 The benefits of CGA are to improve 

diagnostic accuracy, optimize medical treatment, and 

improve medical outcomes (including functional status 

and quality of life). 

Figure 1-7. Organ system–based vertical approach to preoperative 

assessment of the elderly patient by an anesthesiologist 

differs from the traditional diagnostic approach because it 

applies the various techniques of inquiry (shaded bars) sequentially 

to each major organ system (open bars) in order to assess 

organ function and functional reserve. The primary objective of 

preoperative assessment should be evaluation of physical status 

rather than the identification of specific underlying disorders. 

(Reprinted with permission from Muravchick S. Preoperative 

assessment of the elderly patient. Anesthesiol Clin North Am 

2000;18(1):71–89, vi.) 

Table 1-4. Focus areas for assessment of geriatric patients. 

Medical 

Organ function and reserve 

Medical illnesses 

Medications 

Nutrition 

Dentition 

Hearing 

Vision 

Pain 

Urinary incontinence 

Mental 

Cognitive status 

Emotional status 

Spiritual status 

Physical 

Functional status 

Balance and gait 

Falls 

Environmental 

Social, financial status 

Environmental hazards 

In the perioperative arena, cooperative programs that 

feature some version of CGA have been evaluated. The 

most common perioperative environment for these programs 

has been hip fracture services. In a review of orthogeriatric 

care, Heyburn and colleagues 26 described four 

models that have been applied to hip fracture patients: 

the traditional model in which care is directed by the 

orthopedic surgeon and medical queries are directed to a 

consultant; the second is a variation in which multidisciplinary 

rounds with geriatricians and surgeons increase 

awareness of cross-specialty issues; the third involves 

early postoperative transfer to a geriatric rehabilitation 

unit; and the fourth is combined orthogeriatric care in 

which the patient is admitted to a specialized ward where 

care is coordinated by geriatricians and orthopedic surgeons. 

Delirium is a common complication following hip 

fracture and has been the primary outcome of interest 

for some of these studies. (See also Chapters 9 and 24.) 

Edward Marcantonio conducted a randomized trial of 

proactive geriatric consultation based on a structured protocol 

for patients with hip fractures (Table 1-5). The intervention 

reduced delirium by more than one-third. 

In his review for the Freeman lecture, Rubenstein succinctly 

summed up the general state of affairs when he 

remarked that, despite the relatively consistent body of 

evidence supporting the utility of CGA and other geriatric 

follow-up programs, they have failed to be instituted 

on a wide scale. Soon after the initial successful reports, 

the institution of prospective payment diagnostic related 

groups (DRG) as part of the Medicare program made 

any additional stay in the hospital unprofitable. In fact, 

although CGA is effective at preventing rehospitaliza-


Table 1-5. Module with recommendations from Marcantonio’s Active Geriatric Consultation. 

1. Adequate central nervous system oxygen delivery: 

a) Supplemental oxygen to keep saturation >90%, preferably >95% 

b) Treatment to increase systolic blood pressure >2/3 baseline or >90 mm Hg 

c) Transfusion to keep hematocrit >30% 

2. Fluid/electrolyte balance: 

a) Treatment to restore serum sodium, potassium, glucose to normal limits (glucose


maintains the Syllabus on Geriatric Anesthesiology which 

can be found on the ASA’s Web site, www.asahq.org/ 

clinical/geriatrics/geron.htm. The Society for the Advancement 

of Geriatric Anesthesia (SAGA) was formed in 

1999 with the mission of improving the care of older 

patients having surgery. SAGA sponsors an annual 

meeting and provides organizational guidance for individuals 

interested in the perioperative care of the elderly 

(www.sagahq.org). A longer-standing effort in the United 

Kingdom is the Age Anaesthesia Association (www. 

aaa-online.org.uk/). The American Geriatrics Society 

has developed a Section on Surgical and Related Specialties 

that organizes educational efforts as well as supports 

a number of research funding opportunities to sup - 

port investigation into perioperative geriatrics (www. 

americangeriatrics.org/specialists/). The Section supports 

the Geriatric Syllabus for Specialists as well as the 

Research Agenda Setting Process. 28 

Conclusion 

This introductory chapter outlines the broad scope of 

perioperative geriatric care and provides a perspective 

with which to utilize the information in the remainder of 

this text. Geriatric care is, by nature complex, multidisciplinary, 

and evolving. There is much yet to be learned in 

the area of perioperative geriatrics, but still many practices 

and procedures are known and can be used to 

improve the quality of perioperative care today. 

References 

1. Reuben DB, Herr KA, Pacala JT, Pollock BG, Potter JF, 

Semla TP. Geriatrics at Your Fingertips. 8th ed. New York: 

American Geriatrics Society; 2006. 

2. DeFrances CJ, Podgornik MN. 2004 National Discharge 

Survey. 371. 5-4-2006. Hyattsville, MD: National Center for 

Health Statistics. Advance Data from Vital and Health 

Statistics. 

3. Mangano DT. Preoperative risk assessment: many studies, 

few solutions. Is a cardiac risk assessment paradigm possible? 

Anesthesiology 1995;83:897–901. 

4. Ochsner A. Is risk of operation too great in the elderly? 

Geriatrics 1927;22:121. 

5. Klopfenstein CE, Herrmann FR, Michel JP, Clergue F, 

Forster A. The influence of an aging surgical population on 

the anesthesia workload: a ten-year survey. Anesth Analg 

1998;86:1165–1170. 

6. Lakatta EG, Levy D. Arterial and cardiac aging: major 

shareholders in cardiovascular disease enterprises. Part I. 

Aging arteries: a “setup” for vascular disease. Circulation 

2003;107:139–146. 

7. Rowe JW, Kahn RL. Human aging: usual and successful. 

Science 1987;237:143–149. 

8. Tiret L, Desmonts JM, Hatton F, Vourch G. Complications 

associated with anaesthesia: a prospective survey in France. 

Can Anaesth Soc J 1986;33:336–344. 

9. Rothschild JM, Bates DW, Leape LL. Preventable medical 

injuries in older patients. Arch Intern Med 2000;160:2717– 

2728. 

10. de Rosnay J. Homeostasis: resistance to change. Heylighen 

F, Joslyn C, Turchin V, eds. Brussels: Pincipia Cybernetica; 

1997. Available at: http://cleamc11.vub.ac.be/homeosta.html. 

11. Lindeman RD. Renal physiology and pathophysiology of 

aging. Contrib Nephrol 1993;105:1–12. 

12. Whalley LJ, Deary IJ, Appleton CL, Starr JM. Cognitive 

reserve and the neurobiology of cognitive aging. Ageing 

Res Rev 2004;3:369–382. 

13. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: 

evidence for a phenotype. J Gerontol A Biol Sci Med Sci 

2001;56:M146–M156. 

14. Morley JE, Haren MT, Rolland Y, Kim MJ. Frailty. Med Clin 

North Am 2006;90:837–847. 

15. Wolfe RR. The underappreciated role of muscle in health 

and disease. Am J Clin Nutr 2006;84:475–482. 

16. Wolfe RR. Optimal nutrition, exercise, and hormonal 

therapy promote muscle anabolism in the elderly. J Am Coll 

Surg 2006;202:176–180. 

17. Hamel MB, Henderson WG, Khuri SF, Daley J. Surgical 

outcomes for patients aged 80 and older: morbidity and 

mortality from major noncardiac surgery. J Am Geriatr Soc 

2005;53:424–429. 

18. Verbrugge LM, Jette AM. The disablement process. Soc Sci 

Med 1994;38:1–14. 

19. Lawton MP, Brody EM. Assessment of older people: 

self-maintaining and instrumental activities of daily living. 

Gerontologist 1969;9:179–186. 

20. Palmer RM, Counsell S, Landefeld CS. Clinical inter - 

vention trials: the ACE unit. Clin Geriatr Med 1998;14: 

831–849. 

21. Lawrence VA, Hazuda HP, Cornell JE, et al. Functional 

independence after major abdominal surgery in the elderly. 

J Am Coll Surg 2004;199:762–772. 

22. Sessler DI. Perianesthetic thermoregulation and heat 

balance in humans. FASEB J 1993;7:638–644. 

23. Aronovitch SA. Intraoperatively acquired pressure ulcer 

prevalence: a national study. J Wound Ostomy Continence 

Nurs 1999;26:130–136. 

24. Kim HH, Barrs DM. Hearing aids: a review of what’s new. 

Otolaryngol Head Neck Surg 2006;134:1043–1050. 

25. Rubenstein LZ, Joseph T. Freeman award lecture: comprehensive 

geriatric assessment—from miracle to reality. 

J Gerontol A Biol Sci Med Sci 2004;59:473–477. 

26. Heyburn G, Beringer T, Elliott J, Marsh D. Orthogeriatric 

care in patients with fractures of the proximal femur. Clin 

Orthop Relat Res 2004;(425):35–43. 

27. Vidan M, Serra JA, Moreno C, Riquelme G, Ortiz J. Efficacy 

of a comprehensive geriatric intervention in older patients 

hospitalized for hip fracture: a randomized, controlled trial. 

J Am Geriatr Soc 2005;53:1476–1482. 

28. Solomon DH, LoCicero J, Rosenthal RA, eds. New Frontiers 

in Geriatrics Research. An Agenda for the Surgical and 

Related Medical Specialties. New York: American Geriatrics 

Society; 2004.

2 

Demographics and Economics of Geriatric 

Patient Care 

Maria F. Galati and Roger D. London 

Anesthesiologists in geriatric practice care primarily for 

patients who are insured via Medicare, the federal health 

insurance program for citizens over the age of 65. The 

Medicare program has grown steadily in complexity and 

cost since its inception in 1965. It is expected to come 

under significant financial pressure as the population of 

the United States ages and the costs of providing health 

care continue to grow at ever-increasing rates. 

This chapter is intended to provide those anesthesiologists 

who care for the geriatric patient population with 

an introduction to key health policy issues related to the 

Medicare program and to facilitate understanding of the 

demographics and economics of geriatric care with special 

emphasis on Medicare. The first part of the chapter is a 

general introduction and overview of the demographic 

and financial issues facing Medicare in the near future. 

The second part of the chapter raises some of the major 

policy issues that are specific to the practice of anesthesiology 

under the Medicare program. 

Medicare Demographics and 

Financing Issues 

The Enactment of the Medicare Program 

Medicare is the federal program that provides health care 

insurance to all citizens who are at least 65 years old and 

to some disabled Americans. The program was enacted 

in 1965 with passage of one of the most important pieces 

of domestic legislation of the post-World War II period, 

but the legislative process that preceded it was marked 

by years of debate and controversy. 

From the Eisenhower administration forward, the 

United States government struggled with how best to 

meet the high cost of health care for the elderly. Results 

of the 1950 census revealed that since 1900 the aged 

population had grown from 4% to 8% of the total population. 

Two-thirds of the elderly had annual incomes of 

less than $1000, and only 1 in 8 had health insurance. 1 In 

response to the crisis, bills proposing hospital insurance 

for the aged were introduced in every Congress from 

1952 through 1965. 2 

Legislators recognized and feared the power of organized 

medicine to thwart passage of legislation that 

involved government-sponsored health insurance. Therefore, 

when the Johnson Administration made its proposal, 

it included only a mandatory plan for covering hospital 

expenses for the elderly. This plan is what eventually 

became known as “Medicare Part A.” 

It was the Chairman of the House Ways and Means 

Committee in 1965, Congressman Wilbur Mills, who fashioned 

a compromise that led to the creation of “Medicare 

Part B,” a voluntary plan for coverage of physician 

expenses for the elderly that was acceptable to the 

American Medical Association (AMA). In the compromise 

proposal for Medicare Part B, physician expenses 

were to be reimbursed on “usual and customary” charges 

as long as they were “reasonable.” 3 Physicians also 

retained the right to bill patients directly and in excess of 

the amount reimbursed by the government. 

On July 30, 1965, President Lyndon Johnson enacted 

the Medicare and Medicaid programs by signing the 

Social Security Act of 1965 with these words: 

There are men and women in pain who will find ease. There are 

those alone and suffering who will now hear the sound of ap - 

pro aching help. There are those fearing the terrible darkness 

of despair and poverty—despite long years of labor and expectation—who 

will now see the light of hope and realization. 4 

The Organization and Funding of Medicare 

The Social Security Administration administered the Medicare 

program from 1965 until 1977, when Medicare was 

reorganized under the Health Care Financing Administration 

(HCFA) within the Department of Health, Education 

and Welfare. In July 2001, HCFA was renamed the Centers 

for Medicare and Medicaid Services (CMS). 5 In 1966, the 

15

16 M.F. Galati and R.D. London 

Medicare program covered more than 19 million citizens 

over the age of 65. Coverage for the disabled began in 1973 

and, as of 2003, the program served more than 40 million 

Americans: 35 million elderly and 6 million disabled. 6 

The Medicare program provides coverage to the aged, 

the permanently disabled, and people with end-stage 

renal disease under two parts: Hospital Insurance (HI) or 

Medicare Part A, and Supplementary Medical Insurance 

(SMI) or Medicare Part B. The Medicare + Choice 

managed-care plan, also known as the “Medicare Advantage” 

program or Medicare Part C, was added by the 

Balanced Budget Act of 1997 and allows beneficiaries to 

opt for enrollment in private-sector–managed Medicare 

insurance plans. The Medicare Prescription Drug Improvement 

and Modernization Act of 2003 became effective in 

2006, and extended a new prescription drug benefit to 

Medicare beneficiaries known as Medicare Part D. 

The CMS contracts with private-sector agents to 

administer Medicare program services, including provider 

enrollment and claims administration processes. 

Contractors that process Part A claims are known as 

fiscal intermediaries and those that administer Part B 

claims are known as carriers. These contractors are usually 

insurance companies, many of which are Blue Cross-Blue 

Shield plans around the United States that can act as both 

fiscal intermediaries and contractors. Contractors are 

barred by law from making a profit on services provided 

to the Medicare program. 

Enrollment in Medicare Part A is automatic for eligible 

beneficiaries and covers inpatient hospital care, afterhospital 

care in skilled nursing facilities, hospice care, and 

some home health services. Beneficiary enrollment in 

Medicare Part B is voluntary and covers physician services, 

outpatient hospital services, diagnostic tests, some 

home health services, and medical equipment and supplies. 

By law, 25% of Part B program costs must come 

from beneficiary premiums. 

Employers and employees who make mandatory contributions 

to the Part A Hospital Insurance Trust Fund 

finance the majority of the Medicare program costs. Other 

funding sources include general tax revenues, and the 

premiums, deductibles, and copayments paid by the 

beneficiaries. Of the Medicare program’s annual expenses 

($214.6 billion in 1997), 89% are funded by people under 

the age of 65 in the form of payroll and income taxes and 

interest from the trust fund. Only 11% comes from 

monthly premiums paid by the beneficiaries. 7 

Twenty-First Century Realities and the Future 

of the Medicare Program 

Baby Boomer Demographics 

The so-called “baby boomer generation,” the post-World 

War II Americans born between 1946 and 1964, will have 

a significant impact on the demographics of our society 

and on the Medicare program. It is predicted that as the 

boomers age, the number of people in the United States 

aged 65 years and older is expected to roughly double to 

77 million by the year 2030. 8 

Given the existing Medicare funding system, it is clear 

that the aging of the American population will bring fiscal 

pressures to bear on the Medicare program in two ways. 

There will be more retired beneficiaries, as boomers age 

and live longer than their parents, and there will be fewer 

workers to pay for the retiree expenses. 9 

It is predicted that the over-65 age group will grow 

from approximately 13% of the total population in 2000 

to 20% in 2030 and will remain above 20% for at least 

several decades thereafter. 10 In addition, life expectancies 

are continuing to increase, and typical boomers are 

projected to live approximately 2 years longer than their 

parents did, spending more years in retirement (Figure 

2-1). At the same time, the labor force is expected to grow 

much more slowly than the population of retirees, resulting 

in many fewer workers per retiree. In 2000, there were 

4.8 people ages 20 to 64 for each person age 65 or older. 

This ratio is expected to decrease to approximately 2.9 

people ages 20 to 64 for each person age 65 or older by 

2030 (Figure 2-2). 

Although baby boomers report an intention to work 

longer than their parents did, it remains to be seen 

whether employers will accommodate this expectation 

and what effect this may have on the projected decrease 

in the worker–retiree ratio. Thus, retirement of the baby 

boomer generation will strain the already vulnerable 

Medicare program. The Social Security and Medicare 

90 

85 

80 

Women 

Actual 

Men 

Projected 

75 

0 

1940 1960 1980 2000 2020 2040 2060 2080 

Figure 2-1. Life expectancy of 65-year-olds. (From Congressional 

Budget Office based on Social Security Administration. 

The 2003 annual report of the Board of Trustees of the Federal 

Old-Age and Survivors Insurance and Disability Insurance 

Trust Funds. March 17, 2003. p. 86. Available at: www.ssa.gov/ 

OACT/TR/TR03/tr03.pdf.)

2. Demographics and Economics of Geriatric Patient Care 17 

6 

5 

4 

3 

2 

1 

Actual 

Projected 

0 

1960 1980 2000 2020 2040 2060 2080 

Figure 2-2. Ratio of population ages 20 to 64 to population 

ages 65 and older. (From Congressional Budget Office based on 

Social Security Administration. The 2003 annual report of the 

Board of Trustees of the Federal Old-Age and Survivors 

Insurance and Disability Insurance Trust Funds. March 17, 2003. 

p. 82. Available at: www.ssa.gov/OACT/TR/TR03/tr03.pdf.) 

Boards of Trustees are predicting that starting in 2010, 

when the baby boom generation begins to retire, the 

Hospital Insurance Trust Funds will experience rapidly 

growing annual deficits leading to fund exhaustion by 

2019. 11 The report also predicts that the Supplemental 

Medical Insurance Trust Fund, which pays for physician 

services and the new prescription drug benefit, will have 

to be funded by large increases in premiums and increased 

transfers from general revenues. 

Baby Boomer Expectations 

The baby boomer generation will bring millions of people 

into the Medicare program and these new beneficiaries 

will also bring with them a new set of expectations. Baby 

boomers constitute the first generation born to the Medicare 

program and the first with significant experience 

with managed medical insurance plans. Baby boomers 

also include a significant number of women with working 

experience and, in general, are more affluent than their 

forebears. They expect to enter retirement with more 

assets and with high expectations of the retirement 

experience. 

A survey conducted by Roper Starch Worldwide for 

the American Association of Retired Persons (AARP) 

and entitled, “Baby-Boomers Envision Their Retirement: 

An AARP Segmentation Analysis,” examined the expectations, 

attitudes, and concerns of the baby boomers as 

they approach retirement. There were several key attitudinal 

findings from the survey. Most baby boomers 

believe that they will still be working during their retirement 

years. This is unlike previous generations and has 

important implications for employers as well as the Medicare 

program. 

Only one in five boomers expects to move to a new 

geographic area when they retire and almost one in four 

expects to receive an inheritance that will affect their 

retirement planning. Only approximately 35% expect 

that they will have to scale back their lifestyle during 

retirement and only 16% believe that they will have 

serious health problems when they are retired (AARP 

op. cit.). These are very optimistic views of the extent to 

which baby boomers’ retirement years will be disrupted 

by particular life events. 12 

Less optimistic conclusions emerged when the survey 

examined attitudes toward Social Security and Medicare: 

55% had a very or somewhat favorable view of Social 

Security and 60% had a favorable view of Medicare. 

However, only 46% said that they were very or somewhat 

knowledgeable about Medicare and only 40% were confident 

that Medicare would be available to them during 

retirement. Indeed, baby boomers were much less confident 

in their abilities under Medicare to access care, 

choose their own doctors, or to consult specialists at 

the same level as under their current health plan (AARP 

op. cit.). 

Medicare Coverage Gaps 

These less optimistic baby boomer attitudes may reflect 

an astute appreciation of the limitations of the Medicare 

program. Benefits under the Medicare program are significantly 

limited. One study has found that 80% of 

employer-sponsored fee-for-service plans cover a larger 

proportion of medical expenses than Medicare does. 13 

Medicare has not traditionally covered services such as 

long-term nursing care, outpatient prescription drugs, or 

routine vision, dental, hearing, and foot care. The 

Balanced Budget Act of 1997 extended coverage to 

include annual mammograms, Pap smears, prostate and 

colorectal screenings, diabetes management, and osteoporosis 

diagnosis. In December 2003, when the new prescription 

drug benefit was signed into law, it was projected that 

average out-of-pocket prescription drug spending for 

Medicare beneficiaries would be lower; however, it was 

also expected that 25% of beneficiaries would actually 

pay more as a result of the new coverage. 14 Furthermore, 

it is estimated that 3.1 million low-income subsidy-eligible 

beneficiaries are not receiving this assistance and therefore 

still face financial barriers in accessing necessary prescription 

drugs. 15 It will take years to fully assess the 

impact of this latest change in Medicare benefits on beneficiaries, 

providers, and the program itself. 

Medicare beneficiaries rely on privately purchased or 

government-sponsored supplemental insurance plans to 

“tie in” and complement the array of services covered by 

the Medicare program. Supplemental insurance coverage


As a result of these various coverage options, Medicare 

beneficiaries are either not covered at all or are partly 

covered in a somewhat unpredictable way. This variability 

challenges practicing geriatric medicine providers to 

become knowledgeable about the specific situation in 

which each of their Medicare-eligible patients can find 

themselves, especially as it may relate to the patient’s 

ability to comply with treatment plans. 

Figure 2-3. Supplemental insurance status of Medicare beneficiaries, 

1999. (From Rice and Bernstein. 16 ) 

for these services has been historically provided by Medicaid 

plans (for the poor) and by so-called “Medigap” 

policies for those able to afford additional coverage. 

In 1999, approximately 91% of Medicare beneficiaries 

relied on supplemental insurance plans. Of those with 

supplemental insurance, 27% purchased Medigap insurance 

and 36% received supplemental insurance related 

to employment. An additional 17% were enrolled in 

Medicare + Choice plans and 11% qualified for coverage 

through Medicaid. The remaining 9% had no supplemental 

coverage (Figure 2-3). 16 In 1996, Medigap premiums 

across the nation ranged from $233 annually for the leastexpensive 

basic coverage, to $2205 annually for the most 

comprehensive plan. 17 

Some employers, mostly large companies, also sponsor 

plans that cover retired workers and their spouses. In 

2006, 35% of firms with more than 200 employees offered 

retiree health benefits, with 77% of firms in this category 

covering Medicare-eligible retirees. In 1988, before implementation 

of the Part D drug benefit, 66% of large firms 

offered retiree coverage. 18 

The poorest Medicare recipients have their medical 

costs paid in part by the Medicaid program. Of these 

“dual eligibles,” those with incomes and resources substantially 

below the federal poverty line are entitled to 

full Medicaid coverage. Specifically, eligibility for full 

Medicaid coverage is determined by whether an individual 

qualifies for Supplemental Security Income, an income 

maintenance program designed for very poor aged, 

disabled, and blind Americans. Thus, Medicaid provides 

complementary coverage for a portion of Medicare 

beneficiaries. 

Unlike Medicare, Medicaid coverage includes benefits 

such as prescription drugs, hearing aids, and payment 

for nursing home services. The Medicaid program also 

makes premium payments and pays a portion of Medicare 

deductibles and other copayments required of 

beneficiaries. Because this assistance must be claimed 

by beneficiaries through an application process, a substantial 

portion of potentially eligible low-income individuals, 

perhaps as many as 3.9 million, do not receive 

this aid. 19 

Prescription Drug Benefit 

Medicare was late in providing prescription drug coverage 

compared with most private insurance plans, and the 

universal public health plans in other developed nations, 

that have traditionally provided this benefit as an important 

part of comprehensive health coverage. Drug therapies 

can reduce the need for hospitalization by effectively 

managing chronic health problems of the elderly such as 

heart disease, diabetes, and depression. Chronically ill 

patients have been found to underuse essential medications 

because of cost considerations and to suffer serious 

health consequences, including an increased number of 

emergency room visits and inpatient admissions, as a 

result. 20 

In 1998, 73% of noninstitutionalized Medicare beneficiaries 

had drug coverage of some kind for at least a 

portion of the year through supplemental insurance, such 

as managed Medicare plans, employer-sponsored plans, 

and Medigap plans. 21 However, the out-of-pocket spending 

by older Americans for prescription drugs amounts 

on average to 50% of total costs, compared with just 34% 

of costs for those under age 65. 22 The prices of the prescription 

drugs used most often by the elderly have been 

increasing in recent years. Expensive new brand-name 

drugs, some of which are more effective than the older 

drugs that they are superseding, are being brought to 

market at an increasingly rapid rate. 23 

In a recent nationwide survey of chronically ill older 

adults, it was reported that 33% underuse prescription 

drugs because of concerns about out-of-pocket drug 

costs. Furthermore, 66% of these patients failed to discuss 

their intention to underuse medications with a clinician 

citing that no one asked about their ability to pay and 

that they did not believe that providers could offer any 

assistance. 20 

Impact on the Near-Poor 

It is the near-poor, those with annual incomes between 

$10,000 and $20,000, who are most often caught in the 

prescription drug cost quandary. In 1999, only 55% of the 

near-poor had coverage for the entire year and more than 

20% of those with prescription drug coverage received it 

via a Medicare Advantage plan. Access to prescription 

drugs and levels of reimbursement for prescription 

drugs has decreased significantly under these managed-


$250 

Benefit Limit 

$2,250 

Limit for Catastrophic Care 

$5,100 

Beneficiary responsible for costs 

Costs covered by Medicare 

100 

Prescription-Drug 

Coverage (%) 

75 

50 

25 

Medicare covers 

75% 

Beneficiary pays 100% 

of discounted drug price Medicare covers 95% 

0 

0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 8,000 9,000 10,000 

Beneficiary’s Prescription-Drug Costs in a Year ($) 

Figure 2-4. Prescription drug coverage under Medicare effective 2006. (Reproduced with permission from Iglehart. 25 Copyright 

© 2004 Massachusetts Medical Society. All Rights Reserved.) 

Medicare plans since the Balanced Budget Act of 1997. 

As a result, the near-poor had higher out-of-pocket costs 

for prescription drugs in 1999 than other Medicare 

beneficiaries who were poorer (and therefore, Medicaideligible), 

and those with higher incomes. 24 Unfortu - 

nately, the new prescription drug benefit may not lead 

to a significant reduction in out-of-pocket prescription 

drug costs for these near-poor beneficiaries who will 

incur costs that fall through gaps in the coverage 

(Figure 2-4). 

In the intervening years before implementation of the 

new prescription drug benefit, there were some opportunities 

for the more than 33% of beneficiaries with no 

prescription drug benefits at all. Between 2004 and 2006, 

Medicare beneficiaries were eligible for drug-discount 

cards that were expected to save them up to 10%–15% 

on their total drug costs. In addition, beneficiaries with 

incomes below 135% of the federal poverty level were 

eligible for a $600 per year subsidy. 25 These opportunities 

expired when the new drug benefit took effect in 2006. 

Medicare and the Academic Health Center 

The Medicare program has many shortcomings and, over 

the next two decades, significant reform will be required 

to maintain even the current level of protection that it 

offers to America’s elderly. This looming crisis in health 

care insurance for the elderly as well as the more than 40 

million uninsured is of great concern to lawmakers and 

the public but should also be of great concern to health 

care providers, hospitals, and physicians, who rely on 

Medicare as a significant source of their revenues. 

In 2000, payments made by the Medicare program 

accounted for 31% of total national spending on hospital 

care and 21% of total national spending on physician and 

clinical services. 26 

Physicians in academic practice have even greater 

reason to be interested in the plight of the Medicare 

program. In addition to the significant flow of funds 

received by Academic Health Centers (AHCs) in the 

form of clinical revenues, AHCs are dependent on the 

Medicare program for support of graduate medical education 

(GME) and care provided to indigent patients. All 

undergraduate medical students and almost 50% of all 

residents are trained in AHCs, which also provide most 

of the charity care and medical specialty services such as 

neonatal, burn and trauma intensive care, and organ 

transplant services. 27 

Graduate Medical Education Payments 

Since the initiation of the Medicare Prospective Hospital 

Payment System in the mid-1980s, GME payments have 

been made to AHCs to reimburse them for Medicare’s 

share of the costs of resident physician education. AHCs 

are eligible for two types of reimbursements: direct GME, 

covering direct costs such as resident and faculty salaries 

and benefits; and indirect GME, recognizing the relatively 

larger inpatient costs at hospitals with teaching 

programs. 

The Federal government has provided more than $100 

billion in GME support to AHCs since the mid-1980s. 

These funds are distributed to approximately 1000 institutions 

based on the number of residents trained, their 

costs in the reference year 1985, and their share of Medicare 

beneficiaries served. The top ten AHCs receive an 

average of $60 million each (12% of the total), and the 

next 40 institutions receive approximately $30 million


each (24% of the total). The remaining institutions share 

approximately 64% of the total. 27 

The Federal government also provides disproportionate 

share payments to 4000 institutions based on the 

number of Medicare and Medicaid patients served. The 

top ten institutions receive only 5% of the total or an 

average of $20 million each and the next 40 institutions 

receive approximately 11% of the total for an average 

of $10 million each. The remaining institutions share 

approximately 85% of the total. 27 

Hospital and physician providers at the AHCs serve 

important roles in meeting the health care needs of 

underserved populations and in advancing the science of 

health care through education and research. These providers 

are paid by Medicare to play this important role 

in shaping the future of the health care system. However, 

the same federal system continually challenges these providers 

to maintain a commitment to education, research, 

and charity care despite declining reimbursement for 

these important activities. 

“Pay for Performance” Initiatives 

The CMS has recognized the need to provide incentives 

to hospital and physician providers who can innovate to 

create improved patient outcomes at lower costs. Several 

demonstration projects are in place to provide hospitals 

with reimbursement bonuses if they meet quality standards 

and report their results to CMS. 

Physicians got their first opportunity to apply to Medicare’s 

physician Pay for Performance (P4P) initiative 

effective in April 2005. The CMS selected 10 physician 

group practices, with 200 or more physicians, which were 

eligible to earn performance payments in addition to 

usual fee-for-service payments. The payments were based 

on how well the groups managed the care of patients to 

prevent complications and avoidable hospitalizations 

thereby enhancing quality and reducing costs under both 

Part A and Part B of the Medicare program. 28 These 

programs do not reward academic activities such as 

teaching, research, and grant work. Therefore, success of 

P4P programs in the academic setting will depend on how 

much of physician compensation is based on clinical 

activity. 29 

Summary 

Many solutions to the looming Medicare crisis have 

been proposed. Common reform measures include 

changes to the age of eligibility, linking premiums to beneficiary 

incomes, increasing revenues via higher payroll 

taxes or counting Medicare benefits as taxable income, 

and altering the concept of Medicare as a defined benefit 

program. 

Pundits will continue to debate the strategy of choice 

for addressing the Medicare funding crisis. Meanwhile, 

physicians and hospitals, especially those with academic 

missions, can have an important role in the public policy 

debate. Health care providers, working with their professional 

organizations, can serve as patient advocates in the 

ongoing debate to facilitate the improvement of insurance 

coverage and the quality of health care services 

provided to the growing elderly population. 

Medicare Policy Issues for the 

Geriatric Anesthesiologist 

The regulations and processes governing a physician’s 

interaction with the Medicare program are quite complex 

and a full description is well beyond the scope of this 

chapter. However, it is the authors’ intention to provide 

the practicing geriatric anesthesiologist with an introduction 

to policy issues specific to the practice of Anesthesiology 

under the Medicare program. These key issues 

include: 

1) Participation status in the Medicare program 

2) Medicare’s Resource Based Relative Value System 

(RBRVS) for physician reimbursement 

3) Medicare’s rules for the anesthesia care team 

4) Compliance-related issues for anesthesiologists 

The CMS provides a specialty-specific page on its Web 

site that is dedicated to Medicare regulations and information 

specific to the practice of Anesthesiology. Physicians 

interested in further study of Medicare claims processing, 

fees and policies for the reimbursement of anesthesia services 

should consult CMS’s anesthesiologist Web page at: 

http://www.cms.hhs.gov/center/anesth.asp. 

Anesthesiologist Participation in 

the Medicare Program 

The decision to enroll as a participating provider in the 

Medicare program is one of the first decisions that an 

anesthesiologist faces when starting a clinical practice. 

Anesthesiologists employed in geriatric practice can 

expect that the Medicare program will be the primary 

insurer for most of their patients. Anesthesiologists, who 

typically encounter their patients in an operating room 

setting where they are not the patient’s primary provider, 

need to be aware of the political, patient satisfaction, and 

reimbursement issues related to their participation status 

in the Medicare program. 

In 1990, only 30.8% of anesthesiologists participated in 

the Medicare program; this was the lowest rate of participation 

as a percentage of physicians by medical specialty. 

By 2003, participation by anesthesiologists had increased


to 95.5%. This rate of participation closely matches that 

of physicians in related practices such as surgery, cardiovascular 

disease, ophthalmology, orthopedic surgery, 

pathology, radiology, urology, and nephrology. 30 

It is likely that the anesthesiologist’s obligation to care 

for all surgical patients and new Medicare rules limiting 

charges from nonparticipating providers, influenced anesthesiologist 

enrollment decisions in the 1990s. Unfortunately, 

as anesthesiologist Medicare participation rates 

increased dramatically in the period from 1990 to 2003, 

the Medicare anesthesia conversion factor in the same 

period was decreased by almost 20%. 31 One might speculate 

that, during a decade of significant growth in managed 

care and public outcry concerning increasing health care 

costs, the pressures from patients, colleagues, local government, 

affiliated institutions, and the Medicare charge 

limitations combined to favor participation by anesthesiology 

providers. 

In general, participation in the Medicare program by 

anesthesiologists is a voluntary decision. [Medicare participation 

by Certified Registered Nurse Anesthetists 

(CRNAs) and Anesthesiologist Assistants (AAs) is mandatory. 

32 ] However, some states encourage physician 

participation through legislative actions and regulatory 

requirements, such as in The Commonwealth of Massachusetts, 

where Medicare participation is a condition 

of medical licensure. Physicians can consult with their 

local Medicare carrier or their regional CMS office for 

local Medicare participation requirements. 33 

Physicians who enroll as participating providers enter 

into a 1-year, automatically renewable agreement to 

accept assignment for all covered services provided to 

Medicare beneficiaries. When a physician accepts assignment, 

they agree to accept the Medicare allowable charge 

as payment in full for the covered services rendered. 

After patients satisfy an annual deductible, Medicare 

pays 80% of the approved allowable charge. The remaining 

20% is termed the “coinsurance” and it is the responsibility 

of the patient to pay this and any remaining 

portion of the annual deductible. Participating providers 

must bill the patient, or the patient’s Medigap insurance 

plan, for coinsurance, deductible, and charges not covered 

by the Medicare Part B program. 

In addition to the likely political and patient sat - 

isfaction advantages to Medicare participation, there 

are also financial and administrative opportunities. The 

most significant are that Medicare fee schedule allowances 

are 5% higher for participating physicians, and 

assigned Medicare claims filed with Medigap insurance 

information are automatically forwarded by Medicare 

to supplemental insurance carriers for processing of 

coinsurance and deductible charges. 34 A copy of the 

Medicare Participating Physician or Supplier Agreement 

(Form CMS-460) is available at http://www.cms.hhs.gov/ 

cmsforms/downloads/cms460.pdf. 

Medicare Payment Methodologies for 

Anesthesia Services 

Medicare’s Resource Based Relative Value System 

In 1992, Medicare implemented the Resource Based 

Relative Value System (RBRVS) that established a 

Medicare Fee Schedule (MFS) of national values for each 

clinical procedure code. The value comprises three relative 

value units that represent the physician’s work effort 

in rendering the service, the practice’s overhead expenses 

for items such as rent, office staff salaries and supplies, 

and malpractice insurance premiums. Under RBRVS, 

Medicare also implemented a new definition of allowed 

charges that paid physicians based on the lesser of the 

submitted charge or the new relative value scale feeschedule–based 

amount. 35 

At the time of the introduction of the MFS in 1992, 

Anesthesiology had already had a relative value scale for 

anesthesia payment in place for 30 years. 36 The American 

Society of Anesthesiologists (ASA) Relative Value Guide, 

adopted almost in its entirety by the HCFA in 1989, uses 

values that represent components of anesthesia services: 

the base unit value related to the complexity of the service 

performed; and the time units based on the actual time 

the anesthesiologist spends with a patient. 

Note the CMS definition of anesthesia time: 

Anesthesia time means the time during which an anesthesia 

practitioner is present with the patient. It starts when the anesthesia 

practitioner begins to prepare the patient for anesthesia 

services in the operating room or an equivalent area and ends 

when the anesthesia practitioner is no longer furnishing anesthesia 

services to the patient, that is, when the patient may be 

placed safely under postoperative care. . . . 37 

Medicare does not reimburse for modifier units, such 

as those designated by the ASA recognizing physical 

status, extremes of age, or unusual risk. 38 

Medicare reimburses anesthesia services via a separate 

methodology under RBRVS that uses the sum of procedure-specific 

relative value units and the variable time 

units. The sum of these units is then multiplied by an 

anesthesia-specific conversion factor that is corrected for 

geographic cost differences. It was the retention of the 

time unit factor in the anesthesia payment methodology 

that drove HCFA to create a separate anesthesia conversion 

factor under RBRVS. 

The Medicare Fee Schedule for Anesthesia Services 

The distinction in the MFS for anesthesiologists has 

disadvantaged the specialty. A good illustration of the 

problem is the differential between Medicare and private 

insurance fees for anesthesiologists versus the differential 

for other medical and surgical specialists. The AMA 

reports that Medicare’s conversion factor for physician


services represents approximately 83% of the conversion 

factor paid by private insurers. For anesthesiologists, the 

Medicare conversion factor represents less than 40% of 

a private insurer’s rate. Therefore, Medicare payments for 

anesthesia services are less than half of Medicare payments 

for other medical and surgical services. 39 

The ASA has raised this issue of disparity in Medicare 

fees many times with the AMA/Specialty Society Relative 

Value Update Committee (RUC). The RUC is the 

body charged with reviewing and advising CMS on 

updates to work-related relative value units that are 

required, by law, at least every 5 years. In the first 5-year 

review, HCFA acknowledged the undervaluation and 

approved a nearly 23% increase in work values for anesthesia 

procedures, effective January 1, 1997. 40 In the fee 

schedule effective after the second 5-year review, CMS 

again received endorsements for reconsideration of the 

anesthesia work relative value units but responded with 

an insignificant adjustment. 41 

The MFS is often referenced by private insurers as a 

standard in setting physician reimbursement rates. It is 

also common for physicians from other specialties, who 

enjoy a more favorable Medicare-to-private insurer fee 

ratio, to suggest the MFS as a proxy for valuing physician 

services. This often occurs during joint negotiations such 

as those used in dividing fees for contracts paid on a 

global basis to physician groups. Anesthesiologists are 

disadvantaged when the MFS is used in this manner. It 

is, therefore, important for anesthesiologists to remain 

active in the discussion of these physician payment disparities 

and to work to educate others and thereby mitigate 

the effect of these disparities in the Medicare system 

and beyond. 

Proposed Changes to the Anesthesia 

Payment Methodology 

Anesthesiologists are involved in these important public 

policy debates via the activities of their professional 

society, the ASA, and the ASA Political Action Committee. 

In late 2003, the ASA charged the “Task Force to 

Study Payment Methodology” with studying the relationship 

of the anesthesiology payment methodology to 

Medicare’s relative value payment system. The Task Force 

projected the threat of decreasing revenues from the 

ongoing undervaluation of anesthesia services under 

Medicare, the adoption of the MFS and payment policies 

by private insurers, and the projected increase in numbers 

of Medicare beneficiaries in the United States. 

The Task Force estimated that, with Medicare beneficiaries 

representing approximately 30% of anesthesia 

services nationwide, a blended conversion factor of 

Medicare and private insurers is $40.25. When Medicare 

accounts for 50% of services, the blended conversion 

factor will decrease to $33.75. Furthermore, if the MFS 

becomes the model for a single-payer system, they predict 

that the blended conversion factor will decrease to $17.50 

(personal communication, Karin Bierstein, Esq., American 

Society of Anesthesiologists, November 30, 2004). 

The Task Force has been exploring a flat fee payment 

methodology that would capture elements both of the 

time and the complexity of care for a continuous period 

of anesthesia for each operative period, involving one or 

more surgical procedures. This methodology would rely 

on a greatly expanded anesthesia code set that would 

incorporate an average anesthesia time representative of 

procedures performed in both the private practice and 

academic settings. 

The Task Force recommendations for a new Medicare 

anesthesia payment methodology will be presented to the 

RUC and, if approved, will be reflected in future fee 

schedule revisions. The principles of the new methodology 

were announced in the following Task Force resolution 

passed by the ASA House of Delegates in October 

2004: 

RESOLVED, That the Executive Committee in consultation 

with the Administrative Council is authorized to propose a 

restructuring of Medicare payments for anesthesia services 

based on the following principles: 

That any new coding system must accurately reflect both the 

complexity and duration of the associated surgical procedures 

to compensate for the elimination of separately reported anesthesia 

time; 

That the inevitable influence of a uniform Medicare conversion 

factor on payment rates in the private sector be thoroughly 

considered; and 

That any transition to a uniform Medicare conversion factor 

must be based on a value sufficient to protect the specialty, as 

a whole and in aggregate, from economic damage. 

These resolutions were referred for further study, and 

the ASA does not expect that a modification in the 

anesthesia payment methodology will occur in the near 

term. 42 

The Sustainable Growth Rate Formula 

The CMS uses a Sustainable Growth Rate (SGR) system 

to determine annual changes in the physician fee schedule. 

This system compares physician spending based on the 

volume and intensity of services provided against spending 

targets tied to inflation and the gross domestic product, 

and adjusts physician fee schedules accordingly to meet 

the targets. In 2002, this process resulted in a 5.4% reduction 

in physician fees, and the need for ongoing reductions 

was predicted up through 2016. This triggered congressional 

interventions that overrode the SGR system in the 

years 2003, 2004, and 2005 and mandated a Government 

Accounting Office (GAO) review of the problem. 43 

Anesthesiologists have a large stake in securing the 

success of these efforts, and other efforts to reform the


Medicare payment methodology specific to anesthesia 

services. However, it is important to note that unless 

there is modification of the SGR statute, any updates to 

the MFS must meet spending targets and, therefore, 

where one physician group gains, others must lose. 

In a period when the Medicare program faces many 

economic challenges, it is unlikely that the interests of 

any one group of physicians will prevail without a strong, 

well-targeted political effort. A focus of this political 

effort in the future will be the discussion of the looming 

problem of access to anesthesia care by the ever-growing 

numbers of Medicare beneficiaries. 

The Anesthesia Care Team 

There are a variety of ways for anesthesiologists to 

provide services for reimbursement under Part B of the 

Medicare program. Medicare reimburses the services of 

an anesthesiologist when the physician personally provides 

them or if an anesthesia care team provides them 

under medical direction or supervision. Anesthesia claims 

modifiers are used to denote whether services were 

provided personally, “medically directed,” or “medically 

supervised.” Medicare reduces reimbursement based on 

the series of claims modifiers that denote how the services 

were delivered (Table 2-1). 

The anesthesia care team is defined as an anesthesiologist 

working with any of the following professionals: 

CRNAs 

AAs 

Residents or interns 

Student Nurse Anesthetists (SNAs) 44 

In most cases, when an anesthesiologist and a CRNA 

are providing a single anesthesia service, Medicare 

recognizes the service as if personally performed by the 

anesthesiologist. 

Medical Direction Versus Supervision of 

Concurrent Procedures 

When an anesthesiologist is involved in directing up to 

four concurrent procedures, Medicare recognizes the services 

as concurrent medical direction and sets out specific 

guidelines for documentation and reimbursement of 

these services. (See Compliance section for documentation 

requirements.) 

Anesthesiologists are allowed to furnish additional 

services to other patients under an exception to the four 

concurrent case limits. This exception, which varies by 

state, generally applies to the following services, if they 

do not “substantially diminish the scope of control exercised 

by the physician” providing the medical direction: 

Addressing an emergency of short duration in the immediate 

area; 

Administering an epidural or caudal anesthetic to ease 

labor pain; 

Providing periodic, rather than continuous monitoring, of 

an obstetric patient; 

Receiving patients entering the operating suite for the 

next surgery; 

Discharging patients in the recovery room; or 

Handling scheduling matters. 44 

When services are provided in excess of four concurrent 

cases and the allowed exceptions, the services will 

fail to meet the medical direction requirements. These 

services are provided under what Medicare terms medical 

“supervision” and are reimbursed to the physician at a 

fraction of the MFS allowable through limits in billing for 

base and time units. Under the supervision requirements, 

Table 2-1. CMS Anesthesia Care Team Claims Modifiers Matrix. 

Modifier CMS definition Payment % of allowable to provider 

AA Anesthesia services performed personally by anesthesiologist 100% to anesthesiologist 

AA/GC Anesthesia services performed personally by anesthesiologist with resident 100% to anesthesiologist 

involvement 

QK Medical direction of up to 4 concurrent anesthesia procedures involving 50% to anesthesiologist 

qualified individuals 

50% to qualified provider* 

QK/GC Medical direction of up to 4 concurrent anesthesia procedures involving 50% to anesthesiologist 

2–4 residents 

QX CRNA service with anesthesiologist medical direction (reported by CRNA) 50% to CRNA 

QY Medical direction of CRNA by anesthesiologist for 1 case (reported by 50% to anesthesiologist 

anesthesiologist) 

AD Medical supervision by a physician; more than 4 concurrent anesthesia 3 base units, no time units. 1 unit if 

procedures 

anesthesiologist documented presence at 

induction 

Source: Author’s compilation from Medicare Carriers Manual, Part 3: Claims Process. Transmittal 1690, Section 4830, Claims for Anesthesia Services 

Performed on and after January 1, 1992. Department of Health and Human Services, The Health Care Financing Administration. Published 

January 5, 2001. 

*Residents are not qualified for reimbursement.


the physician must still ensure that a qualified individual 

performs any procedure in which they do not personally 

participate. 45 

Requirements of the Attending 

Physician Relationship 

Physicians in academic practice fall under additional 

Medicare requirements that govern the “attending physician” 

relationship. This relationship exists when an attending 

anesthesiologist provides care to a patient in a teaching 

hospital involving anesthesia residents. 

In 1992, when RBRVS was introduced, a new rule was 

announced that was to eliminate the practice of full reimbursement 

for an anesthesiologist medically directing 

two concurrent cases with anesthesia residents. The ASA 

was able to persuade Medicare to postpone implementation 

of the new rules until 1994; however, the impact of 

this change has been significant. The ASA estimates that 

the cost to academic anesthesiology programs of this 

change alone exceeds $50 million annually. 46 The ASA 

has been working to encourage CMS to restore full 

payment for two concurrent teaching cases. 

In January 2004, CMS took an interim step toward 

changes in the reimbursement guidelines for medical 

direction of residents. The new rule expands billing 

options for teaching anesthesiologists who are involved 

in providing care with residents for two concurrent anesthesia 

cases. In the new ruling, anesthesiologists can 

choose to bill the usual base units and anesthesia time 

only for the period they are actually present with the 

resident if they are present throughout pre- and postanesthesia 

care and if this is documented. 

In the rule, CMS has also included language that allows 

the attending anesthesiologist to determine if a request 

for payment of the full time payment for both cases is 

warranted. This request must be provided with written 

documentation that he/she spent “sufficient time” with 

each patient considering factors such as patient condition, 

residents’ experience, proximity of the operating rooms, 

and the actual time the attending anesthesiologist spent 

in each operating room in making the determination. 47 

Anesthesiologists choosing to use the interim rule as a 

revenue opportunity must weigh potential benefits against 

the compliance risks and the investments in faculty education 

and system modifications needed to support a new 

documentation and billing process. 

Compliance Issues 

All physicians who interact with the Medicare program 

are obligated to assure that their business practices 

conform to the requirements of the program. This can be 

a daunting task because although a busy participating 

physician can delegate Medicare transaction authority to 

others, he/she retains all of the responsibility and risks 

related to the actions of his/her agents. Furthermore, the 

stakes for providers are high. Physicians who are found 

to be in violation of Medicare regulations can suffer both 

civil and criminal penalties as well as exclusion from the 

program. Physician practices can minimize the risks by 

adopting comprehensive compliance plans and assuring 

thorough internal controls, and training for all physicians 

and staff. 

The Office of the Inspector General (OIG) does not 

mandate the adoption of compliance programs, but they 

have formulated seven fundamental elements of an effective 

compliance program. These elements are: 

• Implement written policies, procedures, and standards 

of conduct 

• Designate a compliance officer and compliance committee 

(e.g., a billing clerk and physician in a small 

practice) 

• Conduct effective training and education 

• Develop effective lines of communication 

• Enforce standards through well-publicized disciplinary 

guidelines 

• Conduct internal monitoring and auditing 

• Respond promptly to detected offenses and develop 

corrective action plans 48 

Anesthesiologists should consult with their compliance 

officers to gain what should be an in-depth understanding 

of their obligations as providers in the Medicare program. 

An introduction to some of the key compliance issues 

affecting anesthesia practice, including reassignment of 

benefits, Medicare fraud and abuse initiatives, and medical 

record documentation follows. 

For further information on compliance programs, one 

should consult the OIG postings in the Federal Register 

and on the OIG Web site at http://oig.hhs.gov/fraud/ 

complianceguidance.html. 

Reassignment of Medicare Benefits 

Anesthesiologists who provide care to Medicare beneficiaries 

undertake responsibility for compliance with 

myriad complex and sometimes conflicting regulations. 

Anesthesiologists who practice in a group or academic 

setting, where administrative duties for billing and collections 

are delegated and Medicare payments are frequently 

reassigned to another entity, should be best informed of 

these responsibilities. 

When a physician reassigns benefits under the Medicare 

program, they legally authorize another person or 

entity to bill Medicare on their behalf and to receive 

payments that would otherwise be sent directly to them. 

However, despite this written delegation of authority, 

the physician retains all responsibility for ensuring that 

the claims made on their behalf are in full compliance


with Medicare regulations. In addition, the physician 

retains responsibility for assuring that their agent meets 

all confidentiality obligations and other state and federal 

regulations. 

Even the best-intentioned physician may encounter 

difficulties in determining how to meet his/her obligations 

for compliance with Medicare regulations. The 

GAO tested the accuracy of carriers’ responses to inquiries 

in a telephone audit. The GAO asked staff at the 

Medicare carriers to respond to “frequently asked questions” 

concerning physician billing procedures that were 

taken from the carriers’ own Web sites. The GAO survey 

report concluded that physicians who do call their carriers 

with questions would “more often than not receive 

wrong or inaccurate answers.” These problems were 

attributed to limits on resources for information system 

modernization and oversight activities, and limits on 

CMS’s authority imposed by the Congress and Executive 

branches. 49 

Medicare Fraud and Abuse 

Although the federal government has chosen to limit 

CMS resources for facilitating its administrative mission, 

it has significantly increased resources for the investigation 

of fraud and abuse. Public administration experts 

have noted that these resources could be better spent on 

preventive measures such as improved management of 

the program and effective measures to monitor and deter 

inappropriate payments, thereby minimizing the need 

for enforcement. However, this has not occurred and, 

as of 2000, CMS spent more than 25% of its total administrative 

expenses in its campaign against fraud and 

abuse. 49 

Many federal agencies are involved in protecting the 

Medicare program and ensuring provider compliance 

with all regulations. The OIG in the Department of 

Health and Human Services investigates suspected Medicare 

fraud or abuse and develops cases against providers. 

It has the authority to audit and inspect CMS programs 

and to act against individual providers with civil money 

penalties and/or exclusion from participation in all federal 

health care programs. The OIG also has authority to refer 

cases to the United States Department of Justice for 

criminal or civil action. 50 In its 2006 semiannual report, 

the OIG evidenced an active role in combating waste, 

fraud, and abuse, citing savings of more than $38.2 billion, 

3425 exclusions, 472 criminal actions against individuals 

and entities, and 272 civil actions. 51 

Medicare defines fraud as “the intentional deception 

or misrepresentation that an individual knows to be false 

or does not believe to be true and makes, knowing that 

the deception could result in some unauthorized benefit 

to himself/herself or some other person.” Abuse relates 

to practices that directly or indirectly result in unnecessary 

costs to the Medicare program. It is similar to fraud 

but is found when there is no evidence that the acts were 

committed knowingly, willfully, and intentionally. 52 

Some examples of fraud that should be immediately 

apparent to providers include activities such as the 

falsification of records, billing for services that were not 

furnished, or misrepresenting the type of service provided 

by using inappropriate codes. However, other 

actions that also constitute fraud and abuse may not be 

as apparent to providers. These include providing incentives 

to Medicare patients not provided to other patients 

such as the routine waiving or discounting of patient 

coinsurance and deductible payments. Other actions 

include billing Medicare on a higher fee schedule than 

other patients, breaching the agreements to accept assignment 

or participate in the Medicare program, or failing 

to provide timely refund of overpayments made by Medicare 

and beneficiaries. 52 

Physicians at Teaching Hospitals: Office of the 

Inspector General Initiative 

Physicians in academic practice have been made most 

keenly aware of government efforts to enforce compliance 

with Medicare rules. Over the past decade, the government 

recovered $149 million from 15 universities that 

failed to document compliance with Medicare payment 

policies related to attending physician supervision of services 

provided with resident involvement. 49 

The Physicians at Teaching Hospitals (P.A.T.H.) initiative 

of the OIG has had long-lasting and costly effects on 

academic practices. Physician groups that paid settlements 

or were subject to civil or criminal prosecution 

were required to enter into multi-year Institutional Compliance 

Agreements with the federal government. These 

agreements impose requirements that closely follow the 

structure of a compliance program but can be more stringent. 

53 They obligate practices to develop and adhere to 

a rigorous set of compliance standards involving audits 

of physician billing practices and annual physician and 

staff education, under threat of additional penalties. 

AHCs have reported that annual compliance program 

costs, after P.A.T.H. settlement, are absorbing millions 

of dollars. 54 

Documentation Requirements 

Medical record documentation is the primary source 

used for judging compliance with Medicare regulations. 

Documentation should be timely and must support the 

medical necessity of the service as well as the level and 

scope of service provided. As with all medical record 

documentation, it must be legible and signed by the 

provider. Bills should not be submitted unless adequate 

documentation exists for the services.


Documentation of Anesthesia Time 

The prominence of time in the Medicare reimbursement 

methodology for anesthesiologist services drives documentation 

requirements. Since January 1, 1994, Medicare 

has reimbursed anesthesia time based on the actual 

number of minutes of anesthesia provided calculated in 

fractions of 15-minute units, rounded to one decimal 

place. 37 This standard for the precise documentation and 

reporting of anesthesia time presents challenges, especially 

in practices without automated anesthesia recordkeeping 

systems. 

Unsynchronized timepieces within the operating room 

suite can create disparities in timekeeping documentation 

as recorded by the anesthesiologist and other 

members of the surgical team such as nurses, perfusionists, 

and surgeons. Unsynchronized timepieces between 

anesthetizing locations and a lack of diligence can also 

cause an anesthesiologist to create the appearance of 

overlap of anesthesia services (i.e., concurrency) when 

indeed the services were provided consecutively. These 

discrepancies frequently become apparent upon subsequent 

audit of the documentation when it is more difficult 

to initiate corrections. 

Documentation of Medical Direction 

When an anesthesiologist is involved in directing up to 

four concurrent procedures, Medicare recognizes the services 

as concurrent medical direction. 

Documentation of concurrent medical direction must 

support the physician’s completion of “7 steps.” This documentation 

evidences that the physician: 

Performs a preanesthesia examination and evaluation; 

Prescribes the anesthesia plan; 

Personally participates in the most demanding procedures 

in the anesthesia plan, including, if applicable, 

induction and emergence; 

Ensures that a qualified individual performs any procedures 

in the anesthesia plan that he or she does not 

perform; 

Monitors the course of anesthesia administration at frequent 

intervals; 

Remains physically present and available for immediate 

diagnosis and treatment of emergencies; and 

Provides indicated postanesthesia care. 44 

In May 2004, CMS issued new interpretive guidelines 

for surveyors regarding the documentation of the inpatient 

postanesthesia assessment as required in the Hospital 

Conditions of Participation for the Medicare Program. 

The revision allows the postanesthesia follow-up to be 

performed and documented by the individual who administered 

the anesthesia, or by a delegated practitioner who 

is qualified to administer anesthesia. 55 

Documentation by Teaching Physicians 

In January 1997, Medicare imposed a requirement for use 

of the “GC” claim modifier to denote the involvement of 

residents in the delivery of anesthesia services and to 

certify that the teaching anesthesiologist was present 

during key portions of the service and immediately 

available during other parts of the service. In 1999, CMS 

extended the requirement to include a written attestation 

from the attending physician that these requirements 

were met. 56 

In November 2002, CMS implemented revised guidelines 

governing the documentation requirements for 

teaching physicians who care for patients with the involvement 

of resident physicians. These requirements restrict 

payment for teaching physician services to those that 

support the presence of the teaching physician during key 

portions of an anesthesia procedure and during the entire 

time for separately reimbursable procedures such as line 

and catheter insertions. 

The most complex of these guidelines govern the 

documentation of teaching physician involvement with 

residents in the provision of evaluation and management 

services. Interested physicians should consult the Medicare 

Carriers Manual, Section 15016 for specifics of these 

guidelines. However, there are important general principles 

that the anesthesiologist should follow in all cases 

whether or not the resident and teaching physician services 

are provided contemporaneously: 

• Teaching physicians cannot evidence their presence 

and participation via documentation of these activities 

by the resident or by “countersigning” a resident’s note. 

They may reference the resident’s note in their own 

note, but must independently document presence and 

participation in the critical portions of the service. 

• The composite of the teaching physician’s note and the 

resident’s note may be used to support the medical 

necessity and level of service billed. 57 

Physician providers must be proactive in assuring compliance 

with the complex and dynamic requirements of 

participation in the Medicare program. Development of 

a compliance program, review of physician billing and 

documentation, and ongoing education and training of 

providers and staff will help physicians minimize compliance 

risk. 

Summary 

Medicare is the primary health plan serving our nation’s 

elderly, an important source of revenue for physician and 

hospital providers, and a major underwriter of medical 

education and charity care in the United States. The 

program will experience growing, annual deficits start - 

ing in 2010 when Medicare costs are first predicted to


exceed financing sources as the baby boomers begin to 

retire. In the interim, strategies for dealing with the 

impending crisis in Medicare will be a continual source 

of debate and providers should be represented in the 

discussions. 

A large majority of anesthesiologists in the United 

States are enrolled as participating providers in the Medicare 

program. Many of the rules and regulations governing 

their interactions with the program are unique to the 

practice of anesthesiology and have significant implications 

for how clinical and business operations are conducted 

and whether, indeed, participation remains a 

viable strategy for anesthesiologists in the future. Geriatric 

anesthesiologists, by virtue of their subspecialty focus, 

should be best informed of Medicare policy issues and 

should participate in ongoing discussions to reshape 

Medicare as it enters an uncertain future. 

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Accessed October 17, 2004.

3 

Theories of Aging 

Stanley Muravchick 

“Gerontology” refers to the application of the various 

scientific disciplines to the study of aging. Aging manifests 

itself in most organisms as a gradual decline in the 

capacity to maintain anabolic processes or to respond to 

environmental change. Degenerative changes in both the 

physical structure and the functional capacity of organs 

and tissues are the clinical characteristics of human aging. 

In all species, regardless of how aging makes itself apparent, 

the implied consequence of aging is an increased 

probability of death as a function of time. 

Longevity can be expressed either in terms of lifespan 

or life expectancy (Figure 3-1). Lifespan is an idealized, 

species-unique parameter that quantifies maximum 

attainable age under optimal environmental conditions. 

Life expectancy represents an empirical estimate of typical 

longevity under prevailing or predicted circumstances. 

Increased life expectancy is therefore a socioeconomic, 

not a biologic, phenomenon. Consequently, biogerontologists 

usually limit the scope of their investigations to the 

physiologic and biochemical mechanisms of aging and to 

those biologic factors that determine lifespan. 

Concepts of Aging 

It is clear that genetics are intrinsically and fundamentally 

involved in aging and therefore in longevity, but 

exactly how this occurs is only now being established. 

Almost a century ago, a controversial and apparently 

flawed study of chick fibroblasts cells grown in vitro 

suggested that immortality might be achievable in the 

absence of all noxious or detrimental environmental 

influences. 1 However, it now seems that freedom from 

senescence may be possible only for cancer cells, not for 

fully differentiated cells or functional tissues. 2 Therefore, 

at least for the foreseeable future, human aging and death 

are inevitable realities. 

The precise mechanisms that underlie the aging process 

and ultimately determine lifespan in biologic systems 

remain unknown. To date, no single theory of aging has 

explained satisfactorily all the observed patterns of 

human senescence or accounted for the differences 

between human aging and the aging of other species. 3 In 

general, however, theories of aging fall into two major 

categories. One category encompasses nonrandom, 

predictable, and centrally determined or preprogrammed 

processes. The other grouping includes several theories 

that describe random or “stochastic” mechanisms. 

Programmed Aging 

Theories of programmed or predetermined aging are 

similar in that they invoke a common theme of a “biologic 

clock” or “life pacemaker” that confers the unique 

longevity of each species. For example, there is good correlation 

between species lifespan and the number of cell 

doublings that can be expected when cells of a single type 

such as an embryonic fibroblast are taken from a wide 

variety of animals and grown in culture. 4 This suggests 

that there may be an intracellular mechanism that limits 

reproductive capacity, or perhaps there is a section of the 

nuclear genome that provides a species-specific phenotype 

dedicated to lifespan. Similarly, the “codon restriction 

theory” suggests that there are programmed changes 

in the capacity of cells that vary the kinds of proteins that 

will be generated during different stages of life. 5 

If either of these theories are valid, experimental 

manipulation of the “pacemaker” or “clock” sections of 

the genome should produce dramatic changes in lifespan. 

Every genomic segment is, however, also subject to the 

processes of natural selection that affect the entire 

genome. 6 There is little selective evolutionary advantage 

for a species to survive past the age of sexual maturity 

and rearing of offspring. For humans, for example, this 

would require a lifespan of only 30–40 years. 7 Because 

reproductive capacity seems to be the major determinant 

of species survival, phenotypic changes that favor longevity 

without altering fecundity should be unaffected by 

29

30 S. Muravchick 

Figure 3-1. The concept of organ system functional reserve has 

been described as a “wedge” broadest at birth that then declines 

progressively after maturity. Applying this concept to human 

aging, genetically determined organ system functional reserve 

may determine lifespan but life expectancy reflects “real world” 

estimates of human longevity given extrinsic environmental 

factors. (Data from Jazwinski SM. Longevity, genes, and aging. 

Science 1996;273:54–59.) 

evolutionary processes. Consequently, evolutionary theories 

of aging and longevity are unable to support the 

concept that there are specific genes that cause aging or 

control lifespan. 8 A “programmed aging” locus would 

have no species survival value and therefore would not 

be expected to persist intact in the genome throughout 

the long time course of evolution, although some evidence 

suggests that human cellular senescence could be 

a manifestation of evolutionary pressures to prevent 

malignant transformation. 9 

In fact, favorable changes in the genome segments that 

control reproduction and enhance species survival could 

have deleterious effects on postmaturation viability and 

lifespan. Senescence characterized by decreasing viability 

may be the price to be paid to sustain immortality of the 

species-specific germline at the expense of individual survival. 

10 A genomic locus that determines lifespan is rarely 

found in nature unless the reproduction of that species 

requires the death of the mature adult as the final step of 

the reproductive process. This phenomenon is seen in 

plants, insects, and some fishes where the linkage between 

reproduction and death is mediated by programmed neuroendocrine 

mechanisms. 11 

Mammals express a well-defined aging phenotype with 

great similarities between mammalian species, yet many 

amphibians, reptiles, and sharks and other primitive fishes 

fail to show obvious physical signs of aging. Mammalian 

aging could therefore have evolved along with other 

unique phenotypic mammalian characteristics, and it may 

not be the same process as the age-related biologic phenomena 

seen in some nonmammals. 12 Examination of the 

properties of genetic variation in Drosophila also supports 

the concept that aberrancies and mutations may not 

be nearly as important in determining longevity as is the 

underlying species phenotype. 13 

An external pacemaker tissue or organ must also 

be present to coordinate the aging-related interac - 

tions between tissues and multiple organ systems that 

characterize normal senescence, especially in humans. 

Therefore, this type of theory usually requires that 

neuroendocrine or immune mechanisms have a central 

role in processes of aging. Despite considerable investigation 

and some early data suggesting the importance of 

changes in hypothalamic activity in aging, 14 however, 

there has been little objective evidence that a neuroendocrine 

or other hormonal “pacemaker” tissue as envisioned 

actually exists. It is therefore highly unlikely that 

aging or longevity are precisely programmed genetic 

events. 15 

Stochastic Aging 

Stochastic aging theories include a thermodynamic perspective 

that looks at increases or decreases in specific 

entropy production (SEP). In effect, viability is seen as a 

struggle against breakdown of intracellular order and 

structure. Growth and development represent an increase 

in order but aging is characterized as a breakdown in 

biologic order and an increase in randomness. 16 The 

higher and more complex the organism, the greater the 

maximum SEP. Biologic stress and aging have similar 

thermodynamic properties and their underlying principles 

have been described using common parameters. 17 

Cells and tissues are conceptualized as “open systems” 

that are subject to energy and material flux and therefore 

require active energy expenditure to maintain 

physical order. They are in a nonequilibrium or “far-fromequilibrium” 

steady state. From this perspective, “normal” 

aging is an evolving, slowly changing state characterized 

by increased cell damage (less order) and decreased bioenergetic 

capacity. SEP therefore declines during aging 

as the ability to extract energy from the environment 

decreases. 

In simplest terms, stochastic theories propose that 

physical and biochemical signs of aging may be a simple 

function of time and probability. The now-classic “genetic 

wear and tear” or “error-catastrophe” theory of aging is 

an example of this group. Originally, it suggested that 

degradation of the integrity of nuclear DNA (nDNA) 

over time generated random errors of genomic reproduction 

and transcription that accumulate. Eventually, the 

essential molecules needed for cell viability are no longer

3. Theories of Aging 31 

synthesized. 18 Progressive compromise of cellular and 

tissue function over time, therefore, produces the physical 

and clinical signs of aging. This theory predicts that 

there is an age-related increase in the fraction of proteins 

that are functionally defective, and that the error rate 

eventually rises exponentially as the key components of 

protein synthesis are themselves subject to defects or 

shortages. 

Overall, however, the evidence that mammalian aging 

is a random breakdown in biologic order because of lifelong 

accumulation of genomic errors caused by genetic 

mutations, remains very weak. 19 At least in human cells, 

faulty protein accumulates slowly throughout adulthood 

and the geriatric years and damage to the cells and microarchitecture 

seems to reflect secondary, not primary, 

errors in amino acid sequence. Nor does biologic order 

deteriorate at an accelerating or exponential rate. 

It is true, however, that many of the enzymes that accumulate 

in the tissues of older subjects are less active and 

more susceptible to heat inactivation and proteolysis, 20 

but these seem to be oxidized proteins that appear 

gradually, usually with methionine moieties or as various 

“glycated” molecules. Biologic amines can react nonenzymatically 

with glucose and other reducing sugars to 

form yellow-brown or fluorescent crosslinked complexes. 

They are precursors to irreversibly bound crosslinking 

agents called advanced glycation end products (AGEs). 

Advanced glycation, originally seen in vitro, now is known 

to occur in living tissues. AGEs randomly interconnect 

lipoproteins and proteins and disrupt uniform molecular 

alignment, reducing elasticity and increasing “stiffness” in 

tissues containing structural collagen. 21 

AGEs in the vascular tree may accumulate even more 

rapidly with chronic exposure to high levels of reducing 

sugars, as occurs in poorly controlled diabetics, and may 

predispose to intravascular plaque formation and produce 

loss of cardiovascular elasticity. 22 Ethanol is metabolized 

in vivo to acetaldehyde which then produces a chemically 

stabilized complex that resists rearrangement in the presence 

of reducing sugars and therefore does not progress 

to AGE formation. This may explain the so-called “French 

paradox,” by which moderate chronic ethanol ingestion, 

for example, daily wine consumption, seems to confer a 

significant degree of protection from coronary artery 

disease. 23 Work in laboratory animals confirms that drugs 

or chemicals that block glycation or act as “crosslink 

breakers” 24 may reverse at least some of the clinical stigmata 

of the senescent cardiovascular system. However, 

confirmation of this concept in human studies has yet to 

be reported. 

Aging is also associated with a progressive decline in 

the ability of cells and organelles to scavenge and degrade 

these and other types of defective proteins. 25 Normally, 

oxidized proteins undergo preferential degradation 

within the cell by the proteasomal system. There is a 

multicatalytic protease complex–-the proteasome–-as 

well as numerous other regulatory factors involved in 

the degradation of oxidized proteins. 26 The proteasome is 

present in the cytosol, nucleus, and endoplasmic reticulum 

of mammalian cells, but is itself subject to oxidative 

deterioration during aging and therefore may become 

progressively less effective in older individuals. 27 

Telomere shortening is another form of stochastic 

nDNA damage that has been invoked as a possible source 

of age-related decline. Located at the ends of eukaryotic 

chromosomes and synthesized by telomerase, telomeres 

are the genomic units that maintain the length of chromosomes. 

Human cancer cells demonstrate high telomerase 

activity. However, although there is a general 

association between cellular senescence and telomere 

shortening in vitro, 28 there is little evidence that telomere 

shortening is intrinsically associated with, or causally 

related to, normal human aging. Similarly, there is general 

correlation between species longevity and nDNA repair 

capacity but no firm evidence that the ability to recover 

from random nDNA damage is, in fact, progressively or 

universally compromised in older human subjects. 

Other potential stochastic mechanisms include random 

nDNA methylation, a process that correlates with transcriptional 

silence of many genes. When nDNA mutations 

occur, enzyme systems that repair DNA are a second 

line of defense designed to return nDNA to its original 

genetic integrity. Another potential genomic mechanism 

for aging, therefore, is compromised expression of the 

enhancer and repressor/suppressor elements that, in turn, 

activate or inhibit gene expression, particularly of the 

components of DNA repair mechanisms. This may 

become important in cancer biology because tumor genes 

are not expressed until the environmental stimuli that 

maintain the suppression are removed. A similar process 

could be important in aging. A third possible mechanism 

of aging at the cellular level relates to messenger RNA 

(mRNA) production. Many proteins and enzymes 

decrease in concentration with aging. This seems in some 

cases to be a direct result of decreases in the mRNA 

levels which encode the protein. Hence, age-related limitation 

of the rate or accuracy of the transcription of 

mRNA from nDNA may be involved. 

Altered Receptor Systems 

Recent research in the discipline of molecular pharmacology 

has generated huge amounts of data with regard 

to biologic receptor systems, especially within the nervous 

system. With aging, there are decreases in acetylcholine 

synthesis and release as well as reduction of muscarinic 

receptor plasticity. This suggests a causal connection 

between impairment of central cholinergic function and 

aging. A “cholinergic” theory of aging 29 is even more 

attractive given the clear role of cholinergic deficiencies


in Alzheimer-type dementia 30 and perhaps other 

age-related neurodegenerative disorders. Gammaaminobutyric 

acid (GABA), a major inhibitory 

neurotransmitter, is an important site of drug action for 

anesthetic agents and another possible locus for aging 

within the nervous system. GABA receptors and other 

ligand-gated ion channels have been shown to have 

decreased specificity to their agonist molecules in older 

adults. 31 Although the demonstration of consistently 

decreased anesthetic requirement in older adults 32 is 

another intriguing clue supporting the concept of a link 

between aging and altered neurotransmitter dynamics, 

these observations have yet to be formulated into a 

coherent theory of aging that proposes a fundamental 

role for central nervous system receptors. 

Oxidative Stress 

Not all stochastic theories of aging focus on the state of 

DNA within the cell nucleus. Reactive oxygen species 

(ROS) or “free radicals” are routinely produced in the 

mitochondria as a byproduct of aerobic metabolism and 

oxidative phosphorylation. 33 If allowed to accumulate to 

high levels, ROS such as superoxide, impose a state of 

“oxidative stress” within the cell that can damage or 

destroy organelle and even molecular microarchitecture. 

34 These toxic effects may be direct or they may be 

the consequences of a cascade of biochemical events. 

Investigations of oxidative phosphorylation in aging 

mitochondria confirm that aging is associated with both 

progressive decreases in mitochondrial energy generation 

35 and increased levels of defective mitochondrial 

DNA (mtDNA), 36 presumably because of excessive ROS. 

Older mitochondria also demonstrate a loss of membrane 

potential and a decrease of both fusion and fission activity. 

37 It is less clear whether increased ROS levels in the 

cytosol of a cell can damage nDNA, which is centrally 

located in the nucleus and relatively shielded from 

oxidation. 

According to this general concept, sustained and lifelong 

oxidative stress compromises the enzymatic machinery 

required for full bioenergetic capacity and also 

damages the mtDNA needed for synthesis of enzymes 

such as glutathione peroxidase and superoxide dismutase. 

These enzymes protect cells from metabolic byproducts 

by scavenging ROS as they are produced in the mitochondria. 

Two centuries ago, the renowned scientist 

Joseph Priestly, discoverer of oxygen’s life-sustaining 

properties, speculated quite presciently that too much 

oxygen might lead to premature failure of oxidative processes. 

Therefore, from this perspective at least, aging at 

a cellular level can be considered a form of chronic 

oxygen toxicity. ROS, the byproducts of aerobic metabolism 

that is essential for life in all higher organisms, may 

generate a “vicious cycle” of progressive bioenergetic 

Figure 3-2. Insidious increases in concentrations of reactive 

oxygen species (ROS) throughout the adult years generate a 

“cycle of aging” that may explain both the decreased bioenergetic 

capacity that characterizes senescent tissues and the 

increased morbidity and mortality exhibited by a geriatric 

patient population. (Data from Ozawa. 66 ) 

failure and functional compromise in the mitochondria 

(Figure 3-2). 

Reconciling the Theories 

Nevertheless, purely stochastic theories such as those 

invoking oxidative stress fail to explain the dramatically 

different patterns of aging that are seen in various animals 

despite the fact that virtually all species share a common 

ecosystem, have similar metabolic processes and byproducts, 

and are exposed to similar catabolic environmental 

forces. In fact, aging may reflect the degenerative consequences 

of a lifetime of exposure to the byproducts of 

aerobic metabolism that have not been successfully 

detoxified by the genetically determined processes available 

to protect the integrity of the cell genome, maintain 

normal neurotransmitter dynamics, and preserve full 

bioenergetic capacity (Figure 3-3). Viewed as progressive 

failure of a species-specific, genetically predetermined 

capacity to avoid or repair random damage to proteins, 

lipids, nDNA, and mtDNA by ROS, a concept that identifies 

accumulated oxidative stress as the underlying driving 

force of aging is compatible with most aging theories, 

both stochastic and nonstochastic. 38 Nor does the consistency 

of observed lifespan for a given species necessarily 

imply a discrete “biologic clock” or a “lifespan” gene for 

each species. Rather, it may reflect the net effect of many 

genes in the phenotype of each species whose expression 

influences the aging and longevity of that life form. These 

genetic factors have been described as “gerontogenes.” 39


Figure 3-3. Proposed molecular mechanisms of aging include damage to the cellular and mitochondrial genome and disruption 

of cellular microarchitecture, including membrane-bound receptor complexes. 

It is becoming plausible, therefore, that lifespan may 

reflect a stochastic interaction between the genetically 

determined biochemical and physiologic attributes of 

each species and the internal and external destructive 

factors that disorder biologic systems. 40 Consequently, 

exploring how each species is equipped genetically to 

deal with metabolic and environmental stress, therefore, 

has become a fundamental and crucial step in understanding 

the molecular biology of aging. The “theory of 

disposable soma” postulates that some species have 

increased their reproductive capacity in exchange for 

decreased lifespan. 41 However, other evolution theory 

suggests that the longer-lived species have evolved 

because of their greater degree of genetic investment 

in a more durable soma, including mechanisms, many 

perhaps complex and requiring considerable cell re - 

sources, that enhance cellular resistance to stress. “Hormesis,” 

the low-level state of chronic oxidative stress that 

induces expression of genes that can increase the effectiveness 

of stress responses in mammals (also described 

as ischemic, hypoxic, or anesthetic “preconditioning”), 

may be more easily initiated in some species than in 

others. In fact, stress-induced expression of genes that 

facilitate cell repair is well established: cold stress has 

been shown to prolong lifespan in the nematode Caenorhabditis 

elegans 42 and heat stress significantly increases 

longevity of the fruit fly, Drosophila melanogaster. 

Birds, and perhaps other nonmammalian species, also 

possess a mitochondrial lipid structure that is more resistant 

to oxidative damage than that of mammals. 43 This 

may confer a special adaptation that prevents the agerelated 

tissue damage seen in mammals that is caused 

by ROS or AGEs. Avian lifespan is markedly prolonged 

relative to that of most mammals with comparable metabolic 

rates. Bird mitochondria also produce significantly 

less ROS than those of mammals, but it is not clear 

whether their specific bioenergetic capacity is significantly 

different. 44 In the nematode C. elegans, a genetic 

mutation with increased activities of antioxidative 

enzymes also has lifespan significantly greater than the 

wild-type strain. 

Point mutations and deletions of mtDNA accumulate 

in adult humans, monkeys, and some laboratory rodents. 

Although these mutations are only a small proportion of 

total mtDNA and are randomly or clonally distributed in 

different tissues, the amount of defective mtDNA found 

in the heart and brain of mammalian species ranging in 

maximum lifespan from 3.5 to 46 years has been shown 

to be inversely correlated with lifespan. In addition, 

genetically altered mice that express a proofreadingdeficient 

version of mtDNA polymerase develop into a 

young adult mouse phenotype with a three- to fivefold 

increase in mtDNA point mutations and increased 

mtDNA deletions. In these mice, the increased number


of somatic mtDNA mutations has recently been shown 

to be associated in young adulthood with age-related 

phenotypic characteristics such as reduced subcutaneous 

fat, hair loss, and osteoporosis as well as significantly 

reduced lifespan. 45 However, it remains unclear whether 

these changes are similar to, or actual premature manifestations, 

of aging. 

It has also not yet been demonstrated that genetic 

manipulation of mtDNA repair and replication mechanisms 

can produce mice with decreased mtDNA mutation 

rates and increased longevity, although it has been 

shown that there is less mitochondrial ROS generation in 

long-lived than in short-lived mammalian species. Most 

relevant to human aging, cellular resistance to oxidative 

stress has recently been shown to be closely correlated 

with mammalian longevity. Skin fibroblasts and lymphocytes 

from eight mammalian species with a range of lifespans 

show a direct correlation between cellular resistance 

to chemical, alkaline, and oxidative stress and the 

maximum lifespan of the species. 46 These results agree 

with the concept that ROS in mitochondria produce 

accumulating oxidative damage to mtDNA 47,48 (Figure 

3-4) and perhaps to other key cellular components that 

in some way is related to the aging rate of each mammalian 

species. 49 

The theory that aging is a direct consequence of the 

accumulation of oxidative damage caused by ROS is consistent 

with the observed effectiveness of caloric restriction 

as a therapy that prolongs the life expectancy of 

laboratory rodents. 50 Caloric restriction may lower mitochondrial 

ROS levels and may reduce oxidative damage 

to mtDNA. This or a similar mechanism may also explain 

the evolution of species with different longevities. 51 

Species with higher metabolic rates, or, within a given 

species, individuals with an increased demand for oxidative 

energy may have a higher “rate of living” that generates 

more ROS and reduces life expectancy. Alternatively, 

some recent data suggest that caloric restriction, perhaps 

through selective gene expression, actually increases 

mitochondrial bioenergetic efficiency and is associated 

with suppression of metabolic stress responses. 52 Changes 

in the glucose–fatty acid cycle that occur in response to 

near starvation may be protective when calories are 

reduced in aging tissues. 53 

Nevertheless, it would be premature to attribute aging, 

in particular human aging, to simple bioenergetic deterioration 

caused by oxidative stress. 54 There is a general 

correlation between species longevity and the capacity to 

repair damaged DNA but evidence that the ability to 

recover from random oxidative DNA damage is progressively 

or universally compromised in older human 

subjects remains elusive. 55 In addition, although several 

investigations have confirmed that defective mtDNA 

increases in the cells of older subjects, it is not established 

that this produces a critical reduction of the macromolecules 

needed for normal bioenergetics. 56 In addition, the 

interaction between ROS and the bioenergetic apparatus 

is now known to be far more complex than was once 

believed. Peroxiredoxins represent a group of at least six 

isoforms of a multifunctional peroxidase. 57 They have 

recently been identified in many species and are believed 

to provide protection against the low-level oxidative 

stress associated with peroxide accumulation yet they do 

not appear to influence longevity. 58 Similarly, the overexpression 

of superoxide dismutase and catalase enhances 

resistance to experimental oxidative stress but decreases, 

rather than increases, lifespan of transgenic Drosophila 

melanogaster. 59 Taken together, these observations 

suggest that normal lifespan reflects a subtle and complex 

equilibrium between the byproducts of oxidative metabolism 

and endogenous mechanisms that respond to oxidative 

stress. 

Human Aging and Geriatrics 

Figure 3-4. Recent studies of human tissues support the evolving 

concept that accumulation of damaged mitochondrial DNA 

(mtDNA) in the early geriatric era leads to a progressive decline 

in bioenergetic capacity and oxidative phosphorylation. (Data 

from Mandavilli et al. 47 ) 

The term “geriatrics” was coined at the start of the twentieth 

century 60 to describe the clinical subspecialty area 

of medicine that focuses on care of the elderly patient. 

But, as yet, there is still no consensus as to when the 

“geriatric” era begins in human subjects or whether any 

single physiologic marker can unequivocally identify a 

patient as “elderly.” Therefore, establishing rigid or finite 

chronologic definitions of the term “geriatric” has little 

value other than for administrative, actuarial, or epidemiologic 

applications. Nevertheless, although it may have


increased rapidly from the onset of human evolution 

until about 100,000 years ago, when the brain weight/ 

body ratio of our hominid ancestors stabilized at the 

current value for modern humans, 61 empirical evidence 

and historical anecdote suggest that human lifespan has 

remained constant at about 120 years for at least the past 

20 centuries. 

In contrast, the past century has seen dramatic advances 

in medical science and health care that have greatly 

increased life expectancy in industrialized societies, 

especially in Japan and the United States, increasing the 

relative “agedness” of those societies. 62 However, the 

increased life expectancy so often invoked in discussions 

of “the graying of America” is a socioeconomic, rather 

than a biologic, phenomenon that steadily enlarges that 

fraction of the general human population considered 

“elderly.” If, in fact, maximum human lifespan is fixed but 

life expectancy increases in response to elimination of 

disease and other external threats to longevity, the human 

survival curve may continue to undergo the “rectangularization” 

63 that results in the compression of age-related 

morbidity and mortality into the later years of the geriatric 

era. 64 Yet, there is some evidence that human lifespan 

may not yet have reached its ultimate maximum 

value. The time perspective of metrics used in modern 

biology is so limited relative to the many millennia of 

human existence that subtle increases in lifespan may 

actually be occurring undetected. 

Clinical Studies of Aging 

All geriatricians accept increased interindividual variability 

as a hallmark of their patient populations. As they 

age, adults continually exhibit a progressively more varied 

array of physical responses to concurrent disease states 

which, in turn, reflect their lifelong exposure to environmental 

and socioeconomic conditions and to the accumulated 

stigmata of prior traumatic injuries and medical 

therapies. Prolonged longevity also enables complete 

expression of intrinsic genetic qualities in all their subtle 

physiologic manifestations. In effect, people are never 

more alike than they are at birth, nor more different or 

unique than when they enter the geriatric era. 

Therefore, interpretation of clinical studies of human 

aging remains difficult and progress in understanding 

mechanisms of aging has been correspondingly slow. Yet, 

much has been learned about the relative strengths and 

weaknesses of the various forms of epidemiologic 

investigation used by gerontologists and geriatricians. 

Cross-sectional studies measure physiologic parameters 

simultaneously in young and in elderly subjects. Changes 

caused by undiagnosed age-related disease may be erroneously 

attributed to aging, and this experimental design 

cannot be controlled for cohort-specific factors such as 

nutritional and environmental history, genetic background, 

or prior exposure to infectious agents. Crosssectional 

designs do not provide sufficient evidence for 

the interdependence of aging-related changes and therefore 

they probably should not serve as the final basis for 

theories and hypotheses of aging. 65 

Longitudinal designs provide a much stronger basis for 

inference regarding rates and characteristics of human 

aging. They require that the investigator obtain repeated 

measurements in each individual subject over several 

decades. Each subject therefore generates his own “young 

adult” control value for comparison with subsequent 

measurements. If any of the subjects in a longitudinal 

study eventually manifest signs of age-related disease, 

their data points can be excluded from the study, thereby 

leaving behind a smaller but more homogeneous group 

of healthy elderly subjects. Survival to and through adulthood 

and beyond also permits the full expression of even 

the subtlest genetic differences between individuals that 

might not be fully apparent over shorter lifespan intervals. 

In longitudinal studies, the signs and symptoms of 

aging become progressively more apparent or severe 

with increasing chronologic age. Any changes in structure 

or function that are not found in all members of a geriatric 

population, or those changes that do not seem to 

have a direct relationship between severity and chronologic 

age, can be attributed to age-related disease rather 

than to aging itself. 

Although difficult and expensive to organize and maintain, 

long-term longitudinal studies have therefore produced 

substantial amounts of extremely valuable data 

related to human aging. Nevertheless, this methodology 

has some pitfalls. It requires establishing a chronologic 

“starting point” for the geriatric era, an arbitrary value 

that may change significantly during the study because of 

increases in life expectancy. In addition, the validity and 

utility of the data may be compromised by the inevitable 

evolution or revision of physiologic concepts and the 

refinement of measurement techniques that invariably 

occur over the time periods required to study human 

aging. Last, it is difficult to attract new physician scientists 

to a form of clinical investigation in which the answers to 

the scientific questions that are being asked may not be 

known during the lifetime of the investigator himself. 

Summary 

There is currently great scientific interest and experimental 

activity under way to fully define the role of long-term 

oxidative stress as a cause of increasing damage to 

mtDNA and intracellular protein. 66 As awareness of the 

roles of mitochondrial genetics and oxidative stress in 

mechanisms of senescence and death has increased 

among biogerontologists, the various theories of aging 

have begun to coalesce and unify. Genetically determined


ability to scavenge ROS and to repair accumulated or 

randomly acquired damage to intracellular enzymes and 

organelles does, in general, correlate with longevity, both 

in humans and in other species that show phenotypic 

change with age. Declining bioenergetics and a reduction 

in capacity for oxidative phosphorylation also seems to 

explain the age-related clinical deterioration of maximal 

organ function that inevitably occurs throughout human 

adulthood, even in the most fit older subjects. In fact, 

many researchers already believe that it is progressive 

failure of mitochondrial bioenergetics that produces 

normal human aging as well as many aspects of agerelated 

degenerative disease. 67 

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4 

Ethical Management of the Elderly Patient 

Paul J. Hoehner 

Because of the increasing growth of the elderly population, 

geriatric care is rapidly emerging as a unique medical 

specialty in its own right. Advancements in medical 

science and changes in the health care delivery system 

that impact the care of the elderly are accompanied by 

myriad ethical dilemmas that confront not only the physician 

and patient, but social workers, nursing home staff, 

and relatives. Settings involving the extremes of age and 

illness are the most complex in ethical deliberation. 

Although anesthesiologists may confront a variety of 

ethical issues, such as patient confidentiality, care of Jehovah’s 

Witnesses, substance abuse, and so forth, this chapter 

will focus on those issues unique to and more likely to be 

encountered in the elderly patient. 

Social Views of Aging 

Social views of aging are inherently present and basically 

informative within any application of ethical principles to 

ethical problems involving the elderly. Therefore, it is 

important to recognize that one’s view of aging can and 

will influence both clinical decision making as well as the 

application of ethical principles to individual concrete 

situations. Although contemporary views of aging are 

complex and varied, Gadow 1 helpfully outlines a spectrum 

of views, each of which contribute to the apparent 

social and moral value of the elderly patient and the resolution 

of ethical problems. First, aging can be viewed as 

the antithesis of health and vigor. This negative interpretation 

of the aging process is expressed in deceptively 

“objective” descriptions of the clinical changes in aging 

as “deterioration,” “disorganization,” and “disintegration,” 

from the level of psyche to the level of cellular 

physiology. Gadow points out, however, that there is 

nothing a priori degenerative about changes in aging 

unless one “uncritically accepts as the only ideal of health 

the condition that younger individuals manifest.” 1,2 Furthermore, 

it is a mistake to think of the elderly as generally 

sick and impaired. Patricia Jung notes that, “Clearly, 

to expose as false those myths that portray the old as 

inescapably and increasingly physically decrepit, mentally 

incompetent, desexualized persons best kept isolated 

in nursing homes is an important first step toward 

discerning what it means to age.” 3 For many, old age is 

not a time of disability or disease; instead it is a time of 

remarkably good health. According to one government 

study, 72.3% of noninstitutionalized elderly persons 

described their health as “excellent,” “very good,” or 

“good,” and only 27.6% described their health as “fair” 

or “poor.” 4 Nevertheless, this same study showed that in 

1990 persons over the age of 65 experienced more than 

two and a half times the number of days of activity restriction 

because of acute and chronic conditions as persons 

between the ages of 25 and 44, with 37.5% of people over 

the age of 65 experiencing some activity limitation caused 

by chronic conditions. Health care workers, whose contact 

with the elderly is naturally skewed toward those who 

are acute or chronically ill, and/or institutionalized, are 

especially prone to this unambiguously negative account 

found in the “decline model” that so powerfully dominates 

our cultural interpretation of aging. 

Second, aging can be viewed as an unwelcome reminder 

of our mortality. Medicine, at least a little like Shelley’s 

modern Prometheus, 5 tends to seek for and attain progress 

within the human condition in ways that defy its own 

ability to know what to do next. Shaped by the pervasive 

story of our therapeutic culture, 6 health care workers and 

their patients are driven by an interest in longevity that 

reaches far beyond the merely academic, emanating as it 

does from a desire to avoid suffering and certainly from 

a fear of death. Growing old in our therapeutic culture 

encourages us to desire perpetual youthfulness and gives 

us the power to strive for it (to some degree successfully, 

or, at least, cosmetically), but also forces us to ask just 

how old we really want to live to be. And as we age, for 

how long and in what ways do we care for ourselves? 

Advances in medicine bring new psychologic and ethical 

38

4. Ethical Management of the Elderly Patient 39 

challenges, both for those who are older and for those 

who are living with and caring for them. For instance, the 

more natural and acceptable mortality is thought to be 

for the elderly, the more unthinkable it is for the nonelderly. 

This view can lead to the avoidance of the elderly 

as symbols of the unthinkable. 

Medical and social views of aging can reflect the full 

diversity of a spectrum ranging from the philosophy that 

the elderly have less social and moral value than other 

individuals, to the other extreme of having greater value 

than others. The most positive of all attitudes is that of 

the elderly as a cultural treasure, a repository of wisdom, 

and an embodiment of history. Gadow 1 also observes 

another emerging perspective that treats the elderly as 

underprivileged citizens. This view bypasses the question 

of the intrinsic value of the elderly for society and brings 

them “out of the closet” to become recipients of our 

benevolence toward them as an “oppressed” group. The 

potential danger with this view is that by designating 

the elderly as “handicapped” individuals, and thereby 

as a special group needing services, the beneficiaries 

remain subordinate to the benefactor and may even 

become victim to the extremes of unwarranted paternalistic 

care. 

A development inherent to the rise of geriatric medicine 

as a specialty is the view of aging as a clinical entity 

in its own right. Positively, aging is viewed as a unique 

human phenomenon worthy of specialized attention. The 

elderly are not health deviants but present special problems 

as well as special strengths not found in other populations. 

Surely this is a welcome view that will, and has 

already, greatly contributed to the understanding and 

care of many issues unique to this growing population 

(the focus of this textbook being one example). Negatively, 

the subspecialty approach to geriatric medicine 

may become a model for a broader social approach to 

the elderly whereby aging would be of interest as a “highly 

specific class of unusual phenomena, bearing little relation 

to the more general features of experience shared 

by persons of all ages.” 1 Aging may be viewed not as 

a normal life process, with little or no purpose, but as a 

disease in itself. Yet much of what has been assumed 

mistakenly to be the “plight” of the elderly is in fact the 

consequence of specific pathologies not properly associated 

with aging. Chronic illnesses and degenerative diseases 

often associated with aging are frequently a result 

of lifestyle choices. Although aging may be associated 

with some rote memory loss, recent studies repeatedly 

indicate that the basic cognitive competence of the elderly 

does not deteriorate with age. There is some evidence of 

positive growth in certain more complex, integrative 

mental abilities. Peter Mayer notes in his essay “Biological 

Theories about Aging” that even physical changes 

such as osteoporosis among postmenopausal women and 

immune system decline which were once presumed to be 

an inevitable result of growing old are now understood 

to be the consequence of specific medical conditions or 

other factors such as malnutrition. 7 

Ethical Principles 

In our modern society, categories of right and wrong or 

decisions regarding the “good” are frequently characterized 

by competing rational philosophical theories (such 

as deontology, utilitarianism, natural law), as cultural and 

tradition-dependent artifacts, or as arising from individualistic 

or relativistic (e)motives. The classic paradigm of 

modern medical ethics, often referred to as “principlism,” 

originated in a pragmatic attempt to overcome the 

impasse of these competing ethical theories in order to 

derive common and self-evident “principles” that would 

serve to guide a common language/paradigm of biomedical 

ethical decision making. This almost universally 

accepted paradigm of modern medical ethics revolves 

around the principles of respect for personal autonomy, 

beneficence, nonmaleficence, and justice. This paradigm, 

which has been extensively discussed in many basic 

medical ethics texts, will be assumed for the remainder of 

this chapter. 

Recent work in medical ethics has focused on alternative 

frameworks based on such concepts as “virtue ethics,” 

the “narrative life,” and “personhood.” These concepts 

may overcome some of the philosophical limitations of 

the traditional approach and provide a more firm theoretical 

grounding that can thereby proceed to the level of 

principles more appropriate for use in the elderly population. 

One exemplary approach is that of Spielman 8 who 

appropriates the moral anthropology of Hauerwas to 

build a more adequate principled approach to geriatric 

ethics. Hauerwas emphasizes an ethic of virtue that grows 

out of his conviction that “what one does or does not do 

is dependent on possessing a ‘self’ sufficient to take 

responsibility for one’s actions.” 9 Three aspects of the self, 

which are relevant to applying Hauerwas’ work, are its 

temporal dimension, its social dimension, and its tragic or 

limited dimension. 

Unlike the standard account of post-Kantian ethics in 

which the moral life is seen in terms of obedience to a set 

of rational, timeless principles, Hauerwas presents character, 

developed within the context of a particular story 

or narrative, as the key to the moral life. According to this 

temporal dimension, life is not seen as a series of discontinuous 

decisions but rather as a challenge to be faithful 

to a true story or history. Contemporary ethical theory 

tends to view the ideal human as a self-sufficient, 

independent moral agent, without social ties. Hauerwas’ 

social dimension emphasizes the fact that we are all historical 

beings and cannot avoid being part of larger 

communities. Our ability to think and our ability to act

40 P.J. Hoehner 

Figure 4-1. Principles of a geriatric ethic derived from 

Hauerwas’ dimensions of human nature. (Adapted with permission 

from Spielman. 8 ) 

are embedded in a social structure in which even the 

descriptions of our actions depend on language, which is 

a public possession. Human existence also has a necessarily 

tragic or limited dimension. Medicine cannot eradicate 

suffering and death in our lives. By using MacIntyre’s 

characterization of medicine as a tragic profession, Hauerwas 

suggests that medical ethics cannot be limited to 

casuistic analyses of particular sets of problems and issues. 

He notes the continuity between the kind, of issues raised 

by medicine and the rest of our lives and raises important 

issues involved in the practice of medicine relative to the 

elderly, such as limited resource allocation. Hauerwas 

shows that not only are the history and the relationships 

of the self significant, but that the limitations inherent in 

medical treatment of the elderly cannot be ignored. 10 

Figure 4-1 illustrates how the temporal, social, and 

tragic or limited dimensions of human existence can be 

used to develop principles more appropriate to developing 

a geriatric ethic according to Spielman. The dimensions 

of temporality and sociality can be recognized in 

the increasing dependence on others as one ages. A more 

useful principle than autonomy is one of continuity. This 

principle may be stated as: “Act so that you avoid disrupting 

the continuity of past, present, and future values, commitments, 

and relationships in older people’s lives.” The 

purpose of the principle is to prevent the loss, as one ages, 

of a sense of the unity of one’s life. Balancing the aspects 

of limitation and sociality helps to recognize and not 

ignore the elderly patient’s social needs and desire to 

maintain some degree of independence. This avoids the 

temptation of caregivers to rely on institutional care 

when independence cannot be maintained. Silverstone 11 

notes that the tendency for the physician to view chronically 

impaired patients with a biomedical disease-oriented 

framework contributes to a hospital-like solution 

to the patient’s problems. This principle can be stated: 

“seek out the appropriate level of support and care for 

older patient,” a level of care that maximizes independence 

and maintains the highest level of functioning. 

Because complete independence is usually neither possible 

nor desirable, “interdependence” with friends, relatives, 

and service providers more aptly describes this 

principle. Finally, the aspects of limitation and temporality 

suggest the principle of normality. Aging does not 

have to be seen as a disease or as a form of deviance. This 

principle would argue against treating every age-related 

change as a disease or problem to be solved. Rather, the 

aging process is valued, given the limitations it imposes, 

as a normal part of the human life narrative. 

Informed Consent in the Elderly 

Respect for Personal Autonomy 

Many ethical conundrums in medical ethics are the result 

of specific principles coming into conflict in specific cases. 

The principle of respect for personal autonomy is sometimes 

taken to be the overriding principle in modern 

ethical deliberation. However, respect for personal autonomy 

does not, and should not, exhaust moral deliberation. 

Other principles are important and not only when 

autonomy reaches its limits. Childress notes that focusing 

on the principle of respect for personal autonomy can 

foster indifference and that the principles of care and 

beneficence are important even in discussions of informed 

consent. The role played by the principle of respect for 

personal autonomy is one of setting limits, such that, 

“without the limits set by the principle of respect for 

autonomy, these principles (beneficence, nonmaleficence, 

and justice) may support arrogant enforcement of “the 

good” for others.” 12 Yet, the principle of respect for 

autonomy is not absolutely binding and does not outweigh 

all other principles at all times. Two different 

approaches have been used by ethicists to resolve conflicts 

or apparent contradictions between competing 

principles. First is to construct an a priori serial ranking 

of the principles, such that some take absolute priority 

over others. Second, principles can be viewed as prima 

facie binding, competing equally with other prima facie 

principles in particular circumstances. This view requires 

one to view more closely the complexities and particularities 

of individual cases and is more situational in 

context. The prima facie principle of respect for autonomy 

can be overridden or justifiably infringed when the 

following conditions are satisfied: (1) when there are 

stronger competing principles (proportionality); (2) when 

infringing on the principle of respect for personal autonomy 

would probably protect the competing principles 

(effectiveness); (3) when infringing the principle of 

respect for personal autonomy is necessary to protect the 

competing principle(s) (last resort); and (4) when the 

infringement of the principle of respect for personal 

autonomy is the least intrusive or restrictive in the circumstances, 

consistent with protecting the competing 

principle(s) (least infringement). 12


Shared Decision Making 

Aside from the legal requirements and the specter of 

malpractice, recent discussions of “informed consent” 

have focused on the concept of “shared decision making” 

and the clinical-therapeutic role of the informed consent 

process in improving patient care. These discussions 

recognize that there should be a collaborative effort 

between physicians and patients to arrive at appropriate 

treatment decisions. The physician brings knowledge and 

trained judgment to the process, whereas the patient 

brings individual and unique priorities, needs, concerns, 

beliefs, and fears. Focusing on the process of informed 

consent, as opposed to bare legal requirements, increases 

a patient’s participation in his or her own care, which 

may result in increased patient compliance and selfmonitoring. 

Informed consent as “teaching” (indeed, the 

origin of the word “doctor” is from “teacher”) further 

diminishes patients’ misconceptions or inaccurate fears 

about their situation and prospects and may improve 

patient recovery or comfort with a better understanding 

of the care that is being provided. No good data are available 

regarding these “therapeutic” effects of informed 

consent, and further studies seem warranted. Despite 

these theoretical positive aspects, issues surrounding 

informed consent remain vexing for physicians in a 

number of clinical situations from both legal and ethical 

perspectives. Even the ideal model of “shared decision 

making” does not address many of the realities of medical 

practice, including emergency situations, conflicts of interest, 

and questions of futility. 

By emphasizing informed consent as a temporal 

“process,” one can avoid the pitfalls of viewing informed 

consent as a single event. Informed consent can never be 

reduced to a signature on a consent form. “Perhaps the 

most fundamental and pervasive myth about informed 

consent is that informed consent has been obtained when 

a patient signs a consent form. Nothing could be further 

from the truth, as many courts have pointed out to physicians 

who were only too willing to believe this myth.” 13 

Although a matter of routine in many institutions because 

they are seen as providing protection against liability, 

informed consent forms actually provide very little. The 

informed consent form does have value in that it provides 

an opportunity for the patient to read the information on 

the form and to create a locus for the appropriate patient– 

physician discussion that is the key element. An informed 

consent form merely documents that the “process” of 

informed consent has taken place. 

Traditionally, consent to anesthesia in the past was 

subsumed under the consent to the surgical procedure 

and included within the surgery consent form. The anesthesiologist 

was one step removed from the formal 

consent process. Today, separate specific consent for anesthesia 

is required in most states. It is imperative that the 

Table 4-1. Elements of the process of informed consent. 

Threshold elements (preconditions) 

Decision-making capacity or competency 

Freedom or voluntariness and absence of overriding state or legal 

interests 

Informational elements 

Adequate disclosure of material information 

Recommendation 

Understanding 

Consent elements 

Decision 

Authorization 

anesthesiologist make a concerted effort to adequately 

complete this process with the patient and, when appropriate, 

the patient’s family regarding the anesthetic procedure 

and adequately document in a note the patient’s 

consent on the chart or anesthetic record (above and 

beyond any signature on a standard form issued by a 

ward clerk). 

Beauchamp and Childress 14 have broken down the 

process of informed consent into seven elements (Table 

4-1). These include threshold elements or preconditions, 

which include (1) decision-making capacity or competency 

of the patient, (2) freedom or voluntariness in decision 

making, including absence of overriding legal or 

state interests; informational elements including (3) adequate 

disclosure of material information, (4) recommendations, 

and (5) an understanding of the above; consent 

elements, which include (6) decision by the patient in 

favor of a plan and (7) authorization of that plan. Several 

of these elements can pose particular challenges in the 

elderly population. 

Threshold Elements 

Decision-Making Capacity 

Physicians are frequently faced with the problem of 

making treatment decisions for elderly patients who no 

longer have decision-making capacity. Many diseases and 

conditions that can make continued life contingent on 

life-prolonging therapies can also destroy or substantially 

impair a person’s decision-making capacity and are more 

likely to do so in older people. In addition, Alzheimer’s 

disease and other forms of dementia are more likely to 

be present in older persons. One estimate is that 5% to 

7% of persons over 65, and 25% of those over 84, suffer 

from severe dementia. 15 Assessment of decision-making 

capacity even in cases of mild dementia can be particularly 

difficult. 16 Decision-making capacity requires: (1) a 

capacity to understand and communicate, (2) a capacity 

to reason and deliberate, and (3) possession of a set of


values and goals. 17–19 Although there is general agreement 

regarding these three requirements, there is no single, 

universally accepted standard of decision-making capacity. 

This is because decision-making capacity is not an 

all-or-nothing concept. Decision making is also a taskrelated 

concept and the requisite skills and abilities vary 

according to the specific decision or task. The relevant 

criteria should also vary according to the risk to a patient. 

Basically, one must ask the following questions: Does the 

patient understand his or her medical condition? Does 

the patient understand the options and the consequences 

of his or her decision? Is the patient capable of reasonable 

deliberation? Is the patient able to communicate 

his or her decision? Does the patient possess a coherent 

set of values and/or goals? Several reviews provide 

helpful discussions of the clinical assessment of elderly 

patients’ decision-making capacity within these contexts. 

20–22 Instruments such as the MacArthur Competence 

Assessment Tool-Treatment (MacCAT-T) may 

provide a flexible yet structured method with which physicians 

and other caregivers can assess, rate, and report 

patients’ abilities relevant for evaluating capacity to make 

treatment decisions. 23 

Informed consent in the elderly patient presents other 

unique aspects. 24 Sugarman et al. 25 conducted a structured 

literature review in the published empiric research 

on informed consent with older adults (aged 60 years and 

older). Diminished understanding of informed consent 

information was associated with older age and with fewer 

years of education. Although showing some impairment 

in their quality of reasoning, the elderly are able to reach 

reasonable risk-taking decisions to the same degree as 

young adults. 26,27 

To what extent must a patient “understand” his or her 

condition, treatment options, and risks? 28 If fully 

“informed” is meant to mean fully “educated” 29 then 

“informed” consent may be seen as an impossible standard. 

However, the primary object of information is to 

facilitate the patients’ care rather than providing a litany 

of possible complications in order to avoid a lawsuit. 

Factual knowledge is used, not as an end in itself, but as 

a means to extend the patients’ own understanding in 

such a way as to meet their own unique priorities, needs, 

concerns, beliefs, and fears so that they may decide about 

their care in the manner in which they normally make 

similar choices. This will vary from patient to patient and 

with the risks of the procedure involved. It is a mistake 

to assume that a patient must understand information to 

the same extent and in the same manner as a physician, 

or even as a well-educated layman. This may indeed be 

seen as just as paternalistic as not permitting patients to 

participate in decision making at all. 13 

Visual and hearing impairments and diminished 

memory and comprehension in the elderly patient require 

the clinician to exercise particular caution when obtaining 

informed consent. 30 One must also be careful to avoid 

the mistake of equating recall, a standard endpoint in 

many studies on the adequacy of informed consent and 

which may be problematic in the elderly, with understanding 

and comprehension. Meisel and Kuczewski 13 

note that, “While it may be true that someone who cannot 

retain information for a few seconds might not be said to 

understand it, people often make reasonable decisions 

but cannot later recall the premises that supported the 

reasoning or the process that led to the conclusion.” 

Distant recall of the informed consent process may be an 

indicator of the adequacy of a patient’s understanding, 

but its absence says little about the patient’s understanding 

at the time of consent. Physicians also tend to underestimate 

patients’ desire for information and discussion 

and, at the same time, overestimate patients’ desire to 

make decisions. 31–33 Elderly patients and their physicians 

often differ on patient quality-of-life assessments that 

may be associated with clinical decisions. 34 These studies 

and others underscore the need for clear communication, 

individualization, and compassion in obtaining adequate 

informed consent in the elderly. New strategies to maximize 

comprehension of informed consent information 

(e.g., storybooks, videos, and so forth) also may be 

useful. 25 

Assessment of patient capacity to enter into the process 

of informed consent or competency to make rational 

medical decisions is a complicated issue. Much has 

been written on the criteria for determining individual 

capacity and the legally defined characteristic of “competency.” 

19,35–38 Competency, unlike the decision-making 

capacity, is a legal term and an all-or-nothing concept 

specific to a given task. In the absence of a clear medical 

diagnosis such as delirium or unconsciousness, decisions 

regarding competency must be made with assistance from 

psychiatric services, ethics consult services, and/or legal 

counsel. In general, decisions must be made in these situations 

on the patient’s behalf, either by “substituted judgment” 

(a decision based on what the patient would have 

wanted, assuming some knowledge of what the patient’s 

wishes would have been) with or without the help of 

proxy consent or by a decision made according to the 

“best interests” of the patient on the basis of a balancing 

of a “benefit versus burdens” ratio. An appropriate hierarchy 

for surrogate decision makers is delineated, for 

example, in a provision of the Virginia Health Care Decisions 

Act (Code of Virginia §54.1–2981) as follows: 1. A 

legally appointed guardian or committee. 2. The patient’s 

spouse if no divorce action has been filed. 3. An adult son 

or daughter of the patient. 4. The patient’s parent. 5. An 

adult brother or sister of the patient. 6. Any other relative 

of the patient in descending order of relationship. It must 

be remembered that the caregiver has an ethical obligation 

to evaluate the competency of the surrogate’s 

decisions with regard to (1) lack of conflict of interest,


(2) reliability of the evidence of the patient’s desires on 

which the surrogate is relying, (3) the surrogate’s knowledge 

of the patient’s own value system, and (4) the surrogate’s 

responsible commitment to the decision-making 

process. 39 All these situations involve complex issues and, 

again, may require the assistance of hospital ethics committees 

or consult services. 

Voluntariness 

A second threshold element is one of freedom or voluntariness. 

Here one asks the question of whether the 

patient’s decision is free from external constraints. These 

constraints can consist of myriad social, familial, and 

even financial factors that can be difficult, if not impossible, 

to sort out. However, it is not true that the principle 

of respect for autonomy is at odds with all forms of heteronomy, 

authority, tradition, etc. Competent individuals 

may autonomously choose to yield first-order decisions 

(i.e., their decisions about the rightness and wrongness 

of particular modes of conduct) to a professional, family, 

spouse, or to a religious institution. In these instances, the 

person is exercising second-order autonomy in selecting 

the professional, person, or institution to which they 

choose to be subordinate. In these cases, second-order 

autonomy becomes central. 40 The distinguishing feature 

becomes whether the second-order decision was free and 

voluntary. Frequently, elderly patients decide on specific 

treatment options with respect for the opinions of family 

members, or a concern for their psychologic, physical, 

and/or financial well-being. As Waymack and Taler 

observe, “It is often the case that health care professionals 

find themselves in the care of elderly patients where, 

because of the nature of chronic care, families often ask 

or are asked to play a significant role.” 41 It is perfectly 

appropriate for elderly patients to consider the preferences 

of loved ones, and they should not automatically 

be encouraged to make decisions concerning treatment 

options, particularly life-extending treatments, for exclusively 

self-regarding or purely selfish reasons. Moreover, 

although undue pressure and influence are clearly 

improper, it is a mistake to assume that any advice and 

counsel from family members constitutes undue pressure 

or influence. However, when elderly patients possess 

decision-making capacity, generally they and only they 

have the moral authority to decide how much weight to 

give the preferences and interests of family members. 

While it is true that elderly patients can have ethical 

obligations toward family members that have a bearing 

on treatment decisions and the interests of family 

members can be “ethically relevant whether or not the 

patient is inclined to consider them,” 42 they should generally 

retain decision-making authority even if physicians 

believe that they are failing to give due consideration to 

the interests of family members. 43 

Informational Elements 

Adequate Disclosure 

The first of the informational elements of informed 

consent is adequate disclosure. This is the process of 

properly informing the patient of his or her diagnosis, 

prognosis, treatment options, risks, and possible outcomes. 

The anesthesiologist should reveal the specific risks and 

benefits of each anesthetic option, the complications of 

instrumentation of the airway, the risks and benefits of 

invasive monitoring, the presence and use of a fallback 

plan, and basis for the anesthesiologist’s recommendations. 

44 “Transparency” is a useful term describing the 

openness by which the anesthesiologist discusses the 

treatment plans with a patient. By “thinking out loud” 

regarding the options and plans, the anesthesiologist 

communicates the thought processes that he is making 

that is going into his or her recommendation, thus 

allowing the patient to understand and participate in this 

process. Most patients and parents of patients want assurance 

and explanation regarding anesthesia, not necessarily 

detailed and exhaustive information. 

The discussion of risks and hazards of the diagnostic 

or therapeutic options, as well as information about anticipated 

pain or suffering, are, in theory and practice, the 

most troublesome aspects of informed consent. According 

to the President’s Commission for the Study of Ethical 

Problems in Medicine and Biomedical and Behavioral 

Research, “Adequate informed consent requires effort on 

the part of the physician to ensure comprehension; it 

involves far more than just a signature on the bottom of 

a list of possible complications. Such complications can 

be so overwhelming that patients are unable to appreciate 

the truly significant information and to make sound 

decisions.” 19 The law does not require one to give a list 

of every possible complication of a planned procedure 

(which may inflict an undue amount of emotional distress), 

but only a “reasonable” amount of information. 

Negligence is not failure to achieve a good outcome, nor 

failure to disclose all remote risks. 45 

But just how does one define “reasonable”? The courts 

have had difficulty as well assessing what a “reasonable” 

standard of disclosure may be. The most cited standard is 

the professional practice standard. 46 This standard defines 

reasonable disclosure as what a capable and reasonable 

medical practitioner in the same field would reveal to a 

patient under the same or similar circumstances. Some 

courts have ignored this prevailing standard of disclosure 

and shifted the focus from the professional community as 

forming the standard to the patients themselves. It focuses 

on the “new consumerism” in health care, an extension 

of the patient’s right of self-determination, where the 

patient is viewed as consumer of health care and the 

physician as provider. 47 The “reasonable patient standard” 

asks what a reasonable patient would consider


reasonable and material to the decision of whether to 

consent to a procedure offered. The burden, however, is 

still on the physician to ascertain just what is reasonable 

and material for a hypothetical “reasonable patient.” This 

recognizes a significant shift in consent law. As legal standards 

continue to evolve, the reasonable patient standard 

may become more commonly accepted and eventually 

displace the professional practice standard as the majority 

opinion in American informed consent law. A further 

extension of this line of thinking is the “subjective person 

standard.” This standard recognizes that all patients are 

different, there is no hypothetical “reasonable person,” 

and hence the standard of disclosure must recognize not 

only the local standard of care but individual patient 

needs and idiosyncrasies as well. One important factor in 

all the above is the notion of “causality,” i.e., would additional 

information have affected this particular patient’s 

decision? What specific, individual concerns did the 

patient have that would have most affected his or her 

decision whether or not they are part of the local standard 

of care for disclosure? The risk of vocal cord damage 

from a routine intubation may be so small as to not 

require mentioning in the normal situation (although this 

is debatable). It may, however, be very important for a 

professional singer in opting between regional or general 

anesthesia. 

Recommendation and Understanding 

Providing a recommendation and patient understanding 

are the other two informational elements in the informed 

consent process. The principle of patient autonomy does 

not require the physician to present the information in 

a totally neutral manner, if this were even possible. 

Indeed, part of the informed consent process is to present 

information to the patient in a way that buttresses a 

physician’s recommendations. Persuasion is a justifiable 

way for educating patients. This is different from manipulation, 

which is defined as inappropriately causing a 

certain behavior, and coercion, which is actually threatening 

a patient with a plausible punishment so the patient 

will act in a certain way. 

Assessing patient understanding of the information 

presented can be a difficult issue, especially if “standard” 

consent forms are relied upon. In one study, 27% of postoperative 

surgical patients signing consent forms did not 

know which organ had been operated upon, and 44% did 

not know the nature of the procedure. 48 Cassileth et al. 49 

showed that 55% of cancer patients could list only one of 

the major complications for chemotherapy within 1 day 

of signing consent forms. Other studies have shown that 

risk-specific consent forms do not aid retention 50 and that 

decision makers often sign consent forms that they do not 

understand. 51 Attempts must be made to educate patients 

according to their individual needs and, as has been stated 

previously, not to assume a patient must have complete 

understanding, but only that necessary given their own 

particular situation to come to a reasonable decision. This 

will vary from patient to patient and from situation to 

situation, and consent forms cannot be relied upon to 

provide this information, no matter how detailed. 

Consent Elements: Decision and 

Autonomous Authorization 

Finally, there are the two consent elements: decision and 

autonomous authorization. The patient must be able to 

reach a decision and authorize the physician to provide 

the care decided upon. The physician must document the 

consented-to technique as well as the invasive monitoring 

to be used. The patient may consent either verbally or in 

writing, both are ethically and legally just as valid. It may 

be more difficult to provide evidence of verbal consent 

after the fact, however, making it all the more important 

to document adequately the patient’s response in the 

chart. Although lack of an objection is not equivalent to 

an authorization, cooperation of patients during performance 

of a procedure in the absence of overt verbal 

authorization has usually been deemed equivalent to 

implied consent and sufficient in cases specifically 

addressing these issues. 52 

Advance Directives 

Advance directives are statements that a patient makes, 

while still retaining decision-making capacity, about how 

treatment decisions should be made when they no longer 

have the capacity to make those decisions. California was 

the first state to legalize the “living will” in 1976; by 1985, 

35 states and the District of Columbia had enacted similar 

laws. In 1991, the Patient Self-Determination Act (PSDA) 

became federal law involving all Medicare and Medicaid 

providers. The PSDA provides that all health care providers 

must give all patients written information at the time 

of their admission advising them of their rights to refuse 

any treatments and to have an advance directive. The 

presence of an advance directive must be documented in 

the patient’s record, and discrimination against a person 

because they do or do not have an advance directive is 

prohibited. 

There are two general forms of advance directives. 

Living wills are documents stating the desires of the 

patient for treatment alternatives, usually to die a 

“natural” death and not to be kept alive by advanced 

life-support measures. In many states, the patient may 

also stipulate wishes regarding fluid and nutrition discontinuation 

in the event of persistent vegetative state. Living 

wills become effective on the determination of “terminal 

illness” or when death is imminent (within 6 months) or


Table 4-2. Living will. 

Strengths 

1. Allows the physician to understand the patient’s wishes and 

motivations. 

2. Extends the patient’s autonomy, self-control, and 

self-determination. 

3. Relieves the patient’s anxiety about unwanted treatment. 

4. Relieves physician’s anxiety about legal liability. 

5. Reduces family strife and sense of guilt. 

6. Improves communication and trust between patient and physician. 

Weaknesses 

1. Applicable only to those in persistent vegetative state or the 

terminally ill (patients who have a disease that is incurable and 

who will die regardless of treatment). 

2. Death must be imminent (likely to occur within 6 months). 

3. Ambiguous terms may be difficult to later interpret. 

4. There is no proxy decision maker, so: 

• It requires prediction of final illness scenario and available 

treatment. 

• It requires physician to make decisions on the basis of an 

interpretation of a document. 

Source: Junkerman C, Schiedermayer D. Practical Ethics for Students, 

Interns, and Residents. 2nd ed. Hagerstown, MD: University Publishing 

Group; 1998. Copyright © 1998 by University Publishing Group. Used 

with permission. All rights reserved. 

family members with vested interests), legal or regulatory 

obstacles, or other problems may hinder a clear decisionmaking 

process. The American Geriatric Society Ethics 

Committee has published a position statement that outlines 

a strategy for dealing with these situations. 54 They 

recommend that health care providers and institutions 

develop methods to make decisions for incapacitated 

persons without surrogates and to establish mechanisms 

for intra-institutional conflict resolution, such as an ethics 

committee, to mediate conflicting situations. They also 

recommend that surrogate decision-making laws and 

policies should not hinder the patient’s ability to die naturally 

and comfortably. Evidence from competent patients 

in similar circumstances should shape the plan of care for 

an individual patient in the absence of evidence that the 

patient’s wishes would be otherwise. 54 Other strategies 

include the “prior competent choice” standard, which 

stresses the values the patient held while competent. 

The “best interest standard” moves the focus to the 

patient’s subjective experience at the time the treatment 

is considered. 21 

when two physicians make the diagnosis of persistent 

vegetative state. The strengths and weaknesses of the 

living will are outlined in Table 4-2. Living wills have 

several weaknesses, including the frequent lack of specific 

instructions and the impossibility of any person foreseeing 

all the contingencies of a future illness. 53 Therefore, 

many advocate an alternative form of advance directive 

known as a Power of Attorney for Healthcare (PAHC). 

A PAHC provides for the appointment of a person to act 

as a health care agent, proxy, or surrogate to make treatment 

decisions when the patient is no longer able. The 

PAHC allows a person to add specific directives and often 

will give the designated agent authority to have feeding 

tubes withheld or withdrawn. Most PAHCs become 

effective when two physicians, or one physician and a 

psychologist, determine that the patient no longer has 

decision-making capacity. However, this requirement is 

not universal, and individual state statutes may vary. 

Table 4-3 lists the advantages of the PAHC that may 

make it a better option than a living will. Individual state 

statutes may differ regarding certain components such as 

witnesses and need for notarization. Whichever form of 

advance directive a patient chooses to use, both serve a 

valuable role in preventing ethical dilemmas if designed 

properly and implemented. 

In many instances, elderly patients who lack decisionmaking 

capacity have neither executed an advance 

directive nor previously discussed their preferences 

regarding treatment options. Even when surrogates are 

available, disagreements among parties (particularly 

Table 4-3. Power of Attorney for Healthcare (PAHC). 

Activation of PAHC 

Lack of decision-making capacity must be certified by two physicians 

or one physician and a psychologist who have examined the patient. 

Until then, the patient makes all the decisions. 

Advantages 

1. Physician has someone to talk with—a proxy, a knowledgeable 

surrogate—who can provide a substituted judgment of how the 

patient would have chosen. If the agent is unable to provide a 

substituted judgment, the agent and physician together can use the 

best-interest standard (how a reasonable person might choose in 

consideration of the benefit–burden concept of proportionality). 

2. Provides flexibility; this decreases ambiguity and uncertainty 

because there is no way to predict all possible scenarios. 

3. Authority of agent can be limited as person desires. 

4. Avoids family conflict about rightful agent. 

5. Provides legal immunity for physicians who follow dictates. 

6. Allows appointment of a nonrelative (especially valuable for 

persons who may be alienated from their families). 

7. Most forms can be completed without an attorney. 

8. Principal may add specific instructions to the agent, such as the 

following: “I value a full life more than a long life. If my suffering 

is intense and irreversible, or if I have lost the ability to interact 

with others and have no reasonable hope of regaining this ability 

even though I have no terminal illness, I do not want to have my 

life prolonged. I would then ask not to be subjected to surgery or 

to resuscitation procedures, or to intensive care services or to other 

life-prolonging measures, including the administration of antibiotics 

or blood products or artificial nutrition and hydration.” (Adapted 

with permission from Bok S. Personal directions from care at the 

end of life. N Engl J Med 1976;295:362–369.) 

Source: Junkerman C, Schiedermayer D. Practical Ethics for Students, 

Interns, and Residents. 2nd ed. Hagerstown, MD: University Publishing 

Group; 1998. Copyright © 1998 by University Publishing Group. Used 

with permission. All rights reserved.


There remains an urgent role for physicians to educate 

their patients, their institutions, and their legislatures 

regarding the important role of advance directives in 

clinical decision making and the need to remove legislative 

and institutional hindrances to providing excellent 

care to dying patients and their families. Although playing 

an important role in unique circumstances, advance directives 

are not a substitute for adequate communication 

among physicians, patients, and family about end-of-life 

decision making and, in themselves, do not substantially 

enhance physician–patient communication or decision 

making. 55 

Do-Not-Attempt-Resuscitation Orders 

in the Operating Room 

The anesthesiologist is most likely to come into contact 

with ethical issues involving advance directives when a 

patient is scheduled for surgery with a “do-notresuscitate” 

(DNR, or the preferred and more realistic 

terminology “do-not-attempt-resuscitation,” DNAR 56 ) 

order on the chart. As many as 15% of patients with 

DNAR orders will undergo a surgical procedure. 57 Wenger 

et al. 58 studied a subgroup of the SUPPORT (Study to 

Understand Prognoses and Preferences for Outcomes 

and Risks of Treatment) database and found that of 745 

patients presenting to the operating room (OR), 57 had 

a DNAR order. Operative procedures ranged in complexity 

and risk from tracheostomy and vascular access 

to liver transplantation and coronary artery bypass grafting. 

Twenty of the 57 patients had their DNAR order 

reversed preoperatively. Two of these patients suffered an 

intraoperative cardiac arrest and were resuscitated. Both 

patients subsequently died postoperatively. Only one 

patient without DNAR order reversal arrested during 

surgery and died without attempted resuscitation. 

Anesthesiologists and surgeons are generally reluctant 

to proceed with surgical intervention if they are not 

allowed to intervene in the dying process. They feel that 

consent for anesthesia and surgery implies consent for 

resuscitation and is inconsistent with a DNAR order. 59,60 

Anesthesiologists tend to claim that the induction and 

maintenance of anesthesia can often involve creating 

conditions in which resuscitation is required. 59 Indeed, 

anesthesia itself has at times been referred to as a “controlled 

resuscitation.” Because anesthetic agents or procedures 

may create conditions requiring resuscitation, 

the anesthesiologist ought to have the right to correct 

those conditions when possible. Surgeons and physicians 

doing other procedures use similar arguments to claim 

that if cardiac or pulmonary arrest is a consequence of 

their actions they should be allowed to prevent or reverse 

those conditions. In a 1993 survey of anesthesiologists by 

Clemency and Thompson, 60 almost two thirds of the 

respondents assumed DNAR suspension in the perioperative 

period and only half discussed this assumption 

with the patient/guardian. 

This dilemma represents a classic problem in the principled 

approach to medical ethics: the conflict of two or 

more prima facie ethical principles. If the physician 

chooses to act paternalistically to provide what is believed 

to be the best treatment at the time, he is giving precedence 

to the concept of beneficence over the patient’s 

autonomy. If, however, the physician acts to preserve 

patient autonomy, he may feel that the duty to do good, 

as directed by the principle of beneficence, has been compromised. 

Further complicating the issue is that “DNAR” 

has multiple definitions and interpretations and involves 

a spectrum of procedures that the general public is not 

aware of. 61 

Although automatic suspension of DNAR orders 

during a surgical procedure and for an arbitrary period 

postoperatively is the most unambiguous and straightforward 

policy, it is now argued that this is inappropriate. 62,63 

Statements from both the American Society of Anesthesiologists 

and the American College of Surgeons recognize 

that this policy effectively removes patients from the 

decision-making process, even if they are willing to accept 

the risk of operative mortality. They recommend instead 

a policy of “required reconsideration” of the DNAR 

order, as the patient who undergoes a surgical procedure 

faces a different risk/benefit ratio. Both statements are, 

however, ambiguous about just how resuscitation is to be 

handled in the OR. Two alternatives are presented: (1) to 

suspend the DNAR order in the perioperative period, 

and (2) to limit resuscitation to certain procedures and 

techniques. Because of the complexities surrounding the 

nature of resuscitation, public misconceptions and lack of 

awareness of these complexities, and the desire to honor 

the goals reflected in a patient’s decision to forgo CPR, 

a third alternative has been proposed involving a valuescentered 

61 or goal-directed 64 approach. By ascertaining 

the patient’s goals, values, and preferences rather than 

individual procedures, the anesthesiologist is given 

greater flexibility in honoring the objectives of the DNAR 

order within the clinical context of the arrest. Although 

seeking to honor both the autonomy of the patient and 

the physician’s duty to beneficence within the spirit of 

the original DNAR order, this alternative is not without 

its problems. 65 The establishment of a physician–patient 

relationship that will facilitate a full understanding of a 

patient’s values and goals is a daunting, if not impossible, 

task for the anesthesiologist confronted with the demands 

of a limited preoperative encounter. These concerns may 

be even more profound in the elderly population. 66 Physicians 

have not been good at predicting the wishes of their 

patients regarding resuscitation in other situations, even 

after discussion has taken place. 67–69 It does, however,


provide a third alternative and recognizes that, despite its 

practical limitations and high regard for patient autonomy 

in our society, there must always exist a degree of 

physician–patient trust in any clinical encounter. 

Anesthesiologists need to be actively involved in 

their own institutions to develop policies for DNAR 

orders in the OR. Open communication among the anesthesiologist, 

surgeon, and patient or family must exist to 

reach an agreement about DNAR status. Appropriate 

exceptions to suspension of a DNAR order in the OR 

should be honored. Timing of reinstitution of DNAR 

status should also be addressed and agreed upon before 

the procedure. Actual experience shows that very few 

times will a patient insist on a DNAR status during the 

procedure. 

Treatment Futility 

With respect to informed consent, what if the patient’s 

decision is counter to the recommendations of the anesthesiologist 

or amounts to something the anesthesiologist 

regards as dangerous? Must the physician necessarily do 

whatever a patient wants? In short, no. In nonemergent 

circumstances, physicians are not obligated to provide 

care that they feel is not in their patients’ best interest. 

“First, do no harm” is the operative principle in these 

situations. It is important again to distinguish in these 

cases the negative and positive rights based on or related 

to the principle of respect for personal autonomy and to 

recognize that the limits on positive rights may be greater 

than the limits on negative rights. For example, the positive 

right to request a particular treatment may be severely 

limited by appropriate clinical standards of care, physician 

judgment, or just allocation schemes. Clinicians 

should, however, be very cautious when making this claim 

and should only do so if absolutely convinced that no 

other options are available. 

Occasionally, physicians have found it necessary to 

justify unilaterally deciding that certain medical interventions 

(such as CPR) are “futile” and withhold these interventions 

even when a patient or a patient’s family wants 

them. The notion of medical futility is particularly confusing 

and open to different interpretations and abuses. 

“Futility” can be defined in several senses. “Strict sense 

futility” or “medical” futility is defined when a medical 

intervention has no demonstrable physiologic benefit, 

e.g., when there have been no survivors after CPR under 

the given circumstances in well-designed studies, or in 

cases of progressive septic or cardiogenic shock despite 

maximal treatment. There are no obligations for physicians 

to provide medically futile treatment, even when 

families want “everything done.” Unilateral decisions to 

withhold treatment (such as DNAR orders) are appropriate 

under these circumstances. Usually a DNAR order 

may be written on the basis of “futility” when two or 

more staff physicians concur in writing and give justification 

for their decision. The patient or surrogate need not 

agree with the decision but must be notified. If there is 

disagreement, an ethics consultation may be appropriate 

and helpful. 

It is rare that a given medical intervention is unlikely 

to have any physiologic effect whatsoever and hence futility 

may also be defined in a “less strict sense.” In this 

instance, there may be a low survival rate but the rate is 

not zero. In this case, although the physician may have the 

particular expertise to determine whether a particular 

intervention is reasonable according to a particular standard 

of reasonableness, setting a particular standard 

involves a value judgment that goes beyond that expertise. 

For example, a 79-year-old cancer patient wants CPR in 

the event that he suffers cardiopulmonary arrest because 

he believes that any chance that CPR will restore cardiopulmonary 

function is worthwhile and that any prolongation 

of his life is also valuable and worthwhile (for instance, 

by allowing for a family member to return from overseas). 

Whereas the physician may assess that the chance of CPR 

restoring function is x%, x is greater than zero and whether 

the chance of restoring function is reasonable, valuable, or 

worthwhile only if it is greater than x% depends primarily 

on the patient’s own values. Unilateral decisions may not 

be appropriate in this instance, and discussions with the 

patient and family should be initiated to provide information 

and advice. 

Whereas a physician may have the expertise to assess 

whether a particular intervention is likely to achieve a 

specified outcome, determining whether an outcome is an 

appropriate or valuable objective for a patient is dependent 

on the patient’s own value judgments. A medical 

intervention can be futile in a third sense when it will 

have no reasonable chance to achieve the patient’s goals 

and objectives. For example, CPR is futile in this sense if 

there is no reasonable chance that it will achieve the 

patient’s goal of leaving the hospital and living an independent 

life. Because medical interventions are futile in 

relation to the patient’s goals, this sense of futility provides 

a very limited basis for unilateral decisions to 

withhold medication interventions that patients want. 

The American Medical Association Council of Judicial 

and Ethical Affairs has commented that resuscitative 

efforts “would be considered futile if they could not be 

expected to achieve the goals expressed by the informed 

patient. This definition of futility not only respects the 

autonomy and value judgments of individual patients but 

also allows for the professional judgment and guidance 

of physicians who render care to patients.” 70 

Because the term “futility” tends to communicate a 

false sense of scientific objectivity and finality and to 

obscure the inherent evaluative nature of the judgments, 

it is recommended that physicians avoid using the term


to justify unilateral decisions to withhold life-sustaining 

treatment. Rather, physicians should explain the specific 

grounds for concluding that interventions generally, or 

particular life-sustaining measures, are inappropriate in 

the given circumstances. Whereas the statement that a 

given intervention is futile tends to discourage discussion, 

explaining the grounds for a given judgment in light of 

the circumstances and with an understanding of the 

patient’s own values and goals tends to invite discussion 

and point it in the right direction. 

Treatment Redirection and 

Palliative Care 

Jean Paul Sartre said that “the meaning of life is found 

in death,” and how we deal with the aging process determines 

how we deal with death and our philosophy of life. 

This is most important for the physician and patient when 

faced with end-of-life decision making involving treatment 

redirection and palliative care options. 

Treatment redirection refers to that point in the 

patient’s care plan when the patient or surrogate, along 

with the health care team, recognizes the need to move 

from aggressive curative treatment to supportive palliative 

care. The 1995 SUPPORT study found that as many 

as 50% of patients were subjected to burdensome, curative 

treatment because the patient, family, and physician 

had not recognized or discussed the realities of the 

patient’s condition. 71 Potter suggests three barriers to 

meeting the need for treatment redirection. 72 First, clinicians 

and patients often are narrowly focused on curative 

or ameliorative intervention. Lack of communication 

between the physician, who assumes that “they want 

everything done,” and the patients and families, who have 

different expectations, contributes to this problem. Furthermore, 

patients and their families often assume that 

physicians have reliable knowledge about what therapies 

are effective and which are not because of their intense 

focus on curative treatment. A study by Feinstein and 

Horwitz, 73 however, shows that evidence-based medical 

decisions can only be claimed for less than 20% of clinical 

situations. 

Second, physicians and patients are often reluctant 

or unable to discuss palliation as a treatment option. 74 

Although evidence suggests that physicians are more 

willing to withhold or withdraw treatment from seriously 

ill patients, 57 patients and families continue to report that 

there is a lack of physician communication in the area of 

shifting treatment to palliative care. 75 Disparity of beliefs 

and preferences causes much of this communication 

problem. 

Finally, there is a lack of knowledge of and confidence 

in palliative care by both physicians 76 and society. 77 Part 

of the problem is that patients are referred to palliative 

care and hospice programs far too late in their hospital 

course to do any good. Furthermore, Potter notes that, 

“although there is a growing trend toward patients 

wanting to be in control of their own death, cultural 

diversity factors, belief in the power of medical technology, 

and a strong tendency to deny death prevent a 

working consensus about how to approach the experience 

of dying.” 72 Patients and their families may also be 

suspicious that palliative care is a way to save money, a 

form of rationing, although there is no empirical evidence 

that palliative care is more cost effective. 78 

Effective treatment-redirection involves three sequential 

steps. 72 First, there must be a system to recognize 

clues, both patient signals and physiologic signs, to indicate 

that the current form of treatment may not be wanted 

or may not be warranted. 79 Second, there must be deliberation 

as part of the informed consent process that 

focuses on the appropriateness of the current treatment 

options. Potter reminds one that “because the patient is 

embedded in a social context of family and friends, there 

must be an inclusive attitude that searches out the wider 

origin of beliefs and preferences in the patient’s moral 

community.” 72 Furthermore, the health care providers 

themselves must analyze their own personal beliefs and 

preferences that can create biases and distort clinical 

judgment. An open dialog is a necessary part of the deliberation 

process. Third and finally, there must be an implementation 

plan that activates excellent palliative care. 80 

The aim is for both the patient and the health care team 

to make a smooth transition from the ultimate goal of 

curing to that of caring. 

End-of-Life Care 

End-of-life palliative care options and decision making 

have become increasingly complicated as new forms of 

therapy and pain control become available. Pain control 

in the terminal stages of many illnesses is one of the 

primary goals of effective palliative care and is an area 

in which anesthesiologists have a great deal to offer. One 

of the most pervasive causes of anxiety among patients, 

their families, and the public is the perception that physicians’ 

efforts toward the relief of pain are sadly deficient. 

Studies indicate that their fears may be justified. In a 

study of 1227 elderly patients, approximately 20% experienced 

moderate or severe pain during the last month of 

life and the final 6 hours before death. 81 In another study 

of a random sample of 200 elderly community residents 

in the last month before death, 66% had pain all or most 

of the time. 82 Pain influenced behavioral competence, 

perceived quality of life, psychologic well-being, depression, 

and diminished happiness. A recent editorial raises 

concern that medical, radiation, and surgical oncologists


are not effectively treating the pain of patients with 

cancer. 83 

Fear of inadequate pain relief during the terminal 

stages of illness may be responsible for the increasing 

interest in euthanasia and physician-assisted suicide 

(PAS). It is now commonly accepted that the administration 

of large quantities of narcotic analgesics is not euthanasia 

when the purpose is to alleviate pain and suffering, 

not to shorten the life of the patient. Wanzer et al. 84 note 

that: 

In the patient whose dying process is irreversible, the balance 

between minimizing pain and suffering and potentially hastening 

death should be struck clearly in favor of pain relief. Narcotics 

and other pain medications should be given in whatever dose 

and by whatever route is necessary for relief. It is morally 

correct to increase the dose of narcotics to whatever dose is 

needed, even though the medication may contribute to the 

depression of respiration or blood pressure, the dulling of consciousness 

or even death, providing the primary goal of the 

physician is to relieve suffering. The proper dose of pain medication 

is the dose that is sufficient to relieve pain and suffering, 

even to the point of unconsciousness. 

In this regard, there is clearly a strong need for increased 

physician and patient education as well as careful ethical 

analysis. 

The terminal stages of the dying process can be accompanied 

by a number of other disturbing symptoms, both 

for the family and the patient. Symptoms recorded in the 

last 48 hours of life include noisy and moist breathing 

(death rattle), restlessness and agitation, incontinence of 

urine, dyspnea, retention of urine, nausea and vomiting, 

sweating, jerking, twitching, plucking, confusion, and 

delirium. 85–87 Appropriate palliative care must take into 

account the comfort and care of the patient with regard 

to these symptoms as well. 88,89 

Despite even the highest quality of palliative care, 

many patients still report significant pain 1 week before 

death, 90 some of whom request help in hastening death. 

Furthermore, patients request a hastened death not 

simply because of unrelieved pain, but because of 

the wide variety of other unrelieved physical symptoms 

in combination with loss of meaning, dignity, and 

independence. 91 

Confusion may exist about the physician’s moral 

responsibility for contributing to the patient’s death. The 

principle of double effect has an important role in ethical 

decision making in these instances. Double effect 

acknowledges that the intent and desired effect of treatment 

is mitigation of symptoms rather than cessation of 

life, even though life may be shortened. As frequently 

formulated, the principle stipulates that one may rightfully 

cause evil (shortening of life) through an act of 

choice (treatment of pain) if four conditions are verified: 

(1) the act itself, apart from the evil caused, is good or at 

least indifferent; (2) the good effect of the act is what the 

agent intends directly, only permitting the evil effect; (3) 

the good effect must not come about by means of the evil 

effect; and (4) there must be some proportionately grave 

reason for permitting the evil effect to occur. 92 

Public and professional debate and confusion over 

PAS continues even after its legalization in Oregon, the 

trials of Jack Kevorkian in Michigan, and the experience 

in the Netherlands. Anesthesiologists should be particularly 

concerned with the debate for two reasons: (1) 

because of their unique skills, anesthesiologists may have 

a very active role as practitioners of euthanasia, 93 and (2) 

the fear of uncontrolled pain relief, an area that anesthesiologists 

can provide particular expertise, is a primary 

motivation for euthanasia and PAS. 94 

PAS differs from euthanasia in that the physician is not 

the direct agent in PAS whereby in euthanasia the physician 

is the direct agent. However, not all ethicists agree 

that PAS and euthanasia differ significantly because of 

agency. The 1994 edition of the American Medical Association 

Code of Medical Ethics states that PAS and 

euthanasia are, “fundamentally incompatible with the 

physician’s role as healer, would be difficult or impossible 

to control, and would pose serious societal risks.” 95 The 

Second Edition (1989) of the American College of 

Physicians Ethics Manual reads, “Although a patient may 

refuse a medical intervention and the physician may 

comply with this refusal, the physician must never intentionally 

and directly cause death or assist a patient to 

commit suicide.” 96 The position statement of the American 

Geriatrics Society Ethics Committee recommends 

that, “For patients whose quality of life has become so 

poor as to make continued existence less preferable than 

death, the professional standard of care should be that of 

aggressive palliation, not that of intentional termination 

of life. . . . Laws prohibiting VAE [voluntary active euthanasia] 

and PAS should not be changed.” 97 A study by 

Koenig et al. 98 showed that the majority of elderly patients 

attending a geriatrics clinic did not favor legalization of 

PAS. Furthermore, relatives of these patients could not 

consistently predict the patients’ attitudes or agree among 

themselves. Recently, public and professional attitudes 

toward PAS and euthanasia have shifted. The Third 

Edition (1993) of the American College of Physicians 

Ethics Manual, although maintaining that physicians 

should make relief of suffering in the terminally ill patient 

their highest priority, does not include the strict prohibition 

included in the previous edition and is much more 

ambiguous regarding PAS and euthanasia. 99 

The politics of euthanasia and PAS remain controversial. 

Physicians should be concerned that renewed interest 

in euthanasia and PAS will not divert attention from 

the pressing concerns of adequate pain control, treatment 

of depression, and symptom management in the terminally 

ill and should actively seek alternate ways to address 

patient worries regarding loss of control, indignity, and


dependence during the final stages of an illness. The 

elderly, particularly the severely demented, are at the 

cutting edge of the debate over PAS and VAE. “Senicide” 

is a very real entity in cultural anthropology. It is not 

unthinkable that in our aging society, pressure will mount 

to take moral guidance from anthropologic data, with 

economic concerns replacing the nomadic. 100 Physicians 

need to resolve not to let public policy matters interfere 

with their duty to the health and welfare of their individual 

patients, regardless of age, and to maintain a commitment 

to both healing and caring. Anesthesiologists 

can provide a unique service to their physician colleagues, 

patients, and general population through education and 

consultation regarding chronic pain and symptom control 

in the terminally ill. Measures must go beyond education 

and become an established part of quality assurance. 101 

Anesthesiologists can contribute by assisting their hospitals 

with means to monitor the treatment of patients in 

pain. Despite the growing acceptance among the general 

population and the medical community regarding physician 

involvement in euthanasia, it is not compatible with 

the healer’s mission and art. At its core, killing patients 

should never be the means by which symptoms or sufferings, 

psychologic or physical, are relieved. 

Resource Allocation and the Elderly 

Concerned over the increasing cost of health care in the 

United States, many health care policy makers claim that 

health care rationing is unavoidable. Rationing by age 

seems to offer a means of reducing spending on health 

care. 102 Many patient-selection decisions in the United 

States, such as for heart transplantation, intensive care, 

and kidney dialysis and transplantation, have long been 

based on age criteria. 103–106 A recent study by Hamel et 

al. 107 concludes that older age was associated with higher 

rates of decisions to withhold ventilator support, surgery, 

and dialysis even after adjustments for differences in 

patients’ prognoses and preferences. Older patients with 

coronary artery disease were less likely to undergo invasive 

and noninvasive testing, 108–110 although studies in 

octogenarians show that coronary artery bypass surgery 

is highly cost effective and improves their quality of life 

in a manner equal to that of a younger population. 111–113 

“Age-rationing” implies that elderly patients are denied 

access to potentially beneficial health care services to 

which younger patients are not denied access. This is to 

be distinguished from cost-containment measures that 

merely result in withholding medical services that are not 

expected to benefit these patients. 114 

There are several arguments advanced to defend the 

denial of access to scarce and/or costly medical care to 

the elderly. One argument is to suggest that elderly 

patients are not medically suitable candidates for certain 

life-sustaining measures. Even if these measures were to 

succeed, the quality of elderly patients’ lives, because of 

continued ill health and chronically poor functioning, will 

remain poor. Extending life under such circumstances is 

not deemed to provide a substantial benefit. This argument 

is “ageist” at its core because it is based on false 

universal generalizations regarding all elderly patients. 

Although the chances of experiencing ill health and 

impaired functioning increase with age, many elderly 

people are medically suitable candidates for a wide range 

of treatment options, and many enjoy good health and 

unimpaired functioning. A patient’s overall health status 

is generally a more reliable indicator of medical suitability 

than age alone. 

Another defense of age-rationing holds that greater 

benefits are obtained when life-extending treatments are 

received by younger patients. These benefits include 

overall social welfare (because younger persons are more 

productive than the elderly) and cost effectiveness 

(because younger patients can be expected to benefit 

more and at a lower cost). 115 There are three major difficulties 

with this line of argument. First, it again is ageist 

in its underlying generalizations. It assumes that elderly 

persons are unproductive and fails to take into account 

other standards of productivity (general health status, 

employment history, and current employment status, 

etc.). Second, elderly persons who would fail to receive 

treatments and who would die because of age rationing 

would bear the burdens, but they would not enjoy any of 

the benefits derived from the increased productivity that 

is said to result from this argument. The shift in the 

benefit–burden ratio to a particular class on the basis of 

age reveals its injustice and inherent age bias. Finally, 

even if it can be claimed that it is more cost effective to 

deny certain classes of people access to beneficial health 

care, this fails to provide a reason for it being fair or just. 

Justice can require greater expenditures. 

The economic, social, and public policy issues are enormously 

complicated and beyond the scope of this chapter. 

Rationing scarce medical resources purely on the basis of 

a certain age cut-off, however, does not seem to be ethically 

justifiable. 114,116–118 The growing support in the United 

States for age criteria in health care does not have a 

sound medical basis. Support more likely reflects certain 

social, economic, or even philosophical attitudes and 

values not universally shared by society or by other cultures. 

This is different from saying that age cannot be 

taken into account as a predictor of medical benefit or 

prognosis. Kilner 119 endorses the use of age as a “symptom” 

or “rule of thumb” in relation to medical assessments of 

patients. He states that age “may serve as a tool the physician 

uses in applying a medical criterion, not as a criterion 

in its own right.” Both the acute physiology and chronic 

health evaluation (APACHE) III and the SUPPORT 

model include age as one prognostic element, along with


other physiologic variables. In neither study does age 

seem to have a major role, compared with other variables. 

120,121 Physicians must utilize the best available data 

on treatment outcomes and costs and assume responsibility 

for developing criteria for appropriateness and medical 

necessity across the spectrum of patient age and economic 

status. Physicians should practice appropriatenessbased, 

not cost-based medicine. 122 The rapid changes 

occurring in the health care system and the recurring 

emphases on “bottom-line” management require physicians 

to be involved in allocation decisions at both the 

professional and public policy level. Rationing policies 

and managed care plans must be accompanied by full 

disclosure to patients regarding the limits to their care 

resulting from these policies and plans, along with a 

process of patient advocacy and appeal. Gag rules that 

restrict such disclosures are inherently unethical. 123 

Clinical Research and the 

Elderly Patient 

The elderly patient with severe dementia or depression, 

or incapacitated in the critical care or emergency setting, 

represents an extremely vulnerable population, not unlike 

that of young children or infants, and presents unique 

dilemmas in the area of clinical research ethics. The 

ethical issues raised can be summarized as one of balancing: 

(1) protecting potentially vulnerable research par - 

ticipants, and (2) advancing knowledge and providing 

potentially beneficial new therapies for a special group of 

patients. These issues become most manifest when dealing 

with psychiatric patients, children, and the adult or elderly 

incapacitated patient, usually in a critical care or emergency 

setting. 124–130 

In terms of the elderly population in particular, there 

is no doubt or argument against the proposition that 

including the elderly, even those incapacitated or suffering 

from severe dementia or depression, in clinical 

research designed to benefit this particular population is 

both important and necessary. Simply to exclude such 

patients from clinical research trials because they lack the 

capability for providing informed consent subjects the 

entire population of such patients to a trial-and-error, 

anecdotally driven practice of medicine that may, ultimately, 

end up doing more harm to these patients and 

result in increased and unnecessary morbidity and mortality 

in the long term. Balanced against this noble task 

of advancing our knowledge base for the benefit of future 

patients, is the necessity of maintaining high ethical standards 

in the process and protecting those participants in 

current research trials who may or may not directly 

benefit from being subject to the nontherapeutic particularities 

and randomization of a research program design. 

The focus on the prior concern is on the many, i.e., the 

entire population of patients who will potentially benefit 

from such studies. The focus on the latter is the one, 

i.e., the individual patient who, by voluntary informed 

consent, has forfeited the right to individualized and 

purely therapeutic concern for participation in the artificial 

environment of the research protocol, whereby the 

focus of concern will be primarily on the efficient and 

statistically valid accumulation of specific information 

for the sake of future benefits. For this reason, patients 

who elect to participate in clinical research studies are 

protected from study designs that impose more than 

minimal risk, that are not designed with expectations to 

maintain or improve the condition of the patient, or that 

are flawed in their design such that a valid answer to an 

appropriate question cannot be obtained. The bar for 

protection needs to be raised to a higher level for those 

patients who are incapacitated and cannot understand 

the nature of the research proposal and/or cannot provide 

appropriate consent to participate. These patients represent 

a particularly vulnerable population that can easily 

be exploited. 

Proxy or surrogate consent has a longstanding history 

in the realm of the purely therapeutic clinical situation. 

But to what extent does the ethical reasoning inherent 

in proxy or surrogate consent still apply in the clinical 

research situation and can the ethical conclusions drawn 

from the purely therapeutic physician/patient situation 

be univocally transferred to the physician-researcher/ 

patient-subject research situation? It is common for clinical 

researchers to presuppose that there is no problem 

with transferring the standards of proxy consent that 

exist in the therapeutic relationship into the domain of 

clinical research. 

There are two major difficulties with this view. These 

difficulties stem from a close examination of the two 

theoretical foundations upon which proxy or surrogate 

consent to treatment rests. The first relies on the ability 

of close family members, friends, or appointed surrogates 

to provide evidence of the patient’s own wishes as to what 

they would want in a particular foreseeable circumstance 

(substituted judgment). This can either be through personal 

knowledge or through available written documents 

executed by the patient beforehand. Few patients, 

however, actually end up discussing relative issues in any 

direct way with friends, family, or their physicians regarding 

their future medical care. 14,131 Even fewer are likely 

to discuss involvement in clinical research trials in the 

event they are incapacitated by an injury or illness. Even 

when these discussions have been conducted, studies 

show that surrogates and physicians do not accurately 

predict patient wishes, in both therapeutic and research 

situations. 128,132–134 Many ethicists have raised the question 

as to whether anyone can speak with authority for “what 

the patient would have wanted” and question whether 

this “mythological foundation” for proxy consent should,


in fact, be abandoned. Yet even if a case could be made 

that sickness, illness, and death are universal concerns 

that can provide at least a point of “sympathy” for a close 

friend or relative and thereby provide a modest grounding 

for substituted judgment, this is categorically different 

from choices that involve participating in medical 

research. Choosing to forgo the “therapeutic” for the 

“experimental” is, with few extenuating circumstances, a 

uniquely personal decision, a decision that is grounded 

on the individual particularities of any given research 

protocol. If this foundation for substituted judgment 

(speaking for what the patient would have wanted) in 

the therapeutic situation is in any sense called into question, 

it certainly must be even more so in the experimental 

situation. Richard McCormick 135 states, “Whether a 

person ought to do such things [enroll in a research study] 

is a highly individual affair and cannot be generalized 

in the way the good of self-preservation can be. And if 

we cannot say of an individual that he ought to do these 

things, proxy consent has no reasonable presumptive 

basis.” 

The second foundation for proxy or surrogate consent 

is that of speaking for the “best interest” of the patient. 

Therapeutic decisions are often made, in the absence of 

any compelling evidence of what the patient specifically 

would have wanted, on the basis of what would be in the 

best interest of the patient (in emergency situations, treatment 

is often assumed to be in the “best interest” of any 

patient until proven otherwise). Yet it is difficult to apply 

this to the research situation, for in this situation the “best 

interest” of the patient is always relegated to the needs 

of the study design (e.g., randomization to a particular 

treatment group). To think otherwise is to fall victim to 

the so-called “therapeutic misconception.” 136–138 Even 

physician-investigators are prone to blur clinical trial and 

patient care such that their attention is diverted from the 

inherent conflicts between the pursuit of science and the 

protection of research participants. 139 The ethical challenge 

is to define the limits on the kinds of research risks 

that the proxy can accept on behalf of a noncompetent 

patient/subject. Most ethicists and institutional review 

boards (IRBs) would agree that if the research is potentially 

beneficial or presents minimal risks and that the 

knowledge that may be gained would be important to the 

class of subjects under study, it would be appropriate for 

a surrogate or proxy to grant consent on behalf of the 

patient/subject. But how does one define what “minimal 

risk” and reasonable benefit is within the context of any 

given research proposal? Similarly, how does one balance 

the risks against the potential benefits for the subjects or 

against the knowledge the research may produce? 

In a recent commentary, Karlawish 130 proposes that a 

distinction should be made between risks that are justified 

by potential benefits for the subjects and risks that are not 

justified by those benefits. Proxy consent is permissible if 

the risks posed by the components of the research that do 

not offer potential benefits for the subjects are no more 

than minimal and are justified by the importance of the 

knowledge to be gained. The risks posed by components 

with potential benefits are justified by the state of equipoise: 

the expert consensus is that the interventions being 

compared are within the standard of care so that equilibrium 

exists in the balance between risks and benefits in 

the intervention and control groups. 

Federal regulations for the protection of research participants, 

known as the “common rule,” require that 

research involving “vulnerable” subjects include “additional 

safeguards” and that the investigator obtains 

informed consent from a “legally authorized representative.” 

140 Although the rule does not describe safeguards 

in detail, and most states have not addressed the question 

of who is legally authorized to provide consent, it does 

underscore the necessity of protecting vulnerable patients 

and their families from exploitation. One possible consideration 

(variously proposed by others) is to provide for 

two patient surrogates, one of which would be the normal 

surrogate that would be provided for in the strict therapeutic 

context, and the other a court-designated or IRBapproved 

representative that would be able to look after 

the particular interests of the patient and family within 

the research context. Consent would be required from 

both, and either would be able to withdraw the patient 

from the clinical trial at any time. Truog et al. 141 have 

noted, “The most effective protection against exploitation 

comes not from the process of informed consent, but, 

rather, from the careful oversight and scrutiny of conscientious 

institutional review boards.” If this is the case, 

then review and control boards, particularly those of 

organizations responsible for the publication and dissemination 

of the results of research studies, need to take 

their role very seriously. The identification and discussion 

of ethical flaws in current research studies need to be 

more openly discussed in the mainstream medical literature 

in the hope that these discussions would elevate the 

level of ethical practices in human research conducted by 

physician-scientists. 142 

Summary 

1. A clinician’s own view of aging can and will influence 

both clinical decision making as well as the application 

of ethical principles to individual concrete situations. 

Aging does not have to be seen as a disease or as a form 

of deviance but rather, the aging process can be valued 

given the limitations it imposes as a normal part of the 

human life narrative. Furthermore, the geriatric patient 

can present with a number of unique perioperative ethical 

dilemmas that can challenge accepted medical ethics 

paradigms.


2. Informed consent is a temporal “process” and can 

never be reduced to a signature on a consent form. Proper 

informed consent is centered on the notions of open communication 

and shared decision making. Compassion, 

understanding, and creativity are necessary to overcome 

many of the challenges geriatric patients present to the 

formal elements of the informed consent process. 

3. Advance directives are statements that a patient 

makes, while still retaining decision-making capacity, 

about how treatment decisions should be made when 

they no longer have the capacity to make those decisions. 

There are two general forms of advance directives: living 

wills and PAHC. PAHCs have several advantages over 

living wills. Although playing an important role in unique 

circumstances, advance directives are not a substitute for 

adequate communication among physicians, patients, and 

family about end-of-life decision making. 

4. Anesthesiologists need to be actively involved in 

their own institutions to develop policies for DNAR 

orders in the OR. Open communication among the anesthesiologist, 

surgeon, and patient or family must exist to 

reach an agreement about DNAR status. Clinicians 

should not automatically assume DNAR status to be suspended 

in the OR and appropriate exceptions to suspension 

of a DNAR order in the OR should be honored. 

Timing of reinstitution of DNAR status should also be 

addressed and agreed upon before the procedure and 

carefully documented. 

5. “Futility” is a value-laden term and tends to communicate 

a false sense of scientific objectivity and finality. 

It is recommended that clinicians avoid the use of the 

term and focus on explaining the specific grounds for 

concluding that particular interventions are inappropriate 

in the given circumstances. Whereas the statement 

that a given intervention is futile tends to discourage 

discussion, explaining the grounds for a given judgment 

in light of the circumstances and with an understanding 

of the patient’s own values and goals tends to invite discussion 

and point it in the right direction. 

6. There are times when clinicians, patients, and their 

families need to redirect care from aggressive curative 

treatment to supportive palliative care without a sense of 

“abandoning” the patient. Anesthesiologists have an 

active role in end-of-life palliative care, both in terms of 

pain and symptom management. Inadequate pain relief 

in the terminal stages of most diseases is a continuing 

problem. Anesthesiologists can contribute by assisting 

their hospitals with means to monitor the treatment of 

patients in pain. Despite the growing acceptance among 

the general population and the medical community 

regarding physician involvement in euthanasia, it is not 

compatible with the healer’s mission and art. Whereas 

there are times the dying process should not be prolonged, 

it should not be intentionally hastened either. At 

its core, killing patients should never be the means by 

which symptoms or sufferings, psychologic or physical, 

are “relieved.” 

7. “Age rationing” implies that elderly patients are 

denied access to potentially beneficial health care services 

to which younger patients are not denied access. 

This is to be distinguished from cost-containment measures 

that merely result in withholding medical services 

that are not expected to benefit these patients. 

8. Some elderly patients in particular settings (such as 

with severe dementia or depression, or incapacitated in a 

critical care or emergency setting) are extremely vulnerable, 

similar to young children or infants, and may present 

unique dilemmas in the area of clinical research ethics. 

Whereas including the elderly in clinical research designed 

to benefit this particular population is both important 

and necessary, there is the equal and sometimes competing 

necessity of maintaining high ethical standards in the 

process and protecting those patients in research trials 

who may or may not directly benefit from being subject 

to the nontherapeutic particularities and randomization 

of a research program design. 

References 

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5 

Teaching Geriatric Anesthesiology to 

Practitioners, Residents, and Medical Students 

Sheila J. Ellis 

Care of the geriatric patient will continue to grow in 

importance as the geriatric proportion of the population 

continues to grow. The increasing life expectancy in the 

United States and improvements in medical care allow 

expansion of surgical procedures into populations once 

considered too unstable or frail to recover from the stress 

of surgery. Geriatric patients undergo the same range of 

surgical procedures as younger patients. Some procedures, 

such as cataract surgery or prostate resection, may 

be performed more frequently in the geriatric patient. 

Virtually every medical provider will need to have a thorough 

understanding of the needs, complications, and 

changes in the elderly. Thus, education in geriatric anesthesia 

is essential. 

Geriatrics in Educational Programs 

Medical School 

Ideally, the introduction to geriatrics begins in medical 

school. The geriatric curriculum in medical schools has 

grown a great deal in the past several decades. The 

Longitudinal Study of Training and Practice in Geriatric 

Medicine by the Association of Directors of Geriatric 

Academic Programs found that in the academic year 

2000 to 2001, 116 of 125 (93%) responding medical 

schools included geriatric topics as part of an existing 

required course, and 10 of 125 (8%) had a separate 

required course. Electives with geriatric topics were 

offered as separate courses in 68 schools (54%) and as 

part of an elective course in 35 institutions (28%). 1 

Anesthesiology Residency 

The formal course of geriatric education usually concludes 

with the end of medical school. However, it is now 

recognized that structured geriatric education should be 

included in anesthesiology training. The Accreditation 

Council for Graduate Medical Education (ACGME) 

requires “appropriate didactic instruction and sufficient 

clinical experience in managing problems of the geriatric 

population” in accredited anesthesiology residency programs. 

2 The type and amount of clinical experience that 

qualifies as sufficient and the amount of appropriate 

didactic instruction remains undefined. 

The joint American Board of Anesthesiology (ABA)/ 

American Society of Anesthesiologists (ASA) content 

outline for in-training examinations also includes a section 

titled “Geriatric Anesthesia/Aging: The Pharmacological 

Implications, MAC Changes and the Physiological 

Implications on CNS, Circulatory, Respiratory, Renal, 

and Hepatic Organ Systems.” This is a very incomplete 

list, obviously. 

Geriatrics as Part of 

Core Competencies 

Residency education in geriatrics can be used to establish 

a curriculum to meet the updated required ACGME 

competencies. ACGME requires evidence of training and 

proficiency in six core areas, including patient care, 

medical knowledge, practice-based learning and improvement, 

interpersonal and communication skills, professionalism, 

and systems-based practice (Table 5-1). 3 

Communication Skills 

Incorporating these competencies into a geriatric curriculum 

may provide a method to evaluate these principles 

while advancing geriatric education. A preoperative 

assessment of a confused patient can be an opportunity 

to teach and assess residents on communication skills. 

Interacting with the patient’s caregiver provides an 

opportunity for development of interpersonal skills. 4 This 

preoperative assessment may be complicated because the 

58

5. Teaching Geriatric Anesthesiology 59 

Table 5-1. Core competencies of accreditation council for 

graduate medical education. 

Patient care 

Medical knowledge 

Practice-based learning and improvement 

Interpersonal and communication skills 

Professionalism 

Systems-based practice 

confused patient may have difficulty transmitting a complete 

medical history. Sensory changes such as hearing 

loss may challenge the anesthesia trainee to utilize additional 

modalities for clear communication, such as hearing 

amplification devices or written communication. Transmitting 

information to the elderly patient regarding preoperative 

medication usage and oral intake requires the 

ability to assess patient understanding. All of these communication 

skills can be directly observed or can be videotaped 

for discussion and additional feedback. 

Teaching residents the skills needed for completing 

such a challenging preoperative assessment can be 

accomplished in a similar manner by direct observation 

or through a media presentation. A taped interview can 

be used to show students and residents methods for eliciting 

information and increasing the information obtained 

by improved interpersonal communication. Providing 

written instructions for patients can demonstrate improvement 

in communication skills. 

Communication with other health care providers is 

also an important component of care of the elderly 

patient. Multiple providers may be involved such as 

primary care physicians, specialist physicians, home health 

attendants, and caregivers. Maintaining appropriate and 

adequate communication with all of these sources should 

be encouraged and evaluated. 

Systems-Based Practice 

A discussion of end-of-life issues and do-not-resuscitate 

orders in the perioperative period may be a way to teach 

systems-based practice. Systems-based practice requires 

an awareness of the larger context and system of 

health care. It is essential to understand what a do-notresuscitate 

order means in the perioperative period. The 

institutional requirements regarding such notations can 

be reviewed while assessing or reconsidering such an 

order with the patient or surrogate. Clarification and, if 

necessary, modification of a do-not-resuscitate order 

should be documented in the medical record. This discussion 

can be integrated into the larger experience of health 

care beyond the immediate anesthetic needs. Such a discussion 

can also be useful to educate the resident and 

student in the core competency of professionalism and 

adherence to ethical principles in care of the patient. 

Practice-Based Learning and Improvement 

Practice-based learning and improvement requires the 

ability to determine an area that needs improvement, 

identify and apply an intervention, and measure impact 

of the intervention. 5 Patient-based learning and improvement 

seeks to improve patient care through appraisal of 

scientific evidence. Perioperative beta blockade can be a 

rich source of material for practice-based learning. The 

ability to recognize the current practice regarding perioperative 

use of beta blockade and the appropriate application 

of this therapy can be an important part of geriatric 

education. Incorporating these competencies into a geriatric 

curriculum can be a very effective method both for 

teaching the student and resident geriatric anesthesia, 

and providing a place for evaluation and assessment for 

the educational program. 

Importance of Geriatric Training 

For completion of anesthesiology residency, specific criteria 

must be fulfilled for pediatrics, including experience 

with a set number of anesthetics on a child younger than 

1 year of age. In adult patients, the emphasis is on physiologic 

changes and specialized procedures, not on the age 

of the patient. By requiring a set number of cardiac procedures, 

for example, the trainee in anesthesiology will 

most likely include a number of elderly patients, but this 

is not guaranteed. It is possible that a resident could 

have an adequate number of cardiovascular procedures 

without performing the majority of these cases on geriatric 

patients. Does this matter? Is there a difference in 

cardiovascular disease in patients 45 versus 85 years of 

age? The disease processes may have widely varying 

causes, and the patients may have very different intraoperative 

and postoperative courses. Elderly patients may 

present with atypical presentations of common problems 

such as angina that may delay or alter treatment. 

The older patient has the potential for many adverse 

perioperative events. The hazards of hospitalization and 

surgery in the elderly include adverse drug events, delirium, 

functional decline, infection, malnutrition, thromboembolism, 

and untreated or undertreated pain. 6 

Hospitalization is often followed by an irreversible 

decline in functional status and a change in quality and 

style of life. Only 20% of patients in a large group returned 

to their preoperative functional level after repair of a hip 

fracture. 7 In a study of community-dwelling, noninstitutionalized 

patients aged 70 years or older hospitalized for 

acute medical illness, 31% of the patients declined in 

activities of daily living (ADL) at discharge compared 

with baseline after a mean length of admission of 8.6 days. 

At a 3-month follow-up, 40% reported disabilities related 

to ADL or instrumental ADL such as meal preparation

60 S.J. Ellis 

or shopping for groceries compared with preadmission 

baseline. 8 

Therefore, it is important to have exposure to and 

experience with elderly patients, not just to diseases 

frequently seen in elderly patients. As a practical matter, 

a sampling of cases on a typical day at a hospital, 

ambulatory setting, or pain clinic servicing a general 

population will provide a number of elderly patients. The 

key should be to look at the patients in these settings as 

valuable educational opportunities. We believe that a 

resident diary of the number of patients cared for over 

the age of 75 would be important to determine if residents 

were exposed to an adequate number of geriatric 

patients. 

Growth of Geriatric Anesthesia 

The subspecialty fellowship in gerontology continues to 

grow with 338 fellows in training programs during 2001– 

2001. 9 However, the number of trainees in fellowship 

programs still falls short of the number needed to serve 

the expanding geriatric population. 

The field of geriatric anesthesiology is relatively new. 

The Society for the Advancement of Geriatric Anesthesiology 

(SAGA) was established in the United States 

in 2000. There is also the Age Anaesthesia Association 

that functions in the United Kingdom. As of 2004, there 

is not a fellowship or subspecialty track in geriatrics 

for anesthesiology trainees. There is a dearth of specific 

citations in the medical literature related to the teaching 

of geriatric anesthesiology. It is expected that the recognition 

of geriatric anesthesia as a separate entity and 

the need for further expertise will fuel this branch of 

anesthesia. 

Teaching Geriatrics 

Education in geriatric anesthesia is a process that can 

be defined separately from teaching. Teaching implies 

an activity by an individual or a group causing another 

person to know new facts or how to accomplish a new 

task. The focus is on the teacher, not the learner. 10 

However, education is a broader process that results in 

a change in behavior on the part of the student. The focus 

of education is the learner, not the teacher. 10 The desired 

end result is not a specific ability to perform a task, or 

retention of a set of data. The goal is a change in behavior 

based on experiences. These experiences may be from 

direct interaction, indirect observations, or a more remote 

learning from lectures, but the desired end result is the 

same. If the instruction produces a change in behavior 

(and, most likely, attitude), education has been 

achieved. 

Who is the target audience for education in ger - 

iatric anesthesia? Certainly residents in anesthesiology, 

student nurse anesthetists, student anesthesiology assistants, 

and medical students are focus groups for this 

training, and fully trained anesthesiologists through 

continuing medical education. Other individuals who will 

participate in anesthesia and the other aspects of patient 

care are also important and should be included when 

considering the establishment or expansion of an education 

program for geriatric anesthesia. Preoperative and 

postoperative recovery nurses, emergency room personnel, 

anesthesia technicians and anesthesia aides, and 

respiratory therapists can be included in geriatric education. 

Primary care physicians and surgeons certainly 

should be exposed to geriatric issues regarding perioperative 

medicine. 

All of these groups are adult learners who should be 

independent and self-directed. 11 There may be many different 

reasons for seeking further education but the usual 

common factor is a desire for improvement as a clinician. 

Whereas formal training programs serve a large number 

of adult learners, there are many who utilize other educational 

avenues. This may take the form of self-study 

continuing medical education courses, lectures at medical 

meetings, Internet-based learning, and other opportunities. 

The desire for professional improvement and the 

active search for educational sources make adult learners 

very involved in their own education. The self-direction 

and independence of adult learners is a key trait in producing 

changes in their behavior. 

Adult learners also use their own experiences as a 

resource for learning. They may view the current experience 

differently based on their background from others 

without a similar amount of experience. This can enhance 

education but must be acknowledged and accepted, not 

rejected by educators. 12 For example, an anesthesiology 

resident with a prior career in nephrology may treat 

acid-base management in the operating room differently 

from a resident without this experience. A faculty member 

who can acknowledge the experience of the student 

in this situation will not only provide better clinical care 

but also enhance the education of the student. This 

approach validates the adult learner and makes the 

learner more receptive to education in other areas. The 

previous learning may color the education of the adult 

learner so the educator must work to integrate and build 

on this, not reject the learning and, in doing so, reject the 

learner. 

Principles to guiding adult teaching include having the 

learner be an active contributor and utilize as much as 

possible the current knowledge and experience in the 

learner. 11 Learning should closely relate to understanding 

and solving real problems that the learner will encounter. 

There should be opportunities for practice, with assessment 

and constructive feedback from the educator.


Developing a Geriatric Curriculum 

Faculty Development 

In developing a program for teaching geriatric anesthesia, 

the prime consideration is to identify an individual who 

will develop geriatric expertise and an interest in geriatric 

education. A leader who will take responsibility is vital. 

This key person, it is hoped, will provide a core of other 

people who can be viewed as mentors to facilitate and 

maintain a geriatric curriculum. In other faculty members 

with specific areas of interest or expertise, increased 

knowledge and emphasis on geriatrics can be used to 

supplement the geriatric anesthesia experts. For example, 

a cardiovascular anesthesiologist may provide education 

in the changes in cardiac function in the elderly whereas 

an anesthesia provider with advanced skills in regional 

anesthesia may provide insight into peripheral nerve 

blocks in this population. 

An impediment to faculty development in geriatric 

anesthesiology can be the attitude that geriatric anesthesiology 

is not sufficiently interesting or academically 

rigorous enough to justify the effort toward further development. 

Because general anesthesiologists already care 

for older patients, many do not feel the need to develop 

skills or devote additional clinical or academic time 

that is already in short supply. This attitude can be countered 

by the requirements for geriatric anesthesia education 

from ACGME and the ASA/ABA content outline, 

the growth in this area in number of patients and understanding 

of aging, and the likelihood for career 

advancement. 

The designation of a geriatric anesthesia faculty 

member can be an opportunity for personal career 

growth. The emergence of geriatric anesthesia as a distinct 

subspecialty can allow anesthesiologists to interact 

with gerontologists, pharmacists, ethicists, and other specialists. 

As an expanding field, there will be multiple possibilities 

for research, publication, and leadership. The 

recognition of a host of common perioperative problems 

in the elderly such as postoperative cognitive dysfunction 

and postoperative delirium that have important longterm 

consequences can be an area of research and academic 

interest. 

Assessment of Resources 

Table 5-2. Resources for teaching geriatric anesthesia. 

Faculty development programs 

Society for Advancement of Geriatric Anesthesia (SAGA) 

Age Anaesthesia Association (United Kingdom) 

American Society of Anesthesiologists Syllabus for Geriatrics 

Portal of Geriatrics Online Education (POGOe) 

American Geriatrics Society 

Geriatrics Syllabus for Specialists 

Geriatrics at Your Fingertips 

Stanford University Geriatrics Education Resource Center 

The John A. Hartford Foundation Consortium for Geriatrics in 

Residency Training 

After identifying the person (or persons) who has an 

interest in geriatric anesthesia and educating others in 

this field, there should be an assessment of the resources 

available for increasing expertise. Is there a Department 

of Geriatrics at the educational institution that will 

partner with the anesthesiology department? If not, one 

could seek local experts in geriatrics in other fields who 

would be willing to provide mentoring and advice. Creating 

a network with others interested in geriatric anesthesia 

can provide support, information, and guidance. This 

can be aided by joining societies and organizations 

that promote and specialize in geriatrics and geriatric 

anesthesiology. 

Membership in geriatric-oriented organizations can 

provide resources such as didactic lectures, speakers, 

journals, and meetings. For anesthesia providers, there is 

the SAGA in the United States and Age Anaesthesia 

Association in the United Kingdom (vide supra). Membership 

in the American Geriatric Society (AGS) promotes 

interaction with geriatric-oriented individuals in 

surgical and related subspecialties, national educational 

meetings, and monthly journals. The ASA has a geriatric 

syllabus available at no cost on their Web site. 13 Organizations 

such as these can provide lists of current, peerreviewed 

geriatric articles in the medical literature, 

available educational grants, geriatric-related meetings, 

and speakers (Table 5-2). 

Specific institutions may choose to develop multidisciplinary 

or specialty-specific seminars for faculty development 

in geriatrics. 14 Grants may provide funds for 

providing speakers and resources for these seminars or 

internal faculty with current geriatric expertise may be 

utilized to lead this expansion of geriatric expertise. 

Determining a Program’s Needs 

Once the geriatric anesthesia specialists have been identified 

and outfitted with resources, there should be an 

assessment of departmental needs. One method to determine 

the needs and desires of the learners is to survey 

the students and residents. This can be done to discover 

areas of interest or areas that are inadequately covered 

by the current curriculum. Determining the aspects of 

caring for the elderly patient that are troubling or rewarding 

may be helpful. Do the residents and students think 

the geriatric curriculum, teaching, and experience are 

adequate? If not, what would they change? Assessing 

the confidence in teaching geriatric skills to fellow residents 

or students may determine areas for improvement.

62 S.J. Ellis 

The faculty can also be surveyed to find areas of expertise 

and interest that may be utilized for teaching geriatric 

anesthesia. The surveys may be repeated to assess the 

efficacy of the geriatric curriculum, and evaluation and 

feedback from the learners may help to guide needed 

changes. 

A survey used at the University of Nebraska Medical 

Center sought information regarding the anesthesiology 

residents’ confidence in performing specific tasks with 

the elderly patient such as functional assessment, discussion 

of advance directives and end-of-life issues, 

assessment of nutritional status, evaluation of sensory 

changes, risk and benefit discussion of proposed surgery, 

management of postoperative pain, evaluation for depression, 

and determination of the patient’s social support 

(personal communication, Dr. Edward Vandenberg, 

Omaha, NE, May 5, 2004). The survey also included the 

residents’ self-assessment of ability to distinguish between 

delirium and dementia and provide appropriate care for 

each, utilize information on aging physiology and agerelated 

pharmacologic changes, and discuss relevant 

regulations regarding Medicare. The survey assessed the 

residents’ desire to learn more about the above topics. 

This information was gathered on an annual basis to 

determine the areas of change desired in the curriculum 

as well as an assessment of the efficacy of the current 

curriculum. 

Producing a Geriatric Curriculum 

After an assessment of the department’s resources and 

needs is completed, a curriculum for geriatric education 

can be developed. Multiple teaching modalities should be 

incorporated into the development of this curriculum. 

There may be considerable overlap between the curriculum 

for residents and medical students although it may 

be necessary to condense the curriculum and didactics for 

medical students. Medical students’ exposure to geriatrics 

will likely be covered in primary care rotations or separate 

geriatric clerkships. In many schools of medicine, it 

is part of a longitudinal educational continuum over at 

least 2 years. Geriatric anesthesia can be included in these 

or in the anesthesiology rotation. 

Sample Curriculum 

Table 5-3 shows an example of a geriatric curriculum for 

an anesthesiology residency. 

Didactics 

The geriatric curriculum can be integrated into the educational 

program of the residency program as a specific 

dedicated geriatric unit or integrated into the educational 

cycle of each subspecialty rotation. At the University of 

Nebraska Medical Center, the residency curriculum is 18 

Table 5-3. Sample geriatric curriculum for an anesthesiology 

residency. 

A. Physiology of aging 

1. Gerontology 

2. Cardiovascular 

3. Respiratory 

4. Central and autonomic nervous system 

5. Renal and hepatic 

B. Pharmacology of aging 

1. Induction agents 

2. Opioids 

3. Neuromuscular blockade 

4. Sedatives and hypnotics 

5. Cardiovascular medications 

C. Preanesthetic evaluation 

1. Anesthetic risk and the elderly 

2. Guidelines for cardiac evaluation for noncardiac surgery 

3. Age-related disease 

4. Managing medical illness in the surgical patient 

5. Atypical presentations of common diseases in the elderly 

D. Pain control in the elderly patient 

1. Acute pain control 

2. Chronic pain management 

E. Regional anesthesia 

F. Ethics and palliative care in geriatrics 

G. Postoperative delirium and postoperative cognitive dysfunction 

H. Special concerns in caring for the elderly 

1. The elderly ambulatory surgery patient 

2. Critical care 

3. Sedation and procedures in remote locations 

4. The elderly trauma patient 

months in length so that residents are exposed to the 

entire didactic schedule twice during residency. The geriatric 

curriculum is inserted into the appropriate block. 

For example, during the time frame for preanesthesia 

evaluation and anesthetic risk, a lecture is given focusing 

on the preanesthetic evaluation of the geriatric patient 

and perioperative beta blockade is emphasized. 

For didactic lectures, speakers may be utilized from 

complementary departments including gerontology, pharmacology, 

surgery, and internal medicine. Visiting professors 

can also be invited to provide information. 

Discussion Groups 

Journal clubs may be used to provide a more informal 

setting for a geriatric discussion group. This can be led 

and organized by the faculty member responsible for 

geriatric education or residents, and can provide interaction 

outside of the operating room. Case conferences and 

problem-based learning discussions allow specific examples 

and small group discussions that may provide for a 

more personal level of interaction and feedback. Such 

discussions with more relevant, reality-based learning in 

a smaller group may be more interesting to the adult 

learner than limiting geriatric education to lectures. 

Problem-based learning discussions can be based on


actual cases or can be altered to incorporate a variety of 

teaching points in a concise manner. 

Journal clubs, problem-based learning discussions, and 

case conferences are excellent opportunities to discuss 

current controversies in medical care, examine the 

medical literature, and reinforce topics covered in didactic 

lectures. 

Reference Books 

A library of geriatric anesthesiology references is helpful 

for consolidating information in an easily accessible location. 

There are multiple textbooks in geriatric medicine, 

gerontology, geriatric anesthesia, and geriatric surgery 

that should be available for consultation. These books 

should be available to the department members. The 

“Geriatric Syllabus for Specialists” and “Geriatrics at 

Your Fingertips,” produced by the AGS, are valuable, 

pocket-sized resources that can be maintained in a reference 

library or acquired for each resident. 

Computer-Based Materials 

Internet-based resources are growing both in number 

and accessibility. The Portal of Geriatrics Online Education 

(POGOe) is an online clearinghouse that provides a 

single source of peer-reviewed educational products for 

those interested in geriatric education. Their site, www. 

pogoe.org, is funded by a grant from the Donald 

W. Reynolds Foundation to the Association of Geriatric 

Academic Programs. Physicians in training and practicing 

physicians may use the programs available. 

Other educational materials that may be utilized are 

computer-based self-instruction modules in geriatrics. 

These may be available via the Internet or on CD or 

DVD formats. The Stanford University Geriatrics Education 

Resource Center and other locations have teaching 

resources available. An initiative funded by the John A. 

Hartford Foundation has developed the Consortium for 

Geriatrics in Residency Training. Institutions or individual 

faculty members may also choose to develop their 

own educational materials tailored to their specific 

requirements. Web-based computer modules can be 

created or utilized from sites such as POGOe or the 

Stanford University Geriatrics Education Resource 

Center to be used for education of medical students or 

residents. These offerings may also be available to practitioners 

who are not in a formal training program. Such 

computer modules can be case-oriented and allow the 

learner to progress at his or her own pace. This can expose 

the student or resident to topics that may not be covered 

in a clinical situation and allow for immediate feedback 

and evaluation. Pre- and postmodule examinations can 

be used to determine information retention. If further 

discussion and evaluation is desired, a faculty-led discussion 

session can emphasize learning points and provide 

another avenue for those using the modules to provide 

feedback and evaluation. The Web-based modules can 

either be tailored to medical student or resident educational 

needs, or both groups can use the same module. 

Simulation 

The use of simulators for education is increasing as a 

greater number of institutions acquire the equipment and 

gain experience with the advantages of simulation education. 

The simulators can be used for multiple types of 

cases and provide a wide range of experience for the 

student and trainee. Simulation should include patients 

with coexisting morbidities and intraoperative and postoperative 

changes in organ systems, as well as providing 

experience with life-threatening processes or rare conditions 

that may not be experienced by the trainee in a 

clinical situation. Simulation can be primarily software 

based or may have intricate mannequins, creating the feel 

and responsiveness of an actual geriatric patient. There 

are many types available, from whole-body simulators to 

specific airway or regional anesthesia modes. Receiving 

feedback and constructive criticism with objective data 

can be a very valuable part of the experience. The encounters 

may be videotaped, and the computer will maintain 

information on each action. An advantage of simulators 

is the ability to teach all levels of learners and a wide 

variety of careers such as anesthesia practitioners, critical 

care nurses, allied health professionals, and medical 

students. 

Evaluation of Curriculum 

The effectiveness of a geriatric anesthesia curriculum 

must be evaluated; this can be accomplished in a number 

of ways. If the geriatric curriculum is covered in a core 

unit, a posttest can be used to determine informational 

retention and attainment of basic facts and knowledge. A 

pretest before introduction of the geriatric curriculum 

could be useful to gauge the change in basic knowledge 

that will be demonstrated in the posttest. An evaluation 

of attitude change and self-perception of knowledge may 

be garnered from a survey of the participants. 

Behavioral change is the ultimate desire of education. 

The ability to measure a change in behavior is difficult 

but may be reflected in the learner’s professionalism and 

practice patterns. In a residency program, the use of 360- 

degree evaluations may be a useful tool for assessment. 

Faculty members, nurses, and other health care and 

support personnel can evaluate the resident attitudes and 

actions. The use of patient and family comments can be 

utilized in a constructive manner to note positive aspects 

of performance as well as areas for improvement. Feedback 

with suggestions for improvement can be given to 

the residents and students.

64 S.J. Ellis 

Summary 

The number of geriatric patients is certain to increase. It 

is recognized that the academic programs in anesthesiology 

need to address the topic of geriatric anesthesia and 

prepare students to care for elderly patients. The expected 

growth in the older population and the increase in the 

number of operations for patients defined as elderly 

demand a well-trained profession able to meet the needs 

of this group. There are many avenues of medical knowledge 

such as postoperative cognitive dysfunction that are 

just beginning to be explored, along with further insight 

into the physiologic changes of aging and the effects of 

coexisting medical conditions. 

The medical school curriculum has changed in the past 

several decades to reflect an increased emphasis on geriatrics 

in the primary care fields. Beyond the primary care 

fields, the establishment of geriatric specialists has been 

lagging. The education of students and residents in geriatric 

anesthesiology will require an increased emphasis in 

these training programs. 

Establishing a geriatric anesthesiology curriculum 

requires an understanding of the needs of the adult learner 

who is self-directed, independent, and driven by internal 

motivation and the need for self-improvement. The adult 

student brings a set of experiences that can serve as a 

resource for further education but must be acknowledged 

and validated by the teacher. The desire for education that 

is practical and useful in everyday situations places an 

emphasis on teaching methods that utilize this, such as 

problem-based learning or case-oriented discussions with 

less desire for traditional lectures. 

Identifying a single individual to be responsible for 

geriatric anesthesiology education is imperative. Identifying 

and encouraging other faculty interested in geriatric 

anesthesia is a key component in establishing and maintaining 

a geriatric curriculum. This interest can be 

enhanced by the realization that a great opportunity 

exists to have an impact on a field that is rapidly growing 

and gaining in recognition. Even one individual can have 

an effect on an institution and, by networking with other 

similarly interested people locally and at a distance, on 

the profession as a whole. 

The involvement in geriatric anesthesia and geriatric 

societies provides a source of information and benefits 

such as scholarly journals, meetings, and educational 

opportunities. 

Development of a geriatric anesthesia program requires 

an inventory of a department’s resources and needs. 

Surveys and evaluations can be used to determine areas 

of strength or inadequate coverage in the current or proposed 

curriculum. Many modalities may be incorporated 

in the educational program including faculty lectures, 

visiting speakers, computer-based modules, journal clubs, 

case conferences and problem-based learning groups, 

simulations, discussion groups, and Internet-based 

resources. Educational materials may be tailored to a 

specific anesthesia program or adapted from available 

sources such as the POGOe. 

Increasing geriatric anesthesiology education in a 

residency program may allow incorporation of core 

competencies required for graduate medical education. 

Education and evaluation in practice-based learning and 

improvement, professionalism, and systems-based practice 

can be used in conjunction with geriatric anesthesiology. 

Proficiency in medical knowledge, patient care, and 

communication are all essential attributes for geriatric 

anesthesiology. 

Geriatric anesthesiology and geriatric anesthesia education 

will continue to grow and improve. By focusing 

time and resources on training anesthesia providers in 

the care of the elderly patient, the results will be better 

trained practitioners who can meet the needs of this 

growing population. The field of anesthesiology must 

incorporate geriatric anesthesiology education in all 

levels of its teaching. 

References 

1. The Association of Directors of Geriatric Academic 

Programs. Longitudinal study of training and practice in 

geriatric medicine. Available at: www.adgapstudy.uc.edu. 

Accessed August 13, 2004. 

2. Accreditation Council for Graduate Medical Education. 

Program requirements for anesthesiology. Available at: 

www.acgme.org/downloads/RRC_progReq.040pr703_u804. 

pdf. Accessed January 15, 2007. 

3. Accreditation Council for Graduate Medical Education. 

Outcome project, general competencies. Available at: www. 

acgme.org/outcome/comp/compMin.asp. Accessed January 

15, 2007. 

4. Barnett SR. Geriatric education: “Start low, go slow.” ASA 

Newslett 2004;68(5):9–10. 

5. Lynch DC, Swing SR, Horowitz DS, et al. Assessing 

practice-based learning and improvement. Teach Learn 

Med 2004;16(1):85–92. 

6. Interdisciplinary Leadership Group of the American Geriatrics 

Society. A statement of principles: toward improved 

care of older patients in surgical and medical specialties. J 

Am Geriatr Soc 2000;48:699–701. 

7. Creditor MC. Hazards of hospitalization in the elderly. Ann 

Intern Med 1993;118(3):219–223. 

8. Sager MA, Franke T, Inouye SK, et al. Functional outcomes 

of acute medical illness and hospitalization in older persons. 

Arch Intern Med 1996;156(6):645–652. 

9. Warshaw GA, Bragg EJ, Shaull RW, et al. Geriatric 

medicine fellowship programs: a national study from the 

Association of Directors of Geriatric Academic Programs’ 

Longitudinal Study of training and practice in geriatric 

medicine. J Am Geriatr Soc 2003;51(7):1023–1030. 

10. Schwartz AJ. Teaching anesthesia. In: Miller RD, ed. 

Anesthesia. 6th ed. New York: Churchill Livingstone; 2005: 

3105–3117.


11. Kaufman DM. Applying educational theory in practice. 

BMJ 2003;326:213–216. 

12. Newman P, Peile E. Valuing learners’ experience and 

supporting further growth: educational models to help 

experienced adult learners in medicine. BMJ 2002;325: 

200–202. 

13. American Society of Anesthesiologists. Syllabus on ger - 

iatric anesthesiology. Available at: www.asahq.org/clinical/ 

geriatrics/syllabus.htm. Accessed August 15, 2004. 

14. Williams BC. Building geriatrics curricula in medical and 

surgical house officer programs through faculty development. 

Acad Med 2002;77(5):458.

6 

Research Priorities in Geriatric 

Anesthesiology* 

Christopher J. Jankowski and David J. Cook 

The implications of an aging population on the practice 

of anesthesiology are profound. Normal aging results in 

diminished functional reserve across organ systems. These 

normal physiologic changes and age-related disease 

combine to limit the ability of the elderly to tolerate 

the stress of the perioperative period. Thus, geriatric 

issues affect every aspect of the care provided by the 

anesthesiologist. 

For example, age-related physiologic changes and 

disease make the preoperative evaluation of geriatric 

patients more complex than that of younger patients. 

Baseline functional reserve is often difficult to assess 

because of limits in physical ability, either from deconditioning, 

age-related disease, cognitive impairment, or a 

combination of the three. The same issues make the maintenance 

of intraoperative homeostasis more challenging 

in this population. Finally, geriatric issues such as postoperative 

respiratory complications and cognitive changes, 

as well as acute and chronic pain management can make 

postoperative care challenging. 

Despite these issues, surprisingly little research has 

been done to address the perioperative care of the aged, 

per se. This chapter will review some of the literature 

pertaining to this population in order to identify potentially 

fruitful areas of research. 

First, some of the normal physiologic changes that 

occur with aging will be reviewed. This is essential to 

frame any discussion of preoperative assessment or intraand 

postoperative management. Second, the preoperative 

evaluation of the older surgical patient will be 

discussed. Third, research related to the intraoperative 

management of geriatric patients will be described. Last, 

*This chapter is based on work performed for “New Frontiers 

in Geriatrics Research: An Agenda for Surgical and Related 

Medical Specialties,” a component of the American Geriatrics 

Society’s Geriatrics-for-Specialists Initiative (GSI), funded by 

the John A. Hartford Foundation of New York. With permission 

of the American Geriatrics Society. 

the chapter will address geriatric issues in postoperative 

management, emphasizing postoperative respiratory and 

cognitive complications, as well as acute and chronic pain 

management. Each section will conclude with a list of 

potential research agenda items. The end of the chapter 

identifies research agenda items of the highest priority. 

Physiologic Changes Relevant to 

Perioperative Care 

The physiology of aging bears on preoperative assessment, 

intraoperative and postoperative management, and 

the types and likelihood of major adverse events. Agerelated 

changes in cardiac, respiratory, neurologic, renal, 

and pharmacokinetics have been well defined. The most 

important generalization from physiologic studies of 

aging is that the basal function of the various organ 

systems is relatively uncompromised by the aging process. 

However, functional reserve, specifically the ability to 

compensate for physiologic stress, is reduced (Figure 6-1). 

This has profound implications for the preoperative 

assessment and the perioperative care of geriatric 

patients. 

Cardiovascular Changes 

Numerous changes in cardiovascular function with aging 

have implications for anesthetic care. With aging, a progressive 

decrease in the elasticity of the arterial vasculature 

leads to an increase in systolic blood pressure. 

Diastolic blood pressure increases through middle age 

and typically decreases after age 60. 1 There is also a 

decrease in the cross-sectional area of the peripheral vascular 

bed, resulting in higher peripheral vascular resistance. 

2 A decrease in the peripheral vasodilatory response 

to β-adrenergic stimulation may also contribute to the 

hypertension of aging. 3 

66

6. Research Priorities in Geriatric Anesthesiology 67 

important as the chronic changes in the myocardium and 

vasculature. 

It is evident that age-related changes in the cardiovascular 

system involve alterations in both mechanics 

and control mechanisms; the same can be said of the 

pulmonary system. 

Pulmonary Changes 

Figure 6-1. Functional reserve is the difference between 

maximal (broken line) and basal (solid line) function. Aging 

inevitably reduces functional reserve even in individuals who 

are physiologically “young.” The configuration of the curve for 

“basal” function is adapted from longitudinal measurements of 

total (not weight-specific) basal metabolic rate. (Reprinted with 

permission from Muravchick S. Geroanesthesia: Principles for 

Management of the Elderly Patient. St. Louis: Mosby-Year 

Book; 1997.) 

Progressive ventricular hypertrophy develops in 

response to increased afterload and leads to cellular 

hypertrophy and deposition of fibrotic tissue. Ventricular 

hypertrophy increases wall stress and myocardial O 2 

demand, making the ventricle more prone to ischemia. 

Although intrinsic contractility and resting cardiac 

output are unaltered with aging, ventricular hypertrophy 

and stiffening limit the ability of the heart to adjust stroke 

volume. 4 Ventricular hypertrophy impairs the passive 

filling phase of diastole. Thus, ventricular preload is more 

dependent on the contribution of atrial contraction. At 

the same time, fatty infiltration and fibrosis of the heart 

increases the incidence of sinus, atrioventricular, and 

ventricular conduction defects. 5,6 In addition, there are 

decreases in myocardial responsiveness to catecholamines; 

maximal heart rate response is correspondingly 

decreased. 4,7,8 The reduction in ventricular compliance 

and the attenuated response to catecholamines compromise 

the heart’s ability to buffer decreases in circulatory 

volume resulting in a disposition to hypotension. 

Similarly, even modest increases in circulatory volume 

lead to congestive heart failure. 

From the standpoint of perioperative hemodynamic 

stability, age-related changes in the autonomic control 

of heart rate, cardiac output, peripheral vascular re - 

sistance, and the baroreceptor response 9–13 are as 

The pulmonary system also undergoes age-related 

changes independent of comorbid disease processes. 

Functionally, there are remarkable parallels with changes 

in the heart. With aging, the thorax becomes stiffer. 14,15 

This may not be evident in the sedentary patient, but 

reduced chest wall compliance increases the work of 

breathing and reduces maximal minute ventilation. 14,16 

Loss of thoracic skeletal muscle mass further aggravates 

this process. 17 Because of a decrease in elastic lung recoil, 

the closing volume increases such that it exceeds functional 

residual capacity by age 65. 18 Inspiratory and expiratory 

functional reserve decrease with aging, and the 

normal matching of ventilation and perfusion becomes 

impaired. 19,20 The latter process increases the alveolararterial 

O 2 gradient and decreases the resting PaO 2 . 18,21 

The respiratory response to hypoxia diminishes in the 

aged 22 (Figure 6-2). In addition, ciliary function and cough 

are reduced. 15 Finally, pharyngeal sensation and the motor 

function required for swallowing are diminished in the 

elderly. 23,24 

These changes have important implications in the perioperative 

period. First, it is difficult to predict from a 

preoperative interview how an inactive, elderly patient 

will respond to the perioperative respiratory challenges. 

. 

VI 

(liter/min 

BTPS) 

60 

50 

40 

30 

20 

10 

0 

40 50 60 70 80 90 100 

PA O2 (mm Hg) 

Figure 6-2. Ventilatory response (V I ) to isocapnic progressive 

hypoxia in eight young normal men (broken line) and eight 

normal men aged 64–73 (solid line). Values are means ± SEM. 

(Reprinted with permission from Kronenberg and Drage. 22 )

68 C.J. Jankowski and D.J. Cook 

Anesthetics, postoperative pain, the supine position, narcotics, 

as well as thoracic and upper abdominal operations 

impair pulmonary function and further depress 

respiratory drive. 14,25,26 Although blood gas analysis or 

spirometric tests may offer some value before thoracic 

operations, the alterations in pulmonary function after 

surgery are complex and typically not predictable from 

preoperative pulmonary function testing. 14,20,27 Agerelated 

changes in pulmonary mechanics and respiratory 

control increase the risk of postoperative hypoxia 28,29 and 

perioperative aspiration in the elderly. 23,30 

Neurologic Changes 

Pulmonary and cardiac complications account for much 

of the morbidity and mortality in older surgical patients. 

However, neurologic morbidity affects many patients as 

well. Also, age-related degenerative changes in the central 

and peripheral nervous systems contribute to a variety of 

other morbidities. In themselves, neurologic complications 

have a dramatic impact on length of stay, discharge 

disposition, functional status, and quality of life. 

Independent of any comorbid process, both the central 

and peripheral nervous systems are affected by aging. 31 

There is a loss of cortical gray matter through middle age, 

resulting in cerebral atrophy, 32 although how much of this 

is attributable to aging itself versus degenerative diseases 

is a subject of ongoing investigation. 33 At the level of the 

neuron, there is a reduction in the complexity of neuronal 

connections, a decrease in the synthesis of neurotransmitters, 

and an increase in the enzymes responsible for their 

postsynaptic degradation. 33–35 Although cerebral metabolism, 

blood flow, and autoregulation generally remain 

intact, 32 neuronal loss and the deficiency of neurotransmitters 

limit the ability of the older brain to integrate 

multiple neural inputs. This has been described as a loss 

of “fluid” intelligence. Neuronal loss and demyelinization 

also occur in the spinal cord. 36 Functionally, there are 

changes in spinal cord reflexes and reductions in proprioception. 

There are also important decreases in hypoxic 

and hypercarbic respiratory drive. 22,37 Decreases in visual 

and auditory function further complicate the ability of 

the nervous system to acquire and process information. 

This combination of changes limits the ability of the older 

patient to understand and process information in 

the perioperative period and probably contributes to 

postoperative delirium, drug toxicity, and falls. 

Aging is also associated with neuronal loss in the autonomic 

nervous system. Both sympathetic and parasympathetic 

ganglia lose neurons, and there is fibrosis of 

peripheral sympathetic neurons. Peripheral autonomic 

neuronal loss is associated with impairment of cardiovascular 

reflexes. At the same time, decreases in adrenoceptor 

responsiveness result in increased adrenomedullary 

output and plasma catecholamine concentrations. 11,13,36 

Skeletal muscle innervation decreases, translating into 

loss of motor units, and a decrease in strength, coordination, 

and fine motor control. 38 Joint position and vibration 

sense may be compromised, and the literature suggests 

some diminution in the processing of painful stimuli. 39–42 

However, this effect, if it exists, seems to be modest at best 

and does not affect all nerve types equally. 42–45 Furthermore, 

given the enormous inter-patient variability in 

nervous system function and in the experience of pain, 

alterations in subtypes of pain perception do not translate 

into a decreased need for analgesia in the elderly. 44–48 

Renal Changes 

Aging is accompanied by a progressive decrease in renal 

blood flow and loss of renal parenchyma. 49,50 By age 80, 

renal blood flow is reduced by half. Renal cortical atrophy 

results in a 30% decrease in nephrons by the end of 

middle age. 49,51 Furthermore, aging is associated with sclerosis 

of nephrons so that some of those remaining are 

dysfunctional. 50,52 Together, these processes result in a 

progressive decrease in glomerular capillary surface area 

and glomerular filtration rate. 50,52–54 However, because of 

loss of muscle mass, aging is not associated with an 

increase in serum creatinine. This physiologic, and often 

occult, aspect of senescence has practical implications in 

the perioperative period. 

The old kidney has difficulty in maintaining circulating 

blood volume and sodium homeostasis in the perioperative 

period. 11,53–55 Sodium conservation and excretion are 

both impaired by aging. Additionally, fluid homeostasis is 

complicated by alterations in thirst mechanisms and antidiuretic 

hormone release that frequently result in dehydration. 

53–56 During the perioperative period, metabolic 

acidosis is also relatively common because elderly patients 

are less efficient in the renal excretion of acid. 57 

Reductions in basal renal blood flow render the elderly 

kidney particularly susceptible to the deleterious effects 

of low cardiac output, hypotension, hypovolemia, and 

hemorrhage. Anesthetics, surgical stress, pain, sympathetic 

stimulation, and renal vasoconstrictive drugs all 

may compound subclinical renal insufficiency. The likelihood 

of acute renal insufficiency is especially great following 

aortic and intraabdominal operations. Finally, 

age-related decreases in glomerular filtration rate reduce 

the clearance of a number of drugs given in the perioperative 

period. 

Aging, Pharmacokinetics, and 

Pharmacodynamics 

Aging is associated with multiple physiologic changes 

that affect drug pharmacology. 58 Decreased lean body 

mass and total body water and an increased proportion 

of body fat alter the volume of distribution of drugs, their


redistribution between body compartments, and, subsequently, 

Table 6-1. Age and drug reactions. 

their rates of clearance and elimination. 59–61 The Age of patients (years) No. with reactions Rate (%) 

effect of changes in body composition on drug distribution 

and action varies depending on the lipid or aqueous 20–29 3 3.0 

10–19 2 3.1 

solubility of the drug. Water-soluble drugs have higher 30–39 7 5.7 

serum concentration and lower redistribution, whereas 

fat-soluble drugs tend to undergo wider distribution and 

40–49 

50–59 

12 

18 

7.5 

8.1 

60–69 27 10.7 

accumulation, followed by delayed release. 

70–79 38 21.3 

While age-related changes in the proportions of different 

plasma proteins make predictions about pharmaco- 

Total 118 10.2 

80–89 11 18.6 

kinetics complex in the elderly, for many drugs, decreased 

protein binding and increased free fraction have the Source: Modified with permission from Hurwitz. 66 

potential to increase the pharmacologic effect of drugs 

administered in the perioperative period. 58 Potential 

alterations in cardiac output, renal, or hepatic clearance 

also may change effective plasma concentrations and 

Pharmacokinetic changes, particularly decreased 

duration of action. 62 Neuronal loss and decreased levels 

metabolism, plus drug interactions coupled with polypharmacy, 

conspire to make the elderly prone to adverse 

of neurotransmitters in the central nervous system 

increase sensitivity to anesthetic agents. The changes in 

drug effects. 66,67 There is an almost linear increase in 

pharmacokinetics that occur with aging make it difficult 

adverse drug reactions with age from below 10% at age 

to identify an independent effect of aging on pharmacodynamics. 

However, age-related changes in the central 

25 to above 20% at age 80. 68,69 The likelihood of adverse 

drug reactions increases with the number of drugs administered 

(Table 6-1). 66,67 Because many patients come to 

nervous system seem to increase the sensitivity to a 

variety of anesthetic agents (Figure 6-3). 63–65 surgery already taking multiple medications, the addition 

of several drugs in the perioperative period makes adverse 

reactions likely. 

Implications 

It is clear from a review of normal changes in physiologic 

function with aging that even the fit elderly patient’s 

ability to compensate for perioperative stress is compromised. 

The cardiac, pulmonary, neurologic, neuroendocrine, 

renal, and pharmacokinetic/pharmacodynamic 

changes that occur with aging make hypotension, low 

cardiac output, hypoxia, hypercarbia, disordered fluid 

regulation, and adverse drug effects more likely in the 

perioperative period. Additionally, because baseline 

cardiac, pulmonary, renal, and neurologic function are 

generally adequate, in the absence of acute challenges, it 

can be difficult to predict the effect of perioperative stress 

on the older patient. 

Preoperative Assessment of 

the Elderly 

Figure 6-3. With advancing age, anesthetic requirement for 

unsedated human subjects expressed as relative median effective 

dose (ED 50 ) or its inhalational equivalent, minimum alveolar 

concentration (MAC), is progressively and consistently 

reduced. Anesthetic requirement declines both for inhalational 

(C, D, H, I, S) and for intravenous (T) anesthetics. (Reprinted 

with permission from Muravchick S. Geroanesthesia: Principles 

for Management of the Elderly Patient. St. Louis: Mosby-Year 

Book; 1997.) 

The underlying health of the patient and the type and 

urgency of the procedure determine the extent of the 

preoperative assessment. The preoperative evaluation 

serves several purposes in most patients. Historically, it 

has served two primary functions: to alert the perioperative 

care providers to physiologic conditions that may 

alter perioperative management and to determine if 

medical intervention is indicated before proceeding. Two


more contemporary uses of the preoperative assessment 

are to provide an index of risk, therefore contributing to 

decisions about the most appropriate intervention, and to 

provide baseline data on which the success of a surgical 

intervention might be judged. 

Physiologic studies of aging and clinical experience 

with this population yield three important conclusions 

regarding preoperative assessment. First, there is tremendous 

heterogeneity in the geriatric population. As 

Muravchick 70 notes, humans are never so similar as at 

birth, and never so dissimilar as in old age. Second, 

whereas basal function in most elderly patients is sufficient 

to meet daily needs, under conditions of physiologic 

stress, impairment in functional reserve becomes evident 

(see above). Third, most older surgical patients have significant 

comorbidities. Up to 80% of elderly surgical 

patients have at least one comorbid condition and one 

third have three or more. 71,72 

Despite those concerns, even extreme age is not a 

contraindication to surgery. Acceptable outcomes are 

reported for operations even in very old patients. 73–77 

What is less clear is how to identify which patients will 

do well and which will do poorly. Although this has been 

the subject of considerable research, no area of perioperative 

anesthetic care and management requires more 

investigation. The preoperative assessment of the patient 

is composed of four interrelated functions: risk stratification 

using population-based studies; history and physical 

examination of the individual patient; preoperative 

testing; and, in some cases, preoperative optimization. 

Each of these areas requires development and better 

definition for the geriatric surgical population. 

Risk Stratification 

Because age itself adds very little additional risk in the 

absence of comorbid disease, 78 most risk factor identification 

and risk predictive indexes have been disease oriented. 

79–83 These investigations typically have studied a 

broad age range of patients and in multivariate analyses 

identified the relative contribution of age and comorbid 

conditions to surgical morbidity and mortality. 80,81,84–87 

Others have examined the predictive value of the number 

of comorbid diseases independent of the operative condition 

or evaluated the impact of American Society of 

Anesthesiologists status, specific surgical factors, and 

intraoperative management. 81,87–92 

The applicability of many existing risk indices to the 

geriatric population is unclear. Because of the prevalence 

of comorbid conditions, it is difficult to stratify the older 

patient population into smaller subsets with better-defined 

risk. The paucity of population studies of perioperative 

risk and outcomes specifically in geriatric populations can 

make choosing the most suitable course of care difficult. 

Furthermore, elderly patients have unique perioperative 

risks. In addition to death, myocardial infarction, or congestive 

heart failure, older patients are unusually prone to 

postoperative delirium, aspiration, urosepsis, adverse drug 

interactions, pressure sores, malnutrition, falls, and failure 

to return to ambulation or to home. Therefore, preoperative 

assessment tools and the variables evaluated in outcomes 

trials require expansion for application to the 

geriatric surgical population. Population studies need to 

examine not only mortality and major cardiopulmonary 

morbidity, but also outcomes specific to the geriatric population. 

Once completed, epidemiologic studies that better 

stratify older patients would help define the preoperative 

assessment appropriate to older patients. 

Functional Assessments 

The efficacy of preoperative functional evaluation in 

elderly surgical patients requires investigation. This is 

important for several reasons. The evaluation of the 

“resting” patient does not indicate how the patient will 

respond to the cardiac, pulmonary, and metabolic 

demands of the perioperative period. This approach is 

emphasized in the American College of Cardiology/ 

American Heart Association guidelines for preoperative 

cardiac evaluation in which the patient’s activity level, 

expressed in metabolic units, is a primary determinant of 

the need for subsequent evaluation. 79 However, this 

concept must be expanded because the geriatric population 

has a unique need for functional evaluation in more 

areas than just cardiopulmonary capacity. Because of 

patient heterogeneity, functional assessments may be 

indicated to better characterize patient differences, 

whether it is for activities of daily living (ADL), instrumental 

ADL, cognitive and emotional status, or urologic 

function. 93,94 Scales such as the Medical Outcomes Study 

Short Form-36 95 have multiple domains that are particularly 

useful in the geriatric population. Although these 

metrics have been applied successfully in orthopedic and 

thoracic surgery 96–98 and can have predictive value for 

longer-term outcomes, 99–103 multidimensional assessment 

and perioperative functional assessment is largely lacking 

in the surgical literature. 97,104,105 

An example of their application is provided in the 

study of hip fracture patients by Keene and Anderson, 101 

who scored patients preoperatively on the basis of physical 

condition, ambulation, ADL, preoperative living situation, 

and preexisting disabilities. The scoring system was 

then used to predict which patients would be discharged 

to nursing homes after surgery. The actual outcome after 

surgery was observed for 1 year and compared with the 

models’ predictions (Table 6-2). Although the study is 

small, it serves as an example for the type of research 

needed in geriatric surgery. 

In regard to preoperative functional assessment, cognitive 

and psychologic evaluation of the elderly surgical


Table 6-2. Predicted outcomes, actual outcomes, and average scores on functional rating scale of 39 patients discharged to nursing 

homes who were alive 1 year after hip fracture. 

Nursing home placement 

No. of patients Residence before fracture (predicted outcome) Actual outcome 1 year after fracture Average score 

10 Home Temporary Temporary 72 

8 Home Temporary Permanent 52 

6 Home Permanent Permanent 51 

15 Nursing home Permanent Permanent 30 

Source: Modified with permission from Keene and Anderson. 101 

patient deserves special comment. Although frank delirium 

or dementia at admission is very evident and clearly 

predicts poorer acute and long-term outcomes, 106,107 subtle 

forms of cognitive impairment are much more common 

in the elderly. In the absence of screening, preoperative 

cognitive deficits may not be evident until the postoperative 

period. Subtle forms of cognitive impairment can 

predict subsequent delirium in hospitalized medical 

patients 108 and worsened cognitive outcome in cardiac, 

orthopedic, and gastrointestinal surgery patients. 109–113 

Therefore, preoperative mental status examination 114,115 

should be considered in all geriatric surgical patients. Preoperative 

depression and alcohol abuse occur frequently 

and can affect postoperative outcomes in similar 

ways, 106,116–118 and, similar to mental status batteries, a 

variety of assessment tools for depression are available. 

119,120 The impact of screening for mental status, 

depression, and alcohol abuse on perioperative management 

of elderly patients is a huge potential area of 

investigation. 

Preoperative functional assessment is also important 

because the goal should be to return the patient to at least 

their preoperative activity level. The success of surgery 

must be questioned if the procedure is technically adequate, 

but the patient suffers loss of independence. Multidimensional 

assessment may help redefine standards for 

success of surgery and reset therapeutic priorities. 96,97,121–123 

Mangione and colleagues 97 applied this type of assessment 

by longitudinally measured quality of life indicators in 

patients undergoing hip, thoracic, and aortic surgery. A 

variety of metrics, including the Short Form-36, were used 

to measure physical, psychologic and social functions, and 

health perceptions preoperatively as well as 1, 6, and 12 

months after surgery (Figure 6-4). Major morbidity and 

Physical Function 

Social Function 

Deviation from population-based 

SF-36 sub-scale score (0–100) 

30 

20 

10 

0 

–10 

–20 

–30 

–40 

30 

20 

10 

0 

–10 

–20 

–30 

–40 

–50 

Preop 1 mo 6 mo 12 mo 

–50 

Preop 1 mo 6 mo 12 mo 

Time 

Time 

Role-Mental 

Figure 6-4. Deviation from age- and gender-adjusted population-based 

Short Form-36 subgroup scores by surgical procedure. 

Triangles indicate thoracic surgery for lung cancer; filled 

circles, total hip arthroplasty; open circles, abdominal aortic 

aneurysm; dotted line, age- and gender-adjusted populationbased 

value. (Modified with permission from Mangione et al. 97 

Published by Blackwell Publishing.)


mortality aside, these types of measures address what 

is fundamentally most important in the management of 

older patients: whether the surgical intervention improves 

functional status and well-being. These measures are of 

unique importance to the elderly because, unlike younger 

patients, the aged are at far greater risk for long-term 

functional compromise after surgery. 

Preoperative Testing 

The third area contributing to the preoperative evaluation 

of the elderly surgical patient is preoperative testing. 

Work in this area has been done for large populations of 

mixed age groups. However, it is not clear whether 

selected preoperative screening tests have a different 

yield in the elderly or, more likely, if specific testing is 

indicated for geriatric patients undergoing certain surgical 

procedures. 

In the general population, there is agreement that the 

bulk of routine preoperative testing is not indicated. 124–127 

In an evaluation of preoperative screening in 1010 individuals 

undergoing cholecystectomy, abnormal results 

were found in only 4.5% of tests. 124 In another investigation 

of 3131 patients aged 0–98 years who underwent 

38,286 tests, unexpected abnormal results were found in 

15% of patients. 125 However, only 3% had a change in 

their anesthetic or surgical plan based on those results. 

Unfortunately, in neither report were age-specific data 

provided, so it is unclear if the results can be translated 

to an older surgical population. 

Smaller studies in elderly populations suggest a higher 

yield for specific tests. Seymour et al. 128 examined the 

value of routine chest X-ray (CXR) in 223 patients older 

than 65 years undergoing general surgery. Of these, 40% 

had an abnormality regarded as clinically significant, 

although in only 5% did the CXR affect the course of 

treatment. The same authors also examined the value of 

the electrocardiogram (ECG) in routine screening in 222 

patients older than 65 years 129 and found that only 21% 

of patients had a normal ECG and that 53% had a major 

abnormality. They reported that, although only 1% of 

patients had abnormalities that delayed surgery, 30% 

developed new ECG abnormalities postoperatively. The 

authors concluded that the screening ECG has little or 

no value for predicting cardiac complications, but recommended 

preoperative ECG in all elderly patients to 

provide a basis for comparison and as a means of detecting 

patients for whom surgery should be deferred. 129 

In a small study of acutely ill elderly (mean age = 81 

years) medical patients (50 admissions), Sewell and colleagues 

130 examined the value of full blood count, sedimentation 

rate, urinalysis, electrolyte, liver, thyroid tests, 

and CXR. Six of 28 patients had abnormalities on CXR 

(21%), although management was only influenced in one. 

The most important finding in the screening battery was 

the frequency of unknown urinary tract infections (16/50 

patients, 32%). A retrospective analysis of 86 patients 

undergoing hip arthroplasty evaluated the impact of 

24 laboratory tests on postoperative course. 131 In four 

patients (4.6%), care was altered, three of whom had 

urinary tract infections. A cost-benefit analysis justified 

routine urinary analysis to reduce hip infections in elderly 

patients undergoing total hip arthroplasties. 

Assessment of nutritional status is useful in certain 

subpopulations of surgical patients. The 44-center 

Veterans Administration study found that serum albumin 

concentration was a better predictor of surgical outcomes 

than many other patient characteristics. 132,133 Although it 

can be difficult to separate the role of the disease process 

resulting in protein-calorie malnutrition from the effect 

of the malnutrition itself, 134 in elderly hospitalized nonsurgical 

patients, adverse outcomes can be attributed to 

malnutrition independent of greater acuity of illness or 

comorbidity. 135 Because of wide confidence limits, laboratory 

assessment of nutritional assessments may make 

their application to individual patients less useful than to 

populations. 134 Thus, it may prove useful to combine laboratory 

tests with anthropomorphic measurements, such 

as body mass index, limb circumferences, and weight 

loss. 136–139 The latter instruments are simple and inexpensive, 

but their clinical yield has not been determined. 

Nutritional assessment may have implications for preoperative 

management, and the timing of surgery as well as 

for risk stratification in certain types of surgery, but nutritional 

evaluation has not been adequately studied in 

elderly surgical patients. 

A recent study of preoperative testing in 18,000 

patients undergoing cataract procedures deserves 

comment. Patients were randomly assigned to undergo 

or not undergo routine testing (ECG, complete blood 

count, electrolytes, blood urea nitrogen, creatinine, and 

glucose). 140 The analysis was stratified by age and showed 

no benefit to routine testing for any group of patients. 

Similar conclusions were drawn in the recent study of 544 

elderly noncardiac surgical patients by Dzankic et al. 141 

From these investigations, and a body of work in 

younger subjects, three themes are evident. First, routine 

screening in a general population of elderly patients 

does not add significantly to information obtained in 

the clinical history. Second, in a general population, the 

positive predictive value of abnormal findings on routine 

screening is limited. Third, positive results on screening 

tests have relatively little impact on the course of patient 

care. Despite those observations, further research is 

required. 

Although the yield for routine screening is very low, it 

can be clinically valuable and cost-effective to develop 

guidelines for preoperative testing based on the type of 

surgery. Differing types of surgery impose different types 

and degrees of physiologic stress. As such, the results of


the cataract trial will not be applicable to patients undergoing 

vascular surgery. Preoperative tests such as echocardiography 

and thallium scanning can have clinically 

relevant predictive value and potentially alter the course 

of care and outcomes if applied to specific populations at 

high risk for perioperative cardiac complications. 79,142,143 

Similarly, nutritional assessment 133,144 might be useful 

before abdominal or major orthopedic surgery, but would 

be of much lower value before carotid endarterectomy. 

Screening for urinary tract infection before orthopedic 

surgery or pulmonary function testing before thoracic 

surgery are other examples. Because the interaction of 

the patient factors and the surgical insult determines 

outcome, specific testing might be equally indicated in a 

very physiologically challenged older patient undergoing 

minimally stressful surgery (e.g., hernia repair), and in the 

mildly compromised older patient undergoing surgery 

that imposes severe physiologic stress (e.g., aortic aneurysm 

surgery). Therefore, future studies in older patients 

will need to stratify patients as to the severity of their 

preexisting risk factors (low, intermediate, or high) and 

specifically examine their interaction with the specific 

surgical challenges most common in the elderly. 

Preoperative Optimization 

In addition to providing (1) an assessment of risk based 

on population studies, (2) functional data to help define 

surgical success, and (3) specific information to guide 

perioperative management, the fourth purpose of preoperative 

evaluation is to determine if medical intervention 

is indicated before proceeding. To some extent, this function 

has been lost with the foreshortening of the preoperative 

period, the “A.M. admit,” and a progressive 

elimination of preoperative testing. 

The research agenda for the care of elderly surgery 

patients must include preoperative optimization of medical 

status. This is an area in which relatively little work has 

been done. Again, in specific populations undergoing 

high-risk surgery, the value of preoperative optimization, 

particularly of cardiac and pulmonary status, can be demonstrated. 

Pulmonary toilet, antibiotics, and steroid therapy 

for some types of thoracic surgery, intervention for coronary 

disease before vascular surgery, and preoperative β- 

blockade for high-risk patients are areas in which the data 

are compelling. 142,143,145–149 Nevertheless, many areas have 

not been evaluated, particularly in the elderly. In addition 

to modifying cardiopulmonary risk, improving nutritional 

status before major elective surgery, preoperative hydration, 

and optimization of renal function in those with 

chronic or acute insufficiency could have broad impact. 

Preoperative management of antibiotic therapy, anticoagulation, 

antiplatelet therapy, and anemia are other obvious 

areas to examine. There are also suggestions that preoperative 

education, psychologic support, and physical therapy 

might facilitate pain management and rehabilitation after 

some types of surgery, 150,151 but this area has not been 

adequately assessed. 

In today’s environment, it will be difficult to conduct 

studies on preoperative optimization. For example, in 

studies of preoperative nutritional optimization, it would 

be difficult to justify randomizing a clearly malnourished 

patient to a control group proceeding directly to the 

operating room without nutritional therapy when surgery 

could be delayed. Conversely, intervention and delay will 

add costs. However, limited studies in orthopedic and 

cardiac surgical patients suggest that appropriately 

applied preoperative care can be cost effective in that it 

shortens hospital stays and improves functional status 

after discharge. 151,152 Preoperative optimization will not 

be practical or necessary in many instances. However, 

much geriatric surgery is elective, so these studies can be 

conducted and, if positive, could influence the care and 

outcome of many patients. 

Preoperative Research Agenda Items 

• There is a need for epidemiologic studies describing 

outcomes, relatively unique to older surgical patients, 

for the most common types of surgery. The frequency 

is probably underestimated by retrospective analysis in 

much of the literature. With few exceptions, future 

studies will need to be prospective, cross-sectional 

studies. In the second phase, patient and surgeryspecific 

risk factors for geriatric complications would 

be identified by multivariate analysis. These investigations 

would stratify surgical risk as low, intermediate, 

or high depending on type of surgery. 

• The most pressing need for preoperative assessment is 

to develop better tools to predict which patients will 

do well and which will do poorly. The positive predictive 

value of these instruments would be first determined 

in prospective nonrandomized or prospective 

cohort trials. After that, prospective randomized trials 

would determine whether the application of these 

metrics could improve outcomes either by perioperative 

intervention or altering the surgical intervention 

based on the patient risk profile. 

• The contribution of simple preoperative functional 

studies to surgical decision making has largely not been 

investigated. Prospective cohort or case-control studies 

would be required to determine if assessment of 

preoperative functional status changes surgical decision 

making (timing or type of surgery) or pre- or 

postoperative care strategies. 

• The impact of screening for cognitive impairment, 

depression, and alcohol abuse on perioperative management 

of elderly patients is a huge potential area of 

investigation. Existing literature provides an incidence 

for these preexisting conditions, but an incomplete


understanding of risk factors. Prospective crosssectional 

or cohort studies will better identify association 

between these patient preexisting conditions and 

adverse geriatric outcomes by multivariate analysis. 

Subsequently, prospective randomized trials could 

determine the effect of pre- or postoperative interventions 

on adverse outcomes related to these risk 

factors. 

• Assessment of preoperative nutritional status, hydration, 

and renal function may have implications for preoperative 

management and the timing of surgery as 

well as for risk stratification but this has not been 

adequately studied in the elderly. First, the positive or 

negative predictive value of instruments to evaluate 

nutrition and hydration would be tested in prospective 

studies. Second, prospective cohort or case-control 

studies would be used to determine if application of 

these metrics would change preoperative care, timing, 

or choice of surgery perioperative management and 

reduce complications. 

Intraoperative Management 

By its nature, anesthetic care is episodic, so most of the 

criteria to judge the success of anesthetic interventions 

are short term. Studies of anesthetic drugs and techniques 

typically address hemodynamic stability, time to awakening, 

extubation time, postoperative nausea and vomiting, 

recovery room time, and length of stay. Awareness of the 

physiologic and pharmacokinetic changes in the elderly 

has led investigators to examine the effects of a host of 

anesthetic agents and adjuncts in this population. The 

effects of intravenous induction agents, narcotics, benzodiazepines, 

volatile anesthetics, neuromuscular blocking 

agents, and various types of local anesthetics all have 

been evaluated in the elderly. Studies have included use 

of these agents for inpatient surgical procedures, outpatient 

procedures, premedication, sedation, and their 

administration by bolus and infusion techniques. Because 

there is a theoretical advantage to shortening recovery 

time in patients for whom awakening, ambulation, and 

discharge might otherwise be delayed (e.g., the elderly), 

much of the more recent work in the elderly has been 

devoted to the ultra–short-acting agents. 

Some of these studies have identified age-related alterations 

in the pharmacokinetics, induction, awakening, or 

recovery room stay. However, perspective is needed. 

Although a drug may shorten extubation time by 10 

minutes, recovery room time by 45 minutes, or total hospitalization 

in an outpatient procedure by 90 minutes, the 

clinical impact of these changes on patient outcomes is 

probably minimal. There is a role for this type of research 

in geriatric anesthesia, but in an era of limited time and 

research dollars, efforts should probably be directed 

elsewhere. 

In addition to the numerous studies on the pharmacology 

and short-term recovery in aged surgical patients, 

a second major area of research effort has been to 

compare the risks and benefits of regional versus general 

anesthesia. 

Regional Versus General Anesthesia 

Because most general anesthetic agents depress cardiovascular 

and pulmonary function, as well as alter consciousness, 

regional anesthesia has been advocated in 

geriatric patients. Many of the most common procedures 

in the elderly can be performed with regional techniques, 

and many investigations have been conducted. Taken 

as a whole, these studies have broad implications for 

determining directions for research. 

Anesthesiologists taking care of elderly patients undergoing 

orthopedic procedures have been the de facto 

leaders in research in geriatric anesthesia. The studies in 

this area have examined intraoperative cardiovascular 

stability in the elderly, cardiac, pulmonary and thrombotic 

complications, pain control, and cognitive outcomes. 

This subject was reviewed recently by Roy. 153 

A few early studies reported that regional anesthesia 

for hip surgery was associated with better outcomes. 154,155 

Reduced mortality, higher postoperative PaO 2 , and fewer 

mental changes have been reported in patients receiving 

regional anesthesia. 154,155 However, these studies were 

very small and their assessment of cognitive function 

would not meet current standards for reliability or 

validity. 156 

Subsequent investigations in elderly patients undergoing 

hip surgery found that intraoperative hypotension 

was more common with regional anesthesia, and although 

the incidence of deep vein thrombosis (DVT) and blood 

loss were typically lower with regional techniques, no 

difference in major morbidity or mortality could be 

identified. 84,157–162 Because most of these studies were 

underpowered for rare events, meta-analysis has been 

used to help address statistical limitations. 

The benefit of regional or general anesthesia was 

addressed in a 1992 meta-analysis. 163 Sorenson and Pace 

examined 13 randomized controlled trials conducted 

between 1966 and 1991 that reported follow-up to at least 

1 month. Meta-analysis endpoints were mortality, DVT, 

and blood loss. Other complications or adverse events 

were not evaluated because of inconsistencies in definitions 

or “the absence of systematic and unbiased application 

of diagnostic tests to record these events.” Sorenson 

and Pace were unable to identify any statistically significant 

difference in mortality or blood loss by anesthetic 

technique, although there was a clearly reduced incidence 

of DVT in regional anesthesia groups. Much of the data


Outcome 

T/P Incidence (regional) Incidence (general) Peto OR (95% CI) Peto OR (95% CI) 

Mortality—1 month 

7/1578 

49/766 (6.4%) 

76/812 (9.4%) 

0.66 (0.47–0.96) 

Mortality—3 months 

6/1491 

88/726 (12.1%) 

98/765 (12.8%) 

0.91 (0.67–1.24) 


3/1264 

103/613 (16.8%) 

105/651 (16.1%) 

1.05 (0.78–1.41) 


2/726 

80/354 (22.5%) 

78/372 (21.0%) 

1.10 (0.77–1.57) 

Operative hypotension 

7/873 

146/426 (34.3%) 

116/447 (26.0%) 

1.51 (1.12–2.02)+ 

1.21 (0.65–2.25)* 

Patients receiving transfusion 

3/228 

63/108 (58.3%) 

68/120 (56.7%) 

1.02 (0.58–1.80) 

Postoperative hypoxia 

1/57 

10/28 (35.7%) 

14/29 (48.3%) 

0.60 (0.21–1.71) 

Pneumonia 

8/1096 

27/529 (5.1%) 

31/567 (5.5%) 

0.92 (0.53–1.59) 

Myocardial infarction 

4/888 

4/431 (0.9%) 

8/457 (1.8%) 

0.51 (0.16–1.63) 

Cerebrovascular accident 

7/1085 

10/529 (1.9%) 

6/556 (1.1%) 

1.72 (0.64–4.63) 

Congestive cardiac failure 

6/902 

11/439 (2.5%) 

12/463 (2.6%) 

0.97 (0.42–2.23) 

Renal failure 

4/796 

2/382 (0.5%) 

3/414 (0.7%) 

0.77 (0.13–4.50) 

Acute confusional state 

3/167 

10/83 (12.0%) 

19/84 (22.6%) 

0.47 (0.21–1.06) 

Urine retention 

2/97 

10/48 (20.8%) 

10/49 (20.4%) 

1.02 (0.39–2.71) 

Nausea and vomiting 

2/95 

2/46 (4.3%) 

3/49 (6.1%) 

0.69 (0.12–4.13) 

Deep vein thrombosis 

4/259 

39/129 (30.2%) 

61/130 (46.9%) 

0.41 (0.23–0.72)+ 

Pulmonary embolism 

9/1184 

8/575 (1.4%) 

10/609 (1.6%) 

0.84 (0.33–2.13) 

0.1 0.2 0 5 10 

Figure 6-5. Comparison of outcome between regional and 

general anesthesia for dichotomous variables. All results were 

derived using fixed effects analysis except those marked with 

an asterisk, which were derived using random effects analysis. 

Statistically significant results are indicated by a plus sign. 

Results to the left of the vertical line indicate an advantage for 

regional anesthesia over general anesthesia. Results show the 

incidence of each outcome measure. T = number of trials, P = 

number of patients, OR = odds ratio, CI = confidence intervals. 

(Reprinted with permission from Urwin et al. 164 ) 

in the study by Sorenson and Pace was recently reanalyzed 

in another meta-analysis with the addition of other 

trials. 164 Similar to Sorenson and Pace, the analysis by 

Urwin et al. 164 identified reduced DVT and 1-month mortality 

in 2162 hip fracture patients receiving regional anesthesia, 

although no other outcome measure reached 

statistical significance (Figure 6-5). The reduction in mortality 

was not evident at 3, 6, or 12 months when those 

data were available. Subsequent large single-center observational 

studies involving 741, 165 1333, 166 and 9425 167 

patients have also not identified meaningful differences in 

cardiopulmonary morbidity or mortality between regional 

and general anesthesia in hip surgery patients. 

Another meta-analysis was conducted by Rodgers et 

al. 168 Those authors examined the effects of regional anesthesia 

in 141 randomized trials including 9559 patients. 

As in the report by Urwin et al., they describe reductions 

in 30-day mortality and DVT in the regional group, with 

the effect on mortality not evident beyond 1 month. They 

also describe reductions in pulmonary embolism, transfusion, 

respiratory depression, myocardial infarction, and 

renal failure. Although the results are enticing, the reporting 

of many outcomes was incomplete across studies so 

the analysis was based on smaller subsets of patients. 

Additionally, studies were not rated for quality, and data 

were included in the meta-analysis that were not reported 

in the published trials. Studies for general, obstetric and 

gynecologic, urologic, orthopedic, and “other” surgeries 

were combined, and no information about age is provided. 

Finally, it is difficult to make practice recommendations 

based on the results of this meta-analysis because 

all of the following treatment modalities were combined 

into the regional anesthesia group: (1) those receiving 

spinal anesthesia alone, (2) epidural anesthesia alone, (3)


general anesthesia followed by postoperative regional 

anesthesia, (4) general anesthesia combined with intraoperative 

spinal anesthesia, and (5) general anesthesia 

combined with intraoperative epidural anesthesia. Additionally, 

in 22 studies in which general anesthesia was 

combined with regional anesthesia, the general anesthetic 

in the combined regional/general anesthesia group differed 

from that in the general anesthesia alone group. 

Thus, it is difficult to determine if the effects described in 

the meta-analysis are real and, if so, their origin or to 

which patients they would apply. 

In addition to the more typical outcome measures, 

several of the studies in orthopedic surgery patients have 

examined the effect of anesthetic technique on cognitive 

or functional outcome, often following patients for 3 

months or longer. Although each of the prospective 

studies is small, only the study by Hole et al. 155 has been 

able to identify any difference in cognitive outcome in 

elderly patients undergoing regional versus general anesthesia 

for hip or knee surgery. The bulk of investigations 

could identify no difference. 116,156,169–171 

In a well-designed, randomized prospective, doubleblinded 

study, Norris and colleagues 172 examined the 

effect of general versus combined general/epidural anesthesia 

and intravenous patient-controlled opiate versus 

epidural analgesia in patients undergoing abdominal 

aortic aneurysm repair. There were no differences in 

length of stay, mortality, major morbidity, and pain 

scores. 

Although not all studies are in agreement, 173,174 similar 

conclusions must be drawn for patients undergoing 

regional or general anesthesia for transurethral prostatectomy, 

and peripheral vascular surgery. 171,175–178 In 

carotid surgery, there is a suggestion of a better outcome 

with regional techniques; however, most investigations 

are retrospective or nonrandomized, so the effect of 

patient selection cannot be eliminated. 179–182 Additionally, 

in the multicenter North American Symptomatic Carotid 

Endarterectomy Trial, an independent effect of anesthetic 

technique (or intraoperative monitoring) on carotid 

surgical outcome could not be found. 183 

The difficulty in identifying clear and meaningful difference 

between regional and general anesthesia has tremendous 

implications for the conduct of research in 

geriatric anesthesia. Probably the most substantive difference 

in the choice of anesthetic is whether the patient 

undergoes a regional or a general anesthetic. The pharmacologic 

difference with that choice is far greater than 

the difference between different induction agents, narcotics, 

local anesthetics or muscle relaxants, or different 

doses of those medications. If little or no difference in 

outcome can be identified for elderly patients undergoing 

major procedures with general or regional anesthesia, 

then the yield for similar outcome studies on differing 

anesthetic agents is likely to be low. 

Physiologic Management 

In addition to establishing a surgical plane of anesthesia, 

the anesthesiologist maintains physiologic stability. 

Although numerous studies have examined the relationship 

between intraoperative physiologic management 

and outcome, outside of relatively rare catastrophic 

events, such as loss of the airway or uncontrolled hemorrhage, 

it seems that physiologic management has a modulatory 

rather than a primary role in outcomes. The best 

example is in cardiac surgery, for which the acute changes 

in blood pressure, hematocrit, and temperature typically 

exceed those seen with any other type of surgery. Additionally, 

most of the patients are older. Despite that, it has 

been difficult to demonstrate a direct relationship 

between physiologic management and outcome. 184–186 

Rather, the primary determinants of outcome are 

technical issues during surgery and the comorbidities 

that the patent brings to the operating room. 187,188 

Although there is a role for specific studies related to 

physiologic or pharmacologic management in the elderly, 

those investigations are likely to have a smaller yield than 

risk stratification based on population studies and subsequent 

tailoring of the surgical procedure to the patient 

based on the preoperative assessment. 

These conclusions are not an indictment on anesthetic 

practice or the role of the anesthesiologist in the operating 

room. Just the opposite is true. Over the past three 

decades, anesthesiology has made tremendous strides in 

patient safety, monitoring, drugs, and education that 

have made the intraoperative period extremely safe. 

Those advances have, and will continue, to expand what 

is possible surgically. At the same time, it is because 

the advances in intraoperative care have been so great 

that the greatest needs for research lie in the preoperative 

assessment and the postoperative management of 

patients. 

There are also broad areas related to intraoperative 

management (rather than the specifics of anesthetic 

choice) in which research in the elderly would be productive. 

It is clear that anesthetics and alterations in autonomic 

function make it more difficult for older patients 

to maintain their body temperature and that postoperative 

hypothermia increases risk of adverse outcomes. 189–193 

Thus, studies of temperature control in older patients 

could be expanded. 

Perioperative β-adrenergic blockade reduces mortality 

and cardiac morbidity in high-risk patients. 194,195 Intraoperative 

β-blockade, per se, may also improve cardiac outcomes 

as well as improve early anesthetic recovery 

and decrease postoperative analgesic requirements. 147 In 

addition, perioperative clonidine may reduce cardiac 

morbidity and mortality. 196 Thus, the appropriate place 

for prophylactic β-blockade and central sympatholysis in 

elderly surgical patients needs to be examined. Similarly,


studies need to address the appropriate roles for antiplatelet 

agents and H 2 -blockers. 

Recent data suggest that tight glucose control may 

improve perioperative outcomes. In a randomized, prospective 

trial involving critically ill, primarily surgical 

patients, van den Berghe et al. 197 found that using an 

insulin infusion to maintain blood glucose 80 and 110 mg/ 

dL reduced intensive care unit (ICU) and in-hospital 

mortality as well as a variety of morbidities compared 

with treating only for blood glucose in excess of 215 mg/ 

dL and a goal of 180–200 mg/dL. Further study is needed 

to determine applicability of this therapy in the elderly 

surgical patient and whether there is benefit to tight 

intraoperative glucose control. 

Given that the immune response may be attenuated in 

the elderly and that infectious complications are very 

common, the appropriate dosage and scheduling for perioperative 

antibiotics may be a useful area of research. 

Furthermore, elderly patients receive most of the blood 

given in the perioperative period, so investigation into 

the immunosuppressive effects of homologous blood 

transfusion would be instructive. Older patients are also 

at increased risk for musculoskeletal and nerve injury as 

well as thrombotic complications. Therefore, documenting 

the relationship among patient positioning, nerve and 

skin injury, and thrombotic complications is indicated. 

Similarly, the timing of the preoperative fast, and its 

relationship to hypovolemia, and aspiration risk in the 

elderly would be an area of research with a large potential 

impact on practice and patient satisfaction. 

In perspective, the lack of an independent effect of 

anesthetic choice or physiologic management on outcome 

is not surprising. Very large studies of perioperative morbidity 

and mortality indicate that the anesthetic episode 

per se seems to have little or no impact on 30-day outcomes 

apart from rare, catastrophic events. 88,91,198 And, 

although certain pathophysiologic processes may be initiated 

during the intraoperative period, with few exceptions, 

major morbidity and mortality in the operating 

room is rare. 

Intraoperative Research Agenda Items 

• Perioperative management of β-blockade, central sympatholysis, 

antiplatelet therapy, anticoagulation, and 

anemia are areas to examine in elderly patients. First, 

cross-sectional or retrospective case-control studies 

could be used to identify the incidence of adverse 

cardiac or thrombotic-embolic complications in elderly 

patients undergoing surgery with and without preoperative 

β-blockade, central sympatholysis, antithrombotic 

or antiplatelet therapy, or a hematocrit above a 

target value. These studies should be in surgeries identified 

as intermediate or high risk for related complications. 

Subsequently, prospective cohort, case-control or 

randomized studies would be used to determine if 

pre- or intraoperative therapies would reduce related 

complications in the elderly. 

• A similar approach as above should be used to examine 

perioperative glucose control. 

• The appropriate dosage and scheduling for perioperative 

antibiotics in prevention of perioperative infection 

in the elderly are important areas of research. As for 

β-blockade or antithrombotic strategies, initial studies 

would use retrospective or cross-sectional studies to 

identify any relationship between the use or timing of 

perioperative antibiotic therapy and postoperative 

pneumonia or wound infection. Differences, if any, 

between younger and older patients undergoing the 

same type of surgery could also be compared. Subsequently, 

prospective, nonrandomized studies would be 

used to determine if preoperative or postoperative 

antibiotic therapies can reduce infectious-related 

complications. 

• Because elderly patients receive most blood given 

in the perioperative period, the immunosuppressive 

effects of homologous blood transfusion deserves 

further investigation in this population. Multicenter 

studies of a prospective case-control or prospective 

cohort design would examine the incidence of perioperative 

infection and immunosuppression in elderly 

patients receiving or not receiving blood in the perioperative 

period. Multivariate analysis would be required 

to separate the effect of homologous blood transfusion 

from the comorbid conditions, making transfusion 

more likely. If a significant independent effect of 

blood transfusion was identified, subsequent analysis 

would need to statistically compare the transfusionassociated 

risk with that of not receiving transfusion. 

Alternate strategies, such as delaying surgery or erythropoietin 

therapy, would need to be compared with 

blood transfusion in case-cohort or prospective, nonrandomized 

trials because a randomized trial could not 

be justified. 

Appropriate preoperative fasting, its relationship to 

hypovolemia, and aspiration risk in the elderly would be 

a practical area of research. In prospective cohort or 

case-control studies, the incidence of perioperative 

hypotension, aspiration, and renal insufficiency should be 

compared in patients undergoing standard fasting orders 

before surgery with elderly patients who would be allowed 

clear liquids closer to the time of surgery. This study 

would need to be conducted in patients undergoing 

specific types of procedures: 

• where liberalization of fluid intake is not contraindicated 

for surgical reasons, 

• in patients undergoing procedures in which they are at 

greater risk for developing hypovolemia (bowel prep), 

and


• in instances in which preoperative hypovolemia 

may contribute to complications (angiographic 

procedures). 

Postoperative Management 

Most surgical morbidity and mortality occur in the postoperative 

period. Pedersen et al. 84 examined perioperative 

mortality in 7306 adult patients undergoing lowerrisk 

surgery (no cardiac, thoracic, or neurosurgical 

procedures) and found that mortality during anesthesia 

was 0.05% (1 : 1800). In the first 24 hours, the mortality 

was twice as high, 0.1%, and increased fivefold over 

the next 6 days to 0.56%. 84 Morbidity, including myocardial 

ischemia and infarction, stroke, renal insufficiency, 

pneumonia, and delirium, is also most common 

postoperatively. 183,199,200 

Postoperative Respiratory Insufficiency 

Respiratory morbidity is very common after noncardiac 

surgery. In the 84,000-patient Veterans Administration 

study (97% male, mean age of 60), 17% of patients 

experienced complications with pneumonia in 3.6%, ventilatory 

failure in 3.2%, and unplanned intubation in 

2.4%. 87 In a study conducted by Seymour and Vaz 201 of 288 

general surgical patients over age 65, 17% of patients had 

atelectasis, 12% acute bronchitis, and 10% developed 

pneumonia. 

Although most elderly patients do not require invasive 

monitoring postoperatively, the appropriate use of pulse 

oximetry, ventilation monitoring, and O 2 therapy requires 

study. 202,203 As highlighted previously, elderly patients 

have an increased A-a gradient, reduced respiratory 

muscle strength, and decreased hypoxic and hypercarbic 

drives at baseline. 14,20,27 Additionally, aging is associated 

with a progressive loss of airway reflexes. 18 And apnea 

and periodic breathing following administration of narcotics 

are more common in older patients. 25,204 Postoperative 

pain, atelectasis, and fluid shifts further increase the 

likelihood of respiratory complications, as do shivering 

and reductions in cardiac output and hemoglobin concentration 

191 The supine position during recovery increases 

the transpulmonary shunt and makes hypoxia more 

likely. 18 Finally, orthopedic and upper abdominal surgeries 

common in the elderly have an independent effect in 

increasing postoperative hypoxia and respiratory complications. 

26,201,205 For these reasons, hypoxia may occur in 

20%–60% of elderly surgical patients. 28,29 

Despite the frequency of postoperative hypoxia and 

hypercarbia in the elderly, clear guidelines for O 2 therapy, 

pulse oximetry, and capnography in older patients have 

not been developed. This issue is of pressing importance 

as “day surgery” becomes more common and continued 

efforts are made to abbreviate the time to discharge. 

Further, more and more patients, most of them elderly, 

undergo conscious sedation outside the operating room 

environment. Although the study by Bailey and colleagues 

206 is more than 10 years old, its implications are 

unchanged. In a study of hypoxemia and apnea after 

sedation with fentanyl and midazolam, the authors 

describe deaths associated with the use of these drugs. Of 

86 reported US deaths, “all but three . . . occurred outside 

the operating room . . . where patients are typically unattended 

by anesthesia personnel.” Determination of the 

requirements for O 2 therapy, pulse oximetry, and capnography 

in elderly patients undergoing inpatient and outpatient 

surgery, as well as procedures with conscious 

sedation, are indicated. 

The risk of postoperative aspiration in the elderly also 

requires attention. Because of alterations in pharyngeal 

function, diminished cough, and an increased incidence 

of gastroesophageal reflux, elderly patients are at 

increased risk of aspiration. 23,24 This risk is accentuated 

by the effect of anesthesia, sedatives, and narcotics as well 

as by endotracheal intubation, nasogastric tube placement, 

and upper abdominal or neck surgery. 30,207,208 

Although the incidence of aspiration in the operative 

period is low and is uncommonly associated with 

clinically important pneumonitis or pneumonia, 209 the 

risk for aspiration extends well beyond the acute 

operative period. 

It is likely that instrumentation of the pharynx, whether 

from an endotracheal tube, 30 nasogastric tube, 208 or a 

transesophageal echocardiography probe, 207 alters sensation, 

motor function, and the protective reflexes preventing 

aspiration. For patients with prolonged endotracheal 

intubation (>24 hours), this effect is persistent for at least 

48 hours after extubation. 30 Nasogastric tubes may also 

contribute to aspiration by increasing the incompetence 

of the gastroesophageal junction. Although pharyngeal 

dysfunction and aspiration may be related to a greater 

acuity of illness, pharyngeal trespass itself has independent 

effects. 

Given perioperative risk factors, the frequency of aspiration, 

and the incidence of postoperative respiratory 

morbidity, insufficient research has been directed to these 

issues in elderly surgical patients. Pharmacologic interventions 

to reduce gastric volume or increase pH have 

received attention in the anesthesia literature, but the 

investigation by Warner et al. 209 of aspiration occurring 

within 2 hours of surgery implies that research on aspiration 

and postoperative pneumonia must look beyond the 

immediate operative period. 210 More important research 

will focus on establishing appropriate use of nasogastric 

tubes, restoration of pharyngeal and tracheal reflexes and 

gastrointestinal motility, and advancement of feeding 

following surgery in the elderly. General studies as well 

as surgery-specific studies are indicated.


Acute Pain Management 

The same questions that dominate research in pain management 

in the general population apply to the elderly. 

However, in many ways, the questions are more pressing 

in the elderly because they might receive the most potential 

harm as well as the greatest potential benefit from 

the treatment of postoperative pain. Because of ischemic 

heart disease, diminished pulmonary capacity, altered 

drug clearance, or increased drug sensitivity, the elderly 

patient is probably more vulnerable to the physiologic 

consequences of inadequate analgesia as well as the 

side effects related to analgesic use. Additionally, there is 

evidence in the literature indicating that in certain circumstances 

pain in the elderly may be less adequately 

treated. 48 

Pain and Adverse Outcomes 

The perioperative period results in stress and inflammatory 

responses that peak postoperatively when cardiopulmonary 

and neurologic complications occur. Therefore, 

efforts have been made to link the adequacy of analgesia 

with the magnitude of the stress response. In particular, 

it has been proposed that inadequate postoperative analgesia 

may be associated with myocardial ischemia and 

pulmonary failure. Researchers have examined the effect 

of the intraoperative anesthetic 211–214 and postoperative 

epidural analgesia on plasma levels of cortisol, epinephrine, 

norepinephrine, leucocyte counts, and acute phase 

proteins and tried to relate these to cardiopulmonary 

outcomes. 173,211,215–219 Both negative and positive conclusions 

have been reached. 

When this subject was reviewed by Liu et al., 220 they 

concluded that intensive analgesia using regional techniques 

had a limited impact on cardiopulmonary outcomes 

or the stress response in a general population of 

surgical patients. They also concluded that pain and the 

stress response were not directly coupled because the 

neuroendocrine response was still demonstrated (al - 

though blunted) in the presence of intense surgical analgesia 

with local anesthetics or opioids. 220 However, studies 

in the highest-risk groups suggest a possible improvement 

in outcome with intense analgesia using regional 

techniques. 173,221 Intensive pain management strategies 

may be indicated in high-risk elderly patients or in lowrisk 

elderly patients undergoing high-risk surgery. Defining 

the circumstances under which epidural analgesia or 

any other pain management strategy can improve outcomes 

is an important area for future research. 

In addition to the stress response typically associated 

with the sympathetic-adrenal axis, most types of surgery 

initiate a significant catabolic state. Although an inhibitory 

effect of analgesia on protein wasting has been 

suggested, 222–224 a more pressing area for research is to 

understand postsurgical catabolism in the elderly. The 

relationship between preoperative nutritional status and 

postoperative catabolism must be better understood. 

Experience with some critically ill patients suggests that 

catabolism may become dissociated from the initial surgical 

stress. Because elderly patients have decreased nutritional 

and metabolic reserve, they are most challenged 

by the postoperative catabolic state. Basic investigation 

into postoperative catabolism in the elderly is fundamental 

as are investigations into interventions that might 

attenuate catabolism or facilitate the transition back to 

an anabolism. 

Although the adequacy of postoperative analgesia 

does not seem to be an independent determinant of outcomes 

in the general population of surgical patients, a 

variety of other issues related to postoperative analgesia 

require attention. The relative benefit of patient-controlled 

analgesia (PCA) 225 versus a PRN or scheduled 

analgesic administration is of special importance in the 

elderly surgical patient. Because of the physiologic and 

psychologic heterogeneity in the geriatric population, it 

is unlikely that fixed formulae for age-appropriate drug 

dosing can be identified. Thus, administration of narcotics 

on a set schedule in the elderly is fraught with the potential 

for both over- and under-dosing. These considerations 

potentially make PCA analgesia an ideal choice. Nevertheless, 

the issue is complicated. The side-effect profile for 

PCA analgesics in the elderly has not been established. 

226,227 It has also been suggested that many elderly 

patients may struggle with the technology. Similarly, the 

application of PCA for patients with altered mental status 

is problematic. Outcomes with PCA in the elderly must 

be compared with fixed and PRN dosing techniques as 

well as with postoperative pain control by regional 

blockade. 

The same is true regarding route of administration for 

analgesic agents. Is there a clear advantage or disadvantage 

to the use of the intravenous, epidural, or intrathecal 

routes for analgesic administration in the elderly? The 

elderly are unusually susceptible to drug interactions and 

have an increased incidence of respiratory depression, 

urinary retention, ileus, constipation, and postoperative 

falls. These are influenced by choices in postoperative 

analgesia and may differ by route of administration. 226–229 

As such, investigations into analgesic strategies for 

elderly surgical patients will need to determine not only 

quality of analgesia, but also a comprehensive examination 

of risks and benefits specific to that population. 

Additionally, because narcotics are associated with frequent 

side effects in the elderly, the use of analgesic 

adjuncts in postoperative pain management requires 

further investigation. Drugs such as ketorolac, clonidine, 

dexmedetomidine, and cyclooxygenase-2 inhibitors have 

the potential to achieve adequate analgesia with lower 

doses of opioids, potentially reducing side effects. 230–234


A final reason why studies of acute pain management 

in the elderly are required is that acute pain management 

may bear on rehabilitation and subsequently on functional 

status on discharge. 235 This has been shown with 

analgesic programs for continuous passive motion 

machines used after knee replacement. 235–237 Research is 

required after other types of surgical procedures to determine 

whether facilitation of rehabilitation by acute pain 

management can improve other functional outcomes. 

Another opportunity for research in the postoperative 

care of hospitalized patients is related to polypharmacy 

and adverse drug events in the elderly. There is a tendency 

for elderly patients to accumulate drug prescriptions 

over time, and there is a clear relationship between 

the number of drugs taken and the incidence of adverse 

drug-related events. 66–69 This problem will be compounded 

during the surgical period when additional medications 

are added. 

A study by Cullen and colleagues 238 prospectively compared 

adverse drug events in ICU and non-ICU, surgical 

and medical, hospitalized patients and found that the rate 

of preventable and potential adverse drug events was 

related to the number of drugs administered rather than 

the type of care delivered (ICU or non-ICU, surgical or 

medical). An earlier report of the same data on 4031 

adult hospital admissions identified, among other things, 

the incidence of adverse drug events, their preventability, 

and the classes of drugs that caused most events. 239 Those 

results have particular bearing for the perioperative care 

of the elderly. 

In that investigation by Bates et al., 239 analgesics were 

the class of drug associated with the most adverse drug 

events. Antibiotics caused the second-greatest number of 

adverse reactions. Analgesics were also the leading class 

of drug with preventable adverse drug events followed 

by sedatives and then antibiotics (Table 6-3). In the 20 

adverse events related to analgesics, 40% were caused by 

overmedication. 

There is a pressing need for research in pain management 

of the elderly surgical patient. There is also a 

Table 6-3. Adverse events by drug class. 

Adverse drug events Preventable adverse drug 

Drug class No. (%) (n = 247) events No. (%) (n = 70) 

Analgesics 73 (30) 20 (29) 

Antibiotics 59 (24) 6 (9) 

Sedatives 20 (8) 7 (10) 

Antineoplastic 18 (7) 3 (4) 

Cardiovascular 9 (4) 3 (4) 

Anticoagulants 8 (3) 3 (4) 

Antipsychotics 6 (2) 5 (7) 

Diabetes 5 (2) 4 (6) 

Electrolytes 3 (1) 3 (4) 

Other 46 (19) 16 (23) 

Source: Modified with permission from Bates et al. 239 

compelling need for research into prevention of adverse 

drug events in hospitalized patients. The intersection of 

pain management and the incidence of preventable 

adverse events related to analgesics and sedatives places 

anesthesiologists squarely in a leadership role for research 

into appropriate analgesic and sedative strategies for the 

elderly. 

In patients who are hospitalized, there is also a window 

of opportunity to review patient medications, in particular 

to examine redundancy in therapeutic profile and look 

for combinations that may make complications such as 

respiratory depression, aspiration, confusion, postural 

hypotension, urinary retention, and falls more likely. The 

development of pharmacy and electronic drug databases 

for this work would be appropriate and are more within 

the resources of hospitals than community practitioners. 

Although it would not be practical or appropriate to 

modify most patient chronic drug regimes in the postoperative 

period, the surgical hospitalization might provide 

an opportunity for drug review and recommendation in 

an effort to reduce iatrogenic complications in the 

elderly. 

Delirium and Cognitive Decline 

Postoperative delirium or cognitive decline affects 5%– 

50% of elderly patients; both have similar predisposing 

factors but the syndromes are not equivalent. 110,200,240–242 

Disordered thinking and confusion that waxes and wanes 

characterize postoperative delirium. The onset is typically 

on the first to third postoperative day. It may be sustained 

for more than a week and is associated with other medical 

complications, prolonged hospitalization, and decreased 

functional status on discharge. 113,120,200,241,243–245 To date, 

much of the research on postoperative delirium has 

centered on the impact of regional versus general anesthesia 

in orthopedic surgery. 116,117,156,169–171,246 Postoperative 

cognitive dysfunction, a deterioration of psychomotor 

capacities such as memory, central processing time, and 

acquisition of new information, has been well described 

in both cardiac and noncardiac surgical patients. 247–250 It 

may be subtle or clinically obvious. The relationship 

between postoperative delirium and cognitive dysfunction 

has not been well studied. 

The effect of differing anesthetics on postoperative 

delirium has been studied, 117,156,171,251–254 and a leading 

hypothesis has been that offending agents aggravate an 

age-associated central cholinergic insufficiency. 116,255,256 

However, from review of the literature, it becomes 

evident that delirium can be triggered by many different 

perioperative events; no single cause is identifiable. Thus, 

no single intervention is likely to be successful. 

In addition to being linked to opiates, sedatives, 

and anticholinergics, delirium has been associated 

with urinary tract infection, pneumonia, hypoxia or


hyper carbia, fever, blood loss, and electrolyte disturbances. 

200,240,241,257–259 Chronic patient factors such as 

preexisting frank or subclinical dementia, other organic 

brain disease, and vision and hearing loss are also predictors 

of postoperative delirium and cognitive de - 

cline. 102,110,113,200,240,260,261 Finally, pain, sleep deprivation, 

sensory deprivation, and an unfamiliar environment may 

contribute to delirium. 112,200,240,262,263 

Although most of the research in the anesthesia literature 

has focused on the effect of anesthetic and analgesic 

agents, the literature in medical patients suggests that the 

yield for those studies will be low. Studies of the type 

conducted by Inouye et al. might serve as a model for 

research in anesthesia. 103,108,259–261,264–266 Inouye describes a 

multifactorial model for delirium involving the interrelationship 

between a vulnerable patient and acute 

insults. 259,264 For example, a minor insult may result in 

delirium in highly vulnerable patients, whereas in less 

vulnerable patients, a major insult may be required to 

precipitate delirium. In a study of elderly medical patients, 

multivariate modeling identified four risk factors for 

developing hospitalization delirium: vision impairment, 

severe illness, preexisting cognitive impairment, and a 

blood urea nitrogen/creatinine ratio ≥18. 264,267 Patients 

were then divided into low-, intermediate-, and high-risk 

groups depending on the number of risk factors. In a 

subsequent validation cohort, the rates of delirium in the 

low-, intermediate-, and high-risk groups were 3%, 16%, 

and 32%, respectively (Table 6-4). 264 In those patients, the 

rate of death or nursing home placement was 3%, 14%, 

and 26%, respectively, an eightfold increase from the 

lowest to highest risk group. 267 Precipitating factors for 

delirium in hospitalized medical patients have also been 

described by Inouye and Charpentier. 259 Twenty-five 

factors occurring at least 24 hours before the onset of 

delirium were considered. Of those, a multivariate model 

identified five as predictive: use of physical restraints, 

Table 6-4. In-hospital events and risk of delirium. 

Risk group No. of factors Delirium rate, by person* RR 

Low 0 5/125 (4)† 1.0 

Intermediate 1–2 31/156 (20)† 5.0 

High ≥3 11/31 (35)† 8.9 

Source: Modified with permission from Inouye. 264 Published by S. 

Karger AG, Basel. 

RR = relative risk. 

Each patient’s risk group was determined by adding one point for each 

precipitating factor present: use of restraints, urinary catheter, more 

than three medications added, any iatrogenic event, and malnutrition. 

Figures in parentheses represent percentage. 

*Corresponds with percentage of patients developing delirium per 

day. 

†x 2 overall = 24.8, p < 0.001; x 2 trend = 24.8, p < 0.001. 

Performance of the predictive model for delirium in medical patients 

in the validation cohort. 

malnutrition, more than three medications added, use of 

a bladder catheter, and any iatrogenic event (volume 

overload, urinary tract infection, pressure ulcer, etc.). 259 

Although the precipitating factors were independent of 

each other, the authors note that “. . . baseline and precipitating 

factors are highly interrelated and contribute 

to delirium in a cumulative fashion.” 259 

In a subsequent publication, Inouye and colleagues 265 

determined the effect of interventions based on their 

predictive model. Four hundred twenty-six elderly 

medical patients in an intervention group were matched 

to an equal number in a “usual care” group. In the 

intervention group, six risk factors for delirium were targeted 

for intervention: cognitive impairment, sleep deprivation, 

immobility, visual and hearing impairment, and 

dehydration. The group receiving intervention, by an 

interdisciplinary team, had a 9.9% incidence of delirium 

versus 15% in the usual care group (a 34% decline). 

Subdivision of patients into intermediate- or high-risk 

groups demonstrated that intervention reduced delirium 

in intermediate-risk patients, but the tendency to reduce 

delirium in the high-risk group was not statistically 

significant. 265 

These studies indicate that presence and severity of 

cognitive deficit are strong predictors of the likelihood of 

delirium during the hospitalization. 264 The same effect has 

been identified in surgical patients. 110–113 This brings us 

back to the recurring theme that subclinical decrements 

in functional status may become evident during the perioperative 

period. These findings are extended by the 

observation that postoperative delirium or cognitive 

decline may be a harbinger of a potentially permanent 

decrease in mental status. 247,268 

Together, the data on the predictive value of preoperative 

cognitive status 264 and the effect of that assessment 

on the success of intervention 265 provide a compelling 

rationale to conduct a simple, short mental status examination 

as part of the preoperative interview. Short functional 

scales have been designed which might be applicable 

in the preoperative interview. 115,269,270 The practicality of 

such metrics in elderly surgical patients must be established. 

After that, the incidence of preoperative cognitive 

impairment and its severity could be identified in populations 

of elderly patients undergoing different types of 

procedures. Research into the effectiveness of differing 

preventative strategies could follow. For example, pharmacologic 

prophylaxis of delirium shows promise. 271 

Those investigations could also examine if reductions in 

delirium translate into reduced medical complications or 

improved functional status on discharge. 

Chronic Pain 

A significant proportion of the geriatric population suffers 

from chronic pain conditions. 46,47 Much of this is related


to osteoarthritis, but many older patients have a variety 

of neuropathic pain disorders including herpes zoster, 

diabetic neuropathies, and complex regional pain syndromes. 

272 Care of these patients is complex and for many 

of these painful conditions therapy is inadequate. 

The factors limiting therapeutic success in chronic pain 

in the elderly are multiple. First, in contrast to acute postoperative 

pain, the conditions responsible for chronic 

pain are typically not reversible. Second, pain conditions 

may have a central nervous system component. Third, 

effective treatment of chronic pain is hampered by the 

side effects of medications and complications from polypharmacy. 

Fourth, depression and behavioral changes 

frequently complicate therapy. 273 Fifth, assessment of 

pain in older patients can be difficult. 46 And, finally, 

chronic pain in the elderly is often associated with unrelated 

comorbid conditions that may alter treatment 

plans. 43,274 Despite these limitations, geriatric patients 

benefit from chronic pain therapy in a manner similar to 

younger patients. 43,275,276 

Most pain syndromes can be classified into one of four 

types: nociceptive, neuropathic, mixed, or unspecified and 

psychogenic. 47 The usefulness of different classes of analgesic 

agents in these types of syndromes is reasonably 

well described. Nociceptive pain includes the pain typically 

associated with arthropathies, myalgias, and ischemic 

disorders; the mainstays of analgesia are initially 

acetaminophen and nonsteroidal antiinflammatory drugs, 

followed later by narcotics. 46,47,272 In contrast, narcotics 

are thought to have a lesser place in neuropathies such 

as diabetic neuropathy, postherpetic neuralgia (PHN), 

and complex regional pain syndromes. 272,277,278 Instead, the 

primary pharmacologic therapies are tricyclic antidepressants 

and anticonvulsant agents. 46,272,279–281 Antiarrhythmic 

drugs are second-tier agents for neuropathic conditions. 

Treatment of mixed or unspecified pain syndromes is 

challenging, because the mechanisms are unknown and 

treatment may require trials of differing analgesic 

approaches. 47 For patients whose pain has been classified 

as psychogenic, psychiatric intervention rather than analgesic 

agents is indicated. 47 

In addition to familiar analgesics and adjuncts, there 

is a clear need for a multidimensional approach to 

chronic pain in the elderly. Neuraxial opioids, local anesthetics, 

and steroids have a role in some patients, as do 

peripheral or central neuromodulatory techniques and a 

host of physical, physiatric, and cognitive-behavorial 

strategies. 43,46,47 

Defining research priorities for anesthesiologists in 

such a broad and complex area is difficult. The first priority 

is that chronic pain trials must have sufficient control 

groups and statistical power. As noted by Stanton-Hicks 

and colleagues, 280 studies of neuropathic pain conditions 

are typically small and anecdotal with few experimental 

findings and “without adequate predictors for the choice 

of therapy, current practice is chaotic, and continues to 

use the trial-and-error approach.” 

After design issues are addressed, probably the most 

salient research recommendation for any of these types 

of pain conditions is that outcomes should emphasize 

functional status 276,282 rather than a change in a pain score, 

per se. This is superbly outlined in the Consensus Report 

on Complex Regional Pain Syndromes. 280 Although 

quantifying pain is relevant, ultimately, determination of 

which interventions facilitate rehabilitation, maintain or 

increase mobility, and support the activities of daily living 

is a priority. 276,282 

The second broad area requiring further investigation 

relates to prevention. One of the best examples is in PHN. 

Although the rash of acute herpes zoster is very common 

in the elderly, a lesser, but significant, percentage of those 

affected develop the chronic debilitating pain condition 

of PHN. 283 Because zoster is chronic and recurring, the 

percentage of the population affected with PHN increases 

with age. 283 Although PHN may develop in fewer than 

5% of younger patients with zoster, it may develop in half 

of patients over age 60. 284 Once established, PHN is difficult 

to treat. Further research is indicated to determine 

whether antiviral, analgesic, antiinflammatory therapies 

during acute zoster can prevent the development of 

chronic PHN. 285–288 In addition, immunotherapeutic 

modalities show promise and deserve more study. 289–298 If 

a better understanding of precipitating events can be 

developed for other chronic pain conditions (as in 

PHN 299 ), it might allow the introduction of preventive 

measures. 

In addition to directing research efforts toward functional 

effects and trying to define opportunities for prevention 

of chronic pain conditions, for any strategy, it is 

important to examine the risk–benefit ratio, emphasizing 

adverse outcomes that are more likely to occur in a geriatric 

population. As in acute pain management, the effect 

of chronic therapy on the incidence of complications such 

as confusion, postural hypotension, falls, urinary retention, 

and constipation must be reported. 

Finally, cognitive impairment is a continuum and in 

milder forms is very common. There is a two-way relationship: 

pain may impair cognition and cognitive impairment 

can interfere with the communication of pain. 46,300 

Therefore, a further area of investigation relevant to the 

care of patients with chronic pain is its assessment in the 

cognitively impaired. 

Postoperative Research Agenda Items 

• Large cross-sectional studies describing analgesic practice 

and its complications in the elderly are needed. 

The effect of regional analgesic techniques, nonopioid 

adjunctive drugs, and nonpharmacologic interventions 

would be investigated in prospective cohort or


case-control studies. These investigations must emphasize 

the type and incidence of adverse drug events in 

the elderly. After that, randomized controlled trials 

comparing outcomes with analgesic programs specific 

to types of surgery could be designed and conducted. 

Those prospective trials should determine if analgesic 

regimes designed for the elderly patient could reduce 

in-hospital morbidity or improve functional status on 

discharge. 

• Prospective studies that better identify patient and 

procedural risk factors for respiratory failure, aspiration, 

and pneumonia are required. Randomized trials 

could then determine if respiratory monitoring, prophylactic 

antibiotics, changes in pharyngeal instrumentation, 

or the way feeding is advanced reduce respiratory 

failure, aspiration, and postoperative pneumonia. 

• The relationship between postoperative nutritional 

support and functional outcome must be better understood. 

Cross-sectional studies that could identify if a 

relationship between nutritional support in high-risk 

surgery and functional status on discharge (chronic 

respiratory failure, ambulation, independent living, 

etc.) are the first step. Data from those investigations 

could then be used to design prospective-cohort or 

randomized controlled trials comparing feeding strategies 

in elderly patients at risk for malnutrition and 

muscle wasting following major surgery. In addition to 

protein and caloric support, interventions that might 

attenuate postoperative catabolism or facilitate the 

transition to an anabolism in the elderly could be 

compared with standard care. 

• Practice governing stopping or resuming anticoagulation 

in the perioperative period is largely empiric. 

Studies determining the relationship between perioperative 

termination of anticoagulation and thromboembolic 

and bleeding risk are indicated. The effect of 

timing of termination and resumption as well as the 

temporizing use of antiplatelet agents should be compared 

in case-control or prospective cohort studies. 

• The surgical hospitalization might provide an opportunity 

for drug review and recommendation in an effort 

to reduce iatrogenic complications in the elderly. Initially, 

a retrospective review could identify the incidence 

of polypharmacy with combinations of drugs 

that might contribute to geriatric complications (hypotension, 

bradycardia, falls, confusion, bleeding diathesis, 

constipation, and urinary retention). Subsequently, 

the presence or absence of an effect of simplifying drug 

regimens in hospital or the effect of communicating 

that information to primary care physicians could be 

identified in nonrandomized controlled trials. 

• Using the models established in medical patients, evaluating 

prevention strategies for postoperative delirium 

must be tested. It should first be determined by crosssectional 

studies, with multivariate analysis, if the risk 

factors for delirium in surgical patients are the same as 

those for medical patients. After that, prospective controlled 

trials in patients at moderate to high risk could 

determine the effect of preoperative or postoperative 

interventions on the incidence of delirium. 

• The first priority in chronic pain trials is large crosssectional 

studies that might identify any relationship 

between pain intervention and functional outcomes. 

After that, it must be determined prospectively if specific 

chronic pain therapies can improve functional outcomes 

in treatment groups relative to a historical or 

concurrent, nonrandomized control. 

• Given the frequency of herpes zoster in the geriatric 

population, further prospective studies are needed to 

determine if antiviral, analgesic, or antiinflammatory 

therapies during acute zoster can reduce, relative to 

standard care, the development of chronic PHN. 

• As in acute pain management, cross-sectional studies 

documenting the effect of chronic pain therapy on the 

incidence of complications such as confusion, postural 

hypotension, falls, urinary retention, and constipation 

in the elderly are indicated. 

• Assessment and treatment of acute or chronic pain in 

the cognitively impaired is largely empiric. Cross-sectional 

studies that describe pain management in this 

population relative to a nonimpaired population are 

indicated. Additionally, pain assessment tools for the 

cognitively impaired must be compared prospectively 

to standard assessment methods. After that, prospective 

trials comparing different analgesic strategies with 

regard to clinical and functional endpoints could be 

conducted. 

Summary and Conclusions 

Perioperative care of the geriatric patient is complex. 

Age-related physiologic changes and disease limit functional 

reserve and render the elderly less able to tolerate 

the challenges of the perioperative period. Thus, they are 

at increased risk for a host of complications. Furthermore, 

it is probably easier to precipitate these complications 

than to directly prevent them. 

Despite the unique challenges of the perioperative 

care of the elderly, existing literature offers clinicians 

insufficient guidance. Nevertheless, previous studies 

provide a framework to guide future research. Rather 

than focus attention on the choice of anesthetic technique 

or on short-term outcomes such as time to extubation 

or recovery room stay, improvement in patient 

outcomes will be better served by studies that yield better 

risk-stratification in the elderly. To some extent, pertinent 

patient risk factors will probably be surgery-specific. Subsequently, 

it can be determined if identified risk factors 

are amenable to therapy and whether such intervention


improves outcome. An essential element of both types of 

investigations will be a focus on preoperative functional 

status and other pertinent geriatric outcomes rather than 

just major cardiopulmonary morbidity and mortality. 

Surgical outcome is determined by the interaction of 

patient factors and the challenges introduced by an operation. 

Clearly, the surgical insult varies by procedure. 

Therefore, development of comprehensive care strategies 

for specific types of surgery common in the elderly is 

indicated. This approach is more likely to generate positive 

results and practical guidelines than pooling elderly 

patients undergoing differing types of surgery. Development 

of comprehensive clinical pathways specific to the 

care of the elderly patient undergoing specific types of 

surgeries is indicated because it would coordinate preoperative, 

intraoperative, and postoperative management in 

a particularly vulnerable population. This approach could 

improve outcomes and serve as a foundation for assessing 

alternative strategies. It might have particular value 

in postoperative care, including prevention of delirium, 

respiratory monitoring, and pain management. 

The perioperative care of the elderly is a growing 

public health issue. Anesthesiologists are involved in the 

care of older surgical patients from the preoperative 

evaluation through the postoperative period. Because of 

this perspective, we offer unique insights into their care. 

Applying these to appropriately conceived studies will 

lead to improved perioperative outcomes and, ultimately, 

benefit society. 

Highest Priority Research Questions 

in Geriatric Anesthesiology 

1. What preoperative assessments are useful in developing 

patient management plans for surgeries common in 

the elderly? 

Hypothesis-generating: Large, observational studies are 

needed to identify preoperative risk factors for adverse 

geriatric outcomes, such as decreased functional status or 

postoperative delirium, following common surgeries. 

These studies will identify both patient and surgerydependent 

factors. Assessment tools for mental status, 

nutrition, hydration, thrombotic risk, and activities of 

daily living must be applied or developed when necessary. 

It then should be determined which risk factors are 

potentially modifiable. 

Hypothesis-testing: Randomized controlled trials to 

determine if preoperative or postoperative intervention 

against modifiable risk factors will result in a decrease in 

perioperative geriatric complications. The adverse effects 

of such interventions, such as delay of surgery or postoperative 

bleeding, must be examined along with the 

potential benefits of the intervention. Examples for 

which such interventions could be reasonably attempted 

include nutrition and hydration, postoperative delirium, 

pre- or postoperative rehabilitation programs for activities 

of daily living, and antiplatelet therapy for thrombotic 

and embolic complications. 

2. Can postoperative analgesic techniques reduce postoperative 

morbidity or improve functional status at 

discharge? 

Hypothesis-generating: Large prospective studies describing 

analgesic practice and its complications in the elderly 

are needed. The efficacy and complications of regional 

analgesic techniques, nonopioid adjunctive drugs, and 

physiatric interventions must be investigated. These 

investigations must emphasize the type and incidence of 

adverse drug events in the elderly. 

Hypothesis-testing: Prospective randomized trials are 

needed to determine if perioperative intensive analgesic 

techniques (including traditional narcotic, regional, nonopioid 

adjunctive drugs, and physiatric interventions) 

designed for the elderly patient reduce in-hospital morbidity 

or improve functional status on discharge. 

3. How can postoperative pulmonary complications in 

the elderly be reduced? 

Hypothesis-generating: Cross-sectional or cohort studies 

that better identify high-risk procedures or perioperative 

periods of vulnerability for postoperative hypoxia, respiratory 

failure, and pneumonia in the elderly surgical 

patient are indicated. These investigations could identify 

both patient and procedure risk factors as well as their 

interaction for these complications. 

Hypothesis-testing: Randomized trials to determine if 

respiratory monitoring, prophylactic antibiotics, changes 

in pharyngeal instrumentation, or the way feeding is 

advanced reduce respiratory failure, aspiration, and 

postoperative pneumonia. 

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Part II 

Cardinal Manifestations of Aging and Disease 

in the Elderly

7 

Alterations in Metabolic Functions 

and Electrolytes 

Michael C. Lewis 

Aging has been characterized as a comprehensive, progressive, 

and irreversible biologic process resulting in the 

maintenance of life but with a diminishing capability for 

adaptation. 1,2 In fact, it has been estimated that after the 

age of 30 years, organ systems lose approximately 1% of 

their function per annum. 3 Implied in this description are 

the concepts of increased biologic entropy, functional 

deterioration, loss of viability, and an augmented likelihood 

of death. 4 

The aging population is rapidly growing 5–7 and utilizes 

a growing proportion of medical resources, 8–10 including 

surgery. 11–14 However, because of factors such as decreased 

functional reserve, existing comorbidity, and polypharmacy, 

older patients have higher morbidity 15 and mortality, 

16 especially when the surgery is emergent. 17,18 Their 

medical management is becoming one of the greatest 

challenges to anesthesiologists. Yet, despite this reality, 

little time is spent on formal training in geriatrics during 

anesthesia residency training. 19 

The Concept of Functional Reserve 

Organ function in the elderly is usually well maintained 

under basal conditions. One measure of “health” in the 

aged is their ability to tolerate increased physiologic 

loads. When an individual can maintain a steady state in 

the face of increased physiologic demand, they are said 

to demonstrate a good functional reserve. In contrast, 

when there is latent disease and diminished ability to 

maintain function in the face of stressors, there is said to 

be decreased functional reserve. Age leads to a gradual 

reduction in functional reserve (Figure 7-1). Consequently, 

when stress exceeds functional reserve, imbalance 

within systems will likely develop and result in a 

breakdown of homeostatic compensation. 

Aging per se is typified by a decreased performance of 

many biologic regulatory processes in the face of biologic 

stress. Because these regulatory mechanisms provide 

functional integration between cells and organ systems, 

growing old may be associated with a failure to maintain 

homeostatic functions. This impaired capability affects 

diverse regulatory systems uniquely in aged subjects and 

may at least partly explain the increased interindividual 

variability in functional reserve that occurs as people get 

older. The decline in functional reserve is inconsistent 

among individuals, with the variability in deterioration 

rooted within lifestyle choices, environmental factors, 

genetics, and the presence of age-related disease. A 

decline in functional reserve may precipitate a serious 

decline in performance when the elderly patient is 

exposed to stress such as those of surgery and anesthesia, 

and thereby increases the risk of age-related disease. 

Aims 

This chapter will function primarily as an introduction to 

the complex area of metabolic changes in the elderly. In 

addition, issues concerning the fluid and electrolyte status 

of the elderly patient will be touched upon. Within each 

of its sections, the impact of these changes on the anesthetic 

management of these patients will be examined, 

and the concept of reduced functional reserve and its 

consequences will be continually reemphasized. 

Basal Metabolic Rate 

Mitochondria, being the powerhouse of biologic processes, 

underlie all of the metabolic functions of the body. 

These organelles provide the power that fuels metabolic 

functions. 

The energy required to maintain basic cellular functions 

is termed basal metabolic rate (BMR) and it is generally 

accepted that it decreases with advancing age. It decreases 

by approximately 1%–2% per decade from the ages of 

20–80 years, 20–22 and additive declines in BMR have been 

shown to decrease the rate of drug metabolism. 23 

97

98 M.C. Lewis 

Body Composition 

% Maximal organ function 

Maximal 

Basal 

Functional 

reserve 

Age (years) 

Figure 7-1. The functional reserve is the difference between 

basal function (solid line) and maximal function (broken line). 

Even in healthy elderly individuals, this functional reserve will 

be reduced. (Modified from Muravchick S. Geroanesthesia: 

Principles for Management of the Elderly Patient. St. Louis: 

Mosby-Year Book; 1997. Copyright © 1997 with permission 

from Elsevier.) 

This decreased BMR is associated with increased levels 

of circulating epinephrine 24,25 and reduced β-receptor 

sensitivity. 26 These receptors are involved in sympathetically 

mediated thermogenesis, hence, the fact that the β- 

response becomes blunted has been used to explain a 

predisposition to obesity. 21 Such a tendency to obesity in 

the elderly may contribute to the observed increase in 

incidence of both Type 2 diabetes 27 and cardiac disease. 28 

Moreover, this diminution of β-receptor sensitivity in the 

elderly results in a decreased ability to cope with physiologic 

stressors. 

Impaired thermogenesis and reduced BMR predispose 

the elderly to more severe postoperative hypothermia 

and a protracted recovery from this phenomenon. 29 Slowness 

to recover from hypothermia is also partly attributable 

to the reduced amount of shivering compared with 

younger patients 30 with total body oxygen consumption 

increasing only about 38% in the elderly. 31 Such vulnerability 

to hypothermia increases the risk of adverse 

physiologic outcomes such as increased risk of wound 

infections 32 and myocardial ischemia. 33 

In summary, changes in BMR in the elderly are characterized 

by: 

• Gradual decline in BMR even allowing for changes in 

body composition 

• Increase in circulating catecholamines, together with 

decreased β-receptor sensitivity, increasing the predisposition 

to obesity 

• Impaired ability to protect against and recover from 

hypothermia exposing the geriatric patient to increased 

intra- and postoperative complications 

The changes in body structure with aging are typified by 

an increase in the percentage of body fat, 34 a loss of 

protein, 35 and intracellular dehydration. 36 These changes 

in body composition have been shown to be even greater 

in women. 18 

Changes in Body Fat 

Age-related accumulation of body fat increases the deposition 

of lipid-soluble drugs including anesthetics. 37 Consequently, 

the larger concentration of these agents in fat 

tissue results in a longer time for redistribution and a 

slower elimination time thereby prolonging anesthetic 

effects. 38,39 

Loss of Protein 

There is a significant loss of body protein with aging. 40 

The following section will describe the sources of this 

protein loss. 

Muscle Mass 

The majority of the age-related loss of body protein is 

accounted for by the up to 20% decrease of skeletal 

muscle mass 41 of unknown etiology 42 and is termed sarcopenia. 

43 This occurs even in the fit adult and is associated 

with a loss of strength. For a person in their second 

decade, muscle comprises up to 60% of the lean body 

mass, and yet at 70 years of age, this decreases to less than 

40%. Although the decrease in muscle tissue begins 

around the age of 50 years, it becomes more dramatic 

beyond the 60th year of life. 44 This decline can be partially 

reversed using resistance exercises. 45 

Despite this degree of muscle loss, there is no difference 

in sensitivity of the elderly to muscle relaxants. 46 The 

pharmacokinetics of such agents are characterized by 

decreased elimination. The initial administration of such 

drugs may not have to be reduced, 47 but the total dose 

administered should be generally reduced. 48 However, 

because of decreased elimination, their effect should be 

carefully monitored using a component of neuromuscular 

function such as the train-of-four tests. 

Transport Proteins 

Intravenous anesthetic induction agents are transported 

through the body bound to plasma proteins. Any agent 

attached to such proteins is not capable of crossing biologic 

membranes to produce the desired drug effect. Conversely, 

the segment that remains free in plasma is able 

to cross these lipid membranes, including the blood–brain

7. Alterations in Metabolic Functions and Electrolytes 99 

barrier, and in the case of induction agents produces the 

preferred effect. 

Albumin 

This is the primary transport carrier 49 and is responsible 

for transporting most of the acidic drugs in the plasma. 

Its synthesis represents a major component of the proteins 

produced by the liver. Increasing age is associated 

with a slight decrease in the concentration of albumin 50 

by 0.54 g/L per decade. The decrease amounts to a total 

reduction in plasma albumin concentration of around 

10% in older people. 51 This reduction in albumin plasma 

level has been shown to reduce the unbound fraction of 

certain drugs. 52 On average, the unbound fraction of drugs 

increases by approximately 10%, paralleling the agerelated 

decrease in albumin. 18,53 Theoretically, the net 

effect is that anesthetic drugs that bind to albumin, such 

as thiopental, should have their dose decreased. However, 

overall age-related effects on protein binding do not 

produce clinical differences. 54 Because of the polypharmacy 

often seen in the geriatric patient, concomitant diseases, 

and the reduced circulating albumin level, there 

may be a greater opportunity for displacement reactions 

between drugs. 

Renal failure has been associated with decreased levels 

of circulating albumin. 55 As a result, the pharmacokinetics 

of anesthetic agents can be altered. 56,57 However, those 

patients with global hypoproteinemia, not just decreased 

albumin, will have decreased binding of both acidic and 

basic drugs. 58 

A 20%–30% reduction in blood volume occurs by age 75 

with total body water (TBW), plasma volume and intracellular 

water content all decreasing. 60 Consequently, 

intravenous administration of an anesthetic drug will be 

distributed in a reduced blood volume producing a higher 

than expected initial plasma drug concentration. Such 

changes can have very important implications on the 

action of anesthetic agents. 61 For example, a patient who 

is relatively dehydrated and is given a bolus of an induction 

agent, will distribute this drug into a reduced circulating 

volume. Anesthetic and hemodynamic effects of 

the drug will be exaggerated. This resultant exaggerated 

pharmacologic effect could give the impression of an augmented 

sensitivity to the agent. Such changes in the distribution 

and half-life of a particular anesthetic agent will 

depend on its relative lipid and water solubility as well as 

the degree of protein binding. 

In summary, changes in body composition in the elderly 

are characterized by: 

• A decrease in protein content, mostly in the form of 

muscle loss, but also in carrier proteins 

• Adipose tissue comprising an increased proportion of 

body mass 

• A decrease in TBW, with this reduction manifest mostly 

in the intracellular component but somewhat in the 

extracellular compartment also 

Hepatic Function in the Elderly 

The effects of maturation on drug clearance by the liver 

have been examined extensively 62,63 and the contentious 

question of whether or not liver function is compromised 

in the aged has still not been clearly determined. As is 

the general pattern with most aging organs, the decline 

in function is gradual and minimal. Senescence is only 

experienced when the normal homeostatic mechanisms 

fail. Decline in biochemical functions are slow and negligible 

and are reflected in assays of liver function such as 

total bilirubin and liver enzymes. 64 

Alpha 1 Acid Glycoprotein 

Whereas acidic drugs are primarily bound to albumin, 

basic drugs tend to be bound to alpha 1 acid glycoprotein. 

Data suggest that this transport protein is either not 

affected by aging 59 or even slightly increased, 54 probably 

reflecting the age-associated increases in inflammatory 

disease. 11 The binding and consequent dosage of basic 

anesthetic drugs, such as lidocaine, is therefore unaffected 

by aging. 

Changes in Total Body Water 

Morphologic Changes 

Gross Changes 

The aging liver develops a classic gross anatomic 

appearance termed “brown atrophy.” 65,66 This discoloration 

is attributed to hepatocyte accumulation of the 

pigment lipofuscin, but it is not clear whether these morphologic 

changes are associated with alteration in 

function. 67,68 

Hepatic blood flow decreases with increasing age. 69–71 

Most of this reduction is associated with a 35% decrease in 

liver mass. 72–76 The reduction in hepatic blood flow is probably 

slightly greater than can be explained by the decrease 

in liver mass, 51 resulting in a 10% decrease in blood flow per 

unit mass of liver. 51 However, the large size of the aging 

liver provides a large measure of functional reserve therefore 

conserving its function relatively well. 51,54,55 

Microscopic Changes 

Age-related subcellular changes in the liver are slight. 26,77 

Hepatocyte volume increases, probably as a function of

100 M.C. Lewis 

intracellular swelling. 78 There are some characteristic 

age-related organelle changes. For example, it has been 

shown that the number and the density of the mitochondria 

decrease with increasing age. 79,80 In addition, there is 

a decline in the amount of both rough and smooth endoplasmic 

reticulum. 81 The reduction in the amount of rough 

endoplasmic reticulum may be a reflection of a reduced 

ability to synthesize proteins. However, the decrease in 

the quantity of smooth endoplasmic reticulum may correlate 

with the decline in the yield of microsomal 

protein. 82 

Physiologic Changes 

Drug Metabolism 

Although there is variability in published reports concerning 

hepatic clearance, 83 it is clear that the hepatic 

metabolism of anesthetic agents is affected by the reduced 

hepatic blood flow. This is probably a reflection of the 

confounding variables already discussed in this chapter, 

such as differences in functional reserve, the effects of 

comorbid conditions, polypharmacy, and numerous environmental 

factors. 

Minimal changes have been noted in the mixed function 

oxidase activity. However, the total capability of the 

liver to metabolize many drugs by these enzymes may be 

reduced 84,85 with aging. This decline is erratic and unpredictable, 

84,86,87 varying from drug to drug and from 

individual to individual. 

The liver converts lipid-soluble drugs into inactive and 

water-soluble metabolites by a number of processes that 

can be divided into two distinct phases, both of which are 

not radically altered 88,89 in the elderly patient: 

• Phase 1 renders functionally reactive chemical locations 

inactive. These reactions consist of oxidation, 

reduction, and hydrolysis, which seem to be the most 

changed with aging. Although the levels of drug-metabolizing 

enzymes in the cytochrome P-450 systems 

do not decline significantly with age, overall hepatic 

metabolism of some drugs by these enzymes is diminished. 

Such changes in phase I reactions, however, 

are probably less significant than the effects of 

alcohol, tobacco, 90 and environmental factors on liver 

function. 91–93 

• Phase 2 reactions involve the addition of a polar group, 

rendering the altered molecule more water-soluble. 

These reactions include glucuronidation, methylation, 

sulfation, and acylation. 

Compounds with a suitable reactive site may skip 

Phase 1 conversion and pass straight into Phase 2. This is 

the case with acetaminophen 94 which contains a hydroxyl 

group and is, for the most part, directly glucuronidated 

and sulfated. 

The decrease in liver mass may have a role in the 

decline 66 in hepatic drug metabolism. As described before, 

total hepatic blood flow is reduced in elderly subjects and 

this may affect drug clearance. 63,64 Also, the reduction in 

hepatic first-pass metabolism of highly extracted drugs in 

the elderly (extraction ratio >0.8 such as morphine 11 ) 

results in increased plasma drug concentrations and a 

propensity to dose-dependent adverse effects. 

Laboratory Tests 

Routine clinical tests of liver function do not change significantly 

with age. The aminotransferases and the serum 

bilirubin levels remain normal in the elderly. It has been 

postulated that a correlation exists between age-associated 

impairment of cell metabolism and specific changes 

in mitochondrial function and structure. 

In summary, hepatic metabolic function in the elderly is 

characterized by: 

• Decrease in hepatic blood flow 

• Decrease in liver size by 35% 

• No clinically significant change in routine tests of 

function 

• Phase I and II metabolism not significantly impaired 

Renal Function 

In both human and animal models, the aging process 

results in structural and functional renal changes 95–98 that 

diminish functional reserve. This creates homeostatic 

limitations on the kidney’s capability to respond properly 

to either volume excess or deficit. 

Renal Blood Flow 

This function progressively decreases by about 10% per 

decade after the age of 50. 99 The elderly often have associated 

medical conditions such as hypertension, vascular 

disease, diabetes, and heart disease that may exacerbate 

the effects of these renal abnormalities. Such reductions 

in flow, paired with a reduced response to vasodilatory 

stimuli, 100–103 render the elderly kidney particularly susceptible 

to the harmful effects of reduced cardiac output, 

hypotension, hypovolemia, and hemorrhage. Anesthetic 

and surgical stress, pain, sympathetic stimulation, and 

renal vasoconstrictive drugs may contribute to perioperative 

renal dysfunction. 

Renal Mass 

The decrease in blood flow as in the case of the liver is 

accompanied by a reduction in renal parenchyma. 104,105 

Primarily there is a loss of about 20%–25% of the renal


cortical mass between the age of 30 and 80 years. At the 

light microscopic level, the aging human kidney is characterized 

by increased fibrosis, tubular atrophy, and arteriosclerosis. 

106,107 The presence of small vessel pathology 

in older people without apparent renal disease or hypertension, 

suggests that even in healthy elderly individuals, 

renal changes may be secondary to vascular disease and 

altered vascular responsiveness. 

Changes in Glomerular Filtration Rate 

A microscopic assessment confirms the loss of the kidney’s 

functional units with increasing age. 108,109 As many 

as half of the glomeruli present in a young adult may be 

gone or rendered nonfunctional by 80 years of age. 

Although the number of glomeruli is decreased, the 

remaining ones are relatively large in size. The reductions 

in cortical mass are accompanied by progressive sclerosis 

of the kidney’s functional units and by the eighth decade 

10%–30% of the remaining nephrons are sclerotic. The 

net result of these changes is that there is a gradual 

decline in the surface area available for filtration and a 

steady reduction of the glomerular filtration rate (GFR). 

Age-related decline in GFR is often considered the most 

important pharmacokinetic change in old age. GFR, normally 

about 125 mL/min in a young adult, decreases to 

approximately 80 mL/min at 60 years of age, and to about 

60 mL/min at 80 years. 

Because GFR decreases less than renal plasma flow, 

the filtration fraction increases to a state of hyperfiltration. 

This compensates to a certain extent for the 

decreased number of functional glomeruli. As a result, 

the pressure within the glomerulus increases, possibly 

accelerating glomerulosclerosis. 

Creatinine Clearance 

Because of the decrease in muscle mass with aging, the 

decrease in GFR does not result in an increase in serum 

creatinine. However, creatinine clearance can be used for 

the approximation of GFR. 110 Although the structural 

and functional changes seem to have minimal consequences 

under normal circumstances, they attain clinical 

significance when the remaining renal function is challenged 

by the imposition of acute physiologic stress. 

When GFR decreases below 80 mL/min, dose adjustments 

should be made to renally excreted drugs. Dosing 

periods for medications that are renally excreted, such as 

aminoglycoside antibiotics and pancuronium need to be 

adjusted, and where indicated, drug levels closely watched. 

Logic dictates that nephrotoxic drugs should be avoided. 

Creatinine clearance decreases by approximately 1 mL/ 

min/year after the age of 40 years. Renal changes with 

aging also result in very tangible problems in the perioperative 

period. Drugs that depend on renal function for 

clearance may accumulate in the elderly, an effect that 

may be exaggerated by preexisting renal disease. In addition, 

the elderly are prone to fluid and electrolyte abnormalities 

and drug-induced renal failure. 108 

Tubular Function 

Fluid and electrolyte status should be carefully monitored 

in the elderly patient during the perioperative 

period. In the absence of disease, and under normal “nonstress” 

conditions, the concentrations of electrolytes in 

the extracellular fluid are within the normal range. In the 

face of physiologic stress, however, the aging kidney has 

difficulty maintaining electrolyte balance and circulating 

volume, 111 because both sodium conservation and excretion 

become more limited with age. 

Under normal conditions, age has no effect on the 

ability of the individual to maintain extracellular fluid 

volume. However, the adaptive systems responsible for 

controlling fluid balance are impaired in the elderly and 

the aging kidney has a decreased ability to dilute and 

concentrate urine. Studies show that tubular function is 

generally decreased in the elderly, 108,112 limiting the degree 

to which urine can be concentrated in response to water 

deprivation. Similarly, the rate at which a salt load can be 

excreted becomes more impaired with age. Additionally, 

the elderly cannot maximally suppress antidiuretic 

hormone secretion when serum osmolarity is reduced. 

These observations, together with decreased efficiency 

of the renin-angiotensin system, means that elderly 

patients’ failure to retain sodium effectively under conditions 

of plasma volume contraction is not solely attributable 

to reductions in the GFR. 

Concentration capacity is an additional sensitive indicator 

of renal function. When fluid is restricted, the aged 

patient shows a reduced capability to concentrate the 

urine. The activity of the renin-angiotensin system 

declines with age, 113 and above 40 years of age there is a 

decline in both plasma renin aldosterone activity, and the 

kidney is less efficient at retaining salt with restricted 

intake. 

Sick patients, especially very elderly ill individuals, 

have a tendency to inadequately regulate their intake of 

nutrients and water, 114 and have impaired release of 

antidiuretic hormone. 106 Therefore, in the perioperative 

period, inadequate electrolyte (via food) and water ingestion 

may result in dehydration plus net sodium loss from 

obligatory sodium excretion. It has been reported that 

11% of acutely ill, aged patients have hyponatremia. This 

figure increases to 22% in those patients in chronic care 

institutions. 115 Often, the characteristics of their fluid 

administration are poorly documented and this contributes 

to the less-than-adequate management. 116 

Low sodium plasma levels may lead to disturbed 

cardiac electrophysiologic function. 117 In addition, the


age-related reduction in muscle mass decreases total 

body potassium content. However, serum electrolytes are 

generally maintained within the same range as is found 

in younger adults, 54,118 until situations of surgical stress 

abnormalities develop. The relationship between abnormal 

preoperative potassium levels and arrhythmias is 

unclear. 119 Yet, if the surgery is significant, it may be 

worthwhile to replenish very low levels. 103 

The aging kidney is able to maintain acid-base homeostasis 

when functioning under baseline conditions. 120 

However, the impaired tubular ability of the elderly 

kidney to excrete an acid load as compared with that of 

the younger patient contributes to the higher incidence 

of metabolic acidosis in the elderly. 121 

Among elderly surgical patients, acute renal failure is 

responsible for up to one-fifth of all perioperative 

deaths. 122 Following thoracic surgery, perioperative renal 

failure may be as much as 30% 123 with an associated 

mortality of 20%–90%. 124,125 Fifty percent of all patients 

requiring acute dialysis do so because of perioperative 

renal failure. The cause of renal failure leading to dialysis 

is not clearly understood. However, most cases are attributable 

to acute tubular necrosis. 

In summary, renal metabolic function in the elderly is 

characterized by: 

• Decreases in renal blood flow 

• Decreases in kidney size 

• Morphologic changes include a decrease in the 

number of glomeruli, compensatory increase in the 

size of the remaining nephrons, and significant 

glomerulosclerosis 

• No clinically significant changes in routine laboratory 

tests, but decreases in creatinine clearance, maximum 

sodium concentrating ability, and free water excretion 

• Decreases in tubular function, including impaired 

ability to handle an acid load, as well as impaired reninangiotensin 

and antidiuretic hormone systems 

• Decreased thirst response 

Implications for Anesthesiology 

Practice 

In light of the previous discussion, it is clear that aging 

results in important changes in drug pharmacokinetics, 

including anesthetic medications. 126,127 These changes are 

summarized in Table 7-1. 

In What Way Does This Affect Our Practice? 

Age-related alterations in the pharmacokinetics of 

administered anesthetic agents give rise to changes in the 

magnitude of effect of anesthetic agents. Reduced lean 

body mass and TBW, and increased percentage of body 

fat alter the volume of distribution of anesthetic agents. 

Altered renal and liver function reduces drug clearance 

from the body. Such changes account for differences 

between younger adult patients and their older contemporaries. 

This has been demonstrated in studies that have 

been performed in the adult population with ages that 

range from 20 to 80 years of age. 14,19 This phenomenon 

affects drugs not usually thought of when considering 

age-related decreases in metabolism. For example, it has 

been shown that the rate of propofol elimination declines 

with age above 60 years of age. 128 

However, much of the information concerning the 

pharmacology of anesthetic or any other agent in the 

elderly is lacking because the aged are often methodically 

excluded from drug trials. 129 Because many drugs are 

tested and formulated for younger adults, consideration 

must be given to the changes described above when 

determining proper dosages for their use in the geriatric 

population. Conclusions are often drawn from inference. 

Although some models of practice have been accepted, 

there remain some contentious issues with regard to 

aging effects. Failure to recognize such reductions in both 

metabolism and excretion will result in adverse drug 

effects. 130 

Table 7-1. Physiologic changes in the elderly and their effect on pharmacokinetics. 

Pharmacologic factor Change with aging Importance 

Absorption 

↑ Gastric pH 

↓ Gastric emptying 

↓ Absorption 

↓ Absorptive surface 

↓ Splanchnic blood flow 

Distribution ↑ Body fat ↑ VD L , lipophilic drugs 

↑ α 1 glycoprotein 

↓ Free fraction of basic drugs 

↓ Albumin 

↑ Free fraction of acidic drugs 

↓ Body water 

↑ Concentration of polar drugs 

Metabolism ↓ Hepatic metabolism ↓ Biotransformation 

Elimination ↓ Glomerular filtration rate ↓ Elimination fluid, pH, and electrolyte disturbance 

↓ Renal tubular function


Adverse Drug Reactions and Aging 

Not surprisingly, the older patient is at risk of adverse drug 

reactions from chronic medications. Pharmacokinetic 

changes, polypharmacy, and drug interactions summate to 

make adverse drug interactions more likely. 131,132 Drug 

elimination is decreased in the aged, leading to higher 

blood concentrations and hence a higher possibility of a 

type A adverse reaction (exaggerated or excessive but otherwise 

normal pharmacologic action of a drug). 133,134 In 

fact, there is an almost linear increase of adverse drug 

reactions with age. 135 Geriatric patients are up to three 

times more likely to experience adverse drug reactions. 136 

In addition, the risk of adverse drug reactions increases 

with the number of medications given. Thus, the addition 

of several drugs, even short-acting ones, in the perioperative 

period makes adverse reactions more likely. 137 This 

situation is further complicated by the fact that advanced 

age is accompanied by comorbidity and the consequent 

polypharmacy for treatment of these disease states. 138,139 If 

we, as perioperative physicians of the elderly, are going to 

use these drugs in a rational and safe manner, it is incumbent 

upon us to acquire an understanding of how such 

age-dependent change occurs. An example of how this 

information may be useful is seen with hypertension. This 

disease is highly prevalent in the elderly and often requires 

multiple medications for its management. Concomitant 

medications, such as β-adrenergic blocking drugs and 

diuretics might further impair reflex heart rate and cardiac 

output increases. The use of a volatile anesthetic in these 

patients may give rise to exaggerated decreases in blood 

pressure, especially if the patient is hypovolemic. 

Summary 

The perioperative care of the elderly patient is challenging. 

Aging progressively diminishes functional reserve, 

and therefore diminishes the patient’s ability to handle 

stress. As illustrated in this chapter, a global understanding 

of the metabolic alterations that take place with aging 

helps us to better manage and respond to pharmacokinetic 

and pharmacodynamic reactions within this patient 

population. Such knowledge will aid us in providing an 

optimal anesthetic for each elderly patient. Part of our 

role as perioperative physicians may well include the 

detection and possible correction of metabolic abnormalities. 

We, as anesthesiologists, should act as “homeostasis 

in absentia.” This may help to preserve existing 

function, and avoid adverse outcomes. 

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8 

Perioperative Thermoregulation 

Daniel I. Sessler 

Perioperative thermal disturbances are common and 

there is considerable evidence that disturbances are especially 

frequent in the elderly. The most common perioperative 

thermal disturbance—hypothermia—is both more 

likely and more severe in the elderly than in younger 

patients. Anesthetic drugs impair thermoregulation in all 

patients, and delayed or insufficient thermoregulatory 

defenses are the primary causes of hypothermia in most 

patients. Excessive hypothermia in the elderly results 

largely because central and efferent thermoregulatory 

controls are particularly disturbed in these patients. 

Perioperative hypothermia has long been associated 

with complications including decreased drug metabolism 

and postoperative shivering. In recent years, mild hypothermia 

has been shown to significantly alter patient outcomes 

by increasing the incidence of myocardial ischemia, 

augmenting blood loss, decreasing resistance to surgical 

wound infections, and prolonging hospitalization. There 

is no reason to believe that the elderly are resistant to 

complications associated with hypothermia. Instead, they 

are especially susceptible to many of them because of 

normal age-related changes in organ function and because 

many have substantial underlying diseases. In contrast, 

thermal management in the elderly does not differ importantly 

from that in younger patients. 

Normal Thermoregulation 

Core body temperature is among the most jealously 

guarded physiologic parameters and is justifiably considered 

one of the “vital signs.” The major thermoregulatory 

defenses are behavior, 1,2 sweating, 3 precapillary vasodilation, 

4 arteriovenous shunt vasoconstriction, 5 nonshivering 

thermogenesis, 6 and shivering. 7 Each can be 

The author does not consult for, accept honoraria from, or own 

stock or stock options in any company related to products discussed 

in this chapter. 

characterized by its threshold (triggering core temperature), 

gain (intensity increase with further core-temperature 

deviation), and maximum intensity. 8 Temperatures 

between the first autonomic warm response (sweating) 

and the first autonomic cold defense (vasoconstriction) 

define the interthreshold range; these temperatures do 

not trigger autonomic thermoregulatory defenses. 9 

Precise control of core temperature is maintained by a 

powerful thermoregulatory system incorporating afferent 

inputs, central control, and efferent defenses. 10 Efferent 

defenses can be broadly divided into autonomic 

responses (i.e., sweating and shivering) and behavioral 

responses (i.e., closing a window, putting on a sweater). 

Autonomic responses depend largely on core temperature 

and are mostly mediated by the anterior hypothalamus. 

In contrast, behavioral responses are mostly 

determined by skin temperature and are controlled by 

the posterior hypothalamus 11 (Figure 8-1). 

Afferent Input 

Warm afferent signals are conveyed by unmyelinated C- 

fibers, as is pain. In contrast, cold signals traverse myelinated 

A-delta fibers, both of which are widely distributed. 12 

Most thermal input is conducted along the spinothalamic 

tracts, although both afferent and efferent thermal signals 

are diffusely distributed within the neuraxis. 13 

The central thermoregulatory control system accepts 

thermal input from tissues all over the body. The relative 

contributions of most tissues have yet to be determined 

in humans. However, animal studies suggest that the 

hypothalamus, other portions of the brain, the spinal 

cord, and deep thoracic and abdominal tissues each contribute 

very roughly 20%. 8,14–16 

Mean skin temperature contributes 5%-20% as much 

as core temperature (deep central tissues and brain) to 

control of sweating and active vasodilation; furthermore, 

the relation between mean skin and core temperatures at 

response thresholds is linear. 4,17–20 That is, a 1°C increase 

107

108 D.I. Sessler 

Core 

Skin 

Core 

Skin 

in skin temperature reduces the sweating and active capillary 

vasodilation thresholds (expressed in terms of core 

temperature) by 0.05–0.2°C. Arithmetically, this relation 

takes the form 

Thres MBT = βT skin + (1 − β)T core , 

where Thres MBT is the sweating or vasodilation threshold 

in terms of physiologic (rather than anatomic) mean 

body temperature, T skin is mean skin temperature, and 

T core is core temperature, all in degrees centigrade. 

The proportionality constant, β, in this case is 0.05–0.2. 

The skin surface contributes 20% ± 6% to control of 

vasoconstriction and 19% ± 8% to control of shivering, 

and the contribution in linear 16 (Figure 8-2). Regional 

sensory contributions to thermoregulatory control have 

not been specifically evaluated in the elderly. However, 

there is little reason to believe that temperature sensation 

fails in the elderly or that integration differs 

markedly. 

Central Control 

Anterior 

Hypothalamus 

Posterior 

Hypothalamus 

Autonomic Responses 

Behavioral Responses 

Figure 8-1. Control of autonomic and behavioral thermoregulatory 

defenses. Efferent defenses can be broadly divided into 

autonomic responses (e.g., sweating and shivering) and behavioral 

responses (e.g., closing a window, putting on a sweater). 

Autonomic responses depend largely on core temperature and 

are mediated largely by the anterior hypothalamus. In contrast, 

behavioral responses are mostly determined by skin temperature 

and are controlled by the posterior hypothalamus. 

Thermal afferent signals are integrated at numerous 

levels within the neuraxis, including the spinal cord and 

brain stem. The dominant controller in mammals, however, 

is the hypothalamus. (Interestingly, the spinal cord dominates 

in birds.) Although core temperature varies with a 

daily circadian rhythm, 21 body temperature is normally 

controlled to within a few tenths of a degree centigrade 

almost irrespective of the environment. 22 Such precise 

control is maintained by a powerful thermoregulatory 

system incorporating afferent inputs, central control, and 

efferent defenses. 

The thresholds triggering thermoregulatory defenses 

are uniformly about 0.3°C greater during the follicular 

phase in women than in men, 22 and would be an additional 

≈10.5°C greater during the luteal phase. 23 However, 

men and women regulate core body temperature with 

comparable precision, usually maintaining core temperature 

within a few tenths of a °C of the target temperature 

(Figure 8-3). 

The major autonomic warm defenses, sweating and 

active vasodilation, are triggered at about the same temperature 

and seem to operate synchronously. 24 In contrast, 

vasoconstriction is the first autonomic response to 

cold. 22 Only when vasoconstriction is insufficient to maintain 

core temperature (in a given environment), is nonshivering 

thermogenesis or shivering initiated. In humans, 

nonshivering thermogenesis is restricted to infancy, and 

infants use this defense in preference to shivering. 25 

In contrast, nonshivering thermogenesis is of little 

importance in adult humans, 26–28 although it is the most 

important cold defense in small animals. 

When one efferent response is inadequate to maintain 

core temperature in a given environment, others are acti- 

36 

34 

Core 38 

Temperature 

(°C) 36 

Vasoconstriction 

38 #1 

34 

38 

36 

Shivering 

#2 

#3 #4 

#5 

#6 

34 

30 34 38 30 34 38 

Skin Temperature(°C) 

Figure 8-2. The relative contribution of mean skin temperature 

to control of thermoregulatory vasoconstriction and shivering 

in six men. The threshold (triggering core temperature) for each 

response is plotted vertically against mean skin temperature. 

Core and skin temperatures at the vasoconstriction and shivering 

thresholds were linearly related. The extent to which mean 

skin temperature contributed to central thermoregulatory 

control (β) was calculated from the slopes (S) of the skin-temperature 

versus core-temperature regressions, using the formula: 

β = S/(S − 1). Cutaneous contribution to vasoconstriction averaged 

20% ± 6%, which did not differ significantly from the 

contribution to shivering: 19% ± 8%. (Reprinted with permission 

from Cheng et al. 16 Copyright © Lippincott Williams & 

Wilkins.)

8. Perioperative Thermoregulation 109 

Threshold 

(°C) 

38 

37 

36 

35 

Figure 8-3. The thresholds (triggering core temperatures) for 

the three major autonomic thermoregulatory defenses: sweating, 

vasoconstriction, and shivering. Temperatures between the 

sweating and vasoconstriction threshold define the interthreshold 

range, temperatures not triggering autonomic responses. 

The thresholds are uniformly about 0.3°C greater during the 

follicular phase in women than in men, and would be an additional 

≈0.5°C greater during the luteal phase. However, men 

and women regulate core body temperature with comparable 

precision. Results are presented as means ± SD. (Reprinted with 

permission from Lopez et al. 22 Copyright © Lippincott Williams 

& Wilkins.) 

vated. Similarly, secondary defenses compensate for those 

working poorly. For example, when arteriovenous shunt 

vasoconstriction is defeated by administration of a vasodilating 

drug, core hypothermia will initiate shivering. 

Because autonomic responses are to some extent compromised 

in the elderly, behavioral responses are probably 

more important in this population—although this 

theory has yet to be formally evaluated. 

Efferent Responses 

Women 

Men 

Sweating Constriction Shivering 

Sweating is mediated by postganglionic, cholinergic 

nerves that terminate on sweat follicles. 29 These follicles 

apparently have no purpose other than thermoregulation. 

In this regard, they differ from most other thermoregulatory 

effectors which seem to have been co-opted 

by the thermoregulatory system but continue to 

have important roles, for example vasomotion in blood 

pressure control or skeletal muscles in postural 

maintenance. 

Heat exposure can increase cutaneous water loss from 

trivial amounts to 500 mL/h. Losses in trained athletes 

can even exceed 1 L/h. In a dry, convective environment, 

sweating can dissipate enormous amounts of heat— 

perhaps to 10 times the basal metabolic rate. Sweating is 

the only thermoregulatory defense that continues to dissipate 

heat when environmental temperature exceeds 

core temperature. 

Active precapillary vasodilation is mediated by a yetto-be-identified 

factor released from sweat glands, and 

thus occurs synchronously with sweating. Although originally 

thought to be bradykinin, 30 recent evidence supports 

nitric oxide as the mediator. 31,32 Active dilation can 

increase cutaneous capillary flow enormously, perhaps to 

as much as 7.5 L/min. 33 The purpose of this dilation, presumably, 

is to transport heat from muscles and the core 

to the skin surface where it can be dissipated to the environment 

by evaporation of sweat. 

Active arteriovenous shunt vasoconstriction is adrenergically 

mediated. The shunts are 100-µm–diameter vessels 

that convey 10,000 times as much blood as a comparable 

length of 10-µm capillary. 5 Anatomically, they are restricted 

to the fingers, toes, nose, and nipples. Despite this restriction, 

shunt vasoconstriction is among the most frequently 

used and important thermoregulatory defenses. The 

reason is that the blood traversing shunts in the extremities 

must flow through the arms and legs, thus altering heat 

content of these relatively large tissue masses. 

Shivering is an involuntary, thermogenic tonic tremor. 7 

Typically, it doubles metabolic rate, 34,35 although greater 

increases can be sustained briefly. The shivering threshold 

is normally ≈1°C less than the vasoconstriction threshold, 

suggesting that it is activated only under critical conditions 

and is not the preferred means of maintaining core 

temperature. One reason may be that shivering is a relatively 

inefficient response. Although shivering effectively 

transfers metabolic energy sources into heat, the heat is 

largely produced in the periphery where the largest 

muscles are located. Loss of the peripherally produced 

heat to a cold environment is further accentuated by the 

metabolic needs of shivering muscle and the resulting 

vasodilation. 

Impaired Thermoregulation 

in the Elderly 

There is considerable epidemiologic evidence that the 

elderly often fail to adequately regulate body temperature. 

Accidental hypothermia is especially likely in three 

populations: drug abusers (especially alcoholics), people 

suffering extreme exposure (such as cold-water immersion), 

and the elderly. 36 While extreme—and usually prolonged—cold 

exposure is required to produce clinical 

hypothermia in young, healthy individuals, serious hypothermia 

is common among alcohol abusers even with 

mild exposure. 37 Hypothermia in these patients presumably 

results from drug-induced inhibition of thermoregulatory 

defenses. The extent to which alcohol impairs 

autonomic defenses remains controversial 38–41 ; however, 

alcohol at the very least significantly impairs appropriate 

behavioral responses to cold exposure. 

Hypothermia in the elderly can occur in only moderately 

cold environments and is typically not associated 

with drug use. 36,37 This observation suggests that hypo-


Shivering 

Threshold 

(°C) 

37 

36 

35 

34 

40 60 80 100 

Age (yr) 

Figure 8-4. The effect of aging on the shivering threshold. 

Fifteen patients aged


moregulatory control. For example, the sweating threshold 

is linearly increased by propofol, 54 alfentanil, 55 

isoflurane, 24 and desflurane. 56 Reduction of the vasoconstriction 

and shivering thresholds is also a linear function 

of propofol, 54 dexmedetomidine, 57 meperidine, 58 and 

alfentanil 55 concentrations. Desflurane and isoflurane, 

however, produce a nonlinear reduction in the major 

cold-response thresholds, reducing the vasoconstriction 

and shivering thresholds disproportionately at higher 

anesthetic concentrations 56 (Figure 8-5). The result is that 

clinical doses of all anesthetics markedly increase the 

interthreshold range, substantially impairing thermoregulatory 

defenses. 

Anesthetic-Induced Thermoregulatory 

Impairment in the Elderly 

39 

37 

Threshold 35 

(°C) 

33 

31 

Sweating 

Vasoconstriction 

Shivering 

0 0.5 0.8 

Desflurane (MAC Fraction) 

Figure 8-5. Thermoregulatory response thresholds during desflurane 

anesthesia. The sweating threshold increased linearly, 

but slightly, during desflurane anesthesia. Desflurane markedly—although 

nonlinearly—reduced the vasoconstriction 

threshold. Consequently, the interthreshold range (temperatures 

not triggering autonomic thermoregulatory defenses) 

increased enormously during desflurane administration. In contrast, 

the vasoconstriction-to-shivering range remained essentially 

unchanged. Results are presented as means ± SD. MAC = 

minimal anesthetic concentration. (Reprinted with permission 

from Annadata et al. 56 Copyright © Lippincott Williams & 

Wilkins.) 

Threshold 

(°C) 

35 

34 

33 

Young 

Intraoperative hypothermia is more common and more 

severe in the elderly than in younger patients. 59 Because 

a major cause of intraoperative hypothermia is anesthetic-induced 

inhibition of thermoregulatory responses, 

these two observations suggest that anesthetics impair 

thermoregulation more in elderly than in young patients. 

This thesis is supported by the observation that the vasoconstriction 

threshold is approximately 1°C lower in 

elderly surgical patients than in younger ones 60 (Figure 

8-6). 

Intraoperative hypothermia is not only more common 

in the elderly, but lasts longer postoperatively. 61 It is associated 

with less shivering than in younger patients, 59,62 and 

what shivering does occur is at a low intensity. 63 Prolonged 

hypothermia without shivering suggests that thermoregulatory 

defenses are not being activated, which is 

consistent with reduced perioperative vasoconstriction 60 

and shivering 50 thresholds in the elderly. 

An additional factor to consider is the age-dependent 

effects of anesthetic drugs. Renal and hepatic function is 

often reduced in the elderly. Consequently, clinically 

important plasma concentrations are likely to persist at 

high levels for longer in the elderly. Equally important, 

any given plasma concentrations of many drugs produce 

a greater effect in the elderly. The minimum alveolar 

concentration of volatile anesthetics, for example, 

decreases about 25% in the elderly. 64,65 Similarly, the 

effect of midazolam is markedly age-dependent. 66 Combined 

pharmacokinetic and pharmacodynamic augmentation 

of anesthetic drug effects is thus likely to further 

impair thermoregulation in the elderly. 

Perioperative Heat Balance 

Elderly 

Figure 8-6. The effect of aging on thermoregulatory vasoconstriction 

during general anesthesia. The vasoconstriction threshold 

was significantly less in the elderly (33.9 ± 0.6°C, mean ± 

SD) than in younger patients (35.1 ± 0.3°C) (p < 0.01). Filled 

squares indicate the vasoconstriction threshold in each patient; 

the open circles show the mean and standard deviations in each 

group. (Reprinted with permission from Kurz et al. 60 Copyright 

© Lippincott Williams & Wilkins.) 

Both physical and physiologic factors contribute to 

perioperative hypothermia. Hypothermia would be 

unlikely without anesthetic-induced inhibition of thermoregulatory 

control because thermoregulatory defenses 

would normally be sufficient to prevent core-temperature 

perturbations even in a cool operating room environment. 

However, all anesthetics so far tested markedly increase 

the range of temperatures not triggering thermoregulatory 

defenses. 67 Within this interthreshold range, bodytemperature 

changes are determined by patients’ physical 

interactions with their immediate environments. Larger 

operations and colder rooms are thus associated with greater 

hypothermia. Once triggered, however (in patients 

becoming sufficiently hypothermic), thermoregulatory


vasoconstriction usually prevents further hypothermia— 

no matter how large and long the operation might be. 68 

Despite multiple modalities of heat loss, each described 

by different (and mostly nonlinear) equations, cutaneous 

heat loss in patients is a roughly linear function of the 

difference between skin and ambient temperatures. The 

physical laws and equations characterizing heat transfer 

are comparably valid for all animate and inanimate substances 

and, of course, apply equally in young and elderly 

patients. 

Mechanisms of Heat Transfer 

There are four types of heat transfer: radiation, convection, 

conduction, and evaporation. 69 Among these, radiation 

and convection are by far the most important in 

patients, together accounting for approximately 85% of 

the total loss. 70 Fractional losses via each route are, 

however, determined by numerous physical and physiologic 

factors including incision size, amount of administered 

(cold) intravenous fluid, and thermoregulatory 

vasoconstriction. 

Radiative losses are mediated by photons and do not 

depend on any intervening media. Losses via this mechanism 

are related to surface properties (emissivity) and 

the difference of the fourth power of exposed skin and 

wall temperature (in degrees Kelvin). Radiative losses 

are thus not directly influenced by ambient temperature, 

although ambient temperature indirectly influences both 

wall and skin temperature. Radiation probably contributes 

about 60% to total heat loss. 70,71 

Conduction is defined by direct transfer of heat energy 

between opposing surfaces. It is related only to the insulating 

properties of the surfaces (or of an intervening 

layer) and the temperature difference between the surfaces. 

It is unlikely that conduction contributes more than 

about 5% to overall heat loss in the perioperative period. 

The reason conduction contributes so little is that only a 

small fraction of the body surface area is in direct contact 

with another solid surface, and that surface is likely to be 

the operating table mattress which is a good insulator. 

Body heat required to warm cold intravenous fluids is 

probably best considered as a conductive loss. Loss via 

this route usually far exceeds conventional surface-tosurface 

heat transfer. 

Convection, which is often termed “facilitated conduction,” 

contributes considerably more than conduction, 

perhaps about 25% of the total loss. Normally there is 

essentially no conduction into air because still air is an 

excellent insulator and because a small layer of still air is 

maintained adjacent to the skin surface. When warm air 

next to the skin is moved away, however, it is replaced by 

cool air from the surrounding environment. This air is 

itself warmed by extracting heat from the skin, only in 

turn to be replaced by additional cool air. The equation 

describing convection is similar to that characterizing 

conduction, with addition of a factor for the square root 

of air speed. 

The heat of vaporization of water is among the highest 

of any substances: 0.58 kcal/g. Evaporation of large 

amounts of water thus absorbs enormous amounts of 

heat, which is why sweating is such an effective defense 

against heat stress. Except in infants though, insensible 

cutaneous water loss is negligible 72,73 and evaporative 

heat loss a tiny fraction of the total. Evaporative loss 

contributes to surgical hypothermia during skin preparation 

when the skin surface is scrubbed with water- or 

alcohol-based solution that is subsequently allowed to 

evaporate. Because skin preparation is usually restricted 

to a relatively small area and because evaporation is permitted 

for only a brief time, total heat loss is generally 

relatively small. 74 

Water is also vaporized and lost from the lungs when 

they are ventilated with dry, cold gases. Numerous clinical 

studies 75,76 and thermodynamic calculations 77 indicate that 

respiratory heat loss in adults is less than 10% of the total. 

Other studies identify effects of airway heating and 

humidification on core temperature that seem difficult to 

reconcile with thermodynamic calculations of heat transfer 

78–80 ; in some cases, these aberrant results are attributable 

to study design flaws. (In contrast, respiratory losses 

are somewhat more important in infants and children 

than in adults. 81,82 ) And finally, heat is lost when water 

evaporates from exposed surfaces within surgical incisions. 

The extent of this loss in humans remains unknown, 

although clinical experience suggests that it may be substantial 

because patients undergoing large operations 

become considerably more hypothermic than those having 

smaller procedures. Evaporative loss from within large 

incisions can may be up to half of the total heat loss in 

animals, 83 although this ratio is likely less in humans. 

Distribution of Heat Within the Body 

Intraoperative hypothermia develops with a characteristic 

three-phase pattern. The first is a rapid, 1–1.5°C 

decrease in core temperature occurring during the first 

hour after induction of anesthesia. 84 This is followed by a 

slower, nearly linear decrease in core temperature lasting 

2–3 hours. 85 And finally, core temperature reaches a 

plateau and does not decrease further. 68 Each portion of 

this curve has a different etiology. 

The initial, rapid decrease in core temperature after 

induction of general anesthesia results from a core-toperipheral 

redistribution of body heat. Redistribution 

results when anesthetic-induced inhibition of tonic thermoregulatory 

vasoconstriction allows heat to flow from 

the relatively warm core thermal compartment to cooler 

peripheral tissues. (Surprisingly, anesthetic-induced vasodilation 

increases cutaneous heat loss only slightly. 86 ) 

Although redistribution, by definition, does not alter 

body-heat content, it does markedly decrease core tem-


100 

Cutaneous 

Loss 80 

(kcal/h) 

60 

² Temp 

(°C) 

0 

-1 

-2 

-3 

-3 -2 -1 0 1 2 3 

Time (h) 

Metabolic 

Production 

(kcal/h) 

perature. Internal redistribution of body heat is a major 

cause of core hypothermia in most patients 84 (Figure 8-7). 

Redistribution is also a major cause of hypothermia 

during epidural anesthesia. 87 

The 2- to 3-hour-long linear decrease in core temperature 

results simply from heat loss exceeding heat production. 

75 In part, this results from an ≈30% reduction in 

metabolic heat production during general anesthesia. 84 

The slope of this curve thus depends on the difference 

between metabolic heat production and cutaneous and 

respiratory heat loss. Metabolic heat production is nearly 

constant during anesthesia and minimally influenced by 

anesthetic technique. 68,88 Respiratory heat (even with a 

nonrebreathing circuit and unwarmed, dry gases) loss is 

simply a linear function of metabolic rate. In contrast, 

70 

50 

30 

Mean Body 

Redistribution 

Core 

Figure 8-7. Changes in body-heat content and distribution of 

heat within the body during induction of general anesthesia. 

Heat loss and metabolic heat production were initially similar. 

Overall heat balance was thus near zero before induction of 

anesthesia (at elapsed time zero), but subsequently decreased 

≈31 kcal/h. The contributions of decreased overall heat balance 

and internal redistribution of body heat to the decrease in core 

temperature were separated by multiplying the change in 

overall heat balance by body weight and the specific heat of 

humans. The resulting change in mean body temperature 

(“mean body”) was subtracted from the change in core temperature 

(“core”), leaving the core hypothermia specifically 

resulting from redistribution (“redistribution”). After 1 hour of 

anesthesia, core temperature had decreased 1.6 ± 0.3°C, with 

redistribution contributing 81% to the decrease. During the 

subsequent 2 hours of anesthesia, core temperature decreased 

an additional 1.1 ± 0.3°C, with redistribution contributing only 

43%. Redistribution thus contributed 65% to the entire 2.8 ± 

0.5°C decrease in core temperature during the 3 hours of anesthesia. 

All results are shown as means ± SD. (Reprinted with 

permission from Matsukawa et al. 87 Copyright © Lippincott 

Williams & Wilkins.) 

cutaneous heat loss is determined largely by surface insulation 

and ambient temperature, and can therefore be 

altered by anesthetic management. 

After 3–4 hours of anesthesia, core temperature usually 

reaches a plateau and does not decrease further. This 

plateau is generally associated with arteriovenous shunt 

vasoconstriction. Vasoconstriction contributes to the 

plateau via two distinct mechanisms. The first is simply 

decreasing cutaneous heat loss. 89 The second is by constraining 

metabolic heat to the core thermal compartment, 

thus re-forming the normal core-to-peripheral 

temperature gradient that was obliterated by the initial 

redistribution hypothermia. Because heat loss may continue 

to exceed heat production during the core-temperature 

plateau, body-heat content often continues to 

decrease during this period—even though core temperature 

is constant 68 (Figure 8-8). For a detailed discussion 

Heat 

(kcal/h) 

Constraint 

(kcal) 

110 

90 

70 

50 

20 

10 

0 

-10 

Loss 

Production 

Core 

Mean Body 

-2 -1 0 1 2 3 

Elapsed Time (h) 

1.0 

0.5 

0.0 

-0.5 

-1.0 

²Temp 

(°C) 

Figure 8-8. Changes in body-heat content and distribution of 

heat within the body during the core-temperature plateau in 

anesthetized subjects. Vasoconstriction decreased cutaneous 

heat loss ≈25 kcal/h. However, heat loss exceeded heat production 

throughout the study. Consequently, mean body temperature, 

which decreased at a rate of ≈0.6°C/h before vasoconstriction, 

subsequently decreased at a rate of ≈0.2°C/h. Core temperature 

also decreased at a rate of ≈0.6°C before vasoconstriction, but 

remained virtually constant during the subsequent 3 hours. 

Because mean body temperature and body-heat content continued 

to decrease, constraint of metabolic heat to the core 

thermal compartment contributed to the core-temperature 

plateau. That is, vasoconstriction reestablished the normal coreto-peripheral 

temperature gradient by preventing metabolic 

heat (which is largely generated in the core) from escaping to 

peripheral tissues. Constrained heat is presented cumulatively, 

referenced to the onset of intense vasoconstriction defined as 

time zero; data are expressed as means ± SD. (Reprinted with 

permission from Kurz et al. 68 Copyright © Lippincott Williams 

& Wilkins.)


of perioperative heat balance, readers are referred to a 

recent review. 89 

Benefits of Mild Hypothermia 

Severe hypothermia (i.e., core temperatures near 28°C) 

has been known for decades to be protective against 

cerebral ischemia. 90 The basis for this protection was 

thought to be a decrease in the cerebral metabolic rate 

to about half of normal levels. 91 Although decreased metabolic 

rate surely contributes to hypothermic protection, 

there is increasing evidence that other mechanisms contribute 

as much or more. These include decreased release 

of excitatory amino acids (such as glutamate) and free 

fatty acids, 92,93 inhibition of calcium/calmodulindependent 

protein kinase II, 94 preservation of the blood– 

brain barrier, 95,96 reduced synthesis of nitric oxide 97 and 

ubiquitin. 98 

More than 100 animal studies in virtually every 

ischemic model demonstrate that just 1–3°C brain hypothermia 

provides substantial protection against ischemia. 

93,99–102 In each case, the protection seems to far 

exceed that resulting simply from reduced metabolic rate. 

There is also evidence that mild hypothermia also protects 

the spinal cord and liver against ischemia. 103 Furthermore, 

mild hypothermia seems protective during 

spinal cord ischemia 104 and is beneficial during hypoxia 

and shock. 

The benefits of mild hypothermia in ameliorating cerebral 

ischemia in humans have only been demonstrated 

after cardiac arrest. 105,106 Many neuroanesthesiologists 

nonetheless allow patients undergoing neurosurgery to 

become at least slightly hypothermic (i.e., ≈34°C) even 

though a major trial of hypothermia for intracranial 

aneurysm surgery failed to identify a benefit from therapeutic 

hypothermia. 107 The elderly are probably at greater 

risk of ischemia because of age-related vascular compromise 

while simultaneously being at greater risk of hypothermia-related 


Complications of Mild Hypothermia 

Although once considered the major complication associated 

with hypothermia, shivering is now known to be a 

relatively unimportant response that is easily treated 

using a variety of techniques. Furthermore, shivering is 

now less common than it was previously, perhaps because 

the use of opioids and propofol has increased. Postoperative 

shivering is especially uncommon in the elderly, and 

its intensity modest in any case. In contrast, recent years 

have seen publication of numerous studies documenting 

other major complications of hypothermia, some of which 

have been shown to alter patient outcome. 

Table 8-1. Mild intraoperative hypothermia increases the incidence 

of myocardial ischemia in elderly patients. 

Myocardial Ischemia and Arrhythmias 

Myocardial infarction remains one of the leading causes of 

perioperative mortality. The incidence of myocardial ischemia 

within 24 hours of surgery is tripled by ≈2°C core 

hypothermia in elderly patients undergoing vascular 

surgery 108 (Table 8–1). Surprisingly, ischemia is not related 

to postoperative shivering and the mechanism by which 

hypothermia triggers ischemia remains unknown. One 

factor may be significantly increased concentrations of circulating 

norepinephrine, with concomitant arterial hypertension. 

109 Perhaps related to increased catecholamine 

concentrations, the incidence of ventricular tachycardia is 

significantly increased by mild hypothermia. 110 Hypothermia 

thus increases the risk of morbid perioperative cardiac 

outcomes, but may be therapeutically useful for preserving 

myocardium once an infarction has occurred. 

Perioperative ischemia presumably requires underlying 

coronary artery disease, a predisposition that would 

be unusual in young patients but is typical in the elderly. 

It is thus the elderly that are most susceptible to perioperative 

ischemia and have most to benefit from maintenance 

of perioperative normothermia. 

Coagulopathy and Allogeneic 

Transfusion Requirement 

Normothermic Hypothermic p Value 

Initial postoperative core 35.9 ± 0.1 34.2 ± 0.1


Table 8-2. Mild intraoperative hypothermia increases blood 

loss during hip arthroplasty. 

allogeneic blood transfusion, as shown in some 115,116 but 

not all 117 studies (Table 8-2). 

Surgical Wound Infections and 

Duration of Hospitalization 

Normothermic Hypothermic p Value 

Final intraoperative core 36.6 ± 0.4 35.0 ± 0.5


threshold proportionately. A typical forced-air warmer 

increases mean skin temperature ≈3°C, thereby reducing 

the shivering threshold ≈0.6°C. If a shivering patient’s 

core temperature is within 0.6°C of the shivering threshold, 

cutaneous warming can thus increase the threshold 

sufficiently to stop shivering. 142 

Numerous drugs have also been proven effective for 

the treatment of postoperative shivering. The prototypical 

drug for this purpose is meperidine, which is far more 

effective than equianalgesic doses of other opioids. 136 For 

example, meperidine reduces the shivering threshold 

twice as much as equianalgesic concentrations of alfentanil. 

55 Furthermore, meperidine markedly reduces the 

gain of shivering, whereas alfentanil does not. 143 The 

special antishivering activity of meperidine was thought 

to result from its kappa-receptor activity, 144 but kappaopioids 

do not share disproportionately to reduce the 

shivering threshold. 145 Meperidine’s central anticholinergic 

activity also fails to explain this drug’s special antishivering 

activity. 145 Clonidine 146–148 and ketanserin 148 are 

also effective treatments for postoperative shivering, as 

are magnesium 149 and doxapram. 150–152 The efficacy of 

various antishivering treatments has been the subject 

of a recent meta-analysis. 153 For a detailed discussion of 

perioperative shivering, readers are referred to a recent 

review. 154 

Impaired Drug Metabolism 

The pharmacokinetic effects of mild hypothermia are 

poorly documented. Nonetheless, the duration of action 

of vecuronium, for example, is doubled by just 2°C core 

hypothermia. 155 Hypothermia prolongs the duration of 

action of atracurium less, ≈70% with 3°C reduction in 

core temperature, 156 perhaps because Hoffman elimination 

is relatively temperature-insensitive compared with 

enzymatic degradation. Antagonism of the neuromuscular 

block is not compromised with either drug. 155,156 And 

finally, steady-state plasma concentrations of propofol 

(during a constant-rate infusion) were increased ≈30% by 

3°C core hypothermia. 156 

Whether the pharmacokinetic effects of hypothermia 

are aggravated in the elderly has yet to be studied. 

However, drug metabolism in the elderly is often already 

compromised. It thus seems likely that hypothermiainduced 

prolongation of drug action, combined with 

age-related deficiencies in drug metabolism, may result 

in anesthetic drugs lasting unexpectedly long times in 

elderly, hypothermic patients. These pharmacokinetic 

effects will, in many cases, be confounded by pharmacodynamic 

ones. Although the magnitude of these effects 

has yet to be quantified, it would seem prudent to prevent 

hypothermia in the elderly and use minimum required 

drug doses to minimize drug-induced thermoregulatory 

impairment. 

Thermal Management 

The combination of anesthetic-induced inhibition of 

thermoregulatory defenses and cold exposure makes 

most unwarmed surgical patients hypothermic. Hypothermia 

produces complications in both young and 

elderly patients, and the severity of these complications 

seems worse in the elderly. Consequently, active thermal 

management is especially important in elderly patients. 

The physical principles of heat transfer, however, apply 

equally in all patients. Thus, the same warming techniques 

proven effective in the general surgical population will 

also be useful in the elderly. For a detailed discussion of 

patient warming techniques, readers are referred to a 

recent review. 157 

Ambient Temperature, Passive Insulation, 

and Cutaneous Warming 

Heat loss is a (very) roughly linear function of the 

difference between skin and environmental temper - 

ature. Typical intraoperative skin temperature is near 

34°C, which is ≈14°C above ambient temperature. 

Consequently, each 1°C increase in ambient temperature 

reduces heat loss ≈7%. Patients become hypothermic 

most rapidly during the initial 30 minutes after induc - 

tion of anesthesia, and this is the period when patients 

are most likely to be undraped. However, core hypo - 

thermia during this period results from internal redistribution 

of body heat, not primarily from heat loss to 

the environment. 84 Increasing ambient temperature 

for the brief period before and after induction of 

anesthesia therefore has little impact on patient 

temperature. 158 

A single layer of passive insulation decreases cutaneous 

heat loss ≈30%. However, the type of insulation 

makes little difference, with the efficacy of cotton blankets, 

plastic bags, cloth or paper surgical drapes, and 

“space blankets” all being comparable 159 (Figure 8-9). 

Patients who remain normothermic during surgery while 

covered only with a single layer of insulation require no 

additional thermal management. But surprisingly, increasing 

the number of layers makes relatively little difference, 

reducing loss by a total of only 50%; furthermore, warm 

and cold blankets provide similar insulation. 160 It is thus 

unlikely that progressive intraoperative hypothermia will 

be successfully treated simply by providing additional 

layers of insulation. Instead, active cutaneous warming 

will be required. 

Circulating-water mattresses remain a common meth - 

od of thermal management, despite evidence that these 

devices are nearly ineffective 161 and cause pressure-heat 

necrosis (“burns”). 162,163 The efficacy of circulating 

water is restricted because relatively little heat is lost


Heat 

Loss 

(W) 

100 

80 

60 

40 

20 

0 

-20 0 20 40 60 

Time (min) 

from patients’ backs into the foam insulation covering 

most operating tables. 75 Instead, most heat is lost by 

radiation and convection from patients’ anterior surfaces, 

loss that cannot be prevented by a water mattress. 

Forced-air warming is far more effective than circulating 

water, and is safer. 161 However, recently developed circulating 

water garments transfer even more heat than 

forced-air. 164–167 

Fluid Warming 

1 Unwarmed 

1 Warm 

3 Unwarmed 

3 Warm 

Figure 8-9. Mean cutaneous heat loss during the control period 

(−20 to 0 elapsed minutes) and when the volunteers were 

covered with a single warmed or unwarmed blanket (“1 Warm” 

or “1 Unwarmed”) or three warmed or unwarmed blankets (“3 

Warm” or “3 Unwarmed”). There was no clinically important 

difference between warmed and unwarmed blankets. Increasing 

the number of layers from one to three slightly decreased heat 

loss, but the decrease was unlikely to be sufficient to prevent 

further intraoperative hypothermia. (Reprinted with permission 

from Sessler and Schroeder. 160 Copyright © Lippincott 

Williams & Wilkins.) 

It is not possible to warm patients by warming intravenous 

fluids. Fluid warming alone is thus unlikely to maintain 

perioperative normothermia because it will not 

compensate for redistribution hypothermia, much less 

heat loss from the skin and from within surgical incisions. 

However, it is certainly possible to cool patients by 

administering fluids much below body temperature. The 

amount of cooling is easy to calculate: in a typically sized 

adult, 1 L of fluid at ambient temperature decreases mean 

body temperature 0.25°C. One unit of blood at refrigerator 

temperatures causes a similar decrease in body temperature. 

168 Fluid warming should thus be restricted to 

patients who are already being warmed with some effective 

surface technique such as forced-air and in whom 

large amounts of fluid (>1 L/h) is being given. Cooling of 

fluid in tubing between warmers and patients is clinically 

unimportant except in the occasional neonate who 

requires large amounts of fluid. 169 

Prewarming 

Internal core-to-peripheral redistribution of body heat is 

among the most important causes of hypothermia in most 

patients. 84 Because the internal flow of heat is large, it has 

proven difficult to treat with surface warming. 75 An alternative 

is to prevent redistribution. One method of minimizing 

redistribution is to produce drug-induced 

peripheral vasodilation well before induction of anesthesia. 

Because central thermoregulatory control remains 

normal before induction of anesthesia, behavioral compensation 

protects core temperature. The result is a constant 

core temperature, accompanied by increased 

peripheral tissue temperature. Because heat flows only 

down a temperature gradient, induction of anesthesia is 

associated with little redistribution because the core-toperipheral 

temperature gradient is small. This concept 

has been demonstrated using nifedipine, 170 phenylephrine, 

171 and ketamine, 172 all of which support the importance 

of redistribution hypothermia. 

An alternative method of minimizing redistribution 

hypothermia is to actively warm peripheral tissues before 

induction of anesthesia. Even just 30 minutes of forcedair 

“prewarming” increases peripheral tissue heat content 

≈69 kcal, and 1 hour of prewarming transfers nearly 

136 kcal. 173 Either amount should be sufficient to minimize 

redistribution. The benefits of prewarming have 

been demonstrated in both volunteers 174 and surgical 

patients 138,175,176 (Figure 8-10). Assuming intraoperative 

forced-air warming is anticipated, there is no additional 

patient cost to prewarming because the same disposable 

cover can be used before and during surgery. 

Core 

Temp 

(°C) 

38 

37 

36 

35 

Before induction 

Prewarmed 

Control 

Surgery 

0 30 

60 

30 

60 

Time (min) 

Figure 8-10. Core temperatures during the preinduction period 

did not change significantly in the control group (open circles) 

or patients prewarmed with forced-air (solid circles). After 

induction of anesthesia, core temperature in the control group 

decreased at nearly twice the rate of that in the prewarmed 

patients. After 1 hour of anesthesia, core temperatures were 

0.6°C greater in the prewarmed patients than in the control 

group. Results presented as means ± SEM. (Reprinted with 

permission from Camus et al. 175 Copyright © 1995 Elsevier.)


Summary 

Normal thermoregulatory control is impaired in the 

elderly, as is thermoregulation during general anesthesia. 

A major factor influencing intraoperative core-temperature 

changes is internal core-to-peripheral redistribution 

of body heat that results from anesthetic-induced inhibition 

of thermoregulatory control. Many of the identified 

complications of mild perioperative hypothermia are 

likely to be more common or more severe in the elderly. 

Similarly, the core-temperature plateau results from 

reemergence of thermoregulatory control, which may be 

impaired in the elderly. In contrast, the physical factors 

influencing heat loss do not differ much in young and 

elderly patients and thermal management strategies are 

similar in young and elderly patients. 

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409–414.

9 

Postoperative Central Nervous 

System Dysfunction 

Deborah J. Culley, Terri G. Monk, and Gregory Crosby 

This chapter reviews common forms and causes of central 

nervous system (CNS) morbidity in the elderly after 

routine surgery and anesthesia. These include, in order of 

descending prevalence, delirium, prolonged postoperative 

cognitive dysfunction (POCD), and perioperative 

stroke. Although these same conditions are also common 

during and after cardiac surgery, we will not deal with 

those situations here because the contributing factors are 

somewhat different and cognitive morbidity after cardiac 

surgery is a topic unto itself. We begin with a brief overview 

of how the brain changes during healthy and pathologic 

aging because aging of the CNS is a prominent 

factor in determining susceptibility to cognitive and 

neurologic morbidity after surgery and anesthesia. 

Central Nervous System Changes 

of Aging 

Normal Aging 

Healthy aging is associated with significant changes in the 

morphology, physiology, and biochemistry of the brain 

(Table 9-1). Brain size and weight inevitably decline with 

age. These changes begin in young adulthood but accelerate 

after age 60, resulting in a 15% decrease in the ratio 

of brain/skull volume in nonarians whereas ventricular 

volume triples. 1 There are also age-associated decreases 

in neuronal size, loss of complexity of the dendritic tree, 

and a reduced number of synapses. 2 In contrast, the physiology 

of the cerebral circulation appears to be remarkably 

normal in the healthy aged. Global cerebral blood 

flow (CBF) is decreased 10%–20% with advanced age, 

not because of “hardening of the arteries,” but rather 

because there is less brain mass to perfuse. 3 Therefore, 

the lower CBF seems to be a consequence of reduced 

metabolic demand, not a cause of it. Hence, although 

CBF and cerebral metabolic rate decline progressively 

with age, they remain tightly coupled. 4 Similarly, cerebral 

autoregulation and responsiveness to carbon dioxide/ 

hypoxemia are reasonably well preserved. 5 Neurotransmitters 

do not fare as well. The range of neurotransmitter 

systems affected by aging is extensive; dopamine uptake 

sites, transporters, and levels are reduced, as are cortical 

serotonergic, α 2 and β 1 , and +-aminobutyric acid binding 

sites, among others. 6 Markers of central cholinergic activity 

also decrease, which is a finding of particular significance 

because failure of cholinergic neurotransmission 

is a central feature of Alzheimer’s disease. 7 Moreover, 

beginning at age 40 and continuing into late old age, there 

is reduced expression in the human brain of genes 

involved in learning and memory and neuronal survival. 8 

Nevertheless, not all the news is bad. Dendritic complexity 

and growth can increase in cognitively normal octogenarians, 

suggesting that neuronal mechanisms involved 

in neural plasticity crucial for learning and memory are 

retained in the aged but healthy CNS. 2 Furthermore, consistent 

with this concept but counter to what many of us 

learned in medical school, the adult brain makes new 

neurons and this capability is preserved, albeit at reduced 

levels, into old age. 9,10 Thus, although it loses some of its 

capacity for plasticity, the healthy brain continues to 

adapt and mold to its environment into old age. 

The real issue, however, is the degree to which these 

changes in brain morphology, physiology, and biochemistry 

affect brain function. Intellectual decline does not 

invariably accompany aging but it is common and there 

are some consistently observed changes. 11 Both reaction 

time and cognitive processing slow with age such that 

there is an inverse relationship between age and speed of 

motor performance, which becomes exaggerated with 

increasing task complexity. 12 In addition, “fluid” intelligence 

(i.e., the ability to dynamically evaluate, accommodate, 

and respond to novel environmental events) 

deteriorates. In contrast, vocabulary, math, and comprehension 

skills are reasonably well maintained, as is “crystallized” 

intelligence (i.e., accumulated knowledge), at 

least into the seventh decade of life. Not surprisingly, 

123

124 D.J. Culley, T.G. Monk, and G. Crosby 

Table 9-1. Neurobiologic changes of aging. 

• Decreased brain weight/volume 

Cell shrinkage and loss 

• Decreased neurotransmitter system function 

Acetylcholine, 5-hydroxytryptamine, dopamine, serotonin, 

γ aminobutyric acid, adrenergic, glutamate 

• Decreased neuronal gene expression 

• Alzheimer-type changes 

Amyloid plaques and neurofibrillary tangles 

short-term memory dysfunction is reported by 30% to 

50% of elders. 13 Much of this impairment is in working 

memory—which requires not only retention but also 

manipulation of information. 14 Thus, the ability to store 

recently processed information while simultaneously 

acquiring new data is compromised in the otherwise 

healthy aged brain. 

Pathologic Aging 

Unfortunately, not all brain aging is healthy or normal. 

With advanced age, the prevalence of dementia increases 

rapidly from 10% to 15% in persons aged 65 to nearly 

50% at age 85. 11 Dementia is always a disease process and 

is characterized by a chronic, progressive decline in cognitive 

performance that interferes with all cognitive domains. 

Although pathologic brain aging can be caused by a 

number of systemic and neurologic disorders (e.g., stroke, 

Parkinson’s disease), Alzheimer’s disease is the most 

common. 15 The histopathologic hallmarks of Alzheimer’s 

disease—neurofibrillary tangles, extracellular amyloid 

deposits, and neuritic plaques—are also seen in normal 

aging, albeit to a markedly lesser degree. 6,16 In the 

Alzheimer’s brain, loss of brain mass occurs at 2.5 times 

the rate observed in healthy aging and neurotransmitter 

hypofunction is likewise more pronounced. 17 Accordingly, 

Alzheimer’s dementia should be considered a major CNS 

and systemic illness; consistent with this perspective, the 

average lifespan from diagnosis to death is 3–4 years. 18 

From the perspective of CNS aging, therefore, the “take 

home” message is that the elderly are heterogeneous. There 

is no such thing as a “typical” older person and chronologic 

age is often not a predictor of cognitive capability. This 

makes studies of this population difficult and means that 

any attempt to evaluate changes in cognition should include 

evaluation of baseline cognitive performance. 

Postoperative Central Nervous 

System Dysfunction 

Delirium 

Delirium is the most common form of cognitive impairment 

in hospitalized patients. It is an acute transient 

organic brain syndrome characterized by disturbances of 

consciousness and cognition that develop over a relatively 

short period of time (hours to days) and fluctuate 

over the course of the day. Delirium can nonetheless be 

subtle enough that it is frequently underdiagnosed by 

health care providers. The diagnosis is based on Diagnostic 

and Statistical Manual-IV diagnostic criteria, which 

include disturbance of consciousness with altered awareness 

of the environment; reduced ability to focus, sustain 

or shift attention; and a change in cognition or development 

of perceptual disturbances that are not better 

accounted for by a preexisting, established, or evolving 

dementia. 19 Delirium is generally divided into three types: 

hyperactive, hypoactive, and mixed. Agitation, irritability, 

restlessness, and aggression characterize the hyperactive 

form whereas hypoactive delirium is typified by somnolence, 

latency in reaction and response to verbal stimulation, 

and psychomotor slowing. As noted above, the 

diagnosis can be difficult for nonpsychiatrists to make, 

meaning many cases go undetected. To aid medical personnel 

without psychiatric training in this regard, a simple, 

standardized assessment tool has been developed. That 

tool, the Confusion Assessment Method (CAM), is the 

most widely used instrument for diagnosing delirium 

because it has the benefits of ease, speed, reliability, and 

validity (Table 9-2). 20 A variant of the CAM, the CAM- 

ICU, has been validated for delirium assessment of intubated, 

nonverbal patients in an intensive care unit. 21 

Delirium is common in hospitalized elderly patients 

regardless of whether the hospitalization is for medical 

Table 9-2. Confusion assessment method.* 

1. Acute onset and fluctuating course 

Is there evidence of an acute change in mental status from the 

patient’s baseline? 

AND 

Did this behavior tend to come and go or increase and decrease in 

severity during the past day? 

2. Inattention 

Does the patient have difficulty focusing attention (i.e., easily 

distractible or having difficulty keeping track of what is being 

said)? 

3. Disorganized thinking 

Is the patient’s speech disorganized or incoherent (rambling or 

irrelevant conversations, unclear or illogical flow of ideas, or 

unpredictable switching from subject to subject)? 

4. Altered level of consciousness 

Is the patient’s level of consciousness alert (normal), vigilant 

(hyperalert), lethargic (drowsy, easily aroused), stuporous (difficult 

to arouse), or comatose (unarousable)? 

Source: Adapted with permission from Inouye et al. 20 

*The diagnosis of delirium requires features 1 and 2 plus either 3 

or 4.

9. Postoperative Central Nervous System Dysfunction 125 

or surgical reasons. It occurs as a comorbidity in 40% of 

elderly, hospitalized medical patients. 22 Postoperative 

delirium is also quite common in surgical patients but the 

reported incidence varies from 9% to 74%, probably 

reflecting differences in the study population, diagnostic 

criteria, and the methods of surveillance. 23–27 Delirium 

usually presents during postoperative days 1–4, often 

following a lucid interval. Postoperative delirium has traditionally 

been considered a temporary or transient phenomenon 

but it can last for days to weeks after the 

surgical procedure, extend hospital stay, increase costs, 

and may even be a marker for subsequent cognitive 

deterioration and predictor of higher mortality. 

Conditions contributing to delirium can be divided into 

nonmodifiable and modifiable factors and there are clinical 

prediction algorithms that take these into account. 28 

Among the former, age greater than 70 years, preexisting 

cognitive impairment, a history of delirium, depression, 

multiple comorbidities, and poor functional status are 

positive predictors for the development of postoperative 

delirium. 25,28–31 Also included in this category is the type 

of surgical procedure; organ transplantation, orthopedic, 

cardiac, thoracic, major vascular, and emergency surgery 

carry the greatest risk. 23 The duration of surgery, however, 

does not seem to be a risk factor. 

The modifiable factors are more interesting because of 

the potential to intervene. Among the more obvious of 

these is the type of anesthesia but, surprisingly, the anesthetic 

technique does not seem to affect delirium risk. 23,27 

Specifically, there is no benefit of regional anesthesia. 

However, certain anesthetic adjuvants such as benzodiazepines 

and anticholinergic drugs may increase the risk 

of postoperative delirium perhaps, at least in the latter 

case, by reducing further cholinergic neurotransmission 

in the already compromised elderly brain. 26,32,33 Thus, 

regardless of whether an elderly patient requires regional 

or general anesthesia, one should choose anesthetic adjuvants 

carefully and consider using an anticholinergic 

agent that does not readily cross the blood–brain barrier 

(e.g., glycopyrrolate) if such an agent is needed. The roles 

of perfusion pressure and oxygen delivery have also been 

investigated. Intraoperative hypotension may contribute 

to the development of postoperative delirium but not all 

studies agree. 23,34,35 For example, in elderly patients having 

knee surgery under epidural anesthesia, those randomly 

assigned to a mean arterial blood pressure (MAP) of 

45–55 mm Hg were no more or less likely to develop postoperative 

delirium than those whose MAP was maintained 

between 55–70 mm Hg. 35 In a similar vein, there is 

evidence that low perioperative hematocrit is associated 

with development of postoperative delirium. 23 However, 

no studies have investigated whether blood transfusion 

decreases the incidence. 23 Hypoxia may in subtle ways 

also be a factor. That is, delirium may be a delayed manifestation 

of hypoxia, with nocturnal oxygen desaturation 

by pulse oximetry on postoperative day 2 correlating with 

altered mental status on day 3. 36,37 Whether enhancing 

oxygen delivery with supplemental oxygen or blood 

transfusion reduces the incidence of delirium is another 

matter but hypoxemia is best avoided or treated. 

Pain can be an important contributor to delirium in the 

postoperative period. Elderly, cognitively intact patients 

with undertreated postoperative pain are nine times 

more likely to develop delirium than those whose pain is 

adequately treated. 38 In fact, the specifics of pain treatment 

are less important so long as the pain is 

controlled. 26,39 Thus, in a study comparing intravenous 

fentanyl with epidural analgesia for management of postoperative 

pain after bilateral total knee replacement 

surgery, the incidence of postoperative delirium was 

similar. 26 Indeed, in the postoperative period, low but not 

high narcotic utilization is a factor in the development of 

delirium. 26,32,38 This is relevant because studies show that 

cognitively impaired patients receive only 30%–50% as 

much narcotic as cognitively intact patients. This suggests 

that suboptimal pain management in demented and delirious 

patients may contribute further to their cognitive 

deterioration. 38,40 Meperidine is an exception to this rule 

and should probably be avoided in geriatric patients 

because it has been associated with the development of 

postoperative delirium, presumably attributable either to 

accumulation of toxic metabolites or its anticholinergic 

activity. 32,38 

Perhaps the most important way to mitigate the risk of 

postoperative delirium is with attentive, careful medical 

management. This is because numerous medical complications 

including hypoxemia, sepsis, electrolyte and 

metabolic disturbances, cardiopulmonary events such as 

myocardial ischemia or pneumonia, and inadequate 

nutrition can trigger delirium. 37 As such, one should expeditiously 

identify and treat these complications. Medications 

can be another problem. More than six medications 

or three new inpatient medications have been shown to 

be precipitating factors for delirium, as have drugs with 

anticholinergic properties that cross the blood–brain 

barrier (i.e., atropine, scopolamine). 33,41,42 Hence, eliminating 

unnecessary or potentially toxic medications may 

be helpful. Another potentially beneficial intervention is 

ambulation. This is best studied in orthopedic surgical 

patients but, given evidence that even minimal exercise 

preserves cognition, is likely to be worthwhile for any 

bedridden hospitalized elderly person. 43–45 Accordingly, 

early ambulation may be an important and simple way to 

prevent postoperative delirium. 

Delirium and Adverse Outcomes 

Postoperative delirium is associated with significant morbidity 

and mortality. 25,28,31,46 The cost of care increases 

because of longer hospitalization and, reflecting a decline


in activities of daily living, the patient must often be 

placed in a long-term care facility. Postoperative delirium 

may also be a predictor of subsequent dementia; in one 

small study of cognitively intact elderly patients, nearly 

70% of those who developed postoperative delirium were 

demented 5 years later whereas only 20% of those who 

did not experience delirium became demented. 34 Moreover, 

5-year mortality was 70% in the patients that had 

postoperative delirium whereas it was 35% in those who 

remained cognitively intact postoperatively. 34 Although it 

is unclear whether delirium triggers a dementing process 

or is simply a marker for preclinical dementia, it is apparent 

that postoperative delirium has important short- and 

long-term implications for the elderly patient. 

Treatment/Prevention 

Effective prevention and treatment of delirium is hampered 

by the fact that some risk factors (e.g., advanced 

age, preexisting cognitive impairment, type of surgical 

procedure) are not modifiable and by poor understanding 

of how the aged brain responds to the rigors of surgery, 

anesthesia, and hospitalization. Thus, the mainstay of 

treatment remains prompt diagnosis and treatment of the 

underlying medical conditions and/or discontinuation of 

unnecessary or toxic medications. Once this is done, 

attention should be directed toward creating a calm, quiet 

environment populated with the familiar faces of the 

patient’s family and friends. Although scientific rationale 

for this recommendation is lacking, there is a growing 

body of evidence that a broad spectrum of preventative 

interventions may be modestly effective. Specifically, 

pre- and postoperative geriatric consultation decreases 

the incidence of delirium by as much as 30%, offering 

hope that relatively simple measures may be useful in 

decreasing the incidence and/or severity of postoperative 

delirium. 46,47 That said, there is no evidence that such 

programs improve the outcome of patients who still 

become delirious. 

The role of medications in treating perioperative delirium 

is a controversial topic, with some experts arguing 

that pharmacologic intervention prolongs the delirious 

phase. Low-dose haloperidol is still considered the standard 

for treatment of hyperactive delirium but evidence 

for its efficacy is not as strong as one might like and atypical 

antipsychotics such as risperidone and olanzapine, 

although gaining in popularity, lack evidence from welldesigned 

clinical studies to demonstrate superiority. 48,49 

Before embarking on a course of pharmacotherapy, 

however, one should be aware of the unique pharmacology 

of psychoactive agents in the elderly. First, as mentioned 

previously, three or more new inpatient medi - 

cations is an independent precipitating factor for delirium 

in hospitalized elderly persons. 42 This suggests that sometimes 

discontinuing medications is the best course of 

action. Second, certain frequently used sedatives can 

actually increase delirium risk. Diphenhydramine, often 

prescribed for sleep or sedation in elderly hospitalized 

patients, nearly doubles the risk of delirium. 50 Meperidine, 

but not other opiates, nearly triples the risk. 32 Third, 

given the paucity of sound clinical evidence to guide the 

choice of pharmacologic agents for treating delirium in 

elderly postoperative patients and their greater susceptibility 

to psychoactive medications, some drugs are used 

inappropriately. Even atypical antipsychotics such as 

haloperidol, the mainstay of pharmacologic treatment of 

agitated delirium, are often given in dosages higher than 

those recommended for elderly patients and have a high 

incidence of extrapyramidal and anticholinergic side 

effects. 51 Lorazepam and other benzodiazepines, used for 

sedation or anxiolysis, have themselves been implicated 

in the development of delirium and can produce a paradoxic 

reaction of agitation and disinhibition. 51 Thus, pharmacotherapy 

has a place in the management in agitated 

delirium in the elderly postsurgical patient but one should 

resort to it only after seeking and treating remediable 

medical or pharmacologic causes of delirium and abiding 

by the geriatrician’s adage to “start low and go slow.” 

Postoperative Cognitive Dysfunction 

It has been suspected for more than 50 years that general 

anesthesia and surgery lead to cognitive dysfunction in 

the elderly. 52 Interest in the topic is increasing, driven 

partially by patients (or their family members) who often 

complain that the ability to think and concentrate is 

impaired for months after surgery and anesthesia. 53 

Recent work justifies concern but we are still far from 

sure about the etiology of the problem. 54,55 What is clear 

is that the structural and functional changes associated 

with normal aging render the elderly more vulnerable to 

the development of mild POCD. 56 

Since Bedford, in a retrospective chart review, first 

reported in 1955 that general anesthesia produces longterm 

cognitive dysfunction in the elderly, there have been 

numerous subsequent studies of the problem. 52–54 Most 

are flawed or inconclusive because they lack a control 

group, did not perform formal neuropsychometric testing, 

or were small and retrospective. That changed in 1998 

with publication of a large, prospective, controlled international 

study. The International Study of Postoperative 

Cognitive Dysfunction (ISPOCD1) included 1218 patients 

aged 60 years or older from 13 hospitals in eight European 

countries and the United States who underwent a 

variety of noncardiac, nonneurosurgical procedures plus 

176 United Kingdom and 145 nonhospitalized, community 

controls. 57 Cognitive performance was assessed with 

a battery of neuropsychometric tests completed before 

surgery as well as 1 week and approximately 3 months 

after surgery. Using this design, nearly a quarter of elderly


Table 9-3. Incidence of cognitive dysfunction after surgery and 

general anesthesia in the elderly. 

Control Surgery and anesthesia 

(321) (1218) 

1 week postoperatively 3.4% 25.8%* 

3 months postoperatively 2.8% 9.9%† 

Source: Moller et al. 57 

*p < 0.01. 

†p < 0.0001. 

patients had cognitive deficits the first week after surgery 

and general anesthesia and, more remarkably, almost 

10% were still impaired 3 months postoperatively (Table 

9-3). 57 In contrast, only about 3% of the age-matched 

community controls were impaired. 57 A subsequent study 

of middle-aged patients (40–60 years) using similar 

methods and criteria for impairment found a slightly 

lower incidence of cognitive impairment during the first 

postoperative week (19%) but no residual deficit by 

objective testing at 3 months postoperatively (Table 

9-4). 58 However, 29% of the patients felt subjectively 

impaired at 3 months, associated in many cases with 

depression. Together, these studies convincingly demonstrate 

that middle-aged and elderly patients experience 

short-term cognitive dysfunction after surgery 

and general anesthesia but that, judging by objective criteria, 

the elderly are uniquely vulnerable to persistent 

cognitive impairment. Further substantiating the agedependence 

of POCD is the fact that incidence is highest 

among patients 75 years of age or older, with nearly 15% 

impaired at 3 months postoperatively. 57 

The natural history of POCD in the elderly has not 

been thoroughly studied but there is some encouraging 

news. The only follow-up study reevaluated 336 older 

adults and 47 controls from the English and Danish sites 

of the original ISPOCD1 study and found that 35 of the 

336 tested (10.4%) still had cognitive dysfunction 1–2 

years later. 59 However, among the 47 controls who had 

not been hospitalized, 10.6% (n = 5) also met criteria for 

POCD—an incidence similar to that of the surgery 

patients. Thus, in elderly persons, cognitive changes occur 

over time even when surgery is not performed. This 

emphasizes the importance of a control group in studies 

Table 9-4. Incidence of cognitive dysfunction after surgery and 

general anesthesia in middle-aged patients. 

Control Surgery and anesthesia 

(183) (463) 

1 week postoperatively 4.0% 19.2%* 

3 months postoperatively 4.1% 6.2% 

Source: Johnson et al. 58 

*p < 0.001. 

Table 9-5. Potential risk factors for postoperative cognitive 

dysfunction. 

• Patient 

Age 

Educational level 

Mental health status 

Preoperative alcohol, benzodiazepine use 

Comorbidities 

• Physiology 

Inadequate oxygen delivery (hypoxia, hypotension, hypocarbia, 

anemia) 

• Surgery 

Inpatient versus outpatient 

Duration 

Type (cardiac/thoracic, orthopedic, major abdominal) 

Stress 

Immobility 

• Anesthesia 

investigating POCD and suggests that POCD is a reversible 

condition in the majority of elderly patients undergoing 

general surgery. That said, the small size of the study 

prevents firm conclusions and other considerations give 

reason for concern. First, of the 318 surgery patients who 

completed cognitive testing at each of the three time 

points postoperatively (discharge, 3 months, 1–2 years), 

three met criteria for POCD at every one. The likelihood 

that the same subject would meet criteria for POCD 

at all three times by chance is remote (1:64,000 or 

0.0002%), making it probable that POCD is permanent 

in some persons. Second, 2-year follow-up may not be 

sufficient. In a prospective but uncontrolled study of 

cardiac surgery patients, for instance, the incidence of 

cognitive impairment decreased from 53% at hospital 

discharge to 24% at 6 months postoperatively but 

increased again to 42% by 5 years postoperatively. 60 Such 

longer-term follow-up of noncardiac patients with POCD 

is not yet available. 

The search for causes of POCD and ways it might be 

prevented or treated is under way but is complicated by 

the fact that it is likely to be a complicated entity with 

numerous contributing factors. For the purposes of this 

review, we will group them into patient, surgical, physiologic, 

and anesthetic conditions (Table 9-5). 

Patient Factors 

Advanced age is the most consistent and least controversial 

risk factor for POCD in both cardiac and noncardiac 

surgery. 55,57,58,61 The close association between age and 

POCD implies that the normal and pathologic changes 

of brain aging contribute in an important way. The association 

between age and POCD is most clearly demonstrated 

by the ISPOCD investigations discussed above. 

The key difference between elderly and middle-aged 

patients in this regard is that objective impairment


persists for at least 3 months in the former but not the 

latter. 57,58 Thus, POCD may be problematic for many 

adult patients early during recuperation, but it is primarily 

older patients who experience subtle cognitive dysfunction 

for a longer period of time. 

Other putative patient-related risk factors include 

years of education, mental health, comorbid diseases, 

gender, and genetics. A low level of education predicts 

cognitive decline at 3 months after noncardiac surgery 

and, conversely, education seems to protect against cognitive 

decline after surgery involving cardiopulmonary 

bypass. 57,61 The reasons for this protective effect of formal 

education are unknown, but possibilities include greater 

“cognitive reserve,” better test-taking abilities in the 

better educated, and known interrelationships between 

educational advancement, social support, and quality of 

medical care. The roles of preexisting mental health status 

and comorbid conditions in POCD are difficult to ascertain. 

In the ISPOCD studies, there was no association 

between functional status, as defined by American Society 

of Anesthesiologists physical status classification, and the 

development of POCD in elderly patients whereas it was 

a predictor of early POCD in middle-aged patients. 57,58 

Similarly, whereas presurgical depression is associated 

with POCD in middle-aged patients, its contribution to 

POCD in the elderly has not been systematically evaluated. 

58 The main reason data on these subjects are limited 

is that most studies of POCD exclude individuals who 

have major depression or anxiety disorders, multiple systemic 

disease, severe systemic illness, or perform below a 

certain cognitive level on screening measures. 57,58,62 

Indeed, even when comorbidity is entered into the final 

multivariate analyses as a possible predictor, the indices 

and score range (e.g., Charlson Comorbidity Index) may 

be too insensitive to serve as a viable predictor of POCD. 63 

The role of gender in POCD is also unresolved because 

the ISPOCD1 study found no differences in the incidence 

of POCD by gender 57 but evidence from cardiac surgery 

hints that it could be a factor under some circumstances. 

Thus, although the frequency of cognitive impairment 

after cardiac surgery is statistically equivalent between 

genders, women decline on tasks believed to depend 

more on the frontal lobes and right hemisphere and have 

worse functional outcome and decreased quality of life 

than men. 64,65 Likewise, women have a higher risk for 

perioperative neurologic deficits than men after cardiac 

surgery. 66 Finally, largely unexplored are genetic factors. 

The only gene investigated thus far is the apolipoprotein 

ε4 (apoE4) allele, a gene that has been associated with 

greater vulnerability of the brain to various insults such 

as Alzheimer’s disease and head trauma. 67–69 Although no 

link with POCD risk was identified, more studies of this 

nature should be forthcoming because it is likely that 

certain patients are predisposed to POCD by virtue of 

their unique genetic profile. 

Preoperative drug usage—particularly for alcohol and 

benzodiazepines—is another potentially important risk 

factor for POCD. 58 Here again, the data are mixed. In the 

elderly undergoing a major surgical procedure, there is 

no association between moderate preoperative alcohol 

consumption and susceptibility to POCD but, curiously, 

lack of preoperative alcohol consumption predicts early 

POCD in middle-aged patients and aged patients undergoing 

minor surgical procedures. 57,58,70 With respect to 

benzodiazepines, there was a favorable association 

between preoperative usage and protection against 

POCD 3 months postoperatively, 57 but this is likely attributable 

to a change in use of benzodiazepines postoperatively. 

Nearly half of the patients using benzodiazepines 

preoperatively in that study were no longer taking them 

3 months postoperatively; among these, none met POCD 

criteria. In contrast, those patients still taking benzodiazepines 

3 months postoperatively had an incidence of 

POCD similar to the study population as a whole. The 

most reasonable interpretation of these data is that discontinuation 

of benzodiazepines postoperatively, not 

preoperative usage, improves cognitive performance. The 

fact that there is also no correlation between blood concentration 

of benzodiazepines and POCD 1 week postoperatively 

71 supports this conclusion. 

Surgery/Illness Factors 

Not surprisingly, the type, duration, and complexity of 

surgery seem to contribute to the risk of POCD. Thus, 

elderly patients undergoing minor surgical procedures 

have a lower incidence of both early and late POCD than 

those undergoing major procedures 57,70 and, even when 

controlling for the nature and duration of the surgical 

procedure, the incidence of early POCD is lowest in 

patients cared for on an outpatient versus inpatient 

basis. 70 This suggests that for minor surgical procedures, 

an outpatient setting may benefit the elderly and that 

postoperative hospitalization contributes importantly to 

development of POCD. Similarly, the duration of the procedure 

(and hence the anesthetic) has repeatedly been 

associated with development of POCD, such that risk is 

greater with longer procedures. 57,58 

The type of operation also matters, at least in middleaged 

persons. In elderly patients, the incidence of POCD 

at either 1 week or 3 months postoperatively does not 

correlate with the type of surgical procedure but in 

middle-aged adults the incidence at 1 week is highest 

after upper abdominal (33%) and orthopedic surgery 

(20%). 57,58 The reasons for these associations are not 

known but proposed mechanisms include endotoxin 

release and cerebral emboli. Interleukin-6 and -8 increase 

during major abdominal surgery, perhaps because of 

bowel hypoperfusion or manipulation. 72 Interleukins, 

which act on the CNS, are peptide mediators of the


systemic inflammatory cascade and are stimulated by 

endotoxin, a component of the gram-negative bacterial 

cell wall. 73 Although no studies have directly investigated 

the role of interleukins in POCD in general surgical 

patients, evidence from cardiac surgery shows that a low 

preoperative level of an antiendotoxin core antibody is 

associated with POCD. 73 This suggests that a reduced 

immune response to endotoxin may contribute to development 

of POCD. In the case of POCD after orthopedic 

surgery, indirect evidence suggests cerebral microemboli 

could be a culprit. Fatty emboli are common during 

certain orthopedic procedures (e.g., total knee replacement) 

and many reach the brain via paradoxical embolization 

through a patent foramen ovale or the pulmonary 

vasculature. 74,75 Although a plausible mechanism for cognitive 

decline in these patients, the hypothesis has not 

yet been systematically tested. 

Surgery, and the associated illness requiring it, may also 

contribute to POCD indirectly. Surgery involves stress, 

loss of mobility, and oftentimes social isolation, each of 

which has been associated with cognitive deterioration in 

the elderly. For instance, chronically elevated plasma cortisol 

is associated with hippocampal atrophy and impaired 

cognitive performance. 76 Similarly, given substantial evidence 

that modest physical exercise and social involvement 

improves cognitive performance in both the healthy 

and cognitively impaired elderly, 43,44,77 it is easy to see how 

a stressed, relatively immobile, socially isolated elderly 

surgical patient may suffer cognitive consequences. 

Physiologic Factors 

Perhaps the oldest and most intuitive hypothesis is that 

perioperative hypoxia or hypotension has a role in the 

development of POCD. Unfortunately, POCD does not 

seem to be that simple. In particular, in the large international 

study, there was no correlation between perioperative 

hypotension (MAP 2 minutes) and POCD in the elderly. 57 

Moreover, another study of elderly patients having 

knee arthroplasty under epidural anesthesia found no 

difference in cognitive outcome between those maintained 

at a MAP of 45–55 versus 55–70 mm Hg. 35 This is 

not to say that perioperative hypoxia or hypotension 

cannot cause significant CNS impairment—because we 

know it can—but rather that variations of the magnitude 

and duration that characterize routine, uncomplicated 

anesthesia do not seem to be responsible for the subtle 

but persistent perioperative cognitive changes that define 

POCD. 

Other physiologic conditions that influence cerebral 

oxygenation have also been implicated but, again, with 

limited evidence. Anemia is one such factor. Anemia 

obviously occurs sometimes during surgery and is associated 

with changes in CBF and oxygenation in animals. 78 

Nevertheless, support for a link to cognitive dysfunction 

is indirect, coming mainly from evidence that isovolemic 

anemia to a hemoglobin concentration of 5–6 g/dL in 

healthy adults is associated with subtle changes in cognitive 

functioning and that normalizing hematocrit with 

erythropoietin in chronic renal failure patients improves 

cognitive performance. 79,80 For similar reasons (i.e., 

reduced cerebral oxygen delivery), there has been concern 

about inadvertent hyperventilation. Studies that have 

looked at this are too small to be conclusive but fail to 

identify an adverse effect of hyperventilation on cognition 

and even suggest that mild hypoventilation is worse 

in this regard than mild hyperventilation. 81 

Anesthetic Factors 

Despite the fact that general anesthesia is obviously a 

form of profound CNS dysfunction, its role in prolonged 

cognitive impairment has received surprisingly little 

attention. There is clinical evidence that general anesthesia 

contributes to early POCD, with one study showing a 

higher incidence after general, as opposed to regional, 

anesthesia 1 week postoperatively 82 and several demonstrating 

an association between POCD and the duration 

of anesthesia. 57,58 Prolonged POCD is another matter. 

Some studies show that the risk of POCD is similar with 

regional or general anesthesia. For instance, the frequency 

of cognitive impairment 6 months postoperatively was 

similar (4%–6%) between epidural and general anesthesia 

in elderly patients undergoing total knee replacement, 

but the study lacked a concurrent control. 62 Moreover, 

intravenous sedation is often used to supplement regional 

anesthetic techniques, making it difficult to isolate the 

influence of anesthesia itself in most, but not all, such 

studies. 62,82 To complicate matters further, there is a strong 

association of supplementary epidural anesthesia/analgesia 

and POCD 1 week postoperatively in middle-aged 

patients. 58 Whether this is a feature of intraoperative use 

of the epidural or accumulation of local anesthetic in the 

blood or cerebrospinal fluid because of continuous postoperative 

epidural infusion is unclear, but it emphasizes 

the sensitivity of the brain to even seemingly minor pharmacologic 

interventions. 

The only studies that have examined the long-term 

effects of general anesthesia without surgery on learning 

and memory have been performed in animals. Most, but 

not all of them, demonstrate long-lasting impairment. 

One recent study in aged mice found no persistent 

memory impairment after isoflurane anesthesia but they 

were also unable to detect well-known differences 

between young and old animals in this regard, indicating 

the behavioral paradigm used was probably not capable 

of detecting more subtle anesthesia-induced changes. 83 In 

contrast, several studies in aged rats with isoflurane– 

nitrous oxide and isoflurane alone, demonstrate spatial


learning impairment for weeks after general anesthesia 

without surgery. 84–86 This was true for a task that was 

partially learned beforehand as well as for one testing 

acquisition of entirely new memory. These results may 

have implications for understanding POCD. Because the 

agents are long cleared from the brain by the time behavioral 

testing was begun 48 h to 2 weeks after anesthesia, 

the data imply that general anesthesia alters the brain in 

some lasting way. There is some biochemical support for 

this notion; the profile of protein expression in the brain 

is changed for at least 72 hours after general anesthesia 

in rats. 87 There is also emerging evidence that some 

general anesthetics (e.g., ketamine, nitrous oxide) can be 

toxic to the brain during certain phases of the lifespan, 

including old age, producing vacuolation, swelling, and 

programmed cell death of neurons. 88–91 Additionally, 

based on recent work in cell culture, it seems that some 

general anesthetics may increase the cytotoxicity of β- 

amyloid, a protein implicated in the pathogenesis of 

Alzheimer’s disease but also present in the normally 

aging brain. 92 Although the relevance of this information 

to the genesis of POCD is the subject of debate, it is 

conceivable—but not yet firmly established—that general 

anesthetics may contribute to lingering postoperative 

cognitive impairment in the elderly. 90,93 

In summary, one can say that POCD occurs commonly 

during the early weeks and months after surgery and 

anesthesia. The etiology of POCD is likely to be multifactorial 

and the relative contributions of age- and 

disease-related processes, surgery, physiologic perturbations, 

anesthesia, and hospitalization are still unclear. 

Longitudinal studies using age- and disease-matched 

control groups will be necessary to clarify the long-term 

impact of surgery on patients’ ultimate cognitive health 

and such investigations will best be accomplished 

through collaborative efforts of anesthesiologists, surgeons, 

neuropsychologists, and geriatricians. Until then, 

because the fundamental mechanisms are uncertain, it is 

difficult to identify prevention or treatment strategies. In 

particular, there is presently no scientific basis for recommending 

(or avoiding) a specific anesthetic agent or technique 

in this regard. This will change as further research 

is conducted on this common, subtle, and troubling complication. 

In the meantime, it is reassuring that the prognosis 

for recovery from POCD seems to be good. 

Perioperative Stroke 

The development of a stroke after routine surgery 

is uncommon and seldom expected. Although the elderly 

represent a high-risk group for this devastating ad - 

verse perioperative outcome, questions remain as to 

whether perioperative stroke is a random event or one 

provoked by perioperative management or altered 

physiology. 

Table 9-6. Risk factors for perioperative stroke. 

• Age 

• Cardiac disease 

• Peripheral vascular disease 

• Hypertension 

• Smoking 

• Previous cerebrovascular insult 

There is a growing body of evidence indicating that the 

risk of stroke increases in the perioperative period but 

that the etiology is often unknown. One large retrospective, 

case-control study reported that the risk of ischemic 

stroke during the first 30 days after routine anesthesia 

and surgery is three times that of nonsurgical controls. 94 

Several smaller studies report similar data, with most 

placing the elderly at substantially greater risk. 95–97 In one 

retrospective study involving patients undergoing general 

surgical procedures, the overall incidence of perioperative 

stroke was 0.07% but the risk was 0.22% when only 

patients over age 65 were considered. 95 The greater risk 

of perioperative stroke in the elderly is presumably 

explained by the prevalence of age-related risk factors 

for stroke such as a history of stroke, hypertension, 

smoking, peripheral vascular and cardiac disease, and 

aspirin or anticoagulant use (Table 9-6). 97,98–101 Nonetheless, 

whereas the risk of stroke seems to be greater in the 

perioperative period, conditions that predispose elderly 

surgical patients to it are not obvious. 95,96 

Factors that have been considered include preexisting 

cerebrovascular disease, hypotension, and thromboembolic 

events. As for cerebrovascular disease, there is good 

agreement that an asymptomatic carotid bruit, which is 

present in 14% of surgical patients 55 years or older and 

20% of vascular surgical patients, is not itself a risk factor 

for perioperative stroke. 102–104 Hence, elective general surgical 

procedures probably need not be delayed in individuals 

without symptoms of focal cerebral ischemia 

but such individuals should be referred for subsequent 

evaluation because carotid endarterectomy may reduce 

long-term stroke risk. 98,105–107 Relationships between 

symptomatic cerebrovascular disease and perioperative 

stroke are controversial. There has been disagreement as 

to whether transient ischemic events, which are predictors 

of stroke in the general patient population, are also 

associated with a higher incidence of perioperative 

stroke. 108,109 However, it is often recommended that 

patients undergoing elective general surgical procedures 

with symptomatic carotid stenosis and a greater than 

70% arterial narrowing be evaluated preoperatively for 

possible carotid endarterectomy or stenting. 106 At the 

other extreme, prior stroke does increase the risk of perioperative 

cerebral reinfarction. In a small study, stroke 

was 5–10 times more common in those patients with a 

history of stroke. 96 The reasons for greater vulnerability


to perioperative reinfarction after a previous stroke are 

unknown but may relate to a prolonged period of altered 

cerebrovascular reactivity after a stroke and known alterations 

in cerebral autoregulation and carbon dioxide 

reactivity in vessels distal to a carotid stenosis. 110,111 After 

an acute cerebral ischemic event, the clinical and radiographic 

picture evolves over days to weeks, indicating 

that stroke is not a static event and suggesting that there 

may be an interval of special vulnerability to physiologic 

perturbations. Perhaps for this reason, it may be prudent 

to defer elective surgery after a stroke but there is no 

demonstrated benefit of doing so and no consensus on 

the optimal timing of elective surgery in patients with a 

recent ischemic stroke. 104 

Hypotension is another potential cause of perioperative 

stroke. Certainly there is no question that hypotension 

can produce cerebral ischemia and infarction if it is 

severe and prolonged. 112 That said, retrospective analyses 

indicate that most patients who had a stroke postoperatively 

experienced hypotension intraoperatively and yet 

emerged from anesthesia without a neurologic deficit. 95,98 

Furthermore, in cases in which perioperative hypotension 

is proposed as an inciting event, there may be a long 

asymptomatic interval between the hypotensive episode 

and the stroke. 101 Thus, at levels of hypotension frequently 

encountered in routine clinical situations, a cause-andeffect 

relationship between hypotension and stroke is 

often difficult to establish, in part because the consequences 

may be delayed and occur by as yet unknown 

mechanisms. 

Further confusing the story of hypotension and cerebral 

ischemia are results of an old underpowered study 

that deliberately exposed conscious patients with transient 

ischemic attacks to as much as a 60% decrease in 

systolic blood pressure. 113 Despite such profound, transient 

hypotension, no patient had a stroke and only one 

had a true transient ischemic attack, even though most 

developed unrelated focal signs or evidence of global 

cerebral ischemia. Also, as described earlier, induced 

hypotension (MAP 45–55 versus 55–70 mm Hg) during 

epidural anesthesia in elderly patients was not associated 

with either stroke or a higher incidence of cognitive 

impairment. 35 Although underpowered for a rare event 

such as stroke, assuming that cerebral infarction occurs 

at lower levels of perfusion than deterioration in cognitive 

performance, the data support the idea that the aged 

brain tolerates a moderate and transient reduction in 

perfusion pressure relatively well. However, in hypertensive 

patients, strokes have been precipitated by a rapid, 

pharmacologically induced, moderate blood pressure 

reduction, suggesting that there may be a vulnerable 

patient population that has not been clearly defined. 114 

Accordingly, although it is difficult to prove that transient 

intraoperative hypotension is benign, there is also little 

evidence to establish a cause-and-effect relationship 

between transient intraoperative hypotension and perioperative 

stroke. 

Indeed, in most cases, perioperative stroke is attributable 

to thrombotic or embolic events. 101 The risk of 

this type of stroke may be related to common perioperative 

complications including cardiac arrhythmias, withholding 

antithrombotic therapy, and hypercoagulability 

related to surgery and anesthesia. Dissection and/or 

thrombosis of the carotid or vertebral arteries have been 

reported perioperatively, ostensibly in conjunction with 

malpositioning of the neck. 99 Similar neurologic catastrophes 

are also reported after common activities such as 

coughing or sneezing, however, so the relationship to 

positioning is speculative at best. With respect to embolic 

events, one retrospective review found that cardiogenic 

embolism accounted for 40% of perioperative strokes 

and the majority of these occurred postoperatively. 95 An 

antecedent myocardial infarction was present in 17% of 

the patients and 33% were in atrial fibrillation at the time 

of the stroke. Moreover, perioperative embolic phenomena 

may be more common than previously appreciated, 

at least in certain procedures. Tourniquet deflation during 

total knee replacement is associated with venous and 

cerebral embolization in a large percentage of patients 

even if they do not have a patent foramen ovale or atrial 

or ventricular septal defect. 74,75 Perioperative changes in 

coagulation are also theorized to have a role because 

alterations in plasma concentrations of coagulation 

factors, platelet number and function, and altered fibrinolysis 

are well documented and may produce a hypercoagulable 

state. 100 

Neurologic consultation and additional diagnostic 

procedures should be sought expediently if a new and 

persistent focal neurologic deficit is identified in the perioperative 

period. Early detection becomes important 

as promising new therapeutic modalities to reverse or 

minimize the permanent consequences of injury are 

tested. Accordingly, the history should be carefully 

reviewed and a through neurologic examination performed. 

In view of the high incidence of embolic stroke, 

an echocardiogram can be diagnostically useful. Precordial 

echocardiograms are not reliable for detecting a 

patent foramen ovale and passage of surgical debris 

through the pulmonary veins is well documented. 74 Hence, 

a negative study does not eliminate the possibility of a 

perioperative paradoxical embolism. 95,115,116 Computed 

tomography and magnetic resonance imaging have long 

been used to provide information about infarct type, size, 

and location but until recently ischemic areas were not 

identifiable radiographically for hours to days after an 

event. This has changed with newer diagnostic modalities 

such as perfusion and diffusion weighted magnetic resonance 

imaging, which permit the detection of cerebral 

ischemia within a few hours after the onset of neurologic 

symptoms. 117


If an acute stroke is diagnosed, care should conform to 

guidelines recently established by the American Heart 

Association. 118,119 Defining the type of stroke (ischemic 

versus hemorrhagic) is essential because certain aspects 

of management are quite different. 118,119 The emphasis in 

both cases is on good physiologic management because 

more specific “protective” measures have proven ineffective. 

120–122 Thus, the ABCs (airway, breathing, circulation) 

of basic life support, including supplemental oxygen until 

the diagnosis is confirmed and/or endotracheal intubation 

as necessary for hypoxia, hypercarbia, or prevention 

of aspiration, are crucial. 118,119 The guidelines for blood 

pressure management differ markedly for patients with 

hemorrhagic and ischemic stroke. 118,119 In the former, 

assuming a history of hypertension, it is recommended 

that MAP be maintained between 90–130 mm Hg. 119 In 

contrast, a more cautious approach is recommended for 

patients with ischemic stroke, with antihypertensives 

given only when systolic blood pressure is >220 mm Hg or 

diastolic pressure is >120 mm Hg. 118 Likewise, if intracranial 

pressure monitoring is available, cerebral perfusion 

pressure should be maintained above 70 mm Hg with 

osmotherapy, hyperventilation (PaCO 2 30–35 mm Hg), 

sedatives, and neuromuscular blocking agents as needed. 

Fever should be treated with antipyretics and hypovolemia 

and hyperglycemia avoided. 118,119 As already noted, 

although the search for an effective stroke treatment has 

been extensive, no neuroprotective agent has proven 

effective. 123 Thus, none is recommended for treatment of 

acute stroke. However, there is a correlation between 

administration of benzodiazepines, dopamine antagonists, 

α-2 agonists, α-1 antagonists, and phenytoin or phenobarbital 

in the first 28 days after stroke and adverse 

neurologic outcome. 124 Although use of such drugs may 

be a marker for illness severity, these data caution that 

common drugs may have unanticipated neurologic consequences 

among patients with cerebral ischemia and 

that unnecessary pharmacotherapy should be avoided. 

The greatest advance in stroke management in recent 

years is the realization that stroke can be treated. 

Whereas treatment of stroke was simply supportive and 

rehabilitative in the past (with the exception of hyperbaric 

therapy for treatment of air emboli), today stroke 

is considered a medical emergency. 125 The main impetus 

for this important change in thinking is the success of 

low-molecular-weight heparin and thrombolytics for 

acute ischemic stroke. 126 Several studies demonstrate that 

tissue plasminogen activator administered within 3 hours 

improves overall neurologic outcome. 127 Although the 

safety of thrombolytics and heparins in the treatment of 

the surgical patient with acute stroke has not been established 

and the risk of hemorrhage remains a concern, 

there are reports of safe and successful administration of 

these agents in the acute postoperative setting. 128 Thus, 

although stroke is a rare and unpredictable complication 

of anesthesia and surgery, it is important to make the 

diagnosis expediently because, for the first time, there is 

real potential for effective treatment and promptness of 

treatment is an important factor. 

Conclusion 

The aged brain is different from the young brain in many 

respects, making elders more vulnerable to common perioperative 

complications such as POCD, delirium, and 

stroke. With the population aging, the challenge for the 

decades ahead is to better understand the role of surgery 

and anesthesia in causation of these complications so that 

perioperative physicians can tailor care for the elderly 

patient with the aged brain in mind. 

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10 

Alterations in Circulatory Function 

Thomas J. Ebert and G. Alec Rooke 

According to a 2006 statistical update published by the 

American Heart Association, 37.3% of all deaths in the 

United States in 2003 were attributable to cardiovascular 

disease (CVD). 1 About 83% of the deaths related to 

CVD occur in people age 65 and older. The prevalence 

of CVD in American men and women aged 65–74 are 

68.5% and 75%, respectively. For those aged 75+, prevalence 

is 77.8% and 86.4%, respectively. These numbers 

demonstrate the strong association between adverse 

cardiac events and the aging process. 

With advancing age, the frequency of concurrent 

disease processes increases in a nearly exponential 

manner, such that many of the CVDs in the elderly have 

been considered an expected process of aging. We now 

recognize that preventing or delaying these disease processes 

through good nutrition and an active lifestyle can 

achieve “healthy or successful” aging. It is also recognized 

that preoperative “medical fitness” (a synonym for “successful 

aging”), rather than chronologic age, is an important 

determinant of postoperative outcome in the elderly 

surgical patient 2 (Figure 10-1). 

Even in the absence of the confounding influences of 

disease and lifestyle, the rate of functional aging on an 

organ or system, such as the cardiovascular system, varies 

from individual to individual. To better understand the 

expected effects of the “usual” aging process on the cardiovascular 

system, we must appreciate the net effect of 

the multiple, interdependent variables of heart rate, coronary 

blood flow, afterload or impedance, preload or diastolic 

filling, and inotropic state in describing cardiac 

function. All show age-dependent changes. The autonomic 

nervous system (ANS) modulates each of these 

variables through both sympathetic and parasympathetic 

mechanisms, and aging of the ANS further contributes to 

modifying cardiovascular function in the elderly. 

Although there is a general bias that age weakens the 

heart, in fact, this is not the case. Several functional adaptations 

of the heart help maintain resting and exercise 

cardiovascular physiology. 3 However, some of these 

adaptations account for problematic physiology in the 

elderly that adversely affects anesthetic management. 

This chapter will identify the critical changes in the cardiovascular 

system related to the aging process and the 

consequent modifications to the clinical management of 

the elderly undergoing anesthesia and surgery. 

Heart and Vessel Structural Alterations 

As the human body ages, it undergoes a variety of 

changes. Some of these changes are relatively benign. 

However, there are alterations that influence and 

even impair the overall health of the aging person. An 

example of such a detrimental digression accompanying 

increasing age is the increased stiffness of the heart and 

vascular tree. 

Many factors contribute to stiffening of the vascular 

tree. Aging can radically transform the endothelial 

layers via changes in extracellular matrix compositions. 

Elasticity in connective tissues depends primarily on the 

properties of its constituent collagen and elastin. Both 

connective tissue proteins are long-lived but slow in 

their production. By the age of 25, production of elastin 

has essentially ceased, and the rate of turnover of collagen 

decreases with increasing age. The consequent 

increase in the collagen-to-elastin ratio, plus an accumulating 

damage to collagen by glycation and free radicals, 

results in progressive connective tissue stiffness. Thus 

arteries, veins, and myocardium become less compliant 

over time. 

Nonenzymatic glycation is a reaction between reducing 

sugars and proteins on the vascular endothelium. Over 

time, these glycation sites cause tight crosslinking of proteins 

called advanced glycation end-products (AGE). 

This AGE formation leads to changes in the physiochemical 

properties of endothelial tissues. AGE crosslinking 

structurally results in vessels with less elasticity and 

137

138 T.J. Ebert and G.A. Rooke 

80 

* 

70 

60 

Active 

Inactive 

% Post-op Complications 

50 

40 

30 

* 

* 

* 

* 

20 

* 

10 

0 

Nil Chest Heart Acute 

Confusional 

State 

Wound 

Any Medical 

Complication 

Any Surgical 

Complication 

Life- 

Threatening 

Complication 

Figure 10-1. Preoperative activity level and percent occurrence 

of postoperative complications. Active = patients who normally 

left their home without assistance, at least two times per 

week. *p < 0.05. (Adapted with permission from Seymour DG, 

Pringle R. Post-operative complications in the elderly surgical 

patient. Gerontology 1983;29(4):262–270. Basel, Switzerland: 

S. Karger.) 

compliance. 4 Furthermore, the interaction of AGE 

with receptors for AGE (RAGE) on endothelial cells 

has been implicated as an initiating event in atherogenesis. 

In smooth muscle cells, binding of AGE-modified 

proteins to RAGE is associated with increased cellular 

proliferation of smooth muscle cells. This interaction 

also causes an increase in vascular cell adhesion molecule-1, 

which enhances binding of macrophages to the 

endothelial surface. This induces oxidative stress on 

the vascular endothelium and contributes to vascular 

stiffness. 5 

Several studies have shown that the nitric oxide 

pathway deteriorates with age. This has implications 

on vascular compliance. Nitric oxide suppresses key 

events in atherosclerotic development such as vascular 

smooth muscle proliferation and migration. It also 

inhibits the adhesion of monocytes and leukocytes in the 

endothelium, as well as platelet–vessel interaction. 

Furthermore, nitric oxide is known to regulate endothelial 

permeability, reducing the flux of lipoproteins into 

the vessel wall. 6 The reduced effects of nitric oxide on all 

of these pathways may contribute to vascular stiffness 

in aging. 

The above mechanisms serve to explain the pathogenesis 

of vascular stiffness associated with aging. As arterial 

walls stiffen, blood vessel compliance is reduced, leading 

to an increase in systolic blood pressure and pulse wave 

velocity (Figure 10-2). The reflected waves return earlier 

to the thoracic aorta, arriving by late ejection instead of 

early diastole. Thus, the left ventricle must pump against 

a higher pressure in late ejection than under normal circumstances. 

This additional afterload places an increased 

MEAN AORTIC PRESSURE (mmHg) 

120 

115 

110 

105 

100 

95 

90 

85 

80 

10 25 35 45 55 65 75 

AGE 

1300 

1200 

1100 

1000 

900 

800 

700 

600 

Figure 10-2. Mean aortic pressure (triangles) and pulse wave 

velocity (circles) in two Chinese populations: rural Guanzhou 

(unfilled symbols) and urban Beijing (filled symbols). (Adapted 

with permission from Avolio AP, Chen SG, Wang RP, Zhang CL, 

Li MF, O’Rourke MF. Effects of aging on changing arterial 

compliance and left ventricular load in a northern Chinese 

urban community. Circulation 1983;68:50–58.) 

AORTIC PULSE WAVE VELOCITY (cm/s)

10. Alterations in Circulatory Function 139 

LV thickness (mm/m 2 ) 

7 

6 

5 

4 

3 

2 

1 

0 

y=3.08 + 0.035x 

r=0.64 

n=62 

10 20 30 40 50 60 70 80 90 

Age (yr) 

Figure 10-3. Left ventricular (LV) posterior wall thickness 

(mm/m 2 ) in normotensive men as a function of age (years). 

(Adapted with permission from Gerstenblith G, Frederiksen J, 

Yin FC, Fortuin NJ, Lakatta EG, Weisfeldt ML. Echocardiographic 

assessment of a normal adult aging population. 

Circulation 1977;56:273–278.) 

burden on the heart, particularly because it occurs late in 

systole when the myocardial muscle is normally losing its 

strength, and therefore provides a significant stimulus for 

cardiac hypertrophy (Figure 10-3). 

The cardiac muscle hypertrophy that develops secondary 

to the increased late systolic afterload also leads to 

myocardial stiffening and diastolic dysfunction. Diastolic 

dysfunction is defined as impairment in the relaxation 

phase of the ventricles. The aging heart contains AGE 

crosslinked collagen, which has the same effect on stiffness 

as it does in the peripheral vascular system. It is 

implicated in the signaling of macrophage recruitment in 

hypertensive myocardial fibrosis that contributes to deteriorating 

diastolic function. 4 

In diastolic dysfunction, there also is a functional component 

to the impairment of relaxation. It has been proposed 

that alterations in the myocyte calcium-handling 

proteins disturb the calcium transient in failing hearts. 

Calcium uptake in the sarcoplasmic reticulum declines 

with heart failure because of reduced expression of 

certain calcium channel enzymes. 7 This contributes to 

delayed relaxation of the myocardial muscle fibers, and 

the stiff ventricles have less ability to “spring open” in 

early diastole. 

As a consequence, there is a progressive decrease in 

the early diastolic filling period between the ages of 20 

and 80. At its worst, the diastolic filling period is reduced 

by 50% compared with younger controls. With increased 

stiffness, there also is a decline in the diastolic filling rate 

(Figure 10-4). However, resting end-diastolic volume 

does not change with increasing age. Because the passive 

early ventricular filling is impaired with age, the heart is 

increasingly dependent on an adequate atrial filling pressure 

and the atrial contraction (Figure 10-5). The atrial 

PEAK FILLING RATE (EDV/s) 

14 

12 

10 

8 

6 

4 

2 

LV Filling 

Young 

Advance Age 

A 

0 

20 30 40 50 60 

AGE (yr) 

70 80 90 

Figure 10-4. Changes in early diastolic left ventricular filling 

and the atrial contribution to filling associated with increased 

age. Age and peak filling rate relationship was obtained at rest 

(squares) and maximum workload (triangles). Inset: top image 

= left ventricular filling, young; bottom image = left ventricular 

filling, advanced age. (Adapted with permission from Lakatta 

EG. Cardiovascular aging in health. Clin Geriatr Med 

2000;16(3):419–444. Copyright © 2000 Elsevier.) 

Figure 10-5. Echo-Doppler evaluation of diastolic filling in 

healthy men and women as a function of age. A: Early diastolic 

filling volume (% of total volume). B: Diastolic filling caused 

by atrial contraction (% of total volume). (Adapted with 

permission from Lakatta. 3 ) 

B


Figure 10-6. The increased ventricular stiffness associated with 

age requires an increased atrial pressure to achieve the same 

end-diastolic volume. (Adapted with permission from Dauchot 

PJ, Cascorbi H, Fleisher LA, Prough DS, eds. Problems in Anesthesia: 

Management of the Elderly Surgical Patient. Vol. 9, 

No. 4. Philadelphia: Lippincott-Raven; 1997:482–497.) 

pressures must rise to maintain the end-diastolic volume 

in the presence of stiffened ventricles. The increased 

atrial pressure can result in increased pulmonary blood 

pressures and ultimately lead to congestion in the systemic 

venous circulation. The cumulative effect of these 

alterations results in diastolic dysfunction (Figure 10-6). 

About half of heart failure in the elderly population 

(older than 75 years) is associated with impaired 

left ventricular diastolic function, but preserved left 

ventricular systolic function. 8 Unfortunately, patients 

with isolated left ventricular diastolic dysfunction are 

not as likely to present with the traditional physical 

manifestations of heart failure. Instead, they are frequently 

asymptomatic or present with only mild pulmonary 

congestion, exertional dyspnea, and orthopnea. 

These symptoms may be aggravated by systemic stressors 

such as fever, exercise, tachycardia, or anemia. As a 

result, prevention and detection of diastolic heart 

failure may be difficult since it is often recognized only 

by echocardiography. 

Systolic function of the heart also is affected by the 

aging process. From a functional standpoint, the prolonged 

myocardial contraction maintains the flow delivered 

to the stiffened arterial tree, thereby maintaining 

cardiac output (Figure 10-7). The functional adaptation 

to vascular stiffening and afterload is able to maintain 

Arterial stiffening 

Increased arterial 

systolic and 

pulse pressure 

Increased pulse wave velocity 

Early reflected waves 

Late peak in systolic pressure 

Increased aortic root size 

Increased aortic wall thickness 

Increased aortic impedance 

and LV loading 

Increased LV wall 

tension 

Increased LV 

hypertrophy 

Prolonged myocardial 

contraction 

Increased left 

atrial size 

Increased 

atrial filling 

Normalization 

of LV wall 

tension 

Increased 

myocardial 

contraction 

velocity 

Prolonged force 

bearing capacity 

Decreased early 

diastolic filling rate 

Increased 

energetic efficiency 

Slightlly increased 

end-diastolic volume 

Preserved endsystolic 

volume and 

ejection fraction 

Maintenance of ejection time 

Figure 10-7. A cascade of functional adaptations to vascular stiffening in the elderly. LV = left ventricular. (Adapted with permission 

from Lakatta EG. Cardiovascular aging in health. Clin Geriatr Med 2000;16(3):419–444. Copyright © 2000 Elsevier.)


cardiac output at rest; however, an age-related decline in 

systolic function may be unmasked in the presence of 

exercise or sympathetic stimulation. For example, 

administration of an α-adrenergic agonist such as phenylephrine 

will acutely increase afterload to the heart, 

increasing left ventricular wall stress during systole, 

unmasking an age-related decrease in contractile 

reserve. 9 

Further studies have shown that there is abnormal systolic 

function in many patients who have hypertensioninduced 

concentric hypertrophy with a normal ejection 

fraction. Reduced midwall shortening in relation to stress 

is clearly evident in patients with greater relative wall 

thickness. This translates to abnormal pump function and 

reduced cardiac output. Subtle systolic dysfunction may 

be present even if patients have seemingly normal ejection 

fractions and are without clinical heart failure, and 

it would be incorrect to equate a normal ejection fraction 

with normal systolic function. 10 

Reduced vascular compliance, diastolic dysfun - 

ction, and systolic dysfunction in the elderly are all interconnected. 

It is reasonable to assume that these are not 

separate pathologies and in fact develop in parallel. 

Reduced vascular compliance resulting in hypertension, 

increased afterload, and eventual cardiac remodeling is 

an extremely common finding in the aging population. In 

a large portion of this group, this inevitably results in 

some evidence of diastolic dysfunction. Furthermore, the 

above concepts demonstrate that some systolic dysfunction 

exists in many of these same hypertensive elderly 

patients. 

The interrelationships among vascular stiffening, 

hypertension, diastolic dysfunction, and even systolic dysfunction 

in the absence of overt cardiac disease have led 

to a reexamination of our concepts of hypertension and 

its management. Conventional wisdom suggests that 

patients who have hypertension can sometimes be classified 

as “systolic” hypertension or “diastolic” hypertension 

if their hypertension is limited to their systolic or diastolic 

pressure, respectively. However, an emerging concept is 

of “pulse pressure” hypertension and is characterized by 

a large difference between systolic and diastolic pressure, 

for example, 80 mm Hg or greater. 11 

A relatively high systolic pressure in comparison to 

diastolic is harmful for several reasons. First, a high pulse 

pressure indicates that the patient’s arterial conduit 

system is stiff. Low compliance means that a high systolic 

pressure is required in order to distend the aorta and 

other large arteries as the stroke volume is received. 

Even though this increase in pressure occurs relatively 

early in ejection, it still forces the ventricle to pump 

against a high pressure and stimulates hypertrophy 

that, in turn, increases myocardial stiffness and further 

impairs diastolic relaxation. Indeed, there is a strong correlation 

between the severity of reduced arterial compliance 

and the severity of diastolic dysfunction. 12 Second, 

when the diastolic pressure is low compared with systolic 

pressure, there is an immediate predisposition to an 

imbalance of myocardial oxygen supply and demand. 

Demand correlates most closely to systolic pressure, 13 

whereas coronary blood flow occurs mostly during diastole, 

making supply highly dependent on diastolic pressure. 

With rapid transit of reflected arterial waves, there 

is loss of the accentuated pressure in early diastole. This 

lowering of aortic pressure during diastole potentially 

diminishes coronary perfusion. In patients with coronary 

stenoses, this imbalance could result in subendocardial 

ischemia, thereby worsening diastolic relaxation and 

increasing atrial pressure. 

Because of the consequences of arterial stiffening, arterial 

compliance has been suggested as a better measure 

of biologic age, as opposed to chronologic age. 14 And it is 

not surprising that there is great interest in strategies to 

reduce or even reverse arterial stiffening in the hope of 

preventing CVD. Current human therapy primarily 

involves drugs that relax smooth muscle tone. 15 Statins 

not only inhibit myocardial remodeling but may reduce 

vascular stiffness. Angiotensin blockers and aldosterone 

seem to lessen fibrosis. In recent studies that have largely 

been limited to animals, drugs have been used to break 

the stiffening links in connective tissue proteins caused 

by glycosylation. 15,16 In the meantime, exercise slows 

vascular stiffening and remains a useful therapy for all 

ages. 

Reflex Control Mechanisms and Aging 

The aging process affects autonomic cardiovascular 

control mechanisms in a nonuniform manner. Attenuated 

respiratory sinus arrhythmia in older individuals suggests 

that parasympathetic control of sinus node function 

declines with age. Because the reflex regulation of heart 

rate in humans is primarily dependent on cardiac vagal 

activity, it is correct to assume that the impaired baroreflex 

regulation of heart rate is related to deficient parasympathetic 

mechanisms (Figure 10-8). Although the 

parasympathetic component of the arterial baroreflex 

becomes diminished in the aging population, the baroreflex 

control of sympathetic outflow and the vascular 

response to sympathetic stimulation are well maintained 

in moderately old, active individuals. 17 It is well established 

that basal levels of plasma catecholamines and 

sympathetic nerve activity increase with age. Plasma noradrenaline 

levels increase 10%–15% per decade. 18 In 

addition, there is an age-dependent reduction in activity 

of the cardiac neuronal noradrenaline reuptake mechanism, 

resulting in higher concentrations of noradrenaline 

at β 1 -receptor sites in the heart. 19


A 

B 

msec 

mm Hg 

cardiac 

baroslope. 

40 

30 

20 

10 

y = -0.31x + 27.9 

r = 0.608, n = 66 

R·R interval, msec 

1400 

1200 

1000 

800 

18-34 yr, n = 35 

35-50 yr, n = 15 

51-70 yr, n = 16 

0 

10 20 30 40 50 60 70 80 

age, yr 

Figure 10-8. A: Individual cardiac baroreflex sensitivities 

versus age. Regression revealed a significant (p < 0.05) inverse 

relationship between reflex sensitivity and age. B: Mean regression 

lines describing relationship between mean arterial 

pressure and corresponding R-R interval for each of the three 

600 

70 80 90 100 110 

mean arterial pressure, mm Hg 

age groups. Regression line slopes were smaller in older and 

middle-aged subjects than in younger subjects. Baseline values 

(mean ± SE) are superimposed on regression lines. (Adapted 

with permission from Ebert et al. 17 ) 

Adrenergic Receptor Activity 

and Aging 

Aging has been associated with a decrease in the response 

to stimulation of β-receptors. This is noted in the peripheral 

circulation by a reduced arterial and venous dilation 

response to the β-agonist, isoproterenol, and the mixed 

agonist, epinephrine, in the elderly (Figure 10-9). In 

CHANGE IN HEART RATE (bpm) 

30 

25 

20 

15 

10 

5 

0 

0.00 0.25 0.50 1.00 2.00 4.00 

ISOPROTERENOL (mcg) 

Figure 10-9. The effect of intravenous isoproterenol infusions 

on increasing heart rate in healthy young (filled circles) and 

older (unfilled circles) men at rest. (Adapted with permission 

from Lakatta EG. Cardiovascular aging in health. Clin Geriatr 

Med 2000;16(3):419–444. Copyright © 2000 Elsevier.) 

cardiac muscle, there is a reduction in the inotropic 

response to exercise and to the administration of catecholamines 

in the aging patient. 20 In isolated cardiac 

myocytes, it has been shown that the EC 50 for isoprenaline 

(a β 1 - and β 2 -agonist) is nearly twice as high in the 

elderly. 18 A result of the decreased contractile response 

to β-adrenergic stimulation in the elderly is a greater 

dependency on the Frank-Starling (length-tension) 

mechanism of contraction to maintain cardiac output. 

Although multiple studies indicate that the heart rate 

increase to β-stimulation of the heart is attenuated with 

age, recent data question the age-related attenuated 

chronotropic response. 20 Studies also provide conflicting 

results regarding age-related changes in myocardial β- 

adrenoceptor density. The mechanism for decreased 

cardiac inotropic response to sympathetic stimulation is 

more likely attributable to changes in the second messenger 

system. Impaired coupling of the β-adrenoceptor 

to the Gs protein and to the catalytic unit of adenylyl 

cyclase is consistently observed in the elderly myocardium. 

Furthermore, an increase in Gi protein levels 

observed in aged myocardial tissue indicates a reduction 

in the catalytic subunit of adenylyl cyclase. 21 Both of these 

mechanisms will attenuate adenosine 3′,5′-cyclic monophosphate 

(cAMP) formation and subsequent β-adrenoceptor 

response. This desensitization of the intracellular 

processing of receptor signaling is likely a compensatory 

adaptation to an increase in endogenous norepinephrine 

resulting from age-related increases in sympathetic activity 

and reduced neuronal uptake of norepinephrine. 

This attenuated β-adrenoceptor response as a result of 

changes in second messenger function has implications in


the peripheral vascular system. Vasorelaxation is accomplished 

in vascular smooth muscle cells via cAMP. cAMP 

activates protein kinase A (PKA) that then lowers cytosolic 

calcium levels, causing vasorelaxation. Decreased 

generation of cAMP in the vasculature leads to impairment 

of this pathway. This may be a contributing factor 

for hypertension in the elderly. And because cAMP is an 

antiproliferative agent, this deficiency may be associated 

with the progression of atherosclerosis. 21 

Genetic variation in β-adrenoceptors is now documented 

and may have a significant role in CVD heterogeneity 

among individuals. There are many known 

polymorphisms of both β 1 - and β 2 -adrenoceptor subtypes. 

These variants may have differing effects on the cardiovascular 

system with age. The most common polymorphism, 

whose allele frequency is 60%, causes enhanced 

down regulation of β 2 -adrenoceptors. Because peripheral 

β 2 -receptors cause vasodilation and a reduction in blood 

pressure, individuals with this polymorphism are more 

prone to hypertension with increasing age. This fact has 

been confirmed in familial studies, which show increased 

prevalence of this allele in families with a history of 

essential hypertension. Another β-adrenoceptor polymorphism 

with important implications in cardiac disease 

is one that causes blunted agonist responsiveness. Studies 

have shown that in heart failure patients, this variant 

carries a relative risk of death or transplant of 4.8 compared 

with the normal allele. There also exists a particular 

polymorphism that tends to improve survival in those 

with heart failure. The existence of β-receptor polymorphisms 

may have additional implications for the efficacy 

of β-blockade. However, at this time, little is known about 

their particular impact on patient therapy. 22 

It would seem logical to expect a down regulation of 

α-adrenergic receptors with age, but surprisingly the 

number of α 1 -receptors remains well preserved. Interestingly, 

in normotensive older subjects, an increased rate of 

infusion of an α-agonist is required to achieve the same 

degree of vasoconstriction compared with young subjects. 

8 Animal studies have shown that maximal binding 

of vascular α 1 -receptors is significantly reduced with 

age. 23 The α 2 -receptors appear to show some age-related 

decline. Normally, α 2 -receptors predominate in the venous 

side of the circulation, suggesting that a compromised 

venoconstrictor response to the upright posture, secondary 

to α 2 -receptor loss, might contribute to orthostatic 

intolerance in the elderly. 17 The evidence of adrenergic 

receptor desensitization with age has further implications 

as hypertension develops in the elderly. In normotensive 

elderly subjects, the decrease in responsiveness of α- 

adrenergic receptors seems to be a regulated compensatory 

effect of the heightened level of sympathetic nervous 

system activity in the elderly. Despite some evidence of 

diminished α-adrenergic responsiveness, it seems that the 

overall baroreflex control of vasoconstriction is well preserved 

with age and might be heightened compared with 

young adults. 7,24 

As with β-adrenoceptors, polymorphisms in α- 

adrenergic receptors may have implications on hypertension 

and cardiac disease in the elderly. It has been 

proposed that individuals with a particular α 2B -adrenergic 

receptor polymorphism may be at greater risk for 

acute coronary events and sudden cardiac death. 25 The in 

vivo effect of the α 2 -agonist dexmedetomidine on patients 

with this polymorphism has been investigated and there 

is a trend toward an increased systolic blood pressure 

response to dexmedetomidine in patients with this 

polymorphism. 25 

Vagal Activity and Aging 

Baroreflex control of heart rate is known to be diminished 

in older individuals. Indeed, there clearly is an 

attenuated respiratory sinus arrhythmia suggesting either 

reduced vagal outflow or reduced intracellular responses 

to muscarinic receptor activation with age. 26 Both changes 

seem to be present in the elderly. Lower resting vagal 

tone in the elderly has been implicated in the diminished 

heart rate increase in response to a large dose of atropine 

compared with younger controls. 8 Studies have shown 

that right atrial muscarinic receptor density is significantly 

and negatively correlated with age. Furthermore, 

it has also been shown that muscarinic receptor function 

declines in the elderly population. This is evident by a 

reduction in carbachol-induced inhibition of forskolinactivated 

adenylyl cyclase in muscarinic receptors of aged 

myocardium. 27 All of these mechanisms, taken together, 

contribute to reduced vagal activity in the elderly. Finally, 

autoantibodies to M 2 -muscarinic receptors exist in the 

sera of normal individuals, and are found in high levels 

in those with idiopathic dilated cardiomyopathy. The 

prevalence of these autoantibodies is significantly 

increased in the elderly. 28 The implications of these findings 

on muscarinic receptor function and cardiac performance 

have yet to be determined. 

Renin and Vasopressin Activity 

As already described, there are many vascular changes 

associated with aging. These changes contribute to renal 

damage and functionally result in decreased glomerular 

filtration rate and renal blood flow. Aging also affects 

sodium balance in the kidney. This results in decreased 

ability to conserve sodium in the face of sodium restriction 

as well as a decreased sodium excretion in the presence 

of increased sodium load. Despite the increased 

sympathetic activity accompanying old age, the elderly 

experience a decrease in plasma and renal levels of renin.


Plasma renin activity is diminished in the supine position, 

and physiologic stimuli such as hemorrhage, sodium 

restriction, and orthostasis are followed by attenuated 

increases in renin release and consequently lower concentrations 

of angiotensin in the circulation. 29 Although 

renin-angiotensin levels are decreased in the elderly, the 

aging population shows an enhanced vasoconstriction in 

response to angiotensin I and angiotensin II. The above 

finding helps to explain the key role that angiotensinconverting 

enzyme inhibitors and angiotensin II receptor 

blockers have in improving renal structure and function 

in the elderly. 30 

In the elderly, there seems to be an elevation in plasma 

vasopressin levels under basal conditions and a heightened 

response to an osmotic challenge such as water 

deprivation. Surprisingly, after a water restriction period, 

older subjects had a relatively low spontaneous fluid 

consumption as well as diminished thirst. 29 In addition, 

by age 80, the total body water content has declined to 

50% of body mass from the average content of 60% in 

younger persons. 31 Such decreases in thirst mechanism, 

total body water, and fluid consumption in combination 

with an age-related decrease in glomerular function cause 

older persons to be increasingly vulnerable to water 

imbalance. 

Arrhythmias 

Several changes with aging predispose the older patient 

to arrhythmias. Sinus node dysfunction develops with the 

progressive loss of pacemaker cells, and contributes to 

the risk of sick sinus syndrome and/or bradycardia. 32 Bradycardia 

promotes atrial fibrillation as does age-related 

atrial fibrosis and atrial enlargement. The incidence of 

atrial fibrillation increases with age such that it is present 

in 10% of those over 80. This predisposition to atrial 

fibrillation undoubtedly contributes to the relatively high 

incidence of new onset atrial fibrillation (and supraventricular 

tachycardia) not only after thoracic and cardiac 

surgery, but after most major surgical procedures. Patients 

presenting for surgery who are found to have previously 

undiagnosed atrial fibrillation should be evaluated before 

surgery, including an echocardiogram to rule out structural 

abnormality. Perioperatively, the management of 

new onset atrial fibrillation is initially rate control, with 

restoration of sinus rhythm within 24 hours as the next 

goal in order to reduce the risk of clot formation and 

thromboembolus. 33 For patients with chronic atrial 

fibrillation, early anticoagulation after surgery may be 

important, especially if the patient is at high risk for 

thromboembolism. 

Heart block and ventricular ectopy are examples of 

other arrhythmias prevalent in older patients. 34 Heart 

block below the atrioventricular node most often occurs 

secondary to idiopathic degeneration of the conduction 

system, but is not likely to carry adverse consequences 

unless there is concomitant cardiac disease. 

Ischemic Preconditioning 

An episode of myocardial ischemia reduces the severity 

of myocardial damage associated with a subsequent, 

more prolonged ischemic event. This phenomenon, known 

as ischemic preconditioning, exists in both an immediate 

(minutes to a few hours) and delayed (many hours to 

days) form. 35 Clinically, ischemic preconditioning is likely 

involved with warm-up angina in which patients who 

exert to the onset of angina, rest, and exert again can then 

achieve higher levels of exertion before developing the 

second bout of angina. 36 Patients who suffer a myocardial 

infarction are much less likely to die or develop heart 

failure if they experienced angina within 48 hours of their 

myocardial infarction. 37 Exposure to volatile anesthetics 

yields a preconditioning effect as well. 35 

Unfortunately, aging is associated with the loss of ischemic 

preconditioning. Warm-up angina is nonexistent 

beyond age 75 38 and in patients older than 65, myocardial 

infarction with or without antecedent angina is associated 

with the same high rates of death and heart failure as 

younger subjects who did not have prior angina. 37 At least 

in an animal model, anesthetic cardioprotection from 

preconditioning is essentially abolished in aged rats. 39,40 

Implications in Anesthesia 

Although normal aging affects virtually all components 

of the cardiovascular system, perhaps the most important 

changes that influence anesthetic management in the 

elderly are the stiffened cardiac and vascular system, 

the diminished β-adrenergic receptor response, and the 

impaired autonomic reflex control of heart rate. Compounding 

these age-related changes are the well-described 

effects of the intravenous and volatile anesthetics on the 

myocardium, vascular tone, and the ANS. 

Many of the elderly patients coming to the operating 

room are in a relatively volume-depleted state because 

of NPO guidelines, reduced thirst mechanisms, and diminished 

renal capacity to conserve water and salt. Additionally, 

increases in heart rate and contractility during volume 

loss are limited by diminished reflex control systems and 

by reduced β-receptor responses. Consequently, further 

hypovolemia, e.g., intraoperative blood loss, can result in 

substantial hypotension. This volume sensitivity of the 

elderly has been demonstrated in the laboratory during 

head-up tilt testing after subjects had been made hypovolemic 

with diuretics and low salt intake. The older subjects 

had greater decreases in blood pressure during


Figure 10-10. Hemodynamic response to high spinal anesthesia 

in older men with a history of cardiac disease. MAP = mean 

arterial pressure, SVR = systemic vascular resistance, CO = 

cardiac output, HR = heart rate, SV = stroke volume, EF = 

ejection fraction, EDV = left ventricular end-diastolic volume. 

(Adapted with permission from Rooke et al. 48 ) 

upright tilting than both the younger hypovolemic control 

subjects and the older normovolemic control subjects. 41 

Impaired responses to hypovolemia are further confounded 

by volatile anesthetics and the sedative-hypnotics 

that impair baroreflex control mechanisms. 42,43 Healthy 

or preserved baroreflex control mechanisms clearly minimize 

the cardiovascular changes that result from anesthetics. 

For example, diabetic patients with preserved 

autonomic reflexes had a lower incidence of hypotension 

during induction and maintenance of anesthesia than 

patients with impaired reflexes. 44 Thus, the net effect of 

physiologic changes with adult aging compounded by 

anesthetic effects should be more frequent and more significant 

blood pressure changes in the elderly. Such blood 

pressure lability has been observed in older patients. 45,46 

In the aged patient, the relative hypovolemic state has 

many important clinical implications. The elderly heart is 

heavily dependent on an adequate end-diastolic volume 

to maintain stroke volume, and cardiac filling is in turn 

dependent on higher atrial filling pressures because of a 

stiffened ventricle and possible diastolic dysfunction. As 

a result, the elderly are very sensitive to hypovolemia. In 

this setting, decreased systemic blood pressure should 

generally be treated with intravenous fluids rather than 

vasopressors to maintain proper diastolic function. One 

study has shown that volatile anesthetics do not impair 

diastolic function whereas propofol has some negative 

effects. 47 

As important as maintenance of an adequate cardiac 

preload is to an older patient, it is equally important to 

avoid excess fluid administration. There are two ways in 

which one can be misled into administration of excess 

volume. First, with anesthetic-induced relaxation of vascular 

smooth muscle and/or sympathectomy comes venodilation 

and increased venous pooling of blood. 

Restoration of preload would therefore seem to require 

significant volume administration just to compensate for 

the effects of the anesthetic. However, once the anesthetic 

is worn off, vascular smooth muscle relaxation 

lessens and sympathetic tone is not only restored, but 

quite possibly heightened because of pain or recovery 

from the surgical trauma. Restoration of normal to 

increased venous tone will then shift that excess volume 

back to the heart and potentially lead to pulmonary and 

cardiac dysfunction as the elderly heart copes with what 

now is volume overload. 

The second mechanism that can mislead practitioners 

into giving excess volume occurs when cardiac filling and 

cardiac output are not diminished, but the patient is still 

hypotensive from arterial vasodilation. The natural reaction 

to hypotension is to assume the patient is hypovolemic 

and therefore give more volume. That treatment may 

not be appropriate with older patients. Young, healthy 

patients have minimal sympathetic tone when supine and 

at rest. Thus, anesthesia is likely to decrease blood pressure 

in young patients more by the direct effects of the 

anesthetic on blood vessels than by removal of sympathetic 

tone. Elderly patients, however, often have high 

levels of sympathetic tone 17 and removal of that tone can 

produce more than just an apparent hypovolemia. In a 

study of older men with varying degrees of cardiac disease, 

high spinal anesthesia produced an average decrease in 

blood pressure of 33% (Figure 10-10). 48 Even though 

pooling of blood in the abdomen and legs caused a 19% 

decrease in left ventricular end-diastolic volume, cardiac 

output only decreased by 10%, largely because the 

decrease in blood pressure (afterload reduction) allowed 

the ejection fraction to increase. The primary mechanism 

for hypotension, however, was the 26% decrease in systemic 

vascular resistance. It is physically impossible to 

increase end-diastolic volume indefinitely and fully compensate 

for such a significant decrease in vascular resistance. 

In fact, it could be argued that the attempt would 

merely predispose the patient to volume overload, especially 

on emergence as discussed above. Increased left 

ventricular end-diastolic pressures from excessive volume 

could also precipitate or aggravate myocardial ischemia 

by creating high left ventricular subendocardial wall 

stress. 49 

In all but the sickest of older patients, therefore, the 

most likely mechanism of intraoperative hypotension is 

either decreased vascular resistance or hypovolemia. 

Should bradycardia be a limiting factor, it is easily detected 

and treated. What should be done, then, to manage the 

patient who is hypotensive with a stable heart rate even 

after adequate volume deficits are replaced? Vasopressors 

are the likely treatment of choice, with ephedrine and 

phenylephrine being the most frequently used agents. 

Phenylephrine has the advantage over ephedrine in that 

it does not exhibit tachyphylaxis and will not promote


tachycardia. Furthermore, α-receptor activation generally 

results in venoconstriction in addition to vasoconstriction, 

thereby shifting blood from the periphery back to the 

heart and alleviating the anesthetic-induced peripheral 

pooling. 50 As with all drugs, adverse consequences can 

occur. Coronary vasoconstriction, decreased cardiac 

output, imbalance in the distribution of the cardiac output, 

and wall motion abnormalities are all potential undesired 

effects. The key to the rational use of pressors such as 

phenylephrine is to minimize hypovolemia, and not feel 

obliged to return overall vascular resistance back to preanesthetic 

levels. In other words, tolerate a mild decrease 

in blood pressure. The cardiac dysfunction that has been 

observed with the use of phenylephrine typically occurs 

when blood pressure is increased to levels above the 

patient’s awake baseline, 9 or under unusual loading conditions 

such as excessive anesthesia. 51 

How can we foresee, prevent, or treat the elderly patient 

who has not successfully aged such that he has a decreased 

cardiovascular reserve and is to be exposed to anesthetic 

and surgical stresses? A pulmonary artery catheter and/or 

transesophageal echocardiography to monitor cardiac 

filling pressures/volumes along with invasive blood pressure 

monitoring are the obvious answers that would 

permit very tight control of preload and afterload. 

However, this approach should be reserved for the elderly 

patient with significant limitation of cardiac performance 

related to coexisting CVD (e.g., coronary artery disease, 

congestive heart failure, or documented significant myocardial 

injury). The need for such extensive monitoring 

also must be weighed against the risks for blood loss and 

stress associated with the planned surgical intervention. 

A more realistic approach is to obtain a careful history 

and chart review to get a reasonably good idea of the 

biologic age of the patient. The importance of determining 

the biologic age or “medical fitness” of the elderly 

patient has been emphasized by a prospective study demonstrating 

a significant relationship between coexisting 

diseases in the elderly patient and postoperative morbidity 

and mortality 52 (Figure 10-11). In addition, the preoperative 

level of physical activity proved to be a sensitive 

predictor of postoperative morbidity. 

In a patient who has aged “successfully,” routine monitoring 

with close attention to fluid status and a more 

gradual titration and thoughtful selection of anesthetics 

may be sufficient to minimize the nearly unavoidable 

hypotension. A useful approach in the anesthetic management 

of the elderly is to replace NPO deficits before 

anesthetic induction and to induce anesthesia with etomidate. 

It has been demonstrated that there is a good preservation 

of sympathetic outflow and autonomic reflexes 

with this sedative/hypnotic. 53 However, opioids or esmolol 

must be given to avoid the reflex response to tracheal 

intubation that is poorly attenuated by etomidate. Benzodiazepines 

should be minimized or avoided because 

Figure 10-11. The influence of age and comorbid disease on 

major perioperative complications. Increased comorbid disease 

is associated with increased risk of complications, regardless of 

age. In patients free of disease, age has a minimal effect on risk. 

In patients with multiple diseases, however, the effect of age is 

substantial. (Adapted with permission from Tiret et al. 52 ) 

they interact with opioids to produce sympatho-inhibition 

and hypotension. 

The goal of anesthesia in the elderly is cardiac stability. 

Volatile agents are direct vasodilators and are known to 

depress baroreflex responses. Furthermore, volatile anesthetics 

can produce myocardial depression and nodal 

rhythms that are poorly tolerated in patients with cardiac 

abnormalities such as aortic stenosis, mitral stenosis, or 

hypertrophic obstructive cardiomyopathy. 54 A preference 

might be given to the new, less soluble, volatile anesthetics 

because they can be titrated up or down quickly, and 

emergence times as well as time to orientation are remarkably 

better than with the older volatile anesthetics. 55 

Maintenance can include nitrous oxide when appropriate, 

because it helps to maintain sympathetic outflow and 

lessens the need for higher concentrations of the potent 

volatile anesthetics. 

Hypertension and tachycardia should be recognized as 

undesirable events in the elderly because of the increased 

myocardial oxygen demand and the reduced time for 

atrial filling and coronary flow. Esmolol can be given 

(0.5–1.0 mg/kg) to attenuate the intubation response and 

avoid excessive increases in heart rate. α 2 -Agonists such 

as clonidine or dexmedetomidine also are effective in 

reducing the sympathetic response to laryngoscopy and 

intubation, but add to intraoperative hypotension because 

of their long half-lives. Additionally, adequate analgesia 

is an important aspect of heart rate and blood pressure 

control. Fentanyl can be titrated (1–3 µg/kg) before intubation 

to attenuate the sympathetic response. Naloxone


should be avoided or used with extreme caution in the 

elderly, because large doses can cause pain, leading to an 

acute increase in catecholamine levels. This may result in 

life-threatening complications such as pulmonary edema, 

myocardial ischemia, arrhythmias, and cardiac arrest. 54 

In patients at higher risk of coronary ischemia and 

undergoing noncardiac surgery, prophylactic, perioperative 

β-blockade should be considered. Many studies have 

shown a decreased incidence of myocardial ischemia, 

as well as an overall survival benefit when β-blockers 

are administered perioperatively, 56 although optimal 

duration of β-blockade both pre- and postoperatively 

remains uncertain. β-Blockade may induce protective 

effects via many mechanisms. It may reduce the neuroendocrine 

stress response with surgery, it may reduce the 

incidence of acute coronary plaque rupture by reducing 

shear stress, and it may decrease the incidence of cardiac 

arrhythmias. 54 For those patients receiving chronic β- 

blocker therapy, it should be continued in the perioperative 

period. In fact, an increase in the dosage may be 

prudent. 49 

Postoperatively, the older patient will be at risk for 

developing pulmonary congestion when significant third 

spaced fluid becomes mobilized. Patients with no history 

of heart failure, but who have borderline diastolic dysfunction, 

stiff vessels, and/or poor renal function, may 

experience significant increases in atrial pressure with 

even modest increases in blood volume. Careful and frequent 

bedside examination of the patient during the first 

several postoperative days may permit timely use of 

diuretics; avoiding fluid overload may prevent progression 

to more serious complications such as hypoxia, respiratory 

failure, cardiac dysfunction, or myocardial 

infarction. 

Summary 

A stiffened heart and vascular system, impaired autonomic 

control mechanisms, and altered β-receptor function 

characterize an aging cardiovascular system. These 

alterations make the aged heart more sensitive to volume 

changes in the face of minimal ability to compensate 

via the ANS. When biologic age (“medical fitness”) 

exceeds chronologic age, these changes are likely worsened. 

The addition of volatile anesthetics or propofol 

causes further changes in the ANS and increases the risk 

of hemodynamic fluctuations. Finally, compounding biologic 

age and anesthetics with surgical stress and blood 

loss could lead to substantial hemodynamic instability. It 

is only with a clear understanding of these additive factors 

(age, fitness, anesthesia, and surgical events) that the 

anesthesia provider can effectively predict and manage 

blood pressure and cardiac function during the perioperative 

period. 

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11 

The Aging Respiratory System: Anesthetic 

Strategies to Minimize Perioperative 

Pulmonary Complications 

Rodrigo Cartin-Ceba, Juraj Sprung, Ognjen Gajic, and David O. Warner 

Because of increased life expectancy, the number of elderly 

individuals over the age of 65 is increasing all over the 

world, especially in developed countries. Although respiratory 

function is relatively well preserved in resting 

elderly patients, reduced respiratory reserve may lead to 

problems in the setting of acute illness or surgery. To anticipate 

and prevent potential problems that may result from 

reduced respiratory reserve, it is important to understand 

the effects of aging on respiratory function. Such changes 

may have particular significance during the perioperative 

period when numerous anesthetic and surgical factors, 

such as body positioning, residual effects of anesthetics on 

control of respiration, structural and functional disruption 

of respiratory muscles, and perioperative changes in lung 

fluid balance, may impose additional burdens on elderly 

patients with diminished pulmonary reserve. Indeed, postoperative 

respiratory complications account for approximately 

40% of the perioperative deaths in patients over 

65 years of age. 1 In this chapter, we review the effects of 

aging on pulmonary function and the effects of anesthesia 

and surgery on this function. Particular emphasis is directed 

to the surgical and anesthetic factors that stress the respiratory 

system of the elderly and how these factors increase 

the risk of postoperative pulmonary complications, such 

as respiratory failure. 

The Physiology of the Aging Lung 

Cellular Mechanisms 

Lung function gradually deteriorates with age even in 

healthy individuals who attempt to maintain aerobic 

capacity. 2,3 Aging is a complex process that begins at the 

cellular level. Normal cells undergo senescence as a result 

of multiple mechanisms such as telomere shortening 

during continuous proliferation, oxidative stress, DNA 

damage, and aberrant oncogene activation. 4 Normal 

mitochondrial respiration is associated with oxidative 

stress for the cell because of a continuous production of 

superoxide and hydrogen peroxide, inevitably resulting 

in minor macromolecular damage. Damaged cellular 

components are not completely recycled by autophagy 

and other cellular repair systems, leading to a progressive 

age-related accumulation of biologic “waste” material, 

including defective mitochondria, cytoplasmic protein 

aggregates, and an intralysosomal undegradable material 

called lipofuscin. 5 At the physiologic level, aging is associated 

with multiple changes in the respiratory system, 

including structural changes in both the lungs and chest 

wall, leading to alteration in measurable mechanical 

properties of the respiratory system, interference with 

gas exchange, and impaired response to hypoxia and 

hypercapnia. 

The respiratory system is a network of organs and 

tissues that exchanges gases between the individual and 

the environment, delivering oxygen to venous blood 

in exchange for carbon dioxide. 6 The lungs continue to 

develop throughout life with the maximal number of 

alveoli attained before 12 years of age. The maximal function 

of the respiratory system, defined as a maximal 

ability to exchange gas, is achieved at approximately the 

mid-third decade of life. 7 

The three most important physiologic changes associated 

with aging are: a decrease in strength of respiratory 

muscles, a decrease in the elastic recoil 8 (Figure 11-1) 

of the lung, and a decrease in the compliance of the 

chest wall. 7 

Age-Related Changes in Mechanics 

of Breathing 

Chest Wall and Respiratory Muscles 

The chest wall progressively stiffens with aging because 

of structural changes of the intercostal muscles, intercos- 

149

150 R. Cartin-Ceba et al. 

Lung compliance increases with aging primarily because 

of the loss in parenchymal elasticity (Table 11-1). 7,8 As a 

result, elastic recoil pressure of the lungs decreases with 

aging (Figure 11-1). 7,8,14 A presumed mechanism of 

decrease in elasticity is attributed to changes in the spatial 

arrangement and/or crosslinking of the elastic fiber 

network. 9 The changes in lung parenchyma become more 

pronounced after 50 years of age, resulting in a homogeneous 

enlargement of air spaces causing the reduction of 

alveolar surface area from 75 m 2 at age 30 to 60 m 2 at age 

70. 9 Because these changes functionally resemble emphysema, 

they are sometimes referred to as “senile 

emphysema.” 6,15 

Figure 11-1. Static elastic recoil decreases throughout life 

starting around the age of 20. TLC = total lung capacity. Shaded 

area represents mean ± 1 SD. (Reprinted with permission from 

Janssens et al. 7 ; publisher: European Respiratory Journal; and 

adapted with permission from Turner et al. 8 ; publisher: American 

Physiological Society.) 

tal joints, and rib-vertebral articulations, leading to a 

decrease in static chest wall compliance. 8,9 The increase 

in the rigidity of the rib cage with age is secondary to 

multiple factors, including changes in rib-vertebral articulations, 

changes in the shape of the chest (mainly because 

of osteoporosis that increases both dorsal kyphosis and 

anteroposterior chest diameter), costal cartilage calcification, 

and narrowing in the intervertebral disk spaces. 7,9 

The changes in the chest wall geometry with aging 

result in flattening of the diaphragm curvature (Figure 

11-2), 1 which has a negative effect on the maximal transdiaphragmatic 

pressure. 1,7 Associated reduction in muscle 

mass contributes to a decrease in the force produced by 

respiratory muscles. In a 70-year-old individual, maximal 

skeletal muscle electromyographic activity is reduced 

by approximately 50%. 10 Respiratory muscle strength 

may be further affected by nutritional status, which may 

be deficient in the elderly. 11,12 The main consequence of 

the reduction in the maximal transdiaphragmatic pressure 

is predisposition of the diaphragm to fatigue in the 

presence of increased ventilatory load, 13 which may lead 

to difficulty in weaning an elderly patient from the 

ventilator. 

Lung Parenchyma 

Spirometry: Static and Dynamic Tests and 

Underlying Physiology 

All lung volumes increase from birth until somatic growth 

stops. Total lung capacity (TLC) decreases slightly with 

age. However, TLC is correlated with height, and, given 

the fact that height diminishes with age (because of flattening 

of the intervertebral disks), TLC, normalized for 

height, remains unchanged (Figure 11-3). 7,16,17 Furthermore, 

the overall effect of loss of inward elastic recoil of 

the lung with aging is somewhat balanced by the decline 

in the chest wall outward force such that the TLC remains 

unchanged. 9 Because TLC remains unchanged, an 

increase in residual volume (RV) of 5%–10% per decade 

results in a decrease in vital capacity (VC); after age 20, 

VC decreases 20–30 mL per year. 18 The RV/TLC ratio 

increases from 25% at 20 years to 40% in a 70-year-old 

subject. Functional residual capacity (FRC) is determined 

by the balance between the inward recoil of the lungs and 

the outward recoil of the chest wall. FRC increases by 

1%–3% per decade (Figure 11-3) because at relaxed endexpiration, 

the rate of decrease in lung recoil with aging 

exceeds that of the rate of increase in chest wall 

stiffness. 18,19 

Forced expiratory volume in 1 second (FEV 1 ) and 

forced VC (FVC) increase up to 20 years of age in females 

and up to 27 years of age in males, followed by gradual 

decrease (up to 30 mL per year) (Figure 11-4). 9,20,21 After 

Figure 11-2. Aging-induced reduction of elastic recoil results 

in enlargement (barrel shaped) of the thorax and flattening of 

the diaphragm. The flatter diaphragm is less efficient in generating 

more muscle power which increases the work of breathing. 

The loss of elastic recoil results in a narrowing of small air - 

ways. Left panel: juvenile lung, right panel: aged lung. (Reprinted 

with permission from Zaugg and Lucchinetti. 1 Publisher: 

WB Saunders. Copyright © 2000 Elsevier.)

11. The Aging Respiratory System 151 

Table 11-1. Changes in respiratory function associated with aging and pathophysiologic mechanisms that explain perioperative 


Function alteration Change Pathophysiology Potential complications 

Upper airway patency ↓ Hypotonia of hypopharyngeal and genioglossal Upper airway obstruction and OSA 

muscles, obesity (redundant tissues) 

Swallowing reflexes and ↓ Clearance of secretions Aspiration risk, inefficient expectoration, 

cough 

pneumonia, atelectasis, hypoxemia 

Chest wall compliance ↓ Structural changes of the intercostal muscles and ↑ Work of breathing; delayed 

joints; and rib-vertebral articulations 

weaning from mechanical ventilation 

Airway resistance ↑ ↓ Diameter of small airways Air trapping, propensity for developing 

intraoperative atelectasis; ↓ maximal 

expiratory flow (airflow limitation) 

during exercise 

Lung compliance ↑ ↓ Lung static elastic recoil pressure Air trapping, potential for dynamic 

hyperinflation during mechanical 

ventilation 

Closing volume ↑ Closing of small airways, sometimes within normal Intraoperative hypoxemia, especially 

tidal volume breathing 

with ↓ FRC (mean lung volume) 

after induction of anesthesia; airflow 

limitation 

Gas exchange ↓ ↑ Ventilation/perfusion heterogeneity and Hypoxemia 

Oxygenation ↓ diffusing capacity 

Gas exchange ↔ In CO 2 ↑ In dead space ventilation counteracted by ↓ in 

CO 2 production because of ↓ in basal metabolic 

rate 

Exercise capacity ↓ ↓ V˙ O 2 max because of ↓ in cardiac output Associated with higher incidence of 

Deconditioning 

postoperative pulmonary complications 

Regulation of breathing ↓ Dysfunction of central chemoreceptors and ↓ Ventilatory response to hypoxemia. 

peripheral mechanoreceptors 

Risk of hypercarbia and hypoxemia 

during use of opioids 

V˙ O 2 max = maximal oxygen uptake, CO 2 = carbon dioxide, OSA = obstructive sleep apnea, FRC = functional residual capacity, ↑ = increased, 

↓ = decreased or reduced, ↔ = no change. 

Figure 11-3. Evolution of lung volumes with aging. TLC = total 

lung volume, VC = vital capacity, IRV = inspiratory reserve 

volume, ERV = expiratory reserve volume, FRC = functional 

residual capacity, RV = residual volume. Aging produces an 

increase in RV with consequent reduction in ERV and VC, 

without changing TLC. (Reprinted with permission from 

Janssens et al. 7 ; publisher: European Respiratory Journal; and 

adapted with permission from Crapo et al. 17 ; publisher: European 

Respiratory Journal.) 

Figure 11-4. Effect of aging on FEV 1 (forced expiratory volume 

in 1 second) and FVC (forced vital capacity) in males and 

females. Both progressively decline after 20 years of age. 

(Reprinted with permission from Crapo 9 ; and adapted with 

permission from Burrows et al. 21 ; publisher: Taylor & Francis 

Group.)


65 years of age, this decline may be accelerated (38 mL 

per year). 22 Chronic smoking dramatically accelerates 

these age-related changes in FEV 1 and FVC. 23 In healthy, 

elderly subjects from 65 to 85 years of age, the normal 

FEV 1 /FVC ratio may be as low as 55%, compared with 

expected ≥70% in younger individuals. 24 Lung volume is 

a major determinant of airway resistance but, when 

adjusted for age-related change in mean lung volume, 

aging has no significant effect on airway resistance. 25 A 

decrease in small airway diameter with aging, associated 

with reduced mean lung volume (Figure 11-2, Table 11-1), 

contributes to a decrement in maximal expiratory flow 

with aging, 26 present even in lifetime nonsmokers. 27 

Airway Closure Concept (Closing Volume) 

The loss of elastic recoil 7,17 also affects the caliber of 

intrathoracic airways (Figure 11-2). 26 These airways are 

normally distended by the transpulmonary pressure gradient 

(P tp ), i.e., the pressure gradient from inside the 

airway to the pleural space (Figure 11-5A). 28 In upright 

subjects, there is vertical gradient in pleural pressure, 

which results in gradient of P tp from the top (high P tp ) to 

the bottom (low P tp ) of the lung. This P tp gradient creates 

differences in the distending forces acting on small 

airways and causes airway diameter to be smaller in the 

dependent lung zones (Figure 11-5B). 28 When the patient 

exhales, the intrapleural pressure becomes less subatmospheric. 

At some point, the pressure at dependent parts 

of pleural space equals or exceeds atmospheric, and the 

airways in the dependent lung zones close (Figure 11-5B). 

Subsequent research has shown that this concept is an 

Figure 11-5. Effects of transpulmonary pressure (P tp ) on airway 

diameter at functional residual capacity (A) and at residual 

volume (B). Because of the vertical gradient of transpulmonary 

pressure, at residual volume the distending pressure across 

dependent airways becomes negative, and these dependent 

airways collapse. The lung volume at which this first occurs to 

a significant extend has been termed the “closing volume.” 

(Reprinted with permission from Sykes et al. 28 ) 

oversimplification of a complicated process. Nonetheless, 

this concept of “closing volume” is a useful means of 

conceptualizing lung behavior at low volumes. Because 

lung static recoil decreases with age, closing volume 

increases with age. In younger subjects, closing volume is 

less than FRC, and the airways remain open during 

resting tidal volume breathing. The increases in FRC with 

aging are less than increases in closing volume, such that 

in erect subjects without lung disease the closing volume 

starts to exceed FRC around the age of 65. 27 Because 

FRC decreases when a subject assumes the supine position, 

airway closure may be present during resting tidal 

volume breathing, and this typically occurs around the 

age of 45. When airways are closed during tidal breathing, 

it may lead to gas-exchange abnormalities (discussed 

below); indeed, changes in closing volume with age are 

correlated with hypoxemia. 1 

Just as the lung volume is determined by the P tp 

gradient (as discussed above), the diameter of intrathoracic 

airways during breathing is determined in part by 

the transmural pressure gradient, i.e., the gradient of 

pressure from inside the airway to the intrapleural space. 29 

For the larger intrathoracic airways, the pressure outside 

the airways is the same as intrapleural pressure (Figure 

11-6A). 28 This transmural gradient is increased with 

increases in lung volume so that airway diameter increases 

with inspiration (Figure 11-6B). 28 During late nonforced 

expiration, the gradient of pressure between the pleural 

space and inside the airway is small, causing narrowing 

of the airway (Figure 11-6C). During forced expiration, 

active contraction of the expiratory muscles generates 

pleural pressure that is above atmospheric, and this 

creates a larger gradient of pressure down the airways 

(Figure 11-6D). The point in the small airway where intrapleural 

pressure equals the intra-airway pressure is called 

“equal pressure point.” From that point downstream, the 

pleural pressure exceeds the intra-airway pressure causing 

it to close. Compression of airways limits the effectiveness 

of the expiratory muscles and sets a maximal flow 

rate for each lung volume (“airflow limitation”). 29–31 With 

aging-induced loss of the lung elastic recoil pressure, 

“flow limitation” occurs at higher lung volumes compared 

with younger subjects. This expiratory airflow limitation 

in elderly subjects causes a significant alteration of ventilatory 

response to exercise compared with younger 

adults (Figure 11-7). 32,33 Older subjects have less ventilatory 

reserve to accommodate the increased ventilatory 

demand of exercise because of marked airflow limitation. 

33 During similar levels of maximal exercise (minute 

ventilation of 114 L/min), 45% of the tidal volume of the 

70-year-old subject is flow-limited because of airway 

compression, in comparison to less than 20% in the 30- 

year-old untrained adult (Figure 11-7). 32 Despite these 

limitations, arterial Pco 2 and Po 2 are well maintained, 

even during maximal exercise.


Figure 11-6. Factors affecting airway diameter. Schematic presentation 

of alveolus and intrathoracic airways. (A) At FRC: 

The intrapleural pressure (−5 cm H 2 O) is generated by the 

elastic recoil pressure of the alveoli (−5 cm H 2 O). The inside of 

the alveoli and airways are at atmospheric pressure (0 cm H 2 O). 

A transairway pressure of 5 cm H 2 O maintains airway patency. 

(B) Early inspiration: The gradient of pressure from alveolus 

(−5 cm H 2 O) to pleural space (−10 cm H 2 O) causes the alveolus 

to expand and draw air in through the airways. The resistance 

of the airways creates a gradient of pressure along the airways 

so that the transairway pressure gradient is greatest in the 

airways closer to the mouth. (C) Late expiration: The activity 

of the inspiratory muscles has ceased and the lung elastic recoil 

pressure is +6 cm H 2 O. The resultant transairway gradient of 

+4 cm H 2 O drives the remaining air out of the alveoli. The gradient 

of pressure between the pleural space and inside the airways 

is reversed and the airway is narrowed. (D) Forced expiration: 

Active contraction of the expiratory muscles generates aboveatmospheric 

pleural pressure. Although the pressure in the 

alveolus still exceeds pleural pressure because of the lung elastic 

recoil pressure, there is a large gradient of pressure down the 

airways. The pleural pressure equals the intra-airway pressure 

at equal pressure point (EPP). Downstream from that point the 

pleural pressure exceeds the intraluminal pressure in the downstream 

portion of the airway which thus closes. This “dynamic 

compression” of the airway limits determines the maximal flow 

achievable at a given lung volume. (Reprinted with permission 

from Sykes et al. 28 ) 

The Effects of Aging on Gas Exchange 

Figure 11-7. Flow limitation with progressive exercise in 30- 

year-old untrained adults and in 70-year-old adults. At a given 

minute ventilation, the incidence of flow limitation during tidal 

breathing is greater in the elderly than in the young. (Adapted 

with permission from Johnson et al. 32 ; publisher: Elsevier.) 

The efficiency of alveolar gas exchange decreases with 

age. One explanation is an imbalance in the ventilation/ 

perfusion ratio mainly caused by increase in physiologic 

dead space and shunting. 34,35 This imbalance leads to 

a gradual decrease in arterial Po 2 with aging (Figure 

11-8). 19,36,37 At the same time, once arterial Pco 2 reaches 

40 mm Hg in the newborn, it remains virtually constant 

for the remainder of life, and the CO 2 elimination remains 

unaffected despite an increase in dead space ventilation 38 

and reduction in CO 2 sensitivity with aging. The latter is 

attributable at least in part to a decline in CO 2 production 

associated with a decrease in basal metabolic rate. Multiple 

factors contribute to the decline in arterial Po 2 

related to age. In young, seated subjects breathing air at 

rest, the alveolar-arterial pressure difference for oxygen 

(A-aDO 2 ) is between 5 and 10 mm Hg. An increase in the 

A-aDO 2 with age occurs because of an increase in venti-


increases with aging, unrelated to oxyhemoglobin desaturation 

or increase in metabolic acidosis. 45 

Figure 11-8. Arterial oxygenation (Po 2 ) as a function of age 

from birth to 80 years. Note the decline in arterial Po 2 after the 

age of 20. (Reprinted with permission from Murray. 19 Copyright 

© 1986 Elsevier.) 

lation/perfusion heterogeneity, thought to be caused by a 

decrease in alveolar surface area and increase in closing 

volume. 39 Additionally, increased body mass index, as 

seen with obesity, that frequently accompanies aging, can 

contribute to the widening of A-aDO 2 . After 75 years of 

age, arterial oxygen tension remains relatively stable at 

around 83 mm Hg. 40 The diffusing capacity of the lungs 

decreases with aging 41 at a rate between 0.2 and 0.3 mL/ 

min/mm Hg/year, 19 with this decline being more pronounced 

after the age of 40. This deterioration is attributed 

to an increase in ventilation/perfusion mismatching, 

decline in pulmonary capillary blood volume, 41 and/or the 

loss of the alveolar surface area. 42 

Regulation of Breathing 

In humans, ventilation is adjusted by inputs from different 

chemoreceptors that respond to metabolic factors 

and by inputs from mechanoreceptors that provide feedback 

from the chest wall, lungs, and airways. Minute ventilation 

at rest is similar in young and elderly subjects, but 

tidal volumes are smaller and respiratory rates are higher 

in the elderly. 46 The mechanism is not fully understood, 

but it may represent an adaptation to decreases in chest 

wall compliance, as well as changes in the function of 

central chemoreceptors and peripheral mechanoreceptors 

in the chest wall and lung parenchyma. 47 Compared 

with younger subjects, elderly individuals have approximately 

50% and 60% reduction in the ventilatory 

response to hypoxia and hypercapnia, respectively. 48 

Moreover, studies have shown that the average increase 

in ventilation in response to an alveolar pressure of 

oxygen of 40 mm Hg in older men is 10 L/min, in contrast 

to 40 L/min for younger individuals. 49 Responses to normocapnic 

hypoxemia during sleep can be even more 

depressed. For example, elderly individuals may not 

arouse from the REM phase of sleep until their oxyhemoglobin 

saturation decreases below 70%. Although 

in elderly subjects the ventilatory response to hypercapnia 

is blunted compared with younger subjects, the ventilatory 

response to exercise is actually increased: for a 

given CO 2 production during exercise, the ventilatory 

response increases with aging compared with younger 

individuals. 45 This cannot be explained by either increased 

anaerobiosis or oxyhemoglobin desaturation, but it seems 

Aging and Exercise Capacity 

Age is a significant factor determining maximal O 2 uptake 

(V˙ O 2 max). V˙ O 2 reaches a peak between 20 and 30 years 

of age and then decreases at a rate of 9% per decade 

(Figure 11-9). 19,43 The V˙ O 2 max decrease is more pronounced 

in sedentary elderly subjects than in the physically 

active. 44 In elderly individuals who maintain athletic 

exercise, the decline in V˙ O 2 max is slowed. Factors that 

limit the V˙ O 2 max in the elderly include a decrease in 

maximal minute ventilation, decrease in the maximum 

arterial-venous O 2 content difference, decrease in O 2 

extraction by the tissues, and reduced peripheral muscle 

mass. The decrease in O 2 transport capacity during senescence 

is also linked to an age-related decrease in cardiac 

output. The O 2 cost of breathing (i.e., proportion of O 2 

consumption by respiratory muscles) is higher than in 

younger subjects. Also, compared with younger individuals, 

the elderly are more responsive to CO 2 during exercise; 

for a given CO 2 production, the ventilatory response 

Figure 11-9. Maximal oxygen uptake (V˙ O 2 max) measured 

during maximal exercise as a function of age. Note the decline 

in V˙ O 2 max starting near 30 years of age. (Reprinted with permission 

from Murray. 19 Copyright © 1986 Elsevier; and adapted 

from Grimby and Saltin 43 by permission from Taylor & Francis 

Group.)


that increased ventilation in the elderly compensates for 

increased inefficiency of gas exchange, allowing for the 

maintenance of normocapnia during exercise. 50 

Other respiratory control mechanisms may be altered 

in the elderly because of reduced efficiency in distinguishing 

respiratory stimuli and/or altered integration of perception 

of stimuli within the central nervous system. 51–53 

The elderly also have a lesser ability to perceive methacholine-induced 

bronchoconstriction. 41 The loss of im - 

portant protective and adaptive mechanisms, which may 

result in lesser awareness of disease and delayed diagnosis 

of pulmonary dysfunction in the elderly, are influenced 

by the blunted response to hypoxia and hypercapnia 

and a lower ability to perceive disease states such as 

bronchoconstriction. 

Upper Airway Dysfunction 

Hypotonia of the hypopharyngeal and genioglossal 

muscles predispose elderly subjects to upper airway 

obstruction, and the prevalence of sleep-disordered 

breathing increases with age. 54 Studies have found that 

up to 75% of subjects over 65 years old have obstructive 

sleep apnea (OSA). 55,56 Indeed, the prevalence of OSA in 

the elderly is so high that authorities are questioning 

whether OSA in the elderly is a different disease from 

OSA in middle age. 55 Some of the consequences of 

chronic hypoxemia associated with OSA may include 

cognitive impairment, personality changes, and hypertension. 

56 OSA may be even more prevalent in elderly obese 

individuals, who may have increased postoperative risk 

of respiratory complications. 57 

The protective mechanisms of cough and swallowing 

are altered in elderly individuals, which may lead to ineffective 

clearance of secretions and increased susceptibility 

to aspiration. Mucociliary transport is also impaired 

in the elderly. Coughing is also less efficient in terms of 

volume, force, and flow rate. The loss of protective upperairway 

reflexes is presumably attributable to an agerelated 

alteration in peripheral signaling together with 

decreased central nervous system reflex activity. 58 In 

addition, elderly individuals have an increased prevalence 

of neurologic diseases that may be associated with 

dysphagia and an impaired cough reflex leading to the 

increased likelihood of pulmonary aspiration 58 and pneumonia, 

59 which may have a significant impact on perioperative 

morbidity and mortality. 

Perioperative Pulmonary 

Complications in the Elderly 

With increased longevity, more elderly patients are 

potential candidates for major surgical procedures. For 

example, in 1997 in the United States, the Agency for 

Healthcare Policy and Research reported 1,350,000 major 

procedures in the 65- to 84-year-old age group and 233,000 

procedures in the 85 and older age group. 60 Postoperative 

pulmonary complications, including atelectasis, pneumonia, 

respiratory failure, and exacerbation of underlying 

chronic lung disease, have a significant role in the risk for 

anesthesia and surgery. 61 These complications have been 

reported in 5%–10% of the general patient population 62 

and usually prolong the hospital stay by an average of 

1–2 weeks. 63 Pulmonary complications in nonthoracic 

surgery are as prevalent as cardiovascular complications 

and contribute in a similar manner to morbidity, mortality, 

and length of stay. 64,65 

Numerous factors may contribute to the development 

of postoperative pulmonary complications in the elderly 

(Figure 11-10). Advanced age is a significant independent 

predictor of pulmonary complications even after adjustment 

for various comorbid conditions. 61,64,66 Age increases 

the risk of pulmonary complications with an odds ratio 

of 2.1 for patients 60–69 years old, and 3.0 for those 70–79 

years old compared with patients younger than 60 

years. 61,64,67 Older age represents the second most common 

identified risk factor for pulmonary complications after 

the presence of chronic lung disease. 61,66,68 A multifactorial 

risk index for predicting postoperative respiratory 

failure in men after major noncardiac surgery 69 showed 

that age above 70 conferred a 2.6-fold increase in the risk 

of respiratory failure compared with subjects less than 60 

years old. 

Factors contributing to an increased risk of pulmonary 

complications in the elderly are: (a) decreases in chest wall 

compliance and muscle strength (increasing the work of 

breathing and the risk for respiratory failure); (b) changes 

in lung mechanics (including increased tendency for small 

airway closure which may impair gas exchange and promote 

atelectasis); (c) increased aspiration risk secondary to swallowing 

dysfunction; and (d) alterations in the control of 

breathing, including impaired responses to hypercapnia 

and hypoxia and increased sensitivity to drugs used during 

anesthesia (especially opioids) in the elderly. 70 

Intraoperative alterations in chest wall function lead 

to atelectasis, which forms within minutes after the 

induction of anesthesia and is an important cause of 

intraoperative gas-exchange abnormalities. Chest wall 

dysfunction persists into the postoperative period because 

of pain (which limits the voluntary actions of the chest 

wall muscles), reflex inhibition of the respiratory muscles, 

and mechanical disruption of respiratory muscles (surgery 

in the thoracic and abdominal cavities). Consequently, 

after thoracic or upper abdominal surgery, FRC and VC 

decrease and breathing becomes rapid and shallow, all of 

which may contribute to the development of pulmonary 

complications. 71 These effects apply to all ages but may 

be of special significance in the elderly patient with 

reduced respiratory reserve.


N 

U 

R 

Figure 11-10. Perioperative strategies used to minimize pulmonary complications. 

Older, nonanesthetized individuals have less efficient 

gas exchange compared with younger subjects. 36 Upon 

assuming the supine position, there is a decrease in FRC 

and hence an increase in airway resistance, which is more 

marked in the elderly (especially those who are obese). 36 

Alveolar gas exchange during anesthesia is less efficient 

in the elderly, and there is an inverse relationship between 

increased age and arterial Po 2 in spontaneously breathing 

anesthetized patients. 37,39 After the induction of anesthesia, 

atelectasis develops in dependent lung regions and 

may produce significant shunting. However, both the 

amount of atelectasis and pulmonary shunting do not 

increase significantly with age. 72,73 A similar phenomenon 

occurs in patients with chronic obstructive pulmonary 

disease (COPD); after the induction of anesthesia, there 

is less formation of atelectasis and less shunting compared 

with normal patients, which is explained by changes 

in the chest wall secondary to hyperinflation that prevents 

alveolar collapse. 74 

Decreased respiratory muscle strength, combined with 

diminished cough and swallowing reflexes (neurologic 

disorders, stroke, etc.), may diminish clearance of secretions 

and increase the risk of aspiration in the elderly. 75,76 

This risk is even higher in the presence of gastroesophageal 

reflux, which is also more prevalent in the elderly. 

Selective, rather than routine, nasogastric tube decompression 

after abdominal surgery may improve the return 

of bowel function and reduce the risk of postoperative 

pulmonary complications, specifically a lower rate of atelectasis 

and pneumonia. 77,78 Interestingly a the aspiration 

rate was not lower in patients with selective nasogastric 

decompression. 78 Finally, age-related changes in control 

of breathing, increased sensitivity to anesthetic agents, 

and diminished response to gas-exchange abnormalities 

predispose elderly patients to postoperative respiratory 

failure. Elderly patients also have a higher incidence of 

postoperative sleep apnea episodes. 70,79 

General Health Status 

Multiple measures of functional status and general health 

predict the risk of postoperative pulmonary complications. 

An American Society of Anesthesiologists Physical 

Status Classification above II, poor exercise capacity, the


presence of COPD, and congestive heart failure are all 

associated with increased risk of pulmonary complications 

in the elderly. 64,80,81 COPD is more prevalent in the 

elderly population and is the most important patientrelated 

risk factor for the development of postoperative 

pulmonary complications, producing a three- to fourfold 

increase in relative risk. 66,81,82 Although obesity is prevalent 

in elderly patients and is associated with decreased 

perioperative arterial oxygenation, obesity is not a significant 

independent predictor of risk. 64,80,83 

Decreased functional status, which may accompany 

aging, is an independent risk factor for pulmonary complications. 

64 Objective measurement of exercise capacity 

in geriatric patients demonstrated that inability to perform 

2-minute supine bicycle exercise and an increase in 

the heart rate to above 99 beats/min was the best predictor 

of perioperative cardiopulmonary complications in 

patients older than 65 years undergoing elective abdominal 

or noncardiac thoracic surgery. 84 Patients with better 

exercise tolerance by self-report, better walking distance, 

or better cardiovascular classification had lower rates of 

postoperative pulmonary complications. 85 

Strategies Used to Minimize Pulmonary Risk 

in Elderly Patients: Preoperative 

Considerations 


The value of routine preoperative pulmonary function 

testing is controversial. For lung resection surgery, the 

results of pulmonary function testing, including measurement 

of arterial blood gases, have proven useful in predicting 

pulmonary complications and postoperative 

function; however, spirometry does not predict postoperative 

pulmonary complications after abdominal 

surgery. 85,86 Warner et al. 87 have demonstrated that the 

degree of airway obstruction assessed by spirometry does 

not represent an independent risk factor for postoperative 

respiratory failure, even in smokers with severe lung 

disease. 87 Spirometry, chest radiograms, and arterial blood 

gases should be obtained as indicated from the history 

and physical examination as a part of this evaluation, but 

should not be routinely ordered. 78 

Preoperative Therapies 

To minimize postoperative pulmonary complications in 

elderly patients, it is important to optimize the respiratory 

status, beginning with a careful assessment of general 

physical status, with particular attention to the cardiopulmonary 

system. Specific therapy should be instituted preoperatively 

if such treatment is likely to result in improved 

functional status, so long as the therapeutic benefit outweighs 

any risk from surgical delay (Figure 11-10). 

Preoperative spirometry should be used only to monitor 

the degree of therapeutic response to treatments such as 

bronchodilators used to treat reactive airway disease. 

Patients with a reversible component of airway obstruction 

must be treated with bronchodilators and/or corticosteroids. 

Antibiotics must be given if a pulmonary 

infection is suspected. Preoperative smoking cessation 

may decrease postoperative pulmonary complications, 

and all patients who smoke should be given help to 

quit. 88,89 Past studies have been interpreted as demonstrating 

that quitting within a few weeks of surgery actually 

increases pulmonary complications by stimulating 

mucous production. 90 However, careful review of these 

studies and more recent data show that, although it may 

take several weeks of abstinence before pulmonary outcomes 

are improved, brief abstinence does not worsen 

outcomes. 89,90 Thus, this consideration should not prevent 

practitioners from promoting preoperative abstinence 

from smoking, even for a brief period before surgery. 


in Elderly Patients: Intraoperative 


Surgical Considerations 

The surgical site is the most important risk factor for the 

development of postoperative pulmonary complications 

and outweighs other patient-related risk factors. 67,69 There 

is a higher likelihood of pulmonary complications with 

incisions closer to the diaphragm because of diaphragmatic 

dysfunction, splinting, and decreased ability to take 

deep breaths. For example, pulmonary complications 

caused by upper abdominal surgeries range from 13% to 

33% as compared with lower abdominal surgeries that 

range from 0% to 16%. 80 Duration of surgery also has a 

significant role in the development of pulmonary complications, 

and surgeries that last more than 3 hours have an 

increased risk of pulmonary complications. 91 When surgically 

feasible, laparoscopic techniques should be considered; 

however, significant respiratory dysfunction can 

occur even after laparoscopically performed operations, 78 

and whether laparoscopic procedures may reduce the 

risk of clinically important pulmonary complications is 

not clear. Nonetheless, other considerations such as 

reduced postoperative pain and length of stay often 

favor the use of laparoscopic techniques. Placement of an 

aortic stent instead of an open aortic aneurysm repair 

may be desirable in patients with significant pulmonary 

comorbidity. 

Induction of Anesthesia 

Preoxygenation is recommended before the induction 

of general anesthesia. In contrast to younger patients,


performing only four deep breaths before the induction 

may not be sufficient in elderly patients, who may require 

a full 3 minutes of 100% oxygen breathing to avoid oxyhemoglobin 

desaturation during rapid sequence induction. 

92 In patients with intact oropharyngeal reflexes but 

significant reactive airway disease, avoidance of endotracheal 

intubation by using a laryngeal mask airway may 

be desirable. 

Use of Muscle Relaxants During Anesthesia 

In elderly patients, inadequate reversal of muscle paralysis 

may be an important factor for postoperative complications 

leading to hypoventilation and hypoxemia. 86 

Pulmonary complications are three times higher among 

patients receiving a long-acting neuromuscular blocker 

than among those receiving shorter-acting relaxants. 93 

Short-acting neuromuscular blocking agents should be 

used in the elderly to avoid prolonged muscle paralysis, 

and adequacy of reversal of neuromuscular block should 

be tested before extubation. 78 

Use of Regional Anesthetic Techniques for Surgery 

Evidence is conflicting whether the use of regional techniques 

instead of general anesthesia will prevent postoperative 

pulmonary complications. 78 Regional anesthesia 

may be indicated for a variety of reasons in the elderly, 

but it has its own potential respiratory-related risks in 

these patients. Unintentional high anesthetic level during 

neuraxial anesthesia may be associated with paralysis of 

the chest wall (respiratory muscles) that may be poorly 

tolerated by the elderly, especially those with COPD. 

Regional techniques performed at the level of the neck 

(interscalene block, stellate ganglion block, axillary block) 

may be associated with paralysis of the phrenic nerve 

(diaphragm), and, if performed bilaterally, the patient 

may develop acute respiratory failure requiring urgent 

tracheal intubation. 

Intraoperative Lung Expansion During 

General Anesthesia 

As discussed before, in contrast to younger patients, atelectasis 

may be a less important cause of intraoperative 

hypoxemia during general anesthesia in the elderly 72 ; 

however, in elderly obese patients, atelectasis may have 

a significant role in deterioration of intraoperative arterial 

oxygenation. 94 The isolated use of positive end-expiratory 

pressure (PEEP) does not predictably reverse 

atelectasis or increase arterial oxygenation. 95 Recently, 

there has been a considerable interest in maneuvers designated 

to recruit atelectatic lung regions. To reexpand 

the atelectatic lung, it is necessary to use a sustained lung 

insufflation (5–10 seconds long) with high inflation pressures 

(40 cm H 2 O or above). 96–98 This technique is called 

a “recruitment maneuver” or “vital capacity maneuver” 

and should be followed by sufficient PEEP to maintain 

the alveolar units open. 99 It is crucial to closely monitor 

changes in blood pressure and heart rate while performing 

the recruitment maneuver because significant hypotension, 

especially in hypovolemic patients, may ensue. 


in Elderly Patients: Postoperative 


Neuraxial Blocks for Pain Management 

Good postoperative pain control is necessary in all 

patients. There is a longstanding debate regarding whether 

neuraxial techniques such as epidural analgesia reduce 

the frequency of pulmonary complications. It is clear that 

these techniques provide excellent analgesia, but their 

benefits regarding pulmonary outcomes are less clear. 71 

In one meta-analysis, 100 regional techniques reduced mortality 

by about a third with reductions of pulmonary 

embolism and pneumonia of 55% and 39%, respectively. 

However, many of the studies used in this and other 

meta-analyses have methodologic limitations. A recent 

unblinded, large clinical trial found few differences in 

outcome between those receiving and not receiving epidural 

analgesia, with the exceptions that: (1) respiratory 

failure was less frequent for some types of operations, 

and (2) postoperative pain control was improved by epidural 

analgesia. 101 A prospective, double-blind randomized 

trial performed by Jayr et al. 102 demonstrated that 

the use of epidural analgesia provided superior postoperative 

comfort without affecting the frequency of postoperative 

pulmonary complications. In addition, another 

blinded trial performed by Norris et al. 103 showed that in 

patients undergoing surgery of the abdominal aorta, thoracic 

epidural anesthesia combined with a light general 

anesthesia and followed by either intravenous or epidural 

patient-controlled analgesia offers no major advantage or 

disadvantage except for slightly shorter time to extubation. 

Postoperative pain management may include the 

use of a full range of adjunctive analgesia techniques, 

such as surgical field infiltration with local anesthetics, 

utilization of peripheral nerve blocks, nonsteroidal antiinflammatory 

agents, clonidine, and dexmedetomidine. 104 

This “multimodal approach” of using the drugs that are 

associated with low potential for respiratory depression 

may be beneficial in elderly patients prone to developing 

postoperative respiratory depression. 

Caution Regarding Perioperative Use of Opioids 

Elderly patients may be especially sensitive to medications 

because of age-related altered pharmacokinetics 

and pharmacodynamics of the drugs. 70,105 Aging affects


all pharmacokinetic processes, but the most important 

change is the reduction in the renal drug elimination. At 

the same time, pharmacodynamic changes also occur 

at the receptor or signal-transduction level or at the level 

of the homeostatic mechanisms. 105 This situation explains 

why the dosing of all anesthetic drugs should reflect the 

differences in pharmacokinetics and pharmacodynamics 

that accompany aging. Opioids are of particular concern 

in the elderly. Opioids reduce the respiratory response to 

chemical (hypoxemia, hypercapnia) load resulting in 

hypoventilation and hypoxemia. Given the fact that 

elderly patients may be particularly sensitive to opioids, 

they should be titrated carefully in order to avoid postoperative 

respiratory depression. 70 

Postoperative Respiratory Assistance to Maintain 

Lung Expansion 

Decreased lung volumes and atelectasis attributable to 

surgery-related shallow breathing, bed rest, diaphragmatic 

dysfunction, pain, and impaired mucociliary clearance 

may be the first events in a cascade leading to 

postoperative pulmonary complications. 78 Postoperative 

use of lung expansion therapy such as incentive spirometry, 

chest physical therapy, effective cough, postural 

drainage, percussion-vibration, ambulation, continuous 

positive airway pressure (CPAP), and intermittent positive-pressure 

breathing is the mainstay of postoperative 

prevention of pulmonary complications in the elderly. 

Preoperative education in these maneuvers may reduce 

pulmonary complications more efficiently than when 

instruction is given after surgery. 106,107 Lung expansion 

maneuvers, when performed appropriately, lower the risk 

of atelectasis by 50%. 108 No modality seems superior, and 

combined modalities do not seem to provide additional 

risk reduction. 78 Incentive spirometry may be the least 

labor-intensive, whereas CPAP may be particularly beneficial 

for patients who cannot participate in incentive 

spirometry or deep-breathing exercises. 78 However, a 

most recent systematic review of randomized trials 

suggested that routine respiratory physiotherapy may not 

seem to be justified as a strategy for reducing postoperative 

pulmonary complications after abdominal surgery. 109 

All patients with diagnosed OSA should have their status 

evaluated preoperatively, and, if they are CPAP-dependent, 

they should receive the CPAP treatment immediately 

after tracheal extubation. In addition, they may 

need close postoperative monitoring (i.e., oxygenation 

and ventilation). Depending on the severity of OSA, type 

of surgery, and anesthesia, they may require admission to 

a monitored bed overnight. 

Noninvasive Positive Pressure Ventilation 

Noninvasive positive pressure ventilation (NPPV) is the 

delivery of mechanically assisted breaths without placement 

of an artificial airway, such as an endotracheal or a 

tracheostomy tube. Bilevel positive airway pressure 

(BiPAP) is noninvasive ventilatory modality that seems 

to be more efficient than CPAP in supporting breathing. 

With BiPAP, continuous inspiratory positive airway pressure 

provides inspiratory assistance and expiratory positive 

airway pressure prevents alveolar closure. 104 

NPPV may be used in patients with COPD exacerbations, 

cardiogenic pulmonary edema, hypercapnic re - 

spiratory failure caused by neuromuscular disease, 

obesity-hypoventilation syndrome, and immunocompromised 

patients with respiratory failure. The role of nasal 

intermittent positive pressure ventilation (NIPPV) in 

hypoxemic respiratory failure attributable to other causes 

is still controversial and lacks adequate evidence support. 

The idea of utilizing NIPPV to manage patients with 

postextubation respiratory failure came from several 

trials demonstrating efficacy of NIPPV in postoperative 

respiratory failure, particularly when cardiogenic pulmonary 

edema was the etiology. 110–114 Immediately after 

extubation, elderly patients may need additional ventilatory 

support to maintain ventilation and oxygenation. 

CPAP has been successfully used to avoid tracheal reintubation 

in patients who developed hypoxemia after elective 

major abdominal surgery, and the use of CPAP was 

associated with lower incidence of other severe postoperative 

complications. 115 Outcomes of patients with postoperative 

postextubation hypoxemia treated by CPAP 115 

may differ from that in the general intensive care population 

116 or in patients with acute exacerbation of COPD. 117,118 

Thus, Esteban et al. 116 demonstrated that NPPV does not 

prevent the need for reintubation and may be harmful in 

intensive care unit patients who develop respiratory 

failure after tracheal extubation. In contrast, in patients 

with acute exacerbation of COPD, comparing noninvasive 

ventilation with a standard intensive care unit 

approach in which endotracheal intubation was performed 

after failure of medical treatment, the use of noninvasive 

ventilation reduced complications, length of stay 

in the intensive care unit, and mortality. 117 The application 

of NIPPV has also been used successfully in the postoperative 

period with morbid obesity patients who were 

undergoing bariatric surgery. 119,120 Prophylactic BiPAP 

used during the first 12–24 hours after bariatric surgery 

resulted in significantly higher measures of pulmonary 

function, but did not translate into fewer hospital days or 

a lower complication rate. 119 

Mechanical Ventilation in the Elderly 

An aging population is projected to substantially increase 

the demand for intensive care unit services during the 

next 25 years. 121,122 An increasing number of elderly 

patients will also require intensive care treatment 

after surgery. The risk of respiratory failure requiring


mechanical ventilation in response to a variety of physiologic 

insults, including surgery, is increased in the elderly 

because of underlying pulmonary disease, loss of muscle 

mass, and other comorbid conditions. 123 In patients that 

develop adult respiratory distress syndrome, older age is 

clearly associated with higher mortality rates. 124,125 Ely 

et al. 126 prospectively studied whether age represents an 

independent effect on the outcomes in a cohort of patients 

requiring mechanical ventilation after admission to an 

intensive care unit. After adjustment for severity of illness, 

elderly patients, compared with younger patients, required 

a comparable length of mechanical ventilation. These 

effects could not be attributed to the differences in mortality; 

therefore, mechanical ventilation should not be 

withheld from elderly patients with respiratory failure on 

the basis of chronologic age. 126 

Patients aged 65 years or older account for 47% of 

intensive care unit admissions. 127 With aging, there are 

several factors known to affect weaning, such as decrease 

in lung elasticity, reduction in FVC, decreased respiratory 

muscle strength, and decreased chest wall compliance. 128 

Kleinhenz and Lewis 129 reviewed the challenges of 

caring for elderly patients with chronic ventilator dependency. 

Long-term ventilator dependence, defined as need 

for mechanical ventilation for 6 hours per day for more 

than 21 days, is disproportionately higher in patients over 

70 years of age. 129 Long-term ventilator dependence complicates 

9% to 20% of the episodes of mechanical ventilation 

treated in the intensive care units of acute care 

hospitals, and it is associated with an average mortality 

rate of 40%. 129 This is an important socioeconomic issue, 

and more research is needed regarding the causes that 

may lead to respiratory failure in elderly patients. There 

is an ongoing investigation of the effects of “protective 

ventilatory strategies” (lower tidal volume, higher PEEP, 

recruitment lung strategies, as well as effects of intraoperatively 

administered fluids and blood products) on 

postoperative pulmonary outcomes. Literature evidence 

is slowly accumulating showing that the use of “protective 

ventilatory strategies” in high-risk patients may be 

beneficial in preventing postoperative ventilatory 

failure 130–133 ; however, more studies are necessary before 

making definitive recommendations. Some specific areas 

that require further investigation are the relationship 

between the influence of age on weaning and the relationship 

between age and the work of breathing. 

Conclusion 

Aging causes significant changes in respiratory function, 

which leads to ventilation perfusion mismatching and 

diminished efficiency of gas exchange. The perioperative 

period represents a time of increased functional demand 

on the respiratory system, and elderly patients with 

reduced respiratory function may be prone to developing 

pulmonary complications. These complications are a significant 

source of morbidity, mortality, and prolonged 

hospitalization. These pulmonary complications may be 

attributed to diminished protective reflexes, increased 

sensitivity to respiratory depressants, and altered 

responses to hypoxemia and hypercapnia. After identifying 

patients at risk for postoperative pulmonary complications, 

anesthesiologists must consider strategies to try 

to reduce the risk throughout the perioperative period. 

Besides optimization of underlying comorbid conditions, 

anesthesiologists and other perioperative physicians may 

utilize strategies that facilitate lung expansion such as 

deep-breathing exercises, incentive spirometry, and adequate 

postoperative pain control. Select patients may 

benefit from postoperative application of NPPV. 

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12 

Operative Debridements of Chronic Wounds 

Andrew M. Hanflik, Michael S. Golinko, Melissa Doft, Charles Cain, 

Anna Flattau, and Harold Brem 

The term “chronic wound” does not refer to duration over 

time, but rather describes a wound that is physiologically 

impaired. All venous, pressure, and diabetic foot ulcers are 

defined as chronic wounds. Elderly patients are more likely 

to experience venous and pressure ulcers, 1–4 which lead to 

more than half of all lower extremity amputations in 

persons with diabetes. 5 Chronic wounds heal at the same 

frequency of closure in elderly populations as they do in 

younger populations, but may heal at a slower rate, primarily 

because of comorbidities associated with age. 6–9 The 

comorbidities that delay healing are prevalent among older 

populations and include venous insufficiency and diabetes. 

Although there are age-related changes to the skin, it has 

yet to be shown, clinically, that age alone decreases an 

elderly person’s ability to heal. 7,10,11 A synergistic effect of 

advanced age and diabetes significantly slows healing. 12 

Chronic wounds in elderly patients heal successfully if 

the care regimen includes a coordinated effort to treat 

skin breakdown early and to prevent further ulceration. 

In the absence of ischemia and osteomyelitis, prompt 

medical treatment will heal most venous ulcers, diabetic 

foot ulcers, and stage I, II, and III pressure ulcers (defined 

below). 6 Delayed wound treatment, combined with multiple 

comorbidities affecting the elderly population, can 

lead to amputations, sepsis, and death. The established 

pathway from untreated chronic wound to death has 

been used as evidence for the manslaughter convictions 

of several care providers of the elderly. 13 

Pain is a complex and almost universal complication of 

this population, and appropriate pain management by an 

anesthesiologist is becoming increasingly recognized as 

essential in the optimal treatment of these patients. 

The Operating Room 

The only universally accepted treatment for chronic 

wounds is surgical debridement. This is the standard of 

care for nonviable and infected tissue and for the stimulation 

of healing. 14 Because these patients usually have 

multiple comorbidities and American Society of Anesthesiologists 

(ASA) scores of 3 or 4, we recommend 

operative debridement under local or regional anesthesia 

whenever possible. Regional blocks of the sciatic, popliteal, 

and femoral nerves are ideal. Many patients will 

require general anesthesia. It is essential that the patient 

and primary care physician understand this, as well as 

understand that the risks of not performing the debridement, 

i.e., leaving necrotic or infected tissue in an elderly 

person, is greater than the risks of anesthesia itself. For 

patients with peripheral arterial disease, treatment of 

underlying ischemia must be achieved before elective 

debridements unless infection is present. 

Chronic Wounds in the Elderly Result 

in Significant Morbidity and Mortality 

Diabetic Foot Ulcers 

There are 20.8 million Americans diagnosed with diabetes. 

15 The elderly are the largest constituent of this group 

because diabetes affects more than 18% of Americans 

greater than 60 years old. 16 In the United States between 

1997 and 2004, the number of new cases of diabetes 

increased 54%. 17 By the year 2030, 366 million persons 

worldwide are estimated to have diabetes, with 130 

million of them over the age of 64. 18 All of these patients 

are at risk for diabetic complications including retinopathy, 

nephropathy, neuropathy, and accelerated atherosclerosis. 

Neuropathy and atherosclerosis are associated with 

the development of diabetic foot ulcers and impaired 

healing. 19–21 

In the United States, the elderly account for 53.3% of 

diabetes-associated amputations per annum. 5 Diabetic 

foot ulcers are defined as any breakdown of skin on the 

foot of a diabetic person. Recent prevalence is as high 

as 12% of all people with diabetes. 22 These ulcers act 

165

166 A.M. Hanflik et al. 

A B C 

Figure 12-1. Examples of diabetic foot ulcers. Note: any break 

in the epidermis on the foot of a patient with diabetes is considered 

a diabetic foot ulcer. A: Typical-appearing ulcer under 

the fifth metatarsal head. B: A more advanced ulcer on the toe. 

C: A callous surrounded by central ulceration on the plantar 

aspect of the foot. 

as portals for infectious organisms. A large multicenter 

study recently reported 58% of all patients with ulcers 

had concomitant foot infection. 23 Half of the patients who 

develop one foot lesion subsequently develop a contralateral 

wound. 24 Each wound is considered to be chronic 

from its inception and should be treated early. Individuals 

with diabetes have a 30- to 40-fold higher risk of lower 

limb amputation. 25 See Figure 12-1A–C for examples of 

the typical locations of diabetic foot ulcers. 

Pressure Ulcers 

The four stages of pressure ulcers are defined as 26,27 : 

Stage I—Observable pressure-related alteration of intact 

skin whose indicators as compared with the adjacent 

or opposite area on the body may include changes in 

one or more of the following: skin temperature (warmth 

or coolness), tissue consistency (firm or boggy feel), 

and/or sensation (pain, itching). The ulcer appears as a 

defined area of persistent redness in lightly pigmented 

skin, whereas in darker skin tones the ulcer may 

appear with persistent red, blue, or purple hues. See 

Figure 12-2A. 

Stage II—Partial-thickness skin loss involving epidermis, 

dermis, or both. The ulcer is superficial and presents 

clinically as an abrasion, blister, or shallow crater. See 

Figure 12-2B. 

Stage III—Full-thickness skin loss involving damage to, 

or necrosis of, subcutaneous tissue that may extend 

down to, but not through, underlying fascia. The ulcer 

presents clinically as a deep crater with or without 

undermining of adjacent tissue. See Figure 12-2C. 

Stage IV—Full-thickness skin loss with ulceration extending 

through the fascia, with extensive destruction, tissue 

necrosis, or damage to muscle, bone, or supporting 

structures (e.g., tendon, joint, capsule). Undermining 

and sinus tracts are frequently associated with stage IV 

pressure ulcers. See Figure 12-2D. 

In 2003, 455,000 patients in the United States alone 

were hospitalized for pressure ulcers, representing a 63% 

increase from 1993: the most common reason for admission 

was septicemia. 28 The true incidence and prevalence 

of pressure ulcers is not known. A recent national study 

of acute care settings found that the prevalence of pressure 

ulcers ranged between 14% and 17%, whereas the 

incidence was between 7% and 9%. 29 At least 10% of 

hospitalized patients, more than 20% of nursing home 

patients, and 20%–30% of spinal cord injury patients are 

affected. 30 In a nursing home study, 6.5%–19.3% of 

patients developed a new pressure ulcer over a 3- to 21- 

month period. Patients at highest risk were those who 

had diabetes or fecal incontinence. 31 Recent studies have 

demonstrated that both age and immobility are strongly 

linked to development of pressure ulcers 32,33 as well as 

cognitive ability. 34 

The presence of a pressure ulcer doubles the risk of 

mortality in an elderly patient. 35,36 Elderly patients discharged 

with a hospital-acquired pressure ulcer have a 

much greater risk of death within a year than patients 

without a pressure ulcer, indicating that stage IV pressure 

ulcers should never be ignored. 37 A recent study of more 

than 100,000 patients revealed an overall age-adjusted 

mortality rate of 3.79%, for which pressure ulcers were 

listed as the cause of death in 18.7% of patients. 38 Stage 

IV pressure ulcers often lead to sepsis, a common cause 

of death in the elderly. 39,40 

Venous Ulcers 

It is estimated that 1.7% of the elderly population is 

affected by venous ulcers, indicating that they are more 

prevalent in the elderly than in younger populations. 41–43

12. Operative Debridements of Chronic Wounds 167 

A B C 

D 

Figure 12-2. Examples of different stages of pressure ulcers. A: Stage 

I, heel. B: Stage II, ischium. C: Stage III, trochanter. D: Stage IV, 

ischium. 

Venous ulcers are often misdiagnosed as traumatic injuries 

and are therefore undertreated. 44 Although these 

wounds are not frequently associated with osteomyeli - 

tis or amputation, when undertreated, they provide a 

gateway for infection that results in multiple hospitalizations, 

substantial suffering, and health care costs exceeding 

$1 billion annually. 45,46 

Venous ulcers are secondary to venous reflux disease, 

which correlates with increased age. 41,47,48 An example of 

a typical venous ulcer is shown in Figure 12-3. Venous 

reflux disease occurs when valvular incompetence prevents 

normal blood flow from superficial veins to deep 

veins. The most common etiologies for valvular dysfunction 

of the deep venous system are advanced age 41,49 and 

a history of deep vein thrombosis (DVT). 50 Valvular 

incompetence causes increased venous pressures, leading 

to venous distention and activation of apoptotic pathways, 

resulting in ulceration. Another hypothesis is that 

leukocytes and other large molecules become trapped in 

the dermis in response to endothelial damage and venous 

hypertension. 51 It is thought the extravasation of these 

large molecules, proteins, and leukocytes inhibits growth 

factors from reaching their targets. 52 

Ischemic Wounds 

Peripheral arterial disease is often the primary etiology 

of an ischemic wound. It can also impair healing in venous, 

pressure, and diabetic foot ulcers because of a decreased 

blood flow to the affected area. Age, hypertension, 

smoking, and diabetes are each independent risk factors 

for developing peripheral arterial disease. 4,53 Although 

the incidence of peripheral arterial disease is only 4.3% 

in patients over 40 years old, the incidence sharply 

increases to 14.5% in patients over 70. 4 Additionally, a 

large study of Asian patients with diabetes over the age


macrophage function in the older animals. 63–65 The 

decrease in angiogenesis causes an initial delay in wound 

healing; yet, despite this, wounds contract with comparable 

frequency. 66 Therefore, a decreased angiogenic 

response in older animals contributes to an impaired 

wound-healing rate. 

Decreased Immune Response 

Review of experimental and clinical research has shown 

physiologic impairments in the immune response of the 

elderly, making them prone to infection. 67 Older animals 

have a markedly decreased adaptive immune response 

(B and T cells), 67 a bolstered but possibly dysfunctio - 

nal regulatory T cell population (CD4+ CD25+), 68,69 a 

decrease in T cell receptor diversity, 70 and a decrease in 

toll-like receptors 65 and γδ-T cells. 71 The decreased 

immune response makes the elderly more susceptible to 

pathogenic invasion. 

Figure 12-3. Example of a typical lower extremity venous 

ulcer. 

of 50 showed the prevalence of peripheral arterial disease 

to be 17.7%. 54 Many if not most of these patients are 

asymptomatic. 55,56 

Experimental Evidence of Physiologic 

Impairments in the Elderly 

Clinical and experimental studies have demonstrated 

that there is a greater frequency of physiologic impairments 

to wound healing in the elderly population. 

Angiogenesis in Wound Healing 

Laboratory research has identified more than 30 regulatory 

mechanisms of angiogenesis that occur during wound 

healing, including growth factors, growth factor receptors, 

chemotactic agents, and matrix metalloproteinases. In 

animal models, decreased angiogenesis significantly 

inhibits wound healing. 16,57–59 In these models, angiogenic 

cytokines such as vascular endothelial growth factor are 

present in smaller concentrations in the wounds of older 

animals compared with younger animals, resulting in 

smaller capillary densities within the wound bed. 60–62 It is 

theorized that the discrepancy is secondary to decreased 

A Multidisciplinary Approach for 

Treating Venous, Pressure, and 

Diabetic Foot Ulcers 

Many wounds that appear minor on initial physical examination 

signal extensive necrosis beneath the skin’s 

surface and consequently may still be a significant source 

of sepsis (Figure 12-4). It is therefore critical to treat all 

wounds early and comprehensively. In the elderly population, 

patient care frequently focuses on the patient’s 

comorbidities, whereas wounds are simply covered with 

a bandage and ignored. Too often, untreated wounds lead 

to preventable complications such as amputation, sepsis, 

and death. As part of an ongoing multidisciplinary collaboration 

among many specialists who care for elderly 

patients with chronic wounds, we have developed protocols 

to treat venous, 44 pressure, and diabetic foot 

ulcers. 6,44,72,73 Outlined below are the precepts of our 

treatment protocol (Table 12-1). 

1. Contact the Primary Care Physician: 

A strong relationship with the primary care physician 

is essential to optimize the many comorbidities of the 

elderly patient. Common medical diseases that must be 

assessed include: coronary artery disease, diabetes, 

obesity, hypertension, dyslipidemia, chronic renal insufficiency, 

malnutrition, muscular atrophy, hepatic disease, 

chronic obstructive pulmonary disease, coagulopathy, 

and pain. In the diabetic population, seeking the counsel 

of a diabetologist may be necessary to maintain proper 

glucose control. The primary care physician, along with 

the assistance of a nutritionist, can also be helpful in 

evaluating the patient’s nutritional status. A small number 

of prospective studies has found that nutritional


Figure 12-4. Pressure ulcers can be deceptively large. Pressure 

ulcers are often much larger than they appear to be. Wounds 

that may look quite small can contain extensive undermining 

and/or tunneling. This figure demonstrates three cases in which, 

upon debridement, the wound was shown to be substantially 

larger than it appeared at presentation. 

supplements are beneficial in treating chronic wounds in 

malnourished patients. 74–76 

2. Comprehensive Physical Examination of At-Risk 

Patients: 

Table 12-1. Summary of the current standard of care for the 

healing of venous ulcers, pressure ulcers, and diabetic foot 

ulcers. 

1. Contact the primary care physician 

2. Comprehensive physical examination of at-risk patients 

3. Prevention of deep vein thrombosis 

4. Laboratory and radiologic evaluations 

5. Evaluation of blood flow in the lower extremities 

6. Objective measurement of every wound weekly with digital 

photography, planimetry, and documentation of the woundhealing 

process 

7. Elimination of cellulitis, drainage, and infection 

8. Local wound care 

9. Debridement of nonviable tissue and wound bed preparation 

10. Offloading pressure from the wound and compression therapy 

11. Growth factor therapies 

12. Addressing comorbidities that may affect anesthesia 

13. Physical therapy 

14. Pain management 

Diabetic and bed-bound patients are at high risk for 

developing diabetic foot and pressure ulcers, respectively. 

These patients often lack protective sensation. As a consequence, 

they do not sense skin breakdown and are 

unable to assess wound progression. All diabetics must 

have their feet examined daily for evidence of skin breakdown. 

All bed-bound patients should have their pressure 

points (heels, ischia, trochanters, and sacrum) examined 

daily for evidence of pressure ulcer development. 

3. Prevention of Deep Vein Thrombosis: 

The physical therapy team should ensure that every 

patient who is able to ambulate is doing so. In nonambulatory 

patients, we recommend moving from the bed to a 

chair at least twice a day. Standard deep vein prophylaxis 

is mandatory, including pneumatic compression boots and 

subcutaneous heparin or low-molecular-weight heparin. 

4. Laboratory and Radiologic Evaluation: 

Baseline laboratory tests should be obtained to evaluate 

the patient’s overall health and to potentially detect 

underlying disease states. We recommend a complete 

blood count with differential, coagulation profile, creatinine 

and blood urea nitrogen levels, electrolyte panel,


lipid panel, glycosylated hemoglobin, albumin and prealbumin, 

erythrocyte sedimentation rate, hepatic panel, 

and thyroid-stimulating hormone level. Plain films of 

the affected area are recommended for all leg and foot 

wounds. Magnetic resonance imaging or bone scan is 

recommended to assess for osteomyelitis in stage IV 

pressure ulcers and in diabetic foot ulcers. 

5. Evaluation of Blood Flow in the Lower Extremities: 

Peripheral arterial disease and venous stasis disease 

are prevalent in the elderly population. All patients with 

limb ulcers should undergo arterial testing, regardless of 

what the primary etiology is thought to be, because the 

etiology may be multifactorial. Arterial testing is crucial 

because patients with ischemia should be revascularized 

before debridement and should not undergo compression 

therapy. Testing for venous stasis disease should be done 

in patients who clinically appear to have venous stasis 

ulcers. 

Noninvasive flow studies, which include bilateral 

ankle brachial indices (comparison of pressures in ankles 

and arms) and pulse volume recordings (to determine 

the amount of blood flow when pressures are falsely 

elevated), are necessary to detect lower extremity ischemia. 

In particular, recent studies have suggested 

high sensitivity to detect peripheral arterial disease using 

the low ankle pressure test defined as the quotient of 

the lowest ankle artery pressure of two measurements 

and the highest of two brachial artery pressure measurements. 

77,78 Depression of these values is associated with 

a greater risk of amputation. 79 An ankle brachial index 

less than 0.9 indicates significant arterial disease that 

requires referral to a vascular surgeon. 80 An elevated 

ankle brachial index greater than 1.30 has been found to 

be predictive of major amputation 81 and, particularly in 

the context of poor waveforms (i.e., monophasic), 82 

may indicate atherosclerosis requiring vascular surgery 

referral. 

When indicated, revascularization should proceed as 

soon as possible. Bypass grafting procedures are often 

avoided in elderly patients because their comorbidities 

make them poor surgical candidates. Alternatively, endovascular 

revascularization provides a minimally invasive 

and effective surgical option. Endovascular correction of 

arterial disease has proven safe and leads to 5-year limb 

salvage rates of more than 89% in diabetic and elderly 

populations. 83–87 If wound debridement is necessary, it 

should be done shortly after revascularization so as to 

utilize the improved blood supply. 88 

Duplex ultrasonography testing determines the presence 

and degree of venous insufficiency in patients with 

venous ulcers. Because venous incompetence is often 

attributable to a previous DVT, it is possible that the 

patient may concurrently have a DVT and a venous ulcer. 

In this scenario, the DVT will be identified by the venous 

flow studies. 

Once venous ulcers have healed, venous insufficiency 

should be corrected. Minimally invasive techniques such 

as radiofrequency ablation of the greater saphenous vein, 

percutaneous vein valve bioprosthesis, and subfascial 

endoscopic perforator vein surgery are treatment 

options. 89–91 Correction of the underlying venous disease 

prevents recurrence of venous ulcers. 92–94 

6. Objective Assessment of Wound Healing: 

Weekly wound-healing assessments should be objectively 

calculated by digital photography and planimetric 

measurements. Although a simple ruler has been shown 

to be reliable for predicting wound healing, 95 digital photography 

and computer-based wound measurements are 

more accurate for larger wounds and allow for easy transportation 

of data. Ideally, all data can be compiled into a 

wound electronic medical record (WEMR), if available, 

which plots a wound graph, demonstrating the healing 

curve of the wound based on planimetric measurements 

and allowing the team to objectively follow the progress 

of the wound. Serial objective measurements of the 

wound area allow the treatment team to accurately and 

rapidly detect a failure to heal and to adjust the treatment 

plan accordingly. A WEMR can also store the patient’s 

medical history, wound history (wound graph, drainage, 

pain, associated pathology, surgery history, radiology, and 

microbiology), laboratory values, antibiotic history, vascular 

studies, medications, wound picture, and contact 

information for the patient’s primary care doctor, pharmacist, 

and next of kin. The WEMR provides all of the 

patient’s pertinent data needed for thorough treatment 

in an easy-to-read format. 

7. Elimination of Infection: 

Infection substantially impairs chronic wound healing. 

Drainage, cellulitis, and pain are indicators of infection. 

Deep tissue cultures reflect the pathogens populating the 

wound bed and surrounding tissue, and they allow the 

physician to tailor the patient’s antibiotic regimen to 

cover only the pathogens grown from cultures, thereby 

helping to prevent drug-resistant organisms. 96–99 Deep 

tissue cultures are taken when the wound is debrided. If 

definitive debridement is not immediately planned, then 

an initial deep culture should be obtained at bedside, in 

the emergency room, or in the outpatient clinic, at the 

time when antibiotics are started. 

8. Local Wound Care: 

Homecare nursing is an integrated element in the 

wound-healing team. All wounds must be properly 

cleaned, treated with topical medications, and covered 

with the appropriate noncompressive or compressive 

dressing. Cleaning the wound includes washing with antimicrobial 

soap and water and scrubbing the wound with 

sterile saline and gauze. The topical therapy, such as 

cadexomer iodine (Iodosorb or Iodoflex; Smith & 

Nephew, Largo, FL), Acticoat (Smith &Nephew), and


Collagenase (Healthpoint, Fort Worth, TX), should 

provide a moist wound-healing environment and prevent 

bacterial colonization. 

9. Debridement of Nonviable Tissue and Wound Bed 

Preparation: 

Debridement of a chronic wound accelerates healing. 88 

It is a recommended treatment for diabetic foot ulcers, 

pressure ulcers, and venous ulcers. 100–103 For ischemic 

ulcers, debridement should be deferred until after revascularization. 

Gene expression is altered in the nonhealing 

edge of a chronic wound, resulting in hyperkeratotic epidermis 

and up-regulation of the oncogene c-myc. 104 

Debriding past this edge into healthy tissue stimulates 

the healthy epithelium to release growth factors and 

reduces local inflammation. It is thought that debridement 

encourages new fibroblasts to invade and replace 

the senescent cells of chronic wound beds, as well as 

release of various growth factors that stimulate wound 

healing, although few rigorous studies demonstrate this. 88 

Debridement also allows the surgeon to obtain microbiology 

and pathology samples that tailor antibiotic treatments 

and guide future debridements. For patients with 

active infection (such as cellulitis, fever, or elevated white 

blood cell count), debridement removes infected necrotic 

tissue that is the source of infection. 

Venous ulcers should be debrided deeply enough to 

remove all underlying scar and infected tissue; only several 

millimeters of the surrounding epithelium need to be 

debrided. Pressure ulcers should be debrided to remove 

all infected, necrotic, and scarred tissue, as well as to allow 

deep packing during dressing changes. Diabetic foot 

ulcers often appear as a callus with a central ulceration. 

We consider the callus as part of the wound, and we recommend 

debridement of a diabetic foot ulcer 2–3 mm 

beyond the callus into healthy epithelium (Figure 12-5). 

Figure 12-5. Proper debridement of diabetic foot ulcers. Diabetic 

foot ulcers are often associated with a thick hyperkeratotic 

callus. This callus impedes the healing process and needs to be 

removed. Debridement of diabetic foot ulcers must extend 

several millimeters past the nonmigratory edge into healthy 

epithelium. Debridement will aid in healing by removing nonviable 

tissue while stimulating reepithelialization with healthy 

tissue.


The surgeon should take pathology samples from the 

postoperative wound bed to confirm whether the remaining 

tissue is healthy. Almost all patients require multiple 

debridements, and the pathology results will guide the 

extent of future debridements. 

Although it is possible to debride some ulcers at the 

bedside, many elderly patients are debrided in the operating 

room because of their significant cardiac and pulmonary 

comorbidities, the size of their wounds, dementia, 

pain control, and concerns regarding hemostasis. The personnel 

involved and close monitoring make the operating 

room the safest place for most elderly patients who 

require debridement. 

Pressure ulcers often have a significant amount of 

tunneling and undermining that are revealed only after 

debridement has begun (Figure 12-4). Bone resection can 

cause significant bleeding, and most debridements of 

wounds extending to bone should be considered for the 

operating room (Figure 12-6). Because of venous reflux 

disease, venous ulcer debridement often causes significant 

blood loss from capillary bleeding, varicose veins, 

and venous perforators. Large venous ulcer debridements 

should be done in the operating room. 

10. Offloading Pressure from the Wound and Compression 

Therapy: 

Pressure is a significant contributor to the development 

and progression of pressure and diabetic foot ulcers. Pressure 

can be alleviated in pressure ulcer patients by using 

specialized air fluidized or alternating air mattresses. 

Heel pressure ulcer patients should be given a Multi- 

Podus splint (Restorative Care of America, St. Petersburg, 

FL) or a foam-based Heelift (DM Systems, Evanston, 

IL) to relieve pressure. Frequent turning and attentive 

skin care are mandatory for the treatment of all patients. 

Many devices have been created to offload pressure from 

diabetic foot ulcers. 105–109 

For venous ulcers, compression therapy with a measured 

multilayered bandage such as the Profore system 

(Smith &Nephew) should be used in conjunction with 

topical therapies. 110 These bandages decrease superficial 

vein distention and venous pressure, and they increase 

the efficacy of venous valves. This promotes the proper 

flow of blood from superficial to deep veins. High compression 

is more effective than low compression bandages, 

but their use is limited to nonischemic patients. 111 

It is therefore imperative that all venous ulcer patients 

be evaluated for arterial insufficiency before compression 

therapy. Compression therapy should not be applied in 

the presence of active infection. 

11. Growth Factor Therapies: 

For the topical treatment of diabetic foot ulcers, the 

Food and Drug Administration has approved only Dermagraft 

112 (Advanced Tissue Sciences, La Jolla, CA), 

Human Skin Equivalent (HSE), Apligraf, 113 a bilayered, 

A 

B 

Figure 12-6. Proper hemostatic control often necessitates use 

of the operating room. A: Preoperative photo. B: Intraoperative 

debridement. The operating room provides a much higher level 

of hemostatic control than can be achieved at the bedside. This 

patient was admitted with a stage IV pressure ulcer. The wound 

permeated deep into the bone, and because of the large amount 

of bleeding that can be associated with the debridement of bone 

in these wounds, this case was safely completed in the operating 

room. 

biologically active construct composed of a bovine collagen 

scaffold seeded with a layer of keratinocytes covering 

a layer of fibroblasts (Organogenesis Inc., Canton, MA), 

and Becaplermin (recombinant platelet-derived growth 

factor) 114,115 for safety and efficacy. Only Apligraf is 

approved for safety and efficacy in venous ulcers. 116 No 

treatment is approved for safety and efficacy in pressure 

ulcers. These agents should not be applied in the presence 

of active infection (cellulitis or wound drainage) and 

should be used only after surgical wound debridement. 

12. Comorbidities Affecting Anesthesia: 

Complicated cardiac conditions are common in the 

elderly and must be appropriately evaluated before


surgery. If the patient has risk factors for coronary artery 

disease, an exercise stress test should be considered 

before surgery. If the patient has a history of coronary 

atherosclerosis, pacemaker placement, valvular disease, 

congestive heart failure, or cardiac arrhythmia, cardiac 

function should optimized. 

Nephropathy is a common comorbidity in the elderly. 

The hypoproteinemia and acidemia seen in end-stage 

kidney disease patients can significantly affect the pharmacokinetics 

and pharmacodynamics of certain drugs 

used in anesthesia. 117 We recommend that end-stage 

kidney disease patients be dialyzed before surgery and 

that blood chemistries be closely monitored perioperatively. 

A venous blood gas is a safe, common approach 

to rapid evaluation of serum potassium and other 

electrolytes. 

Neuropathy is also a common complication in people 

with diabetes and most notably in the vast majority of 

persons with diabetic foot ulcers: in a recent study, 78% 

of diabetic patients with ulcers also had neuropathy. 118 

Because of the decrease in lower extremity sensation, it 

is rarely necessary to use a stronger anesthetic approach 

than a regional ankle block or Monitored Anesthesia 

Care with local anesthetic injections. 

Pressure ulcers frequently affect spinal cord injury 

patients. The level of the spinal cord injury is particularly 

important. If the patient’s injury is above thoracic vertebra 

6, then the patient is at risk for autonomic dysreflexia. 

119 Autonomic dysreflexia is an abrupt and 

exaggerated autonomic response to stimuli in patients 

with spinal cord injuries or dysfunction above the splanchnic 

sympathetic outflow (T5–6). 120 It is imperative that all 

patients with a T6 lesion or higher be debrided in the 

operating room under spinal or general anesthesia and 

with close blood pressure monitoring. 

13. Physical Therapy: 

Physical therapy is advised for patients with limited 

mobility and those with venous ulcers. For patients with 

limited mobility, physical therapy (1) decreases the incidence 

of DVT, (2) decreases respiratory complications, 

(3) increases mental acuity, and (4) decreases the development 

of contractures. 121 In patients with venous ulcers, 

musculoskeletal changes attributable to calf pain and 

venous hypertension dramatically affect the patient’s 

gait. Physical therapy has been shown to improve underlying 

venous disease and patient ambulation. 122 

14. Pain Management: 

Pain is common in patients with ulcers, and effective 

pain management regimens must be instituted. Pain 

should be quantified by the patient at each clinic visit. By 

using a Verbal Analogue Score in conjunction with the 

wound-healing graph from a wound data sheet, a physician 

can track the success of pain treatments as they 

relate to functional outcomes. 123 The end goal is to reduce 

morbidity by eliminating pain. Pain control also facilitates 

appropriate cleaning and dressing of the wound, 

because patients may avoid these tasks if they are very 

painful. It may be necessary to incorporate a pain specialist 

into the treatment team. 

Each category of chronic wounds presents with a unique 

type of pain. In venous ulcers, pain is believed to occur as 

a result of tissue damage, which stimulates the release of 

inflammatory mediators, sensitizing peripheral somatic 

pain receptors. 124 Because of intense pain in many venous 

ulcer patients, we recommend using a tiered system of 

pain medications based on the World Health Organization 

analgesic ladder, 125 in which patients are started on 

nonopioid drugs with or without adjuvant medications, 

to which increasing strengths of opioid medications are 

added depending on pain-control needs. 123,124 Patients 

with multiple comorbidities may have contraindications 

to common pain medications. In addition, in elderly 

patients, special attention must be given to the potential 

side effects of pain medications, such as constipation or 

mental status changes from narcotics. 

Although often associated with neuropathy, diabetic 

foot ulcers and pressure ulcers can present with substantial 

pain management challenges. The pain associated 

with neuropathic diabetic foot ulcers can be treated with 

tricyclic antidepressants, anticonvulsants, capsaicin, mexiletine, 

lidocaine patches, N-methyl-d-aspartate (NMDA) 

inhibitors, clonidine, and tramadol. 124 All have been 

used with varying degrees of success. Spinal cord injury 

patients with pressure ulcers develop central pain that 

occurs when there is neuropathy in the area of the wound. 

Thus, spinal cord patients may also need pain control 

even though the wounded area is insensate. 

Intraoperative Risk and Precautions 

for Development of Pressure Ulcers 

Elderly patients with fragile skin and comorbid conditions 

are at highest risk for development of intraoperative 

pressure ulcers. Patients with a high ASA grade may 

be more likely to develop pressure ulcers. 126 The most 

comprehensive study was conducted in the United States 

in 1998 involving 104 hospitals and 1128 surgical patients, 

all undergoing procedures longer than 3 hours in duration. 

An overall prevalence of stage I and stage II pressure 

ulcers was 7.8% when examining patients up to 4 

days postoperatively. 127 

Part of the intraoperative risk can be assessed by type 

of procedure. Vascular surgery, cardiac surgery, and orthopedic 

surgery are associated with higher risks, although 

rigorous studies have yet to emerge. 128 The risk may 

double for operations lasting more than 2.5 hours. 129 In a 

prospective Dutch study 130 of patients undergoing operations 

lasting more than 4 hours, 44 patients (21.2%)


developed 70 pressure ulcers in the first 2 days postoperatively. 

All but three were stage I and II. 

Various locations may be at higher risk than others. 

The same Dutch study found that most heel ulcers were 

associated with cardiac procedures. They also found head 

and neck procedures most often associated with sacral 

ulcers and that use of a semi-Fowler position (elevating 

both head and lower extremities to 30 degrees) may be 

beneficial. 130 

Full examination of all areas at risk including the 

sacrum, heels, ischia, and trochanteric areas with documentation 

of any skin changes and existing ulcers can 

help identify postoperative changes. Because the heel has 

the smallest surface area, this area may be at greatest risk 

intraoperatively. An ordinary head-pillow placed underneath 

each heel during the operation and through the 

time the patient is immobile is likely the most effective 

pressure-reducing device, followed by a siliconized 

hollow-fiber–based heel protector. 131 Further studies into 

a variety of mattress (foam versus gel) and alternative 

positioning have yet to be evaluated by rigorous randomized 

controlled trials. 

In most cases, if a wound is identified, extra care should 

be taken to relieve as much pressure from the surface as 

possible and to provide extra dressings either with 4 × 4 

sterile gauze or circumferential roll gauze to account for 

extra drainage from the wound during prolonged procedures. 

After the procedure, the dressings on all chronic 

wounds should be examined and changed as necessary. 

Conclusion 

Elderly patients are frequently affected by chronic 

wounds including pressure, venous, and diabetic foot 

ulcers. The elderly have the ability to heal from chronic 

wounds, but they are prone to multiple comorbidities that 

may slow the rate of healing, and complications from 

infection pose significant risks to patients who are already 

fragile. Operative debridement is usually most important 

to remove the source of infection. Safety of the elderly 

patient can be optimized by focusing on glycemic control, 

hydration, and often beta-blockade. If all wounds are 

treated using the protocol described herein, we postulate 

that amputations will be decreased, stage IV pressure 

ulcers nearly eliminated, and morbidity from venous 

ulcers reduced. 

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Part III 

Anesthetic Management of the Aged 

Surgical Candidate

13 

Preoperative Risk Stratification and 

Methods to Reduce Risk 

Linda L. Liu and Jacqueline M. Leung 

Aging increases the likelihood that a patient will have an 

operative procedure. Approximately 12% of those aged 

45 to 60 years are operated on each year, and this number 

will increase to more than 21% by the year 2025. 1 Whereas 

operations performed on patients older than 50 years of 

age were contraindicated in the past, an increasingly 

larger number of elderly patients are undergoing surgery 

at present. Studies of perioperative outcomes in the 

elderly have shown a decline in perioperative mortality 

rate from 20% in the 1960s 2 to 10% in the 1970s 3 to 5%– 

8% in the 1980s. 4 These relatively low mortality rates 

have been attributed to improvement in anesthetic and 

surgical care. 5 As a result, many patients, including those 

who are elderly, do quite well after surgery and have 

improved quality of life as a result of their surgery. 

In contrast to the immediate fatal postoperative complications, 

which are infrequent, more common occurrences 

are complications, which result in morbidity 

instead of mortality. As discussed in the previous chapters, 

age-related changes occur in most organ systems. 

Under normal conditions, the physiologic changes that 

occur with aging usually lead to minimal functional 

impairment. With an acute disease or a surgical procedure, 

however, the elderly may be more prone to complications 

given their diminished reserve capacity, their 

decreased ability to respond to stress, and pathologic 

changes resulting from their coexisting disease. Recent 

studies suggest that surgical risk increases as a result of 

this increased prevalence of comorbid disease and/or 

decreased physiologic reserve rather than simply as a 

result of increased age alone. 6,7 

The increasing number of elderly patients presenting 

for surgery will have a tremendous impact on anesthesia 

practice. As an example, in 1980, one million postoperative 

complications involving the cardiac system alone 

occurred, leading to an estimated $20 billion in annual 

costs from in-hospital and long-term care. 8 A critical component 

of the perioperative care of elderly patients is to 

identify and modify preoperative risk in order to decrease 

postoperative morbidity and mortality. This chapter will 

discuss how to perform risk stratification of elderly 

patients awaiting major surgery and to determine methods 

to reduce perioperative morbidity and mortality using an 

evidence-based approach. 

The Importance of Coexisting Disease 

Several previous studies have examined risk predictors 

of postoperative morbidity and mortality after major 

surgery and anesthesia. The majority of the studies agree 

that the most consistent risk predictor identified is the 

presence of coexisting disease. For example, Tiret et al. 9 

determined that ASA PS classification (American Society 

of Anesthesiologists physical status), age, surgical procedure 

(major versus minor), and type (elective versus 

emergency) were significant predictors. Pedersen et al. 10 

found similar predictors of risk, which included age, 

history of congestive heart failure, renal disease, emergency 

surgery, and the type of surgery to be performed. 

Rorbaek-Madsen et al. 11 studied 594 octogenarians 

undergoing surgery in Denmark. Mortality rates in this 

study ranged from 0% in those with no complicating 

coexisting disease undergoing elective surgery to 21% in 

those with coexisting disease who were undergoing emergency 

surgery. Bufalari et al. 12 found only the ASA PS, 

presence of two associated diseases, and laparotomy procedures 

to be predictors of risk in surgical octogenarians 

in Italy from 1989 to 1993. The combined results from our 

two previous studies in patients aged ≥80 years and those 

≥70 years confirmed that the severity of preoperative 

comorbidities is a more important predictor of postoperative 

adverse outcomes than even intraoperative 

factors. 6,7 

Given the important impact of coexisting disease on 

anesthetic outcome, it should be noted that comorbid conditions 

are prevalent in elderly patients. Vaz and Seymour 13 

prospectively studied 288 general surgical patients aged 

181

182 L.L. Liu and J.M. Leung 

65 years and older, and found a high prevalence of preexisting 

health problems in their cohort. Overall, 30% of the 

patients had three or more preoperative medical problems, 

involving pulmonary disease, a history of congestive 

heart failure, angina, and prior cerebrovascular accidents. 

In a consecutive cohort of patients ≥70 years of age undergoing 

noncardiac surgery, we similarly found that nearly 

30% of patients had three or more comorbid conditions 

including a history of hypertension, cardiopulmonary 

disease, and neurologic disease. 6,7 In a study of a cohort of 

centenarians presenting for surgery, Warner et al. 14 found 

that nearly all of these very old patients had one or more 

pre-existing medical conditions. 

Because mortality and morbidity rates are more 

affected by coexisting disease as opposed to age alone, 

efforts should be made to optimize any coexisting disease, 

if possible, before surgery. The remainder of this chapter 

will present evidence-based data addressing which of the 

coexisting diseases can be modified to reduce the likelihood 

of perioperative morbidity and mortality. However, 

for geriatric patients, postponing surgery to optimize any 

medical conditions must be weighed against the risk of 

delaying surgery because emergency surgical treatment 

is associated with higher morbidity and mortality. Certain 

surgical procedures, such as cancer surgery, may substantially 

alter the prognosis of the patients if delayed. As a 

result, good communication among the anesthesiologists, 

surgeons, and primary care physicians is critical to developing 

an optimal plan as to when a geriatric patient 

should be scheduled for the planned surgery. 

Cognitive Dysfunction and Delirium 

after Noncardiac Surgery 

One of the most common postoperative outcomes is an 

adverse event involving the neurologic system, with postoperative 

delirium and cognitive decline being the two 

most frequently occurring events in geriatric patients. 

Our previous retrospective cohort study in surgical octogenarians 

demonstrated that postoperative neurologic 

complications occurred in 15% of the patients, of which 

91% were related to the occurrence of postoperative 

delirium. 6 Delirium is an acute disorder of attention and 

cognition and a serious problem for hospitalized geriatric 

patients. In contrast, cognitive dysfunction includes a 

wider range of neuropsychologic changes in several functional 

domains, and is often more subtle than delirium. It 

requires a different methodology for ascertainment and 

is frequently underestimated by health care professionals. 

A multinational study reported that postoperative cognitive 

dysfunction (POCD) was present in 26% of patients 

1 week after surgery and in 10% of patients even 3 months 

after surgery. 15 

In the surgical setting, as demonstrated by our previous 

work 6,7 and work from others, postoperative delirium is 

common in elderly surgical patients. 16 In one study, 36% 

of elderly patients undergoing surgery for hip fracture 

under a variety of anesthetic agents were “confused” on 

the first postoperative day. 17 Patients who developed 

delirium required a hospital stay approximately four 

times longer than those who remained lucid. 18 More 

importantly, delirium resulted in increased rates of 

nursing home placement, and associated hospital mortality 

rates of 10%–65%. 19 Numerous risk factors for delirium 

in medical patients have been previously identified. 

They include the use of physical restraints, malnutrition, 

use of a bladder catheter, any iatrogenic event, and the 

use of more than three medications. 20–22 

In the perioperative setting, limited data exist as to 

whether specific intraoperative management precipitates 

POCD or delirium. The main areas that deserve consideration 

include: 

1. Drugs: Although previous studies have demonstrated 

that certain drugs may be associated with postoperative 

delirium, 23 there has been no prospective 

randomized clinical trials to determine if the elimination 

of certain drugs used in the perioperative period will 

actually lead to a lowering of the incidence of delirium. 

As a result, no definitive guidelines can be provided at 

present regarding avoiding certain drugs in the perioperative 

period. However, a sensible guideline is that 

“polypharmacy” is best avoided in elderly patients 

because delirium has been shown to be related to the 

number of medications prescribed. 22,23 

2. Anesthetic techniques: Controversy persists as to 

whether any anesthetic technique (regional versus general) 

has an impact on postoperative neurologic dysfunction. 

Earlier studies suggested an association between a 

higher incidence of cognitive dysfunction and general 

anesthesia relative to epidural anesthesia. 18,24 More recent 

studies, in contrast, have concluded that there is no relationship 

between anesthetic technique and the magnitude 

or pattern of POCD. 25 In a study by Moller et al., 15 

only the duration of anesthesia was found to be one of 

the risk factors for early POCD. A retrospective cohort 

study of consecutive hip fracture patients, aged ≥60 years, 

undergoing surgical repair at 20 United States hospitals 

also found that the anesthesia technique (regional versus 

general) had no impact on postoperative mental status 

change. 26 More recently, a multicenter trial of patients 

≥60 years of age, although not adequately powered, 

reported that the incidence of cognitive dysfunction at 3 

months after surgery was not different after either general 

or regional anesthesia. 27 

3. Anesthetic management: Specifically, is the role of 

blood pressure or intraoperative hypotension associated 

with POCD? In a prospective, randomized study of older

13. Preoperative Risk Stratification and Methods to Reduce Risk 183 

adults (age >50 years) undergoing total hip replacement, 

Williams-Russo et al. 28 demonstrated that patients who 

underwent epidural anesthesia and were rendered markedly 

hypotensive had similar incidence of POCD as those 

who were maintained in the normotensive state. Moller 

et al., 15 by a larger cohort study, also determined that 

neither hypotension nor hypoxemia were related to 

POCD. 

4. Postoperative pain management: In one study of 

older patients undergoing major elective noncardiac 

operations, 29 after adjusting for known preoperative risk 

factors for delirium, higher pain scores at rest were associated 

with a slightly increased risk of delirium in the first 

three postoperative days. It remains to be proven whether 

better control of postoperative pain will reduce POCD. 

Despite the importance and prevalence of postoperative 

neurologic decline, no single anesthetic technique 

has been identified to be superior for elderly surgical 

patients in minimizing POCD or delirium. Until more 

definitive clinical studies become available, minimizing 

the number of medications used, avoiding hypoxemia 

and hypercarbia, and providing adequate postoperative 

pain control seem to be the best approaches in minimizing 

the occurrence of postoperative delirium in geriatric 

surgical patients. 

Cardiovascular Complications 

The elderly are more likely to develop postoperative cardiovascular 

complications. Pedersen et al. 30 presented 

data on 7306 patients undergoing surgery in Denmark. 

The octogenarians had a 16.7% incidence of cardiovascular 

complications compared with a 2.6% incidence in 

patients younger than 50 years of age. The cardiovascu - 

lar complications in this study were defined as systolic 

hypotension or hypertension (systolic blood pressures 

200 mm Hg, respectively), cardiac arrest, 

second- or third-degree heart block, chest pain, ventricular 

tachyarrhythmias, supraventricular tachycardia 

requiring treatment, myocardial infarction, or congestive 

heart failure. A high incidence of cardiovascular complications 

(40%) was found in patients with preoperative 

heart disease, especially in those with clinical signs of 

congestive heart failure, history of ischemic heart disease, 

or previous myocardial infarction. In two separate cohort 

studies of nearly 1000 patients older than 70 and 80 years 

of age undergoing noncardiac surgery, respectively, we 

found a similar cardiovascular complication rate of 10%– 

12%. 6,7 The most common postoperative cardiovascular 

events in these two separate cohorts were congestive 

heart failure, arrhythmias, and ischemic complications. In 

contrast to the Pedersen study, in which the severity of 

the operative case and elective versus emergent surgery 

Table 13-1. Comparison between cardiac risk indexes developed 

by Goldman and Lee. 

Goldman 

• Preoperative S 3 or JVD 

• Myocardial infarction within 

6 months 

• PVC >5 bpm 

• Rhythm other than sinus or 

presence of PACs 

• Age >70 years 

• Intraperitoneal, intrathoracic, or 

aortic operations 

• Emergency surgery 

• Important valvular aortic stenosis 

• Poor general medical condition 

Lee 

• High-risk type of surgery 

• Ischemic heart disease 

• History of congestive heart 

failure 

• History of cerebrovascular 

disease 

• Insulin therapy for diabetes 

• Preoperative serum creatinine 

>2 mg/dL 

Source: Data from Goldman et al. 31 and Lee et al. 32 

JVD = jugular venous distention, PVC = premature ventricular contractions, 

PAC = premature atrial contractions. 

were associated with the occurrence of cardiovascular 

complications, we found that intraoperative variables 

such as type of anesthesia and surgical procedure did not 

increase postoperative cardiovascular complications. 

What are the characteristics of patients who develop 

postoperative complications? Many previous investigations 

have focused on clinical variables and diagnostic 

test procedures obtained preoperatively to identify 

patients at risk for postoperative complications. For 

example, a cardiac risk index was developed by Goldman 

et al. in 1977 31 and subsequently revised in 1999 32 to 

predict the occurrence of postoperative cardiac complications 

(Table 13-1). In this latter revised cardiac index, 32 

variables that were associated with increased risk of postoperative 

cardiac complications included high-risk 

surgery, history of ischemic heart disease, congestive 

heart failure, or cerebrovascular disease, preoperative 

treatment of diabetes with insulin, and preoperative creatinine 

>2.0 mg/dL. Rates of major cardiac complication 

with 0, 1, 2, or ≥3 of the factors were 0.5%, 1.3%, 4%, and 

9%, respectively. 

The American College of Cardiology/American Heart 

Association (ACC/AHA) Task Force recently updated 

the guidelines for preoperative cardiac evaluation for 

patients presenting for noncardiac surgery 33 in an attempt 

to unify the risk stratification process. Although these 

guidelines are based on studies performed in the general 

surgical population and do not specifically target the geriatric 

population, some of the general principles are applicable. 

The main decision points of the guidelines are 

based on the patient’s medical conditions, functional 

capacity, and the acuity and risk of the planned surgical 

procedure. 

The first step is to stratify the patient by medical condition. 

Table 13-2 lists the minor, intermediate, and major


clinical predictors as defined by the ACC/AHA guidelines. 

Advanced age, by itself, is considered only one of 

the minor clinical predictors. However, it should be noted 

that advanced age is associated with increased incidence 

of comorbid conditions, which may be intermediate predictors 

of postoperative cardiovascular complications. 

Diseases such as diabetes mellitus, renal insufficiency, and 

compensated congestive heart failure, are more likely to 

occur in the older population. Major predictors are unstable 

coronary syndromes, decompensated congestive heart 

failure, significant arrhythmias, and severe valvular 

disease. 

The next area of focus in the guideline is the assessment 

of functional capacity. According to the ACC/AHA 

guidelines, the inability to perform activities beyond four 

metabolic equivalents (METs) requires further evaluation. 

A summary of how to evaluate METs is provided in 

Table 13-3. However, the accurate assessment of functional 

capacity may be difficult in the geriatric population 

because many elderly patients may have comorbid conditions 

or chronic pain, which limits their functional capacity. 

As a result, the functional limitation may be secondary 

to noncardiac causes, rather than attributable to a primary 

cardiac cause as the guideline would suggest. Therefore, 

direct adoption of the ACC/AHA algorithm without 

knowing the reason for the functional limitation may 

result in a great majority of elderly patients needing additional 

preoperative cardiac stress testing. 

The ACC/AHA guidelines also take into account the 

operative procedure itself, which has an impact on the 

occurrence of cardiac morbidity and mortality. Emergency 

major operations, major vascular surgery, and any 

prolonged surgical procedures associated with large fluid 

shifts are stratified as procedures carrying higher cardiac 

Table 13-2. Major, intermediate, and minor predictors of cardiovascular 

risk. 

Predictors 

Major 

Intermediate 

Minor 

Source: Data adapted from Eagle et al. 33 

Unstable coronary syndromes 

Decompensated heart failure 

Significant arrhythmias 

Significant valvular disease 

Stable angina pectoris 

History of myocardial infarction 

Compensated heart failure 

Diabetes 

Renal insufficiency 

Advanced age 

Abnormal electrocardiogram 

Rhythm other than sinus 

Poor exercise capacity 

History of cerebrovascular accident 

Uncontrolled hypertension 

Table 13-3. Estimate of metabolic equivalent for different 

activities. 

MET estimate 

Activity 

1 MET Activities of daily living 

Eating 

Dressing 

Walking indoors (2–3 mph) 

Dishwashing 

4 MET More strenuous activities 

Climbing stairs (1 flight) 

Walking (4 mph) 

Running short distance 

Scrubbing floors 

Playing golf, doubles tennis 

10 MET Playing sports 

Swimming 

Singles tennis 

Football 

Source: Data adapted from Eagle et al. 33 

MET = metabolic equivalent. 

risk. More minor surgeries such as cataract removal are 

deemed to be of low surgical risk. Taken together, the 

results of the medical history, current symptoms, and 

physical examination allow the physician to identify 

clinical predictors of increased perioperative cardiovascular 

risk. The clinical predictors, combined with an 

assessment of the patient’s exercise tolerance and the 

risk of surgery, then provides additional guidance to the 

clinicians in determining the value of additional cardiac 

stress testing. 

Strategies to Reduce Cardiac Risk 

The basis of performing preoperative cardiac risk stratification 

assumes the possibility that some or all of these 

risk factors identified may be modifiable with the ultimate 

goal of improving patients’ outcomes. However, this 

assumption has not been completely proven. Eagle et al. 34 

determined that the risk of coronary artery bypass graft 

(CABG) surgery itself, when added to the risk of the 

noncardiac surgery, often exceeded the risk of the same 

surgery in patients who have not undergone CABG 

surgery. They showed that performance of CABG surgery 

before the planned noncardiac surgery may not be justified. 

In other words, it seems that for some of the patients, 

the risk of modifying their perioperative myocardial 

infarction risk by cardiac surgery may actually outweigh 

the benefits because of the risk of cardiac surgery itself. 34 

In fact, a recent randomized multicenter trial in 510 male 

veterans scheduled for vascular operations demonstrates 

that coronary artery revascularization before elective 

vascular surgery does not significantly alter the long-term 

outcome. 35 As a result, a reexamination and further inves-


tigation of the appropriateness of the 2002 ACC/AHA 

guidelines for preoperative cardiac evaluation for elderly 

patients needs to be conducted. 

Despite the varied nature of each study patient population, 

congestive heart failure (CHF) continues to be identified 

as a major predictor of surgical outcomes. In a 

prospective study of octogenarians, clinical signs of congestive 

heart failure increased the odds of an adverse 

cardiac event (odds ratio = 2.1, confidence interval = 

1.1–5.1). 7 The strong association between clinical signs 

of CHF and postoperative complications emphasizes 

the importance of preoperative optimization of heart 

function in the elective surgical patient. The adequacy 

and accuracy of preoperative assessment of heart function 

seems to be a critical area deserving further 

investigation. 

For the elderly patient, heart failure can often be 

caused by diastolic dysfunction associated with left ventricular 

hypertrophy. Older patients with CHF frequently 

present with normal left ventricular ejection fraction, suggesting 

the importance of diastolic dysfunction in this age 

group. 36 In fact, up to one third of patients with heart 

failure may have normal systolic function. 37 Other causes 

of diastolic dysfunction may include myocardial ischemia, 

accelerated hypertension, or intrinsic myocardial diseases 

such as fibrosis. 38 Unfortunately, this diagnosis may not 

be readily apparent preoperatively and the therapeutic 

approach is different. 39 The prognostic significance of diastolic 

function assessment, such as with preoperative 

Doppler echocardiography in patients with a history of 

heart failure remains to be determined. More studies are 

needed to better characterize diastolic function including 

defining normality in older patients before recommendations 

for preoperative care can be made. 

The association between hypertension and end organ 

damage, such as ischemic heart disease, heart failure, 

cerebrovascular disease, and renal impairment, has been 

well established, 40,41 but in assessing perioperative risk, 

hypertension has not been recognized as a major predictor 

of perioperative cardiac risk. 31,32 Patients diagnosed 

with hypertension have increased systemic vascular resistance 

and cardiovascular lability during anesthesia. 42,43 

Reich et al. 44 reported an association between intraoperative 

hypertension and tachycardia and adverse outcome 

in protracted surgery, but a direct causal relationship 

between hypertension and perioperative adverse cardiac 

outcomes is not as evident. In a meta-analysis of 30 

studies, the risk of perioperative cardiovascular complications 

in hypertensive patients was only slightly increased 

(odds ratio = 1.35, confidence interval = 1.17–1.56) and 

the authors advised cautious interpretation of the data 

because of the heterogeneity of the observational 

studies. 45 

To date, there is no evidence to support the approach 

of deferring elective surgery to allow hypertension to be 

treated in order to reduce perioperative risk. 45 The ACC/ 

AHA guidelines state that mild/moderate hypertension 

is not an independent risk factor for perioperative cardiovascular 

complications, but severe hypertension (systolic 

blood pressure ≥180 mm Hg and/or diastolic blood 

pressure ≥110 mm Hg) should be controlled before 

surgery. 33 Unfortunately, there are no data to suggest that 

this strategy reduces perioperative risk. In a meta-analysis 

report, Howell et al. 41 have suggested that surgery may 

proceed, but care should be taken to ensure perioperative 

cardiovascular stability, invasive arterial pressure monitoring 

should be started, and mean arterial blood pressure 

should be kept within 20% of baseline. In patients 

with severe hypertension and evidence of end organ 

damage, Howell et al. did suggest that it would be appropriate 

to defer surgery when possible, but this suggestion 

is based on evidence from medical patients, not from data 

in surgical patients. 

In patients without contraindications, the use of perioperative 

beta-blockade may be of value in controlling 

blood pressure and also reducing perioperative myocardial 

ischemia. Several clinical trials have examined the 

potential beneficial effects of using beta-adrenergic 

blocking agents to improve perioperative surgical outcomes. 

46,47 None, however, has directly focused on geriatric 

patients. The mechanism of beta-adrenergic blockade 

in prophylaxis of perioperative ischemia and postoperative 

cardiac events is probably multifactorial. Proposed 

mechanisms include decreased myocardial demand from 

a reduction in the inotropic and chronotropic state of the 

myocardium, and possible improved perfusion to ischemic 

regions from redistribution of myocardial blood 

flow. Because perioperative tachycardia increases myocardial 

oxygen demand and has been shown to be associated 

with myocardial ischemia, 48 the adequacy of the 

heart rate response to beta-blockers should be a critical 

guide to the dosing of the drug. 

The hemodynamic effects of beta-blockers depend on 

the patient’s cardiovascular status, underlying sympathetic 

tone, concurrent anesthesia, and vasoactive drug 

therapy. The decreased response to beta receptor stimulation 

with aging, together with interaction with anesthetic 

agents, may increase the risk for hypotension in the 

setting of prophylactic beta-blockade. 49 In a study of 63 

elderly patients, Zaugg et al. 50 reported that perioperative 

beta-blockade actually resulted in better hemodynamic 

stability, decreased analgesic requirements, faster recovery 

from anesthesia, and decreased myocardial damage 

as diagnosed by increased levels of troponin I. This study 

is limited in size, but it is one of the first to suggest the 

relative safety and efficacy of beta-blockade in the 

elderly. 

Current practice seems to suggest that beta-blockers 

are underutilized in all patients, especially the elderly. 

In a retrospective study, only 30% of patients who met


Table 13-4. Beta-blockers and suggested dosages used in the 

literature for perioperative myocardial protection. 

Drug name 

Atenolol 

Metoprolol 

Bisoprolol 

criteria for perioperative beta-blockade after cholecystectomy 

received therapy. 51 This number is even lower for 

eligible elderly patients. Gottlieb et al. 52 performed a 

chart review of more than 200,000 cases after myocardial 

infarction. They determined that of the patients who 

should receive beta-blockade, only 27% of those 84 years 

old received beta-blockers versus 37% of those 60, impaired preoperative 

cognitive function, smoking history within the past 8 

weeks, body mass index, history of cancer, and abdominal 

incision site were independent risk factors for postoperative 

pulmonary complications. 

Of note, preoperative spirometry did not reliably 

predict the occurrence of postoperative complications 

in patients with obstructive lung disease. 60 In a study 

involving critically ill patients, the CO 2 levels on arterial 

blood gas and not spirometric testing predicted the 

need for postoperative intubation. 61 Taken together, 

the evidence to date suggests that pulmonary function 

tests should be selectively performed in patients undergoing 

nonthoracic surgery, because they can assess 

the presence and severity of the disease, but they do not 

have great predictive value for postoperative pulmonary 


Strategies to Reduce Pulmonary Risk 

Preoperative optimization of respiratory function may 

improve patient outcomes. Several factors that deserve 

consideration include smoking cessation, optimization of 

asthma medications, and treatment of obstructive sleep 

apnea. Cigarette smoking is a known risk factor for 

COPD, coronary artery disease, and peripheral vascular 

disease. Current smokers are four times more likely to 

develop pulmonary complications than those who have 

never smoked. 62 Other trials have shown that smokers 

have a higher rate of wound infection than nonsmokers. 63 

The institution of a smoking intervention program 6–8 

weeks before joint replacement surgery reduced postoperative 

morbidity. 64 Warner et al. 65 showed that smoking 

cessation at least 2 months preoperatively maximized the 

reduction of postoperative respiratory complications.


From the above data, it seems that preoperative cessation 

of smoking will improve patient outcomes by decreasing 

adverse postoperative pulmonary outcomes and the incidence 

of wound infections. Smoking cessation should be 

encouraged even immediately before surgery, because 

smoking cessation has been associated with immediate 

decreases of carbon monoxide levels and reduced operative 

risk measured 6 weeks after surgery. 65 

Another condition common in geriatric patients is 

asthma. Asthma is often underdiagnosed in the elderly, 

and for those with the diagnosis, treatment may not 

be optimized. Asthma is often underdiagnosed in elderly 

for multiple reasons: (1) patient failure to report symptoms 

to the physician because of a lack of awareness of 

symptoms or misinterpreting the symptoms as deconditioning 

or normal process of aging; (2) presence of 

other conditions such as cardiac failure, ischemic cardiac 

failure, gastroesophageal reflux disease, respiratory tract 

tumors, laryngeal dysfunction, constrictive bronchiolitis, 

hypersensitive pneumonitis, or the use of medications 

(beta-blockers, angiotensin-converting enzyme inhibitors) 

that can mimic symptoms of asthma; (3) presence 

of other respiratory conditions such as COPD; or (4) 

general misperception that new-onset asthma is rare in 

the elderly. 66 With the appropriate diagnosis made, aggressive 

pulmonary rehabilitation, which includes exercise 

training, patient education, psychosocial, nutritional, and 

respiratory therapy counseling, smoking cessation, and 

optimization of medications, has been shown to be effective 

in the elderly population. 67 Unfortunately, some 

practitioners limit the use of beta agonists. They fear that 

systemic absorption of inhaled medications may result 

in tachycardia and hypertension, and precipitate cardiac 

ischemia in patients with coronary artery disease or result 

in drug interactions that may prolong the QT interval. 

The use of beta agonists is relatively safe in the elderly. 

Some earlier studies reported a decreased therapeutic 

response to inhaled beta receptor agonist with increasing 

age, but a recent study did not find any difference in 

the response to albuterol or ipratropium bromide with 

respect to age. 68 

Another comorbidity that is increasing in prevalence 

in the elderly is obesity and obstructive sleep apnea syndrome 

(OSAS). The prevalence of obesity is increasing 

at an alarming rate. 69 The number of obese adults aged 

60 and older will increase from 32% in 2000 to 37.4% in 

2010. 70 This increase has been attributed to a complex 

interaction between age-associated alterations in the 

metabolic rate, dietary changes, and sedentary lifestyles. 

Obesity causes diabetes, hypertension, hyperlipidemia, 

sleep apnea, and arthritis, resulting in reduced quality of 

life and life expectancy. 71 No specific studies addressed 

the impact of OSAS on postoperative complications in 

the elderly. However, in patients undergoing hip or knee 

replacement, procedures typically performed in older 

individuals, those with a preoperative diagnosis of OSAS 

were more than two times more likely to develop complications 

than those without OSAS. In fact, serious complications 

occurred in 24% of the OSAS group versus 9% 

in the control group, and hospital stay was significantly 

longer in the OSAS group. 72 

The data regarding the perioperative risk and best 

management techniques for patients with OSAS are 

scant and virtually nonexistent for elderly patients with 

OSAS. A Clinical Practice Review Committee of the 

American Academy of Sleep Medicine was unable to 

develop a standard of practice recommendation. They 

were only able to make a clinical practice statement 

based on a consensus of clinical experience and a few 

published peer-reviewed studies. They stated that important 

components of the perioperative management of 

OSAS patients include a high degree of clinical suspicion, 

control of the airway throughout the perioperative period, 

judicious use of medications, and appropriate monitoring. 

73 At this point, this advice may be extrapolated to the 

elderly patient with OSAS. Other potentially prudent 

suggestions include having a lower threshold of admitting 

these patients to more intensive postoperative monitoring, 

use of supplemental oxygen, and use of nighttime 

continuous positive airway pressure. 

Renal Dysfunction 

The prevalence of renal insufficiency is quite common in 

the elderly because of a decrease in glomerular function 

with age. In populations ≥age 70, moderately or severely 

decreased glomerular filtration rate was observed in 75% 

of community-dwelling elderly, 78% of the patients from 

the geriatric ward, and 91% of nursing home patients. In 

populations ≥age 85, 99% had evidence of renal impairment 

necessitating dosing adjustments for drugs. 74 Kohli 

et al. 75 showed that surgery and nephrotoxic drugs are 

independent predictors of acute renal failure in elderly 

patients. They also found that mortality in patients with 

acute renal failure was significantly higher than similar 

patients without acute renal failure. In fact, it is estimated 

that acute renal failure contributes to at least one of 

every five perioperative deaths in elderly surgical 

patients. 76 A history of postoperative renal complications 

is a significant predictor of decreased long-term survival. 77 

There are no clinical trials demonstrating that preoperative 

assessment for renal dysfunction will lead to better 

outcomes. However, recognizing that elderly patients 

are at risk of developing renal complications as a 

result of decreased renal function, effect of nephrotoxic 

drugs (aminoglycosides, nonsteroidal antiinflammatory 

drugs, angiotensin-converting enzyme inhibitors, and 

contrast dye), volume depletion, and hypotension seems 

prudent.


Diabetes Mellitus 

Internationally, adults over age 60 will comprise two 

thirds of the diabetic population in developed countries 

by the year 2025. 78 In the United States, because of 

improvements in the identification of chronic diseases, 

declining death rates, and people living longer, diabetes 

is also increasing among persons aged 60 and older. 79 

Currently, nearly one of every five adults in the United 

States over age 60 has diabetes, which puts them at 

increased risk for disability and morbidity. 80 Furthermore, 

the mortality risk is substantially higher in diabetics than 

nondiabetics. For example, McBean et al. 81 found that in 

individuals with diabetes, the overall risk of dying was 1.6 

times greater than those without diabetes in a retrospective 

analysis of a 5% random sample of Medicare fee-forservice 

beneficiaries. The duration of diabetes also has a 

significant impact on the rate of developing complications 

as evidenced by a study demonstrating that patients 

with more than 10 years of diabetes have more significant 

compromise in one or more end-organ systems. 82 Diabetes 

is considered an intermediate clinical predictor for 

risk of perioperative myocardial ischemia 33 and is associated 

with increased risk of complications and death after 

myocardial infarction. 

The recently published guidelines from the California 

Healthcare Foundation/American Geriatrics Society 

Panel on Improving Care for Elders with Diabetes provided 

recommendations on diabetes management for the 

elderly. These guidelines suggested that elderly persons 

in otherwise good health should have the same glycemic 

control goals as younger persons, which is a standard 

hemoglobin A1c target of


identified preoperative albumin level as a good predictor 

of postoperative mortality in the geriatric population. 94 

The National Veterans Administration Surgical Risk 

Study examined 43 preoperative risk factors, 14 preoperative 

laboratory values, and 12 operative variables for 

predicting postoperative complications. The mean age in 

this study was 61 ± 13 years, and 97% of the subjects were 

men, but the results should apply to the general elderly 

surgical patient. The most important variable in predicting 

postoperative mortality was preoperative albumin 

level with ASA PS classification as the second best predictor. 

Albumin levels


Table 13-7. Instrumental activities of daily living. 

Instrumental activity 

Definition of independence 

Telephone 

Shopping 

Food preparation 

Housekeeping 

Laundry 

Mode of transportation 

Responsible for medications 

Handles finances 

medications, and ability to handle finances. Functional 

status before hospitalization has been found to be predictive 

of functional outcome, length of stay, mortality, and 

need for nursing home placement. Davis et al. 110 showed 

that ADL impairment was a powerful predictor of inhospital 

mortality for the elderly and it was the single 

most important predictor of functional outcomes at 2 and 

12 months after hospitalization. 

A preoperative home-based physical therapy program, 

prehabilitation, has been described as a method of 

enhancing the functional capacity of a patient. It has been 

evaluated in frail, community-dwelling elders 111 and in 

preparation for the stress of an orthopedic surgical procedure 

112 or an intensive care unit admission. 113 The goals 

of prehabilitation are to prevent deconditioning and 

improve the ability of the patient to withstand musculoskeletal 

and cardiovascular stressors of surgery. The efficacy 

of this type of approach remains to be validated by 

randomized controlled trials before prehabilitation can 

be recommended as a routine preoperative strategy in 

elderly patients. 

Laboratory Values 

Able to use telephone; able to dial a 

few well-known numbers; able to 

answer the telephone 

Takes care of all shopping needs 

Plans, prepares, serves adequate meals 

Performs light daily tasks, washes 

dishes, makes bed 

Does laundry 

Travels by driving, or using public 

transportation alone or 

accompanied by another 

Takes correct dosages at correct time 

Manages day-to-day finances, can 

require assistance with banking or 

major purchases 

Routine preoperative medical testing before elective 

surgery is estimated to cost $30 billion annually, but data 

show that laboratory abnormalities on routine screen 

often do not lead to changes in management. Schein et 

al. 114 studied nearly 20,000 patients undergoing cataract 

surgery who were randomized to either routine laboratory 

testing or no routine testing. They reported no difference 

in perioperative morbidity and mortality between 

those who did versus those who did not receive routine 

testing. In patients with few comorbidities, there is a low 

prevalence of abnormal laboratory tests. For example, in 

a population study of 7196 ambulatory patients, the prevalence 

of hemoglobin, glucose, and creatinine abnormalities 

was small (5.5%, 8.3%, and 2.7%, respectively). 115 

In contrast, a substantially higher prevalence of abnormal 

results was demonstrated in a group of institutionalized 

elderly patients (11%–33% for hemoglobin, 25%–29% 

for glucose, and 11%–15% for creatinine). 116–118 Dzankic 

et al. 119 used a prospective cohort of patients ≥70 years of 

age undergoing elective noncardiac surgery to evaluate 

the prevalence and predictive value of abnormal preoperative 

laboratory tests. The prevalence of abnormal laboratory 

tests was quite high—electrolyte abnormalities 

(0.7%–5%), abnormal platelet counts (1.9%), glucose 

(7%), hemoglobin (10%), and abnormal creatinine 

(12%)—but in a separate analysis for patients classified 

as ASA 1–2, the incidence of laboratory abnormalities 

was as low as those in the general population (3.6%). In 

fact, in the entire elderly cohort, none of the abnormal 

laboratory values were significant independent predictors 

of adverse outcomes with multivariate regression. 

These results suggest that routine preoperative testing in 

geriatric surgical patients, particularly in those patients 

classified as ASA 1–2, generally produces few abnormal 

results. 

Electrocardiogram (ECG) abnormalities also increase 

with age. 120 The most common abnormalities in a cohort 

of octogenarians 121 included arrhythmias, Q waves diagnosing 

previous myocardial infarction, left ventricular 

hypertrophy, bundle-branch block, and nonspecific 

segment changes. Although these abnormalities are 

common, they had limited value in predicting postoperative 

cardiac complications. There is no demonstrable evidence 

that measurement and investigation of preoperative 

ECGs reduce adverse outcomes, but current recommendations 

to obtain preoperative ECGs for men over age 

40, women over age 50, and other patients with known 

coronary artery disease or cardiovascular risk factors 

such as diabetes or hypertension, are probably reasonable 

so that a baseline ECG is available before major 

surgery to determine whether subsequent abnormalities 

are new or preexistent. 122 

Preoperative chest X-rays (CXRs) have increased clinical 

relevance with increasing age and presence of cardiopulmonary 

disease. 123,124 In patients younger than age 50, 

the likelihood of an abnormal chest film ranges from 0% 

to 20%, whereas the likelihood increases to 20% to 60% 

in patients older than 50. 125 An evaluation of routine 

preoperative CXRs in vascular surgery patients demonstrated 

that no surgery cancellations occurred because of 

an abnormal X-ray, but the beneficial effects of a CXR 

increased in patients with known pulmonary disease. The 

study recommended that CXRs be ordered preoperatively 

only if there is clinical indication in the history and 

physical examination. 126 

There are no controlled clinical trials to show that 

routine laboratory tests, ECG or CXR, are associated


with a decreased adverse event rate. However, information 

from preoperative ECG and/or CXR may be of 

value in the postoperative management because new 

abnormalities may be identified if preoperative baseline 

measurements are available. Although the actual rate of 

laboratory abnormalities is small in the elderly, it is still 

higher compared with the younger population. 127 Therefore, 

total abandonment of routine testing based on age 

must be weighed against the probability that unexpected 

disease may be detected by the testing and that the extent 

of surgery may be modified. 128 

Medications 

Elderly patients frequently take multiple medications, 

both prescription and over-the-counter medications. The 

elderly constitute approximately 13% of the population 

but consume 32% of all prescription drugs in the United 

States. 129 Studies show that greater consumption of medications 

contributes to decreased medication adherence 130 

and to greater risk of adverse drug events. 131 The impact 

of common herbal and alternative medicines is unclear, 

but is already becoming an important focus. In a survey 

of more than 2500 preoperative patients ≥age 18, almost 

40% of the patients admitted to using some form of alternative 

medicine supplements. 132 Women ≥age 65 reported 

using an average of 2.6 herbal products. 133 Most important 

was the fact that more than 50% of the patients in 

the study indicated that they did not inform the anesthesiologists 

before surgery regarding their use of these 

products. 132 The Food and Drug Administration does not 

control these supplements and, therefore, quality is not 

rigorously regulated. Some reported side effects from 

herbal remedies include bleeding when warfarin is combined 

with ginkgo, garlic, or ginseng 134 ; possible monoamine 

oxidase inhibition by St. John’s wort 135 ; coma when 

benzodiazepines are combined with kava 136 ; and mania 

when antidepressants are combined with ginseng. 134 

Other reported risks include contamination, inconsistencies 

and adulteration, and lead poisoning. 137 There are 

no randomized controlled trials to examine the effects 

of herbal medications in the perioperative period and 

to determine when the supplements should be stopped 

preoperatively. A few review articles made several suggestions 

(stopping ephedra, ginkgo, and kava 24–36 hours 

before surgery, and stopping garlic, ginseng, and St. John’s 

wort 5–7 days before surgery) based on limited information 

on the pharmacokinetics of these agents 138,139 

(Table 13-8). 

In terms of prescription medications, the older patient 

is at risk for inappropriate drug use. Inappropriate medications 

may be defined as drugs that pose more risk than 

benefit. 140 In 1996, more than 20% of community-dwelling 

elderly received some inappropriate medication. 141 

Table 13-8. Recommendations for preoperative discontinuation 

of herbal medications. 

Discontinue 

Herbal medicine Perioperative interactions before surgery 

Echinacea • Allergic reactions No data 

• Immunosuppression 

Ephedra • Hypertension 24 hours 

• Arrhythmias 

Garlic • Inhibits platelet aggregation 7 days 

• Increases risk of bleeding 

Ginkgo • Inhibits platelet aggregation 36 hours 


Ginseng • Hypoglycemia 7 days 


Kava • Interactions with sedatives 24 hours 

St. John’s wort • Induces cytochrome P-450 5 days 

• Affects multiple drug levels 

Source: Data adapted from Ang-Lee et al. 138 and Adusumilli et al. 139 

For example, specific medications such as antihistamines 

or benzodiazepines contribute to the risk of falls or confusion. 

Agostini et al. 142 showed that there is a linear 

relationship between the number of medications used 

and the risk of two frequently reported adverse drug 

effects—weight loss and impaired balance. This effect was 

apparent even when comorbidities and indications for 

many of the medications were adjusted for. In terms of 

risk reduction, a study showed that time taken to educate 

the patient on dosages and frequency of medicines, 

reasons for taking medicines, and information about 

adverse side effects improved patient compliance and 

outcomes. 143 The perioperative period has been proposed 

as an ideal time to critically review the medication list for 

polypharmacy, drug interactions, and adverse drug 

events. 144 Although these proposals make intuitive sense, 

no randomized trials have specifically addressed this 

issue. 

Comprehensive Geriatric Assessment 

The team approach to the elderly patient involves the 

geriatrician, nurse coordinator, physical therapist, and 

social worker. Randomized controlled trials have been 

variable in the benefits of a comprehensive geriatric 

assessment (CGA). The selective use of the CGA has 

been proven to be beneficial in the perioperative period. 

For instance, in community-dwelling elders who failed a 

screen for falls, urinary incontinence, depression, or functional 

impairment, CGA was found to be efficacious and 

cost-effective. Although not studied in the surgical population, 

a meta-analysis showed that CGA, along with 

long-term management, is effective for improving survival 

and function. 145 One recent randomized clinical trial 

that targeted patients aged ≥65 years after hip fracture


surgery demonstrated that “proactive geriatric consultation” 

reduced delirium by more than one third and 

reduced severe delirium by more than half. 146 This important 

study demonstrates that certain adverse outcomes 

after surgery such as delirium may be modifiable, and 

suggests that similar strategies, which are multifactorial 

and targeted, may be possible to reduce the trajectory of 

decline after major surgery in the older population. 

Conclusion 

Although surgery in the geriatric population is not 

without risk, the mortality rate has decreased markedly. 

With more emphasis on preoperative medical optimization, 

along with early identification of surgical issues, 

most patients can expect to do well. Patients ≥80 years of 

age undergoing noncardiac surgery who did not have 

postoperative complications were found to survive just as 

well as the age- and gender-matched general population. 

77 Chronologic age is less important as an independent 

risk predictor. A more important predictor is the 

presence of coexisting diseases. With the identification of 

the major risk factors associated with postoperative morbidity, 

opportunity to improve perioperative outcomes in 

elderly patients will be possible when risk factors for 

these adverse events can be modified through randomized 

prospective clinical trials. As more information 

becomes available on risk modification through future 

research, practitioners can then develop a comprehensive 

set of quality indicators for elderly surgical care and 

thereby improve the quality and safety of perioperative 

surgical care of geriatric patients. 

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14 

Anesthetic Implications of Chronic Medications 

Tamas A. Szabo and R. David Warters 

The safe administration of anesthesia to elderly patients 

The prevention and recognition of drug-related problems 

21.3% among noninstitutionalized elderly patients. 5 pam (Valium) are the primary benzodiazepines used in 

in older adults are of paramount importance. Medicationrelated 

problems are estimated to cause 106,000 deaths 

annually at a cost of $75–85 billion. Elderly patients presenting 

for surgery are often taking a large number and 

wide variety of chronic medications, greatly complicating 

their preoperative assessment and anesthesia management. 

requires a thorough evaluation and understanding of 

chronic medications and the potential for interactions. 

The aim of this chapter is to highlight (1) drugs that are 

common in elderly patients, and (2) drugs that have a 

potential interaction with medications used in the anesthetic 

practice. 

The often daunting task of evaluating the potential 

interactions of these medications with one another as 

well as anesthetic medications is further complicated by 

the large number of inappropriate medications prescribed 

in this age group. 

Neuropsychiatric and Pain-Related 

Medications 

Inappropriate medications for elderly patients are 

Benzodiazepines 

defined as medications for which a better alternative drug 

exists and for which the potential risk outweighs the 

potential benefit. In 1997, Beers 1 devised a comprehensive 

set of explicit criteria for potentially inappropriate drug 

use in ambulatory older adults aged 65 years and older. 

Drugs were classified as inappropriate in three categories: 

(1) drugs that generally should be avoided in the elderly, 

(2) drugs that exceed a maximum recommended daily 

dose, and (3) drugs to be avoided in combination with 

specific comorbidities. Recently, the 1997 criteria were 

updated and presented as the 2002 Beers criteria. 2 In these 

updated criteria, the comorbidity list was modified, new 

medications were added, and several drugs were removed. 

The Beers criteria may not identify all causes of potentially 

inappropriate prescribing (e.g., drug–drug interactions 

Benzodiazepines cause sedation, anterograde amnesia, 

anxiolysis, and muscle relaxation, as well as hypnotic and 

anticonvulsant effects. All effects and side effects of benzodiazepines 

are mediated through γ-aminobutyric acid 

(GABA) A receptors. 

Long-acting benzodiazepines are considered potentially 

inappropriate in elderly patients 2,6 because of the 

risk of producing prolonged sedation and increasing 

the potential for falls and fractures. Patients most likely 

to be prescribed benzodiazepines are the elderly with a 

secondary complaint of insomnia. Although sleep fragmentation 

may be reduced by benzodiazepines, their 

long-term use may also elicit health problems, such 

as complete obstructive sleep apnea in heavy snorers. 7 

are not included); however, they represent a widely Examples of long-acting benzodiazepines include 

used and standardized tool for pharmacologic research, 

despite the fact that nothing can substitute careful clinical 

judgment. A Dutch population-based cohort study 

revealed that 20% of ambulatory older adults receive at 

least one inappropriate drug prescription per year 3 ; moreover, 

halazepam (Paxipam), quazepam (Doral), flurazepam 

(Dalmane), chlordiazepoxide (Librium), chlordiazepoxide-amitriptyline 

(Limbitrol), clidinium-chlordiazepoxide 

(Librax), diazepam (Valium), and chlorazepate (Tranxene). 

Because of the increased sensitivity of long-acting 

an epidemiologic study 4 from the United States benzodiazepines in elderly patients, smaller doses of 

reported that 23.5% of people aged >65 years receive >1 

of the 20 medications on the Beers list. The prevalence of 

potentially inappropriate medications was found to be 

short- or intermediate-acting benzodiazepines are considered 

preferable, safer, and more effective. 

Midazolam (Versed), lorazepam (Ativan), and diaze- 

197

198 T.A. Szabo and R.D. Warters 

the anesthetic practice. 8 All three are highly protein 

bound, mainly by albumin. Patients with cirrhosis or 

chronic liver failure and subsequent hypoalbuminemia 

have a greater unbound fraction of benzodiazepines, 

which may increase their sensitivity to these agents. 

Midazolam undergoes rapid hepatic metabolism to 

both active and inactive metabolites. Drugs that inhibit 

the cytochrome P-450 enzyme system [i.e., cimetidine, 

erythromycin, calcium channel blockers (CCBs), and 

antifungal agents] reduce the hepatic clearance of 

midazolam. 9 

Diazepam is metabolized in the liver through oxidative 

demethylation and glucuronidation to inactive metabolites 

that are excreted by the kidneys. An increased 

volume of distribution and reduced metabolic clearance 

may significantly increase the elimination half-life of 

diazepam in patients with cirrhosis. Elderly and/or obese 

patients are also susceptible to prolonged diazepam 

effects secondary to an increased volume of distribution. 

Lorazepam is hepatically conjugated to an inactive 

metabolite. 

Respiratory depression secondary to the decrease in 

hypoxic drive is the most significant side effect of benzodiazepine 

administration. This effect is greater with midazolam 

than with lorazepam and diazepam in equipotent 

doses. Opioids may significantly enhance the respiratory 

depressant effects of benzodiazepines in patients with 

chronic obstructive pulmonary disease. Alpha 2 agonists, 

such as dexmedetomidine, have shown synergistic sedative 

effects, 10 while reversing the cardiovascular de - 

pressant effects of benzodiazepines. Moreover, the 

administration of even small doses of benzodiazepines in 

conjunction with opioids, propofol, or thiopental can also 

result in significant hypotension caused by the synergistic 

effects of these agents. 11 

Clinically significant hypotension may follow parenteral 

benzodiazepine administration in elderly patients. 

Parenteral benzodiazepines may be less effective in 

patients who take oral benzodiazepines on a chronic 

basis; moreover, the benzodiazepine antagonist flumazenil 

may precipitate withdrawal seizures in these patients. 12 

Benzodiazepines reduce the anesthetic requirements for 

both intravenous and inhalational anesthetics, but may 

also decrease the analgesic effects of opiates. 13 Therefore, 

flumazenil may enhance the postoperative analgesic 

effects of morphine, reduce morphine requirements, and 

decrease the sedative, emetic, and cardiopulmonary 

depressant effects of morphine in patients who have 

received benzodiazepines after surgery. 

Carbamazepine 

Carbamazepine (Tegretol, Equetro, Carbatrol) is an anticonvulsant 

that blocks voltage- and frequency-dependent 

fast sodium currents. Sodium channels are kept in the 

inactivated state, inhibiting the spread of synchronized 

depolarization that is associated with the onset of seizures. 

Carbamazepine is structurally similar to tricyclic 

antidepressants. 

The therapeutic index of carbamazepine for neurologic 

side effects is 8:1, making it a relatively nontoxic medication. 

Negative side effects include gastrointestinal (GI) 

irritation, diplopia, ataxia, vertigo, and sedation. Acute 

intoxication may lead to respiratory depression, unconsciousness, 

seizures, and cardiovascular collapse. 14 

The hepatic metabolism of carbamazepine may be 

inhibited by erythromycin, isoniazid, cimetidine, and propoxyphene, 

15 leading to increased, possibly toxic, plasma 

levels. Carbamazepine can induce hepatic enzyme function 

and increase the metabolism of medications dependent 

on hepatic metabolism, including itself. Therefore, 

the half-life tends to decrease with regular use. Carbamazepine 

may reduce the plasma levels of primidone, valproic 

acid, phenytoin, and haloperidol. 

Gabapentin 

Gabapentin is a weak inhibitor of GABA transaminase 

which was originally developed for seizure disorder but 

is frequently used for postherpetic neuralgia and neuropathic 

pain. It has also been proposed as a component of 

perioperative pain control. It acts by increasing GABA 

synthesis. Nausea, vomiting, dizziness, somnolence, headache, 

ataxia, and fatigue are the most common side effects 

of the drug. Rarely, confusion, hallucinations, depression, 

and psychoses may occur. 

Gabapentin is relatively free of drug interactions, 

its gastric absorption may be reduced by administra - 

tion of antacids containing hydroxides of aluminum or 

magnesium, and its renal clearance can be reduced by 

cimetidine. 

Monoamine Oxidase Inhibitors 

Monoamine oxidase inhibitors (MAOIs) are used in the 

treatment of severe depression unresponsive to other 

antidepressants. Intraneuronal monoamine oxidase 

(MAO) is the primary enzyme involved in the oxidative 

deamination of amine neurotransmitters (epinephrine, 

norepinephrine, dopamine, and serotonin). MAOIs in - 

crease the level of intraneuronal transmitters, resulting in 

augmented postsynaptic depolarization and adrenergic 

stimulation. MAO exists in two isoforms: MAO-A preferentially 

metabolizes serotonin, dopamine, and norepinephrine, 

whereas MAO-B preferentially metabolizes 

phenylethylamine and tyramine. 

Phenelzine (Nardil) is a nonselective MAOI that irreversibly 

inhibits the enzyme, and synthesis of new enzyme 

can take 10–14 days. It decreases pseudocholinesterase 

activity and subsequently prolongs depolarizing block-

14. Anesthetic Implications of Chronic Medications 199 

ade. Tranylcypromine (Parnate) is a slightly shorter-acting 

MAOI derived from amphetamine. Selegiline (Deprenyl), 

a selective MAO-B inhibitor, is used as an adjunct 

in the treatment of Parkinson’s disease. 

The interactions of MAOIs with certain drugs (notably 

meperidine, which blocks neuronal uptake of serotonin) 

and foods containing tyramine (aged cheeses, chocolate, 

liver, fava beans, avocados, and Chianti wine) have limited 

their use. 16,17 Concurrent use of MAOI and meperidine 

may result in fatal excitatory reactions. Respiratory 

depression, hypotension, and coma are the signs of a 

depressive form that is secondary to the accumulation 

of free narcotic and has been described after the use of 

fentanyl, alfentanil, or sufentanil. If foods high in tyramine 

are ingested, there is the potential for massive displacement 

of norepinephrine into the cleft and for a 

life-threatening hypertensive crisis. Many patients taking 

MAOIs have symptoms of autonomic dysfunction such 

as orthostatic hypotension, because tyramine is not catabolized 

and remains at high levels in plasma. Tyramine is 

then taken up by sympathetic nerve terminals as a “false 

transmitter” and is converted to the biologically inactive 

octopamine. 

MAOIs exaggerate the actions of indirect-acting and, 

to a lesser extent, direct-acting (phenylephrine, norepinephrine, 

epinephrine) sympathomimetics. A reduced 

dose of a direct-acting sympathomimetic is recommended 

8 for the treatment of hypotension. Ketamine and 

pancuronium should not be used to avoid stimulation of 

the sympathetic nervous system. Morphine may be used 

for perioperative analgesia. 

Selective Serotonin Reuptake Inhibitors 

Selective serotonin reuptake inhibitors (SSRIs) inhibit 

the neuronal reuptake of serotonin. They are used primarily 

as antidepressants, but are also effective in the 

treatment of panic disorder, obsessive/compulsive disorder, 

posttraumatic stress disorder, and social phobia. 

SSRIs do not have anticholinergic effects, have little 

effect on norepinephrine reuptake, do not cause postural 

hypotension, do not cause delayed conduction of cardiac 

impulses, and do not affect the seizure threshold. 

Fluoxetine is a potent inhibitor of certain hepatic cytochrome 

P-450 enzymes and may subsequently increase 

plasma concentrations of drugs that depend on hepatic 

metabolism. MAOIs, lithium, or carbamazepine combined 

with fluoxetine may cause the development of the 

potentially fatal (11% mortality) serotonin syndrome 18 

characterized by hypo- or hypertension, anxiety, restlessness, 

confusion, chills, ataxia, insomnia, and seizures. This 

syndrome is most often reported in patients taking two 

or more medications that increase central nervous system 

(CNS) serotonin levels by different mechanisms. 

Tricyclic Antidepressants 

Amitriptyline and protriptyline are tricyclic antidepressants 

that exhibit the most prominent anticholinergic 

effects (tachycardia, blurred vision, dry mouth, delayed 

gastric emptying, urinary retention); therefore, they may 

be avoided in patients with glaucoma or prostatic hypertrophy. 

Cardiovascular abnormalities, including orthostatic 

hypotension and cardiac dysrhythmias (increased 

PR and QT intervals, widened QRS complexes), can be 

caused by these drugs. 19 Patients with coexisting heart 

block or prolonged QT intervals may be at increased risk 

for cardiac toxicity. Overdose may lead to cardiac conduction 

abnormalities, hypotension, mental status changes, 

seizures, coma, rhabdomyolysis, and renal failure. The 

sedation associated with tricyclic antidepressants may be 

beneficial for patients experiencing insomnia. 

Patients taking tricyclic antidepressants may exhibit 

exaggerated systemic blood pressure responses after the 

administration of indirect-acting vasopressors because of 

the increased availability of norepinephrine at the postsynaptic 

receptors of the peripheral sympathetic nervous 

system. The combination of imipramine and pancuronium 

or ketamine may predispose anesthetized patients to 

tachydysrhythmias. 20 Postoperative delirium and confusion 

may result by the additive anticholinergic effects of 

the tricyclic antidepressants and centrally active anticholinergic 

drugs. 

Antiparkinson Medications 

The treatment of Parkinson’s disease is directed toward 

increasing dopamine levels in the brain but preventing 

adverse peripheral effects of dopamine. Levodopa is the 

single most effective therapy for patients with Parkinson’s 

disease. Side effects of levodopa administration 

include orthostatic hypotension, hypovolemia, depletion 

of myocardial norepinephrine stores, and peripheral 

vasoconstriction. The half-life of levodopa is short, and 

interruption of therapy for more than 6–12 hours can 

result in severe skeletal muscle rigidity that interferes 

with ventilation. Levodopa may alter some liver function 

tests, blood urea nitrogen, and positive Coombs test. Phenothiazines, 

butyrophenones (droperidol), and metoclopramide 

antagonize the effects of dopamine in the basal 

ganglia and should be avoided. 21 

Antidementia Drugs 

Donepezil, rivastigmine, galantamine, and tacrine are 

reversible acetylcholinesterase inhibitors used in the 

treatment of mild to moderately severe dementia in 

Alzheimer’s disease. Adverse effects include abdominal 

pain, nausea, vomiting, diarrhea, dizziness, headache, 

somnolence, muscle cramps, insomnia, sweating, tremor,


and syncope. Angina, sinoatrial (SA), atrioventricular 

(AV), and bundle-branch blocks, bradycardia, cardiac 

arrest, peptic ulcers, GI hemorrhage, extrapyramidal 

symptoms, seizures, depression, hallucinations, agitation, 

confusion, and bladder outflow obstruction have been 

observed. 22 Rivastigmine, tacrine, and donepezil may 

prolong the action of succinylcholine. Cholinergic crisis 

may result from overdose. 

Donepezil is selective for the CNS. It is highly protein 

bound, mainly by albumin. It undergoes partial metabolism 

via the cytochrome P-450 system. Ketoconazole, 

erythromycin, fluoxetine, and quinidine increase plasma 

donepezil concentrations by inhibiting the isoenzymes 

CYP 3A4 and CYP 2D6. Conversely, donepezil concentrations 

may be reduced by enzyme inducers such as 

phenytoin, carbamazepine, and rifampin. 

Rivastigmine is selective for the CNS and has also been 

tried in the treatment of vascular dementia and in the 

treatment of psychosis in patients with Parkinson’s 

disease. It is approximately 40% bound to plasma 

proteins and readily crosses the blood–brain barrier. 

The drug is metabolized by cholinesterase-mediated 

hydrolysis. 23 

Galantamine may also be effective in the treatment of 

vascular dementia. It is not recommended for treatment 

of mild cognitive impairment because of an association 

with increased mortality. Galantamine is partially metabolized 

by the cytochrome P-450 system. A reduced dose 

may be necessary in patients with hepatic or renal impairment 

or when galantamine is given with drugs that inhibit 

CYP 2D6 and CYP 3A4, such as quinidine, fluoxetine, 

fluvoxamine, paroxetine, and ketoconazole. 

Tacrine may delay cognitive decline but many patients 

cannot tolerate the dosage required and have to stop 

treatment because of GI effects or signs of hepatotoxicity. 

It undergoes an extensive first-pass effect in the liver, and 

is metabolized by the cytochrome P-450 system. It may 

competitively inhibit the metabolism of other drugs that 

are also metabolized by the cytochrome P-450 isoenzyme 

CYP 1A2. Cimetidine has been shown to inhibit the 

metabolism of tacrine. Increased serum alanine aminotransferase 

concentrations, mostly within the first 12 

weeks of therapy, are likely to occur in about 50% of 

patients. 24 Some patients may develop unpredictable lifethreatening 

hepatotoxicity. There is no significant correlation 

between plasma-tacrine concentrations and 

hepatotoxicity. Abruptly stopping tacrine therapy may 

result in a decline in cognitive function. 

The N-methyl-d-aspartate (NMDA) receptor antagonist 

memantine is used in the treatment of moderately 

severe to severe Alzheimer’s disease and is thought to act 

through modulation of the effects of glutamate. It undergoes 

partial hepatic metabolism. The majority is excreted 

unchanged via the kidney. Use of other NMDA antagonists 

such as amantadine, ketamine, or dextromethorphan 

may increase the incidence and severity of adverse effects 

and should be avoided. The effects of dopaminergics and 

antimuscarinics may also be enhanced, whereas memantine 

may reduce the actions of barbiturates and antipsychotics. 

Adverse effects include anxiety, hallucinations, 

confusion, constipation, dizziness, headache, somnolence, 

abnormal gait, hypertension, and seizures. Dosage adjustment 

may be required in patients with recent myocardial 

infarction, congestive heart failure, uncontrolled hypertension, 

and renal impairment. 25 

Cardiovascular Drugs 

Alpha 2 -Adrenergic Agonists 

Three categories of alpha 2 agonists exist: phenylethylates 

(e.g., methyldopa), imidazolines (e.g., clonidine, dexmedetomidine), 

and oxaloazepines. The most prominent 

hemodynamic effects of alpha 2 agonists are hypotension 

and bradycardia. Hypotension can be reversed by standard 

vasoactive agents. The pressor response to ephedrine 

and phenylephrine are enhanced, but the response 

to norepinephrine is not. 26 The response to dopamine and 

to atropine is mildly attenuated. Rebound hypertension 

may occur after abrupt discontinuation of these drugs 

after chronic administration. The anesthetic-sparing 

and sedative effects of alpha 2 agonists result from inactivation 

of the locus ceruleus. The sedative effect is antagonized 

by alpha 1 agonists. Alpha 2 agonist or benzodia - 

zepine premedication may attenuate the high incidence 

(up to 30%) of ketamine-induced disturbing emergence 

reactions. Alpha 2 agonists reduce GI motility and co - 

administration of opioids produces a synergistic inhibition 

of GI transit. 

The potential for CNS adverse effects and orthostatic 

hypotension may contraindicate the use of clonidine in 

the elderly, whereas methyldopa (Aldomet) and methyldopa-hydrochlorothiazide 

(Aldoril) may cause bradycardia 

and exacerbate depression in elderly patients. 2 

Alpha 1 -Adrenergic Antagonists 

Doxazosin (Cardura) may cause orthostatic hypotension, 

edema, hepatitis, dry mouth, and urinary retention. Hypotension 

during epidural anesthesia may be exaggerated 

in the presence of alpha 1 -blockers and the resulting 

decrease in systemic vascular resistance may not be 

responsive to alpha 1 -adrenergic agonists (e.g., phenylephrine). 

The combination of alpha 1 -blockers and a betablocker 

could result in refractory hypotension because of 

potentially blunted response to beta 1 as well as alpha 1 

agonists. 26 Intoxication may result in nausea, vomiting, 

abdominal pain, hypotension, reflex tachycardia, and 

seizures.


Digoxin 

Digoxin inhibits Na + /K + adenosine triphosphatase, leads 

to an increase in the intracellular concentration of Na + , 

and thus (by stimulation of Na + –Ca 2+ exchange) an 

increase in the intracellular concentration of Ca 2+ . The 

beneficial effects of digoxin result from direct actions on 

cardiac muscle, as well as indirect actions on the cardiovascular 

system mediated by effects on the autonomic 

nervous system. The autonomic effects include: (1) a 

vagomimetic action, which is responsible for the effects 

of digoxin on the SA and AV nodes, and (2) baroreceptor 

sensitization, which results in increased afferent inhibitory 

activity and reduced activity of the sympathetic 

nervous system and renin-angiotensin system for any 

given increment in mean arterial pressure. The pharmacologic 

consequences of these direct and indirect effects 

are: (1) a positive inotropic effect, (2) a decrease in the 

degree of activation of the sympathetic nervous system 

and renin-angiotensin system (neurohormonal deactivating 

effect), and (3) negative dromotropic and negative 

chronotropic effects. The effects of digoxin in heart failure 

are mediated by its positive inotropic and neurohormonal 

deactivating effects, whereas the effects of the drug in 

atrial arrhythmias are related to its vagomimetic actions. 

The most frequent cause of toxicity is renal failure. 27 

Digitalis toxicity is markedly increased in the presence 

of hypokalemia, and digitalis toxicity may be reversed to 

some degree by the administration of K + . Other causes of 

digitalis toxicity include hypomagnesemia, hypercalcemia, 

and hypothyroidism. Administration of digitalis can 

lead to the development of a wide variety of arrhythmias 

including sinus bradycardia and arrest, AV conduction 

delays, and second- or third-degree heart blocks. 28 Sympathomimetics 

with beta-adrenergic agonist effects as 

well as pancuronium 29 and intravenous administration of 

Ca 2+ may increase the likelihood of cardiac dysrhythmias. 

Oral antacids decrease the GI absorption of digitalis. 30,31 

Amiodarone 

Amiodarone is a potent class III antidysrhythmic agent 

with a wide spectrum of activity against refractory supraventricular 

and ventricular tachydysrhythmias. The antiarrhythmic 

effect of amiodarone may be attributed to at 

least two major properties: (1) a prolongation of the myocardial 

cell-action potential duration and refractory 

period, and (2) noncompetitive alpha- and beta-adrenergic 

inhibition. Antiadrenergic and Ca 2+ channel blocking 

effects contribute to peripheral vasodilation, bradycardia, 

conduction disturbances, negative inotropic effects, and 

hypotension. After oral dosing, however, amiodarone 

produces no significant change in left ventricular ejection 

fraction (LVEF), even in patients with depressed LVEF. 

After acute intravenous dosing, it may have a mild negative 

inotropic effect. Volatile anesthetics, beta-blockers, 

lidocaine, diltiazem, and verapamil can potentiate the 

cardiovascular and negative inotropic effects of amiodarone. 

32 Proarrhythmic side effects of amiodarone are 

reported in less than 1%–2% of patients. Pulmonary toxicity 

is a severe complication that may occur in up to 17% 

of patients treated long term. 33 Pulmonary complications 

may progress to adult respiratory distress syndrome and 

pulmonary fibrosis. Both hypothyroidism and hyperthyroidism 

can occur with chronic amiodarone therapy. 34 

Amiodarone treatment may also lead to increased liver 

function tests. Amiodarone inhibits CYP metabolisms 

resulting in increased levels of digoxin (by as much as 

70%), procainamide, quinidine, warfarin, and cyclosporine. 

It may also directly depress vitamin K-dependent 

clotting factors. Cimetidine can reduce the metabolism of 

amiodarone, and phenytoin increases its metabolism. 

Disopyramide 

Disopyramide is a class IA antiarrhythmic indicated in 

the treatment of life-threatening ventricular arrhythmias 

and is also used to treat supraventricular arrhythmias 

caused by reentrant mechanisms. Of all antiarrhythmic 

drugs, this is the most potent negative inotrope and 

reversible heart failure has been reported after its use. As 

many as 50% of patients with a history of heart failure 

may have a recurrence of the disease with an incidence 

of less than 5% in other patients. Disopyramide should 

not be used in patients with cardiogenic shock, AV block, 

or long QT intervals. It can lead to the development of 

second- or third-degree AV block or torsade de pointes 

ventricular tachycardia. 35 Disopyramide has strong anticholinergic 

side effects including dry mouth, impotence, 

urinary retention, constipation, and exacerbation of glaucoma. 

Because of the large number and severity of side 

effects, disopyramide is contraindicated in elderly 

patients. 

Beta Receptor Antagonists 

Beta receptors are G protein–coupled receptors found 

throughout the myocardium and nodal conduction tissue. 

Beta receptor blockers are competitive antagonists 

at beta-adrenergic receptor sites and are used in the 

management of hypertension, stable and unstable angina 

pectoris, cardiac arrhythmias, myocardial infarction, 

and heart failure. These drugs have been shown to reduce 

mortality when administered prophylactically to patients 

undergoing major vascular surgery 36 who are at high 

risk for ischemia. Beta-blockers have also been found 

to reduce mortality and morbidity rates in patients with 

myocardial infarction 37 and congestive heart failure. 38 

They are also given to control symptoms of sym - 

pathetic overactivity in alcohol withdrawal, anxiety states,


hyperthyroidism, and tremor, and in the prophylaxis of 

migraine and of bleeding associated with portal hypertension. 

Beta receptor antagonism manifests in decreased 

heart rate and increased diastolic perfusion. 

Beta-blockers belong to two general classifications, 

based on whether they are selective beta 1 antagonists or 

combined beta 1 and beta 2 antagonists. The beta 1 antagonists 

or those with intrinsic sympathomimetic activity at 

beta 2 receptors are “cardioselective” and are better suited 

for use in patients with asthma and bronchospastic disease 

and hypertension. With increasing doses of the cardioselective 

drugs, there is a decrease in receptor specificity. 

The beta-blockers with proven effects on prognosis 

include two selective beta 1 receptor blockers—metoprolol 

and bisoprolol—and three nonselective beta-blockers—timolol, 

propranolol, and carvedilol. Sotalol, a 

nonselective beta-blocker, which also has a pronounced 

class III antiarrhythmic effect, does not seem to have a 

significant effect on postinfarction mortality. 

Beta-blockers are generally well tolerated and most 

adverse effects are mild. The most frequent and serious 

adverse effects are heart failure, heart block, and bronchospasm. 

For this reason, these drugs must be used judiciously 

in patients with severe obstructive pulmonary 

disease, bradycardia, heart block, or uncompensated congestive 

heart failure. Abrupt withdrawal of beta-blockers 

may exacerbate angina and may lead to sudden death. 

Reduced peripheral circulation may exacerbate peripheral 

vascular disease such as Raynaud’s syndrome. CNS 

effects include headache, depression, dizziness, hallucinations, 

confusion, and sleep disturbances. 

Beta-blockers are eliminated by several metabolic 

pathways. Propranolol and metoprolol undergo hepatic 

metabolism, esmolol is biotransformed in the blood by 

esterases, atenolol is renally excreted, and timolol is eliminated 

by the kidney and the liver. The metabolism and 

route of excretion is important when considering patients 

with renal or hepatic disease. 

Coadministration of beta-blockers and propofol might 

result in cardiac events including severe bradycardia, 

sinus arrest, heart block, or even asystole. The myocardial 

depression seen with halothane is also exacerbated by 

beta-blockers. 39 

Calcium Channel Blockers 

CCBs inhibit the cellular influx of calcium by binding to 

specific drug receptors on L-type calcium channels and 

maintaining the channels in an inactive state. The L-type 

channel is the predominant type in heart and vascular 

smooth muscle. 

Three major classes of CCBs exist: the dihydropyridines, 

the phenylalkylamines, and the benzothiazepines. 

Each class binds to a unique site on the alpha 1 -subunit of 

the L-type channel. Dihydropyridine CCBs (such as nifedipine, 

nimodipine, and amlodipine) have a greater 

selectivity for vascular smooth muscle than for myocardium 

and their main effect is vasodilatation. They have 

little or no action at the SA or AV nodes, and negative 

inotropic and chronotropic effects are minimal. They are 

used for their antihypertensive and antianginal properties. 

Nimodipine crosses the blood–brain barrier and is 

used in cerebral ischemia. Benzothiazepine CCBs (such 

as diltiazem) and phenylalkylamine CCBs (such as verapamil) 

have less selective vasodilator activity. They 

depress SA and AV nodal conduction and are used for 

their antiarrhythmic, antianginal, and antihypertensive 

properties. Verapamil has the most prominent negative 

inotropic effect and it may precipitate congestive heart 

failure in patients with preexisting left ventricular dysfunction. 

Diltiazem also reduces contractility, but the concurrent 

peripheral vasodilation may preserve cardiac 

output. Verapamil, nifedipine, and nicardipine are 90% 

protein-bound, and their clinical effects can be enhanced 

by drugs that increase the pharmacologically active 

unbound fraction (such as lidocaine or diazepam). Liver 

disease may necessitate reduced dosing of verapamil and 

diltiazem. 40 

CCBs may be responsible for several drug inter - 

actions and may have numerous adverse effects. The 

coadministration of diltiazem and beta-blockers may 

yield profound bradycardia. Diltiazem decreases the 

clearance of a single dose of propranolol, metoprolol, 

and possibly atenolol; therefore, elevated concentrations 

of beta-blockers may be responsible for the brady - 

cardic effects. Cimetidine causes increases in plasmadiltiazem 

concentrations and in plasma-deacetyldiltiazem 

concentrations. 

The combination of verapamil and beta-blockers may 

result in bradycardia, heart block, and left ventricular 

failure. The risks are especially increased when both 

drugs are given intravenously. Bradycardia has also been 

reported in a patient treated with oral verapamil and 

timolol eye drops. 41 Verapamil is extensively metabolized 

in the liver and interactions may occur with drugs that 

inhibit or enhance hepatic metabolism. Verapamil inhibits 

the cytochrome P-450 isoenzyme CYP 3A4 and 

therefore may increase plasma concentrations of carbamazepine, 

cyclosporine, digoxin (by up to 70%), midazolam, 

sim vastatin, and theophylline. Verapamil and 

diltiazem have significant local anesthetic properties, 

because they block fast sodium channels, and therefore 

the risk of local anesthetic toxicity may be increased in 

patients taking these medications. 

Enhanced antihypertensive effects may be seen with 

the combination of nifedipine and beta-blockers. Heart 

failure has also been reported in a few patients with 

angina who were given nifedipine and a beta-blocker. 

Nifedipine may modify insulin and glucose responses. 

Nifedipine is extensively metabolized in the liver by the


cytochrome P-450 isoenzyme CYP 3A4, and interactions 

may occur with quinidine (resulting in increased serum 

nifedipine concentrations), which shares the same metabolic 

pathway, and with enzyme inducers, such as carbamazepine, 

phenytoin, and rifampicin. Inhibition of the 

cytochrome P-450 system by cimetidine and erythromycin 

may lead to potentiation of the hypotensive effect. 

Decreased blood pressure from volatile anesthetics can 

be potentiated by concurrent administration of CCBs. 

Volatile anesthetics significantly decrease intracellular 

Ca 2+ in the myocardium, and thus augment the negative 

inotropic, dromotropic, and vasodilatory effects of 

CCBs. 42 CCBs potentiate depolarizing and nondepolarizing 

neuromuscular blockade, 43 and the antagonism of a 

nondepolarizing neuromuscular blockade may be blunted, 

because calcium is essential for the release of acetylcholine 

at the neuromuscular junction. Edrophonium may be 

more effective than neostigmine in reversing neuromuscular 

blockade that has been enhanced by CCBs. 44 

Angiotensin-Converting Enzyme Inhibitors 

Angiotensin-converting enzyme (ACE) inhibitors de - 

crease angiotensin II and aldosterone levels. They have 

been shown to slow renal dysfunction in diabetic nephropathy 

and to improve long-term outcomes in heart failure 

trials. 45 Accumulation of captopril, lisinopril, and enalaprilat 

occurs in patients with renal impairment, and 

decreased glomerular filtration rate is seen in patients 

treated with ACE inhibitors. These drugs should be 

avoided in patients with renal artery stenosis. Hyperkalemia 

is possible 46 because of reduced production of aldosterone; 

therefore, potassium levels should be monitored. 

The adverse effects of ACE inhibitors on the kidneys may 

be potentiated by other drugs, such as nonsteroidal antiinflammatory 

drugs (NSAIDs). Several ACE inhibitors 

are designed as prodrugs, and they must undergo hepatic 

conversion. Enalapril is the prodrug of the active ACE 

inhibitor, enalaprilat, and conversion may be affected in 

patients with hepatic dysfunction. Captopril and lisinopril 

are not prodrugs. 

The combination of NSAIDs and ACE inhibitors may 

have variable effects on renal function because they act 

at different parts of the glomerulus. When given to 

patients whose kidneys are underperfused (heart failure, 

hypovolemia, or cirrhosis), renal function may deteriorate. 

Indomethacin and possibly other NSAIDs, including 

aspirin, have been reported to reduce the hypotensive 

action of ACE inhibitors. Part of the hypotensive effect 

of ACE inhibitors may be prostaglandin-dependent, 

which might explain this interaction with drugs such as 

NSAIDs that block prostaglandin synthesis. Marked 

hypotension may occur during general anesthesia in 

patients receiving ACE inhibitors, therefore discontinuation 

of ACE inhibitor therapy before anesthesia should 

be considered. Excessive hypotension may occur when 

ACE inhibitors are used concurrently with diuretics or 

other antihypertensives. An additive hyperkalemic effect 

is possible in patients receiving ACE inhibitors with 

potassium-sparing diuretics, potassium supplements, or 

other drugs that can cause hyperkalemia (such as cyclosporine 

or indomethacin). Potassium-sparing diuretics 

and potassium supplements should generally be stopped 

before initiating ACE inhibitors in patients with heart 

failure. 

Pulmonary Drugs 

Beta Agonists 

Inhaled beta receptor agonists are a mainstay in the treatment 

of asthma. The primary action of beta agonists is to 

stimulate adenylyl cyclase, and thus increase adenosine 

3′,5′-cyclic monophosphate (cAMP). Increased levels of 

cAMP mediate smooth muscle relaxation and inhibit the 

inflammatory mediator release from mast cells. Metaproterenol 

was the first beta 2 selective agonist; however, albuterol 

is currently the most widely used agent. Adverse 

effects include tremor, tachycardia, hypertension, palpitations, 

nausea, and vomiting. 47 Direct-acting beta agonists 

should be administered with extreme caution to patients 

who are being treated with MAOIs (clorgyline, isocarboxazid, 

pargyline, phenelzine, selegiline), or within 2 

weeks of the discontinuation of an MAOI, because the 

action of the beta agonist on the vascular system may be 

exaggerated. Acute metabolic responses include hyperglycemia, 

hypokalemia, and hypomagnesemia. Despite 

the relative beta 2 selectivity of these agents, higher doses 

can stimulate both beta 1 and beta 2 receptors. Prophylactic 

administration of beta agonists 1 hour before induction 

of general anesthesia results in reduced airway resistance 

after endotracheal intubation. 48 

Theophylline 

Theophylline is a phosphodiesterase inhibitor, leading to 

increased cellular concentrations of cAMP and cGMP 

(cyclic guanosine 3′,5′-monophosphate). The combination 

of phosphodiesterase inhibition, inflammatory inhibition, 

and catecholamine release may all contribute to 

smooth muscle relaxation and bronchodilation. Theophylline 

is eliminated mainly by hepatic metabolism and 

usual doses can be given to patients with renal impairment. 

Its metabolism and clearance are greatly affected 

by concurrent disease states and altered physiology 

including liver disease, pulmonary edema, chronic 

obstructive pulmonary disease, and thyroid disease. Phenytoin 

markedly decreases the elimination half-life and 

increases the clearance of theophylline by up to 350%,


probably as a result of hepatic enzyme induction. Carbamazepine 

and rifampin have been observed to increase 

theophylline elimination. However, cimetidine, erythromycin, 

amiodarone, mexiletine, and tacrine inhibit its 

hepatic metabolism. Theophylline may enhance lithium 

elimination with a consequent loss of effect. 

Specific drug interactions with numerous anestheticrelated 

medications have been described. There is a risk 

of synergistic toxicity if theophylline is used in the presence 

of halothane 49 because of the sensitizing effects of 

halothane on the myocardium to increased catecholamines 

released by theophylline. Larger doses of benzodiazepines 

may be needed to achieve a desired effect, 

because benzodiazepines increase the CNS concentrations 

of adenosine, a potent CNS depressant, whereas 

theophylline blocks adenosine receptors. Ketamine may 

decrease the theophylline seizure threshold, 50 and theophylline 

can antagonize the effect of nondepolarizing 

neuromuscular blockers possibly because of phosphodiesterase 

inhibition. Theophylline can precipitate sinus 

tachycardia, multifocal atrial tachycardia, and supraventricular 

and ventricular premature contractions at therapeutic 

or supratherapeutic serum concentrations. It can 

also potentiate hypokalemia associated with the administration 

of beta 2 agonists, corticosteroids, and diuretics. 

Gastrointestinal Drugs 

Cimetidine 

Cimetidine is a competitive antagonist for histamine at 

the H 2 receptor. Cimetidine is metabolized in the liver 

where it binds to cytochrome P-450 and interferes with 

the metabolism of several drugs including amiodarone, 

warfarin, theophylline, phenytoin, lidocaine, quinidine, 

tricyclic antidepressants, and propranolol. 51 The effects of 

cimetidine on carbamazepine plasma concentration may 

be temporary; however, carbamazepine toxicity, manifesting 

in ataxia, nystagmus, diplopia, headache, vomiting, 

apnea, seizures, and coma, may occur with cimetidine 

coadministration. Carvedilol is significantly metabolized 

by the cytochrome P-450 enzyme system. Increased 

adverse effects of carvedilol (dizziness, insomnia, GI 

symptoms, postural hypotension) may result when the 

drug is administered with cimetidine. Cimetidine also 

decreases the clearance of benzodiazepines that are 

metabolized by hydroxylation or dealkylation (e.g., diazepam, 

chlordiazepoxide, clorazepate, flurazepam, prazepam, 

halazepam, alprazolam, triazolam, midazolam, 

quazepam, bromazepam). Adverse effects such as pronounced 

sedation and impaired cognitive and psychomotor 

function have been reported. Benzodiazepines for 

which nitroreduction is a prominent metabolic pathway 

might also have their clearance decreased by cimetidine 

(e.g., nitrazepam, clonazepam). Those benzodiazepines 

eliminated primarily by glucuronidation do not interact 

with cimetidine (e.g., lorazepam, oxazepam, temazepam). 

Hepatic metabolism of cimetidine may be enhanced if 

phenobarbital is administered concurrently. Cimetidine 

crosses the blood–brain barrier and interacts with cerebral 

H 2 receptors. Consequently, headaches, somnolence, 

confusion, and delirium may occur. Delayed awakening 

from anesthesia has been attributed to lingering CNS 

effects of cimetidine. Bradycardia, tachycardia, cardiac 

dysrhythmias, and hypotension may occur because of 

interaction with cardiac H 2 receptors. These events have 

generally been associated with rapid intravenous infusion. 

Cimetidine may cause impotence, loss of libido, and 

gynecomastia (by increasing the plasma concentration of 

prolactin) in male patients. 

Metoclopramide 

Metoclopramide is a dopamine antagonist and a selective 

peripheral cholinergic agonist useful for reducing gastric 

fluid volume by increasing lower esophageal sphincter 

tone, speeding gastric emptying time, and acting as an 

antiemetic. Side effects include hypotension, sedation, 

dysphoria, rash, and dry mouth. Anxiety, restlessness, and 

drowsiness may occur with rapid administration of undiluted 

metoclopramide. Bradycardia, supraventricular 

arrhythmias, complete heart block, and asystole have also 

been reported after administration of single doses of 

intravenous metoclopramide. The drug blocks dopaminergic 

receptors in the CNS, thereby inducing secretion 

of prolactin and creating the possibility of extrapyramidal 

symptoms. 51 Metoclopramide should be avoided in the 

presence of GI obstruction or after GI surgery and in 

patients taking MAOIs, tricyclic antidepressants, or other 

drugs that may cause extrapyramidal symptoms. By inhibiting 

pseudocholinesterase, metoclopramide may elicit 

prolonged responses to succinylcholine. 52 

Oral Anticoagulants 

Warfarin 

Warfarin is an anticoagulant that inhibits the hepatic conversion 

of four vitamin K-dependent coagulation factors 

(II, VII, IX, and X) and two anticoagulant proteins 

(protein C and S). It is indicated for the prophylaxis and/ 

or treatment of venous thrombosis, pulmonary embolism, 

thromboembolic complications associated with atrial 

fibrillation, and/or cardiac valve replacement, and to 

reduce the risk of death, recurrent myocardial infarction, 

and stroke after myocardial infarction. An anticoagulation 

effect generally occurs within 24 hours after drug 

administration. However, peak anticoagulant effect may


be delayed 72–96 hours when the vitamin K-dependent 

procoagulant proteins are reduced by 30%–50% of 

normal, which is consistent with international normalized 

ratio (INR) values in the range of 2–3. Warfarin is metabolized 

by hepatic cytochrome P-450 to inactive hydroxylated 

metabolites (predominant route) and by reductases 

to reduced metabolites. The metabolites are principally 

excreted into the urine and bile. No dosage adjustment is 

necessary for patients with renal failure. Hepatic dysfunction 

can potentiate the response to warfarin through 

impaired synthesis of clotting factors and decreased 

metabolism of warfarin. Discontinuation of warfarin will 

result in normalization of the prothrombin time (PT)/ 

INR in 3 days unless the patient has substantial liver 

disease or vitamin K deficiency. Warfarin is >98% bound 

to albumin, meaning that only 1%–2% of the circulating 

drug accounts for the entire biologic effect. 

Pyrazole NSAIDs (e.g., phenylbutazone) compete 

effectively for the same binding sites and may significantly 

increase bleeding risks when coadministered with 

warfarin. Amiodarone also inhibits the metabolic clearance 

of warfarin. Second- and third-generation cephalosporins 

augment the anticoagulant effect by inhibiting 

the cyclic interconversion of vitamin K. Aspirin and 

NSAIDs inhibit platelet function and have the potential 

to increase the risk of warfarin-associated bleeding. 53,54 

Patients 60 years or older seem to exhibit greater than 

expected PT/INR response to the anticoagulant effects 

of warfarin. The cause of the increased sensitivity to warfarin 

in this age group is unknown. Therefore, as patient 

age increases, a lower dose of warfarin is usually 

required. 

Ticlopidine 

Ticlopidine is a platelet aggregation inhibitor. Its active 

metabolite blocks platelet surface adenosine 5′-diphosphate 

(ADP) receptors and, subsequently, ADP-induced 

binding of fibrinogen to the platelet GPIIb/IIIa receptor 

is inhibited. Ticlopidine may also block the binding of von 

Willebrand factor to platelets. The effect on platelet function 

is irreversible. Ticlopidine should be stopped 2 weeks 

before elective surgery. It may cause hepatic impairment, 

neutropenia, agranulocytosis, and thrombotic thrombocytopenic 

purpura. It should be avoided in patients with 

hepatic insufficiency. Intracranial and GI bleeding are also 

serious complications. 55–57 Ticlopidine potentiates the 

effect of aspirin or other NSAIDs on platelet aggregation. 

In clinical studies, ticlopidine was used concomitantly with 

beta-blockers, CCBs, and diuretics without evidence of 

clinically significant adverse interactions. The safety of 

concomitant use of ticlopidine and NSAIDs has not been 

established. Clearance of ticlopidine decreases with age. 

Steady-state trough values in elderly patients are approximately 

twice those in younger volunteer populations. 

Nonsteroidal Antiinflammatory Drugs 

NSAIDs are the most frequently prescribed drugs worldwide 

and are responsible for 21% of all adverse reactions 

reported each year to the spontaneous drug reporting 

system of the United States Food and Drug Administration. 

58 NSAIDs are nonselective inhibitors of both 

cyclooxygenase (COX)-1 and COX-2. Absorption, peak 

plasma concentration, and metabolism can be significantly 

affected by GI pH, concomitant administration of 

other drugs, and the disease state of the patient. Antacids 

and mucoprotective agents can delay the absorption of 

NSAIDs. Elimination is largely dependent on hepatic 

biotransformation and renal excretion. Therefore, patients 

with hepatic and renal disease often demonstrate greater 

and more prolonged peak plasma concentrations. Acute 

renal impairment, papillary necrosis, acute interstitial 

nephritis, and nephrotic syndrome have all been attributed 

to NSAIDs. 59 In the presence of renal vasoconstriction, 

the vasodilator action of prostaglandins increases 

renal blood flow and thereby helps to maintain renal 

function. Patients whose renal function is being maintained 

by prostaglandins are therefore at risk from 

NSAIDs. Such patients include those with impaired circulation, 

the elderly, those taking diuretics, and those with 

heart failure or renal vascular disease. Serious hepatotoxicity 

is rare with typical therapeutic doses. The underlying 

mechanism seems to be immunologic; however, aspirin 

and phenylbutazone may have direct toxic effects. These 

drugs are frequently administered with opioid agents to 

enhance their analgesic potential. Naproxen (Naprosyn, 

Avaprox, Aleve), oxaprozin (Daypro), and piroxicam 

(Feldene) are considered potentially inappropriate for 

the elderly, because these medications all have the potential 

to produce hypertension, heart failure, renal failure, 

and GI adverse effects. 

Ketorolac 

Immediate and long-term use should be avoided in older 

patients, because a significant number have asymptomatic 

GI pathologic conditions. NSAID gastropathy (dyspepsia, 

nausea, epigastric pain) is one of the most frequent 

drug-related side effects in the United States. 60 

Indomethacin 

All NSAIDs should be considered capable of causing 

confusion in the elderly. The more readily lipid-soluble 

agents would be expected to cross the blood–brain barrier 

easier and hence cause greater CNS adverse effects 

than less lipophilic NSAIDs. Of all available NSAIDs, 

indomethacin produces the most CNS adverse effects, 

including cognitive dysfunction, confusion, excessive


somnolence, and behavioral disturbances. 61 Indomethacin 

may also accelerate the rate of cartilage destruction 

in patients with osteoarthritis. 

H 1 Receptor Antagonists 

These drugs are competitive, selective, and reversible 

antagonists of histamine on the H 1 receptor. First-generation 

antagonists may also activate muscarinic cholinergic, 

serotonin, or alpha-adrenergic receptors. Second-generation 

antagonists are unlikely to produce CNS side effects. 

Nonanticholinergic antihistamines are preferred in 

elderly patients when treating allergic reactions. 

Diphenhydramine 

Diphenhydramine is a first-generation H 1 receptor antagonist. 

It may cause confusion and sedation. Anticholinergic 

effects such as dry mouth, blurred vision, and urinary 

retention may be noted. Tachycardia, cardiac dysrhythmias, 

and prolongation of the QT interval may occur. The 

drug should not be used as a hypnotic, and when used to 

treat emergency allergic reactions, it should be used in 

the smallest possible dose. 62 

Hydroxyzine, Chlor-Trimeton 

These are first-generation H 1 receptor antagonists with 

potent anticholinergic properties and as such are considered 

potentially inappropriate for older adults. 

Opioids 

Administration of narcotics (with the exception of meperidine) 

usually results in decreased heart rate. SA node 

depression and prolonged AV conduction can occur, as 

can sinus arrest and even asystole. Decreased sympathetic 

tone and histamine release (morphine and meperidine) 

can contribute to hypotension. Hypotensive effects 

are most prominent in patients with increased sympathetic 

tone, such as those with congestive heart failure or 

hypovolemia. Orthostatic hypotension may be seen in 

patients with autonomic neuropathy (e.g., diabetics). 

Meperidine, because of its structural similarity to atropine, 

may increase the heart rate. In large doses it has 

negative inotropic effects and can prolong the duration 

of action potential, potentiating class I antiarrhythmics. 

Meperidine has a bad reputation in the elderly for causing 

confusion and delirium. 63 Opioids may lessen total anesthetic 

requirements: a single dose of fentanyl may 

decrease the minimal anesthetic concentration (MAC) of 

isoflurane or desflurane by 50%. Likewise, alfentanil and 

remifentanil may also exhibit anesthetic-sparing effects. 

Mixed agonist-antagonists are less effective than pure 

agonists in reducing MAC. The ceiling effect for MAC 

parallels the ceiling effect for respiratory depression. 

Nalbuphine decreases MAC by only 8%. 

Pentazocine 

Pentazocine is a benzomorphan derivative that possesses 

agonist (delta and kappa receptors) as well as weak 

antagonist actions. The most common side effect of pentazocine 

is sedation, followed by diaphoresis and dizziness. 

Pentazocine increases the plasma concentration of 

catecholamines, which may account for increases in heart 

rate, systemic blood pressure, and pulmonary artery pressure. 

Confusion and hallucinations limit its use in the 

elderly. 64 Pentazocine decreases MAC by 20%. 

Propoxyphene 

Propoxyphene offers few analgesic advantages over acetaminophen 

or aspirin, yet has the adverse effects of other 

narcotics. The only clinical use of propoxyphene is treatment 

of mild-to-moderate pain that is not adequately 

relieved by the above two drugs. It does not possess 

antipyretic or antiinflammatory effects, and its antitussive 

activity is not significant. The most common side effects 

of propoxyphene are vertigo, sedation, nausea, and 

vomiting. Overdose—especially in combination with 

alcohol—is complicated by seizures and depression of 

ventilation. 65,66 Propoxyphene may slow the metabolism 

of concomitantly administered antidepressants, anticonvulsants, 

or warfarin-like drugs. Severe neurologic signs, 

including coma, have occurred with concurrent use of 

carbamazepine. 

Conclusions 

The large number and variety of chronic medications 

prescribed to elderly patients presenting for surgery 

greatly complicate the preoperative assessment and anesthetic 

management of geriatric patients. The various 

interactions of medications on metabolism and end effects 

must be understood and considered when formulating an 

appropriate anesthetic plan. 

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15 

The Pharmacology of Opioids 

Steven L. Shafer and Pamela Flood 

There are a lot of old people. In the 1990 census, patients 

over the age of 65 comprised 12% of the United States 

population, or 30,000,000 people. That grew modestly, to 

12.5%, by 2000. However, based on the United States 

population of 301,165,915 as of today,* that amounts to 

38 million individuals. It should come as no surprise, 

therefore, that health care for the elderly consumes 5% 

of the United States gross domestic product. 1 

It is important that anesthesiologists understand the 

differences in pharmacology of opioids in elderly patients 

in order to be able to properly titrate these important 

analgesics. Below are the key points for this chapter: 

1. Elderly patients need about half the dose as younger 

patients. 

2. The reason is primarily pharmacodynamic (change 

in intrinsic sensitivity of the brain to the drug). The pharmacokinetic 

changes with age are modest. 

3. Studies in elderly animals show reduced numbers of 

µ receptors with increased age. That does not explain the 

reduction in dose, as decreased receptor density should 

decrease sensitivity to opioids. The enhancement in drug 

effect seen in the clinic is more likely attributable to 

changes in cyclonucleotide coupling and other downstream 

changes that occur in aging. 

4. Meperidine is a difficult drug to use in elderly 

patients. It should never be used in patient-controlled 

analgesia (PCA) and is best reserved for shivering. 

General Observations 

Opioids are among the most effective, and the most dangerous, 

of the drugs administered by anesthesiologists. 

This is why the World Health Organization proposed a 

three-step analgesic ladder for the treatment of chronic 

pain. They recommended starting with acetaminophen 

*www.census.gov. Accessed February 17, 2007. 

and nonsteroidal analgesics, progressing to opioids of 

intermediate strength, such as codeine, and treating 

severe pain with strong opioids such as morphine. 2 

The Agency for Health Care Policy and Research (now 

called the Agency for Healthcare Research and Quality) 

has issued similar guidelines. 3 Particular care must 

be taken when using opioids in elderly patients. It is 

nearly tautologic that elderly patients are more likely to 

suffer from chronic diseases than their younger counterparts. 

Some fortunate individuals remain physically vigorous 

until very late in life, whereas others seem to 

deteriorate physically at younger ages. Additionally, the 

cumulative effects of smoking, alcohol, and environmental 

toxins can accelerate the deterioration of aging in 

exposed individuals. Thus, it is not surprising that variability 

in physiology increases throughout life. 4 Increased 

physiologic variability results in increased pharmacokinetic 

and pharmacodynamic variability in elderly subjects. 

The clinical result of this increased variability is an 

increased incidence of adverse drug reactions in elderly 

patients. 5 Thus, elderly patients require more careful 

titration and, where possible and appropriate, therapeutic 

drug monitoring. 6 

In their secondary analysis of a retrospective cohort 

study, Cepeda and colleagues 7 noted that the risk of 

opioid-induced ventilatory depression increased with 

increasing age, with patients 61–70 years of age having 

2.8 times the risk of ventilatory depression compared 

with patients 16–45 years old. Interestingly, in their analysis, 

they converted all of the opioids into morphine equivalents, 

and the conversion did not account for the 

increased potency of opioids in the elderly that will be 

described subsequently. 

Although the risk of respiratory depression from 

opioids is greater in older people, the same is not true for 

all opioid side effects. Opioids are among the major 

causes of postoperative nausea and vomiting, increasing 

the risk nearly fourfold. 8 In the study by Cepeda et al., 

age was not a risk factor for nausea and vomiting. 7 In 

209

210 S.L. Shafer and P. Flood 

fact, age may actually decrease the risk of nausea and 

vomiting. Sinclair and colleagues 9 observed a 13% de - 

crease in the risk of postoperative nausea and vomiting 

with each additional decade of life. This is consistent with 

the findings of Junger and colleagues. 8 

The Opioid Receptor 

The existence of an opioid receptor was long suspected 

because of the high potency and stereoselectivity of 

pharmacologic antagonists. The biochemical discovery 

of opioid receptors was independently reported in 1973, 

by laboratories of Pert, 10 Simon, 11 and Terenius. 12 The 

finding of stereoselectivity led to an intense search 

for endogenous ligands, with identification of encephalin 

in 1975. 13 Other endogenous peptide ligands were isolated 

subsequently. 14,15 The fact that endogenous opioid 

ligands differed in their structure and binding sites 

suggested the existence of different opioid receptor 

types. 16 Three classes of opioid receptors were identified 

pharmacologically in the 1980s: µ (mu), 17 δ (delta), 18 and 

κ (kappa). 19 

Activation of the µ receptor is responsible for both 

the analgesic efficacy of the frequently used opioids 

and, unfortunately, for the majority of opioid toxicities. 

Shortly after characterization of the µ receptor, Pasternak 

and colleagues 20 demonstrated that there were 

two populations of opioid receptors: a high-affinity site, 

associated with analgesia and blocked by naloxazone, 

and a lower-affinity site, which was not blocked by naloxazone 

and seemed responsible for morphine lethality. 

It was subsequently demonstrated that morphine-induced 

analgesia was mediated by a population of receptors 

blocked by naloxonazine, which were termed µ 1 receptors, 

whereas morphine-induced ventilatory depression 

was blocked by a population of receptors that were not 

affected by naloxonazine, which were termed the µ 2 

receptors. 21,22 To further complicate matters, a selective 

morphine-6-glucuronide antagonist was identified, 3-Omethylnaxtrexone, 

that had little effect on morphine 

analgesia. 23 This suggested that there was variability 

within the µ 1 receptor itself. Although identification of a 

specific µ 1 antagonist led to the hope that a µ 1 -specific 

agonist could be developed, no such agonist has ever 

been identified. 

Additional evidence for µ receptor subtypes comes 

from the clinical observation of incomplete cross-tolerance 

among the opioids in patients, 24 so that if a patient 

is switched from an opioid to which the patient has 

become tolerant to an “equianalgesic” dosage of another 

opioid, the potential exists for serious overdose. 25 Additional 

evidence for multiple µ receptor subtypes comes 

from variance in the potency for analgesic efficacy and 

toxicity among patients, such that there is no single opioid 

that has the best therapeutic window for all patients. 25 An 

extreme example of differential response to opioids is 

found in the CXBK mouse, which is insensitive to morphine 

but has normal sensitivity to fentanyl and 

morphine-6-glucuronide. 26 

The µ opioid subtypes have unique distributions 

within the body. 27 Specifically, µ 1 is expressed in the 

brain, whereas µ 2 is expressed in the brain, gastrointestinal 

tract, and the respiratory tract. 28 Activation of both µ 

receptor subtypes acts to decrease calcium and potassium 

conductance and intracellular adenosine 3′,5′-cyclic 

monophosphate (cAMP). The recently discovered µ 3 

receptor is expressed on monocytes, granulocytes, and the 

vascular endothelium, where it acts to release nitric 

oxide. 29 Some of the vasodilatation that is associated with 

opioid administration that has been attributed to histamine 

release may be attributable to activation of the 

µ 3 receptor. 

The µ receptor is encoded by a single gene Oprm, 

located on chromosome 10 in the mouse 30,31 and on 

chromosome 6 in the human. 32 A variety of polymorphisms 

of Oprm have been identified in humans, as 

recently reviewed by Lötsch and Geisslinger. 32 The polymorphism 

that has generated the most interest has been 

the substitution of an aspartate for an asparagine in 

the 118 position, which is abbreviated the 118A > G 

SNP. This polymorphism has been associated with a 

decreased analgesic response to morphine. However, it 

does not reduce sensitivity to opioid-induced ventilatory 

depression. 33 

The Oprm gene gives rise to a family of µ receptors 

through selective splicing of the mRNA into µ opioid 

receptor subtypes. 34 In 1993, the first µ receptor was cloned, 

MOR-1. 35,36 Since then, at least 15 different splice variants 

of MOR-1 have been identified in mice, all derived from 

the same Oprm gene. 28 Several splice variants have been 

identified in humans as well. 37 Splice variants likely give 

rise to pharmacologically identified subtypes of µ receptors 

based on the exons that are translated. Unfortunately, 

mapping between individual splice variants and pharmacologically 

identified µ subtypes is incomplete. The currently 

identified splice variants are insufficient to explain 

the pharmacologic groupings, although this will likely 

become clearer as additional splice variants are discovered 

and characterized pharmacologically. 

All opioid receptors so far identified are coupled to G 

proteins. 38 At the cellular level, the opioid receptors have 

an inhibitory effect. When the receptors are occupied by 

opioid agonists, intracellular cAMP content is reduced. 

Reduced levels of cAMP both increase the activation of 

K + channels and reduce the open probability of voltagegated 

calcium channels. These changes cause hyperpolarization 

of the membrane potential and thus reduce 

neuronal excitability. 39

15. The Pharmacology of Opioids 211 

Age and Opioid Receptors 

End-organ sensitivity to various ligands changes with 

age. Part of this change is from differences at the level of 

the drug receptor-effector mechanism. For example, the 

number and structure of the β-adrenergic receptor is 

unchanged in the elderly myocardium. The decreased 

chronotropic and inotropic response of elderly patients 

to β-adrenergic drugs seems to result from downstream 

changes in the mechanism by which binding at the receptor 

is coupled to adrenergic response mechanism. 40 In 

the brain, there seems to be both decreased α- and β- 

adrenergic receptor density in elderly individuals. 41 

There is no decrease in the affinity or density of central 

nervous system benzodiazepine receptors with age. 42 

Barnhill and colleagues 43 studied benzodiazepine binding 

in response to acute or chronic stress. In the absence of 

stress, there was no difference in the number or affinity 

of benzodiazepine receptors. In young rats, receptor 

binding was increased by acute stress, a response not 

observed in older animals. Chronic stress enhanced 

binding in both young and old rats, but the recovery following 

cessation of stress was delayed in older animals. 

Thus, there are age-associated changes in benzodiazepine 

binding, but only in the poststress condition. 

Ueno and colleagues 44 examined opioid receptors in 

young, mature, and aged mice. Aged mice had reduced µ 

receptor density, but increased µ receptor affinity. Hess 

et al. 45 also observed decreased µ receptor density in rats 

with advancing age, associated with decreased sensitivity 

to pain. Similarly, Petkov and colleagues 46 observed 

decreased enkephalin receptors in aged rats, as well as 

decreased sensitivity to enkephalin. Aging may induce 

changes downstream of opioid receptor binding. In 

studies on opioid receptors in polymorphonuclear leucocytes, 

Fulop and colleagues 47 have shown that whereas 

cAMP was reduced on binding in cells from young adult 

animals, it was increased in cells from aged animals. 

Hoskins and Ho 48 have shown age-induced changes in the 

basal activities of adenylate cyclase, guanylate cyclase, 

cAMP phosphodiesterase, and cyclic guanosine monophosphate 

phosphodiesterase. 

Smith and Gray 49 examined the analgesic response to 

opioids in young and aged rats. They applied noxious 

stimulus at two different stimulus intensities. At the lowintensity 

stimulus (immersing the tail in 50°C water), 

there was a trend toward increased sensitivity to opioids 

in the aged rats, but the difference was not statistically 

significant. However, when subjected to the high-intensity 

stimulus (immersing the tail in 55°C water), the aged 

rats were about twice as sensitive to opioids as the young 

rats, an effect that was statistically significant. 

Other investigators have reached quite different 

conclusions using similar experimental paradigms (tail 

flick after immersion in hot water). Van Crugten and 

colleagues 50 looked at morphine antinociception in 

aged rats, and found no difference in antinociception 

between aged and adult animals. Hoskins and colleagues 51 

found that aged mice were about half as sensitive 

to morphine as mature adult mice. Thus, the animal 

studies consistently show decreased numbers of opioid 

receptors in aged brains. However, the story about the 

antinociceptive response to morphine is less clear in 

animal models, with studies showing increased sensitivity, 

decreased sensitivity, or no change in sensitivity with 

advancing age. 

Aging and Pain Perception 

Pain is a part of daily life for many elderly patients, with 

about 50% of patients over the age of 70 reporting chronic 

pain. 52 Elderly patients are particularly more prone to 

chronic pain than younger people. 53,54 However, clinically 

it seems that pain in elderly subjects is indistinguishable 

from the experience of pain in younger subjects. 55 

There are some interesting differences between young 

and older subjects in their response to experimental pain. 

There is some evidence that older patients are more sensitive 

to experimental pain, 56 which may be explained, at 

least in part, by a reduction in the endogenous analge - 

sic response to pain, 57,58 possibly mediated by reduced 

production of β-endorphin in response to noxious stimulation. 

59 Older patients experience a more prolonged 

hyperalgesia after capsaicin injection compared with 

younger subjects. 60 However, older patients seem to also 

require a higher intensity of noxious stimulation before 

first reporting pain. 58 

Some of the differences between studies may also 

depend on exactly which pain pathways are activated 

during the assessment. Chakour and colleagues 61 demonstrated 

that pain transmission via C fibers was unchanged 

in young versus elderly subjects. However, there was a 

substantial reduction in pain transmission via Aδ fibers. 

Thus, the relative perceptions of pain in elderly subjects 

versus younger subjects were influenced by the extent of 

pain transmission via Aδ fibers. 

The Onset and Offset of Opioid 

Drug Effect 

Onset 

The onset of opioid drug effect is determined by the route 

of delivery, the delivered dose, the pharmacokinetics 

of the opioid that determine the plasma concentrations 

over time, and the rate of blood–brain equilibration 

between the plasma and the site of drug effect. Table 15-1 

shows adult pharmacokinetics of fentanyl, 62 alfentanil, 62


Table 15-1. Pharmacokinetic parameters for frequently used opioids. 

Fentanyl Alfentanil Sufentanil Remifentanil Morphine Methadone Meperidine Hydromorphone 

Volumes (L) 

V 1 12.7 2.2 17.8 4.9 17.8 7.7 18.1 11.5 

V 2 50 7 47 9 87 12 61 115 

V 3 295 15 476 5 199 184 166 968 

Clearances (L/min) 

Cl 1 0.62 0.20 1.16 2.44 1.26 0.13 0.76 1.33 

Cl 2 4.82 1.43 4.84 1.75 2.27 2.19 5.44 3.45 

Cl 3 2.27 0.25 1.29 0.06 0.33 0.38 1.79 0.92 

Exponents (min −1 ) 

α 0.67 1.03 0.48 0.96 0.23 0.50 0.51 0.51 

β 0.037 0.052 0.030 0.103 0.010 0.025 0.031 0.012 

γ 0.0015 0.0062 0.0012 0.0116 0.0013 0.0005 0.0026 0.0005 

Half-lives (min) 

t 1/2 α 1.03 0.67 1.43 0.73 2.98 1.38 1.37 1.35 

t 1/2 β 19 13 23 7 68 28 22 59 

t 1/2 γ 475 111 562 60 548 1377 271 1261 

Blood–brain equilibration 

k e0 (min −1 ) 0.147 0.770 0.112 0.525 0.005 0.110 0.067 0.015 

t 1/2 k e0 (min) 4.7 0.9 6.2 1.3 139 6.3 10. 46 

T peak (min) 3.7 1.4 5.8 1.6 93.8 11.3 8.5 19.6 

VD peak effect (L) 76.9 6.0 94.9 17.0 590.2 30.9 143.3 383.3 

Note: The references for the pharmacokinetic parameters are given in the text. 

VD = volume of distribution. 

† 

Data extensively reanalyzed to obtain volume and clearance 

estimates. 

‡ 

Original data provided by S. Bjorkman and fit using population 

model to create estimates in Table 15-1. 

§ 

Based on a time to peak of 8.5 minutes in goats (!). It’s 

not great, but it’s the best onset data available. 

 

Based on a time to peak effect of 15–20 minutes. 

sufentanil, 63 remifentanil, 64 morphine, 65 methadone, 66† 

meperidine, 67‡ and hydromorphone. 68 Table 15-1 also 

shows k e0 , the rate constant for blood–effect-site equilibration, 

for fentanyl, 62 alfentanil, 62 sufentanil, 69 remifentanil, 

64 morphine, 65 methadone, 70 meperidine, 71§ and 

hydromorphone. 72 Based on these data, it is possible to 

predict the time course of concentration change in the 

plasma following an intravenous bolus, as seen in Figure 

15-1. The upper graph in Figure 15-1 shows the concentration 

during 24 hours following a bolus injection, whereas 

the lower graph just shows the first 30 minutes. In both 

cases, the curves have been normalized to start at 100%, 

which permits direct comparison of the pharmacokinetics 

despite differing potencies. As seen in the upper graph, 

the extremes of plasma elimination are remifentanil, 

which is ultra fast, and methadone, which has the longest 

half-life. Alfentanil has the second-shortest half-life 

among the eight opioids. Fentanyl, meperidine, sufentanil, 

hydromorphone, and morphine are all clustered in the 

middle. In particular, note how similar hydromorphone 

and morphine are when one examines the plasma pharmacokinetics. 

Approximately the same trend is observed 

in the first 30 minutes, although the initial distribution 

phase of hydromorphone takes it nearly as low as remifentanil 

in the first 10 minutes. As will be seen shortly, this 

is significant in terms of recovery. 

The plasma is not the site of drug effect, and thus 

the time course of concentration seen in Figure 15-1 will 

not reflect the time course of effect-site concentration 

or behavioral activity. By incorporating the plasma– 

effect-site equilibration delay into our calculations, we 

can examine the time course of the onset of drug effect, 

as shown in Figure 15-2. In this case, we have normalized 

the effect-site concentrations to peak-effect concentration 

73 to again permit comparisons of the time course of 

drugs independent of the differences in potency. Alfentanil 

and remifentanil both reach a peak about 1.5 minutes 

after bolus injection, although the overall remifentanil 

drug effect is more evanescent. The peak fentanyl concentration 

occurs about 3.5 minutes after bolus injection, 

whereas the peak sufentanil effect is about 6 minutes 

after bolus injection. Methadone and meperidine are 

nearly indistinguishable following bolus injection, each 

reaching a peak about 12 minutes after a bolus. The peak 

for hydromorphone is 15–20 minutes after the bolus. 

Morphine is the outlier in terms of onset. Five minutes 

after a bolus injection, morphine is at 50% of the peak 

concentration. However, morphine reaches its peak concentration 

in the effect site about 90 minutes after the 

bolus injection. Table 15-1 shows the time to reach peak 

concentration for each of the opioids, as well as the 

volume of distribution at the time of peak effect, which 

is useful for calculating initial loading doses. 74–76 

One of the key benefits to knowing the time course of 

drug effect following bolus injection is logical program-


ming of the lockout of PCA devices. A 10-minute lockout 

for hydromorphone and methadone is a logical choice, 

because patients are able to make a decision to redose 

themselves after reaching peak drug effect. The slower 

onset of morphine is somewhat problematic, because 

patients will administer another dose while the prior dose 

is still coming on, creating the possibility of stacking bolus 

doses. 

Considerable attention is given to “equianalgesic 

dosing” of opioids. The calculation of the equianalgesic 

dose is complicated by both the relative intrinsic potency 

of the opioids, the different pharmacokinetic profiles, 

and the large differences in the rate of blood–brain equilibration. 

Table 15-2 shows equianalgesic doses of frequently 

used opioids, based on the “minimum effective 

analgesic concentrations” or “MEAC” (also called 

“MEC”) of fentanyl, 77 alfentanil, 78 sufentanil, remifentanil,# 

morphine, 79 ** methadone, 80 meperidine, 81 and 

Figure 15-2. The time course of effect-site concentration following 

a bolus of fentanyl, alfentanil, sufentanil, remifentanil, 

morphine, methadone, meperidine, and hydromorphone, based 

on the pharmacokinetics and rate of plasma–effect-site equilibrium 

shown in Table 15-1. The curves have been normalized to 

the peak effect-site concentration, permitting comparison of the 

relative rate of increase independent of dose. The times to peak 

effect correspond to those shown in Table 15-1. 

hydromorphone. 82,83 †† Reflecting anesthesiologists’ 

familiarity with fentanyl, all of the calculations have been 

made using fentanyl as the reference opioid. The calculation 

of an equianalgesic bolus dose depends on when the 

observation of drug effect is made. For example, because 

fentanyl has a very rapid onset, and morphine has a very 

slow onset, 5 mg of morphine has the same effect at 10 

minutes as 50 µg of fentanyl, whereas 60 minutes after the 

dose, 1 mg of morphine has the same effect as 50 µg of 

fentanyl. Similarly, because the drugs accumulate during 

infusions at different rates, the relative potencies of the 

opioids change depending on how long the infusion has 

been running, as shown in Table 15-2. 

Figure 15-3 shows the increase in effect-site concentration 

during a continuous infusion for each of these 

opioids. As expected, remifentanil increases the fastest, 

whereas methadone increases the slowest. Note, however, 

that even after 10 hours of drug administration, most of 

these opioids are only at 60%–80% of the eventual 

Figure 15-1. The time course of plasma concentration following 

a bolus of fentanyl, alfentanil, sufentanil, remifentanil, morphine, 

methadone, meperidine, and hydromorphone, based on 

the pharmacokinetics shown in Table 15-1. The y-axis is the 

percent of the initial concentration, which by definition is 100% 

at time 0, permitting display of the relative time courses of these 

opioids independent of the dose administered. 

Scaled to fentanyl based on relative electroencephalogram 

(EEG) potency of fentanyl 62 and sufentanil. 69 

# 

Scaled to fentanyl based on the relative EEG potency of fentanyl 

and remifentanil. 64 

**The MEC range given by Dahlstrom was 6–31 ng/mL, with a 

mean of 16 ng/mL. We chose 8 ng/mL, at the lower end of the 

reported range, because the average value of 16 ng/mL predicted 

equianalgesic morphine that seemed excessive. 

†† 

This was the most difficult potency to determine from the literature. 

Hill and Zacny documented a tenfold bolus dose 

potency difference versus morphine, which was the final basis 

for calculating this number, and is similar to the value suggested 

by the Coda paper.


Table 15-2. Relative potency of frequently used opioids, based on the time of the observed effect. 

Fentanyl Alfentanil Sufentanil Remifentanil Morphine Methadone Meperidine Hydromorphone 

MEAC (ng/mL) 0.6 14.9 0.056 1.0 8 60 250 1.5 

Equipotent bolus dose at: (µg) (µg) (µg) (µg) (mg) (mg) (mg) (mg) 

Peak effect 50 92 5.5 17 4.9 1.9 37 0.6 

10 minutes 50 197 4.4 72 5.3 1.4 28 0.4 

30 minutes 50 174 3.9 282 2.0 0.9 17 0.2 

60 minutes 50 175 4.8 1680 1.0 0.9 14 0.1 

Equipotent infusion rate at: (µg/h) (µg/h) (µg/h) (µg/h) (mg/h) (mg/h) (mg/h) (mg/h) 

1 hour 100 323 8.8 135 5.3 2.3 43 0.6 

2 hours 100 332 9.6 182 3.3 2.3 38 0.4 

4 hours 100 365 11.6 252 2.3 2.6 36 0.4 

6 hours 100 409 13.0 310 2.1 2.9 37 0.4 

12 hours 100 536 15.1 436 2.2 3.1 40 0.5 

24 hours 100 675 16.3 554 2.4 2.9 45 0.6 

Note: The references for the relative potency are given in the text. 

MEAC = mean effective analgesic concentration. 

steady-state concentration. This speaks to the problem of 

background infusions for PCA. Even after many hours, 

patients are not at steady state, and the increasing drug 

concentration from the background infusion may expose 

a patient to toxicity 12–24 hours after initiation of the 

infusion. Given the increased sensitivity of elderly patients 

to the effects of opioids, background infusions are likely 

a particularly poor choice in this population. 

Offset 

The offset of drug effect is a function of both the pharmacokinetic 

behavior and the rate of blood–brain equilibration. 

The “context sensitive half-time” 73,84 is a useful 

way to consider the plasma pharmacokinetic portion of 

the offset time, as shown in Figure 15-4. The x-axis on 

Figure 15-4 is the duration of an infusion that maintains 

Figure 15-3. The increase to steady state during an infusion of 

fentanyl, alfentanil, sufentanil, remifentanil, morphine, methadone, 

meperidine, and hydromorphone, based on the pharmacokinetics 

and rate of plasma–effect-site equilibrium shown in 

Table 15-1. The curves have been normalized to the steady-state 

effect-site concentration, permitting comparison of the relative 

rate of increase independent of infusion rate. Only remifentanil 

and alfentanil are at steady state after 10 hours of continuous 

infusion. 

Figure 15-4. The “context-sensitive half-time” (50% plasma 

decrement time) for fentanyl, alfentanil, sufentanil, remifentanil, 

morphine, methadone, meperidine, and hydromorphone, 

based on the pharmacokinetics shown in Table 15-1. Remifentanil 

shows virtually no accumulation over time with continuous 

infusions, whereas the offset of fentanyl changes 

considerably as it is administered to maintain a steady plasma 

concentration.


a steady concentration of drug in the plasma. The y-axis 

is the time required for the concentrations to decrease by 

50% after the infusion is terminated. Remifentanil’s 

pharmacokinetics are so fast that the context-sensitive 

half-time blurs right into the x-axis. Perhaps surprisingly, 

fentanyl is the outlier here. Fentanyl accumulates in fat, 

and so an infusion that maintains a steady concentration 

in the plasma winds up giving patients a whopping dose 

of fentanyl, resulting in slow recovery. Meperidine similarly 

shows long recovery. Note that for infusions of less 

than 10 hours, morphine, hydromorphone, and sufentanil 

are nearly indistinguishable based on the plasma 

pharmacokinetics. 

Once again, we have to consider that the plasma is not 

the site of drug effect. Therefore, we must consider the 

50% effect-site decrement time, 73,85 as shown in Figure 

15-5. Because fentanyl and remifentanil have very rapid 

plasma–effect-site equilibration, they have changed little 

between Figures 15-4 and 15-6. Note, however, the 

huge change for morphine and hydromorphone. One 

might have thought from Figure 15-4 that these drugs 

would result in rapid offset of drug effect following a 

continuous infusion. This is clearly not the case, because 

the blood–brain equilibration delay results in these drugs 

having far slower offset than alfentanil or sufentanil. The 

“surprise” here is methadone. One would rarely think of 

methadone as a reasonable choice for infusion during 

anesthesia, but the pharmacokinetics of methadone 

Figure 15-6. The 20% effect-site decrement curves for fentanyl, 

alfentanil, sufentanil, remifentanil, morphine, methadone, 


and rate of plasma–effect-site equilibrium shown in Table 

15-1. The effect-site levels of all opioids, except morphine, will 

decrease by 20% quickly when an infusion is terminated. The 

slower decrease for morphine is because of its slow plasma– 

effect-site equilibration. 

suggest that it might be a reasonable choice for anesthetics 

of 4 hours or less. 

Figure 15-6 shows the 20% effect-site decrement curve 

for these eight opioids. Figure 15-6 speaks to how often 

one might expect to redose a patient with chronic pain 

who is titrating the analgesic level to a just-adequate 

concentration. Because of its slow blood–brain equilibration, 

morphine would need to be given approximately 

every 2 hours. Hydromorphone, fentanyl, and methadone 

would need to be given approximately every hour. 

Specific Opioids 

Figure 15-5. The 50% effect-site decrement curves for fentanyl, 

alfentanil, sufentanil, remifentanil, morphine, methadone, 


and rate of plasma–effect-site equilibrium shown in Table 

15-1. For drugs with rapid plasma–effect-site equilibrium, the 

50% effect-site decrement curve closely follows the context 

sensitive half-time curve. However, for drugs with slow plasma– 

effect-site equilibration, a 50% decrement in effect-site concentration 

is considerably slower than a 50% decrement in plasma 

concentration (e.g., morphine). 

Morphine 

Morphine has three unique aspects among the opioids 

frequently used in anesthesia practice: it is an endogenous 

ligand of the µ receptor, has an active metabolite, and has 

a very slow onset of effect. Morphine was initially identified 

in the brains of mice that had never been exposed to 

exogenous morphine. 86 It has subsequently been found in 

the brains of cows, 87 rats, 88 and humans. 89 Codeine has 

also been identified as an endogenously synthesized substance. 

However, because codeine is mostly an inactive 

prodrug of morphine, its presence in the brain does not 

diminish morphine’s distinction as the only endogenous 

ligand of the µ receptor that is also a frequently administered 

drug. 

Morphine is metabolized by glucuronidation into two 

metabolites, morphine-3-glucuronide, which is mostly


Creatinine clearance (mls/min) 

250 

200 

150 

100 

50 

0 

20 30 40 50 60 70 80 90 

Age 

inactive, and morphine-6-glucuronide, which is itself a 

potent analgesic. 90 Although the potency of intrathecal 

morphine-6-glucuronide is 650-fold higher than that of 

morphine, 91 morphine-6-glucuronide crosses the blood– 

brain barrier very slowly, so slowly that it is unlikely that 

it contributes to the acute analgesia provided by morphine. 

92,93 However, with chronic administration, the 

levels of morphine-6-glucuronide will increase to pharmacologically 

active concentrations. 94 

Morphine-6-glucuronide is eliminated by the kidneys. 95 

Creatinine clearance is reduced with advancing age, as 

shown in the often cited equation of Cockroft and 

Gault 96 : 

Men: Creatinine clearance (mL/min) 

= {[140 − age (years)] × weight (kg)}/ 

[72 × serum creatinine (mg%)] 

Women: 85% of the above. 

Creatinine 

Figure 15-7. The relationship among age, serum creatinine, 

and creatinine clearance, based on the equation of Cockroft 

and Gault. (Adapted with permission from Cockcroft and 

Gault. 96 ) 

0.5 

1.0 

1.5 

2.0 

Figure 15-7 shows the relationship among creatinine, 

age, and creatinine clearance according to the above 

equation. The key observation from Figure 15-7 is that, 

even in the presence of normal creatinine, the creatinine 

clearance of an 80-year-old patient will be about half that 

in a 20-year-old patient. Thus, morphine-6-glucuronide 

will accumulate more in elderly patients, necessitating a 

reduction in dose of chronically administered morphine. 

Of course, if the patient has renal insufficiency, it might 

be better to select an opioid without an active 

metabolite. 

The second unique aspect to morphine is the slow 

onset of effect. The peak effect following a bolus dose of 

morphine occurs approximately 90 minutes after the 

bolus. This has been demonstrated using pupillometry, 97–99 

ventilatory depression, 98 and analgesia 99 as measures of 

morphine drug effect. The likely explanation for this is 

that morphine is a substrate for P-glycoprotein, which 

actively transports morphine out of the central nervous 

system. 100 

Figure 15-8 shows a simulation of the analgesic (y-axis 

> 1) and ventilatory (y-axis < 1) effects of three different 

morphine doses: a bolus of 0.2 mg/kg, a bolus of 0.2 mg/kg 

followed by an infusion of 1 mg/70 kg per hour, and 

repeated boluses of 0.1 mg/kg every 6 hours. 101 The solid 

line is the median prediction, whereas the shaded area 

represents the 95% confidence bounds. As seen in Figure 

15-8, the time course of analgesia and ventilatory depression 

is similar, although the analgesia wanes somewhat 

faster than the ventilatory depression. 

It is important to appreciate the slow onset of morphine 

when titrating to effect. Aubrun and colleagues 102,103 

have advocated postoperative titration of morphine in 

elderly patients by administering 2- to 3-mg boluses every 

5 minutes. This is not logical for a drug with a peak effect 

Effect 

4 

3 

2 

1 

A. Bolus 0.2 mg/kg B. 0.2 mg/kg + 1 mg/70 kg per h C. 0.1 mg/kg @ 6 h intervals 

4 

6 

3 

4 

3 

2 

2 

1 

1 

0.6 

0.4 

0.6 

0.6 

0.4 

0.4 

0 4 8 12 16 20 24 0 4 8 12 16 20 24 0 4 8 12 16 20 24 

TIME (h) TIME (h) TIME (h) 

Figure 15-8. Simulated analgesic (y > 1) and ventilatory (y < 1) 

effects of three different doses of morphine: 0.2 mg/kg (A), 

0.2 mg/kg plus an infusion of 1 mg/70 kg/h (B), and a bolus of 

0.1 mg/kg every 6 hours (C). The analgesic and ventilatory 

effects peak concurrently, about 90 minutes after the morphine 

bolus. Because the concentration versus response relationship 

is steeper for analgesia than ventilatory depression, the analgesic 

effect dissipates before the ventilatory depression. (Reprinted 

with permission from Dahan et al. 101 Copyright ©Lippincott 

Williams & Wilkins.)


about 1.5 hours after bolus injection. Aubrun and colleagues 

did not see any toxicity with this approach. That 

is surprising, given the potential for accumulation with 

repeated titration of small doses of morphine to effect. 

However, it does explain why their study is unique in 

finding that elderly patients require the same amount of 

opioid as younger patients. 

Meperidine 

The bottom line on meperidine is that it has little role in 

the management of pain. Meperidine is still a popular 

drug because of familiarity of its use, particularly among 

surgeons and obstetricians. Meperidine is unique among 

opioids in that it has significant local anesthetic activity. 

104,105 Meperidine has been used as the sole analgesic 

intrathecally for obstetric anesthesia, but its benefit over 

a combination of local anesthetic with another opioid is 

unclear. One logical use of meperidine is in the treatment 

of postoperative shivering, in which doses of 10–20 mg are 

typically effective. 

The problems with meperidine are its complex pharmacology 

and its toxic metabolite. Holmberg and colleagues 106 

examined the pharmacokinetics of an intravenous meperidine 

bolus in young and elderly surgical subjects. They 

found that elderly patients had reduced meperidine clearance, 

resulting in a longer half-life for meperidine. There 

was minimal change in the initial volume of distribution. 

The clinical implication is that the initial dose of meperidine 

in elderly subjects should not be reduced based on 

pharmacokinetics, but meperidine will accumulate in 

elderly subjects with repeated administration. This makes 

meperidine a particularly poor choice for administration 

by PCA in elderly patients. 107 

A worrisome aspect of meperidine is the toxic metabolite, 

normeperidine. In a subsequent study, Holmberg and 

colleagues examined the renal excretion of both meperidine 

and normeperidine in elderly surgical patients. 108 

Renal excretion was reduced in elderly patients, par - 

ticularly for normeperidine. The result is that normeperidine 

will likely accumulate with repeated doses in 

elderly patients. Because normeperidine is highly epileptogenic, 

meperidine is probably a poor choice for PCA 

or other forms of continuous opioid delivery in elderly 

patients. 

Meperidine has several other unique aspects to its 

pharmacology. It is the only negative inotrope among the 

opioids. 109 Meperidine also has intrinsic anticholinergic 

properties, which can result in tachycardia. Elderly 

patients with coronary artery disease are clearly at risk 

for adverse events if given drugs that have negative inotropic 

or positive chronotropic effects. 

Last, meperidine is associated with several unusual 

reactions, including the potential for acute serotonergic 

syndrome when combined with a monoamine oxidase 

(MAO)-A inhibitor. Fortunately, the classic MAO-A 

inhibitors, phenelzine (Nardil), tranylcypromine 

(Parnate), and isocarboxazid (Marplan) are now rarely 

used. Selegiline, often used in Parkinson’s disease, is a 

weak MAO-B inhibitor, and has been implicated in one 

nonfatal interaction with meperidine. 110 However, given 

the polypharmacy common in elderly patients, it would 

seem wise to avoid using meperidine when opioids with 

more selective pharmacology and inactive metabolites 

are available. 

Hydromorphone 

Hydromorphone in many aspects acts as a rapid-onset 

morphine. However, it lacks the histamine release associated 

with morphine and does not have active metabolites. 

There are no studies explicitly examining the role of age 

in hydromorphone pharmacokinetics or pharmacodynamics. 

In fact, there are surprisingly few studies examining 

perioperative use of hydromorphone. Keeri-Szanto 111 

found intraoperative hydromorphone to be approximately 

8 times more potent than morphine, with a halflife 

of 4 hours versus 5 hours for morphine. Kopp et al. 112 

investigated whether 4 mg of hydromorphone provided 

any evidence of preemptive analgesia. It did not. 

Rapp and colleagues 113 compared hydromorphone 

PCA to morphine PCA in postoperative patients following 

lower abdominal surgery. They found that hydromorphone 

PCA was associated with better mood scores, but 

with increased incidence of nausea and vomiting. They 

found that 1 mg of hydromorphone was approximately 

equianalgesic with 5 mg of morphine. This is about twice 

as potent as suggested by Hill and Zacny, 83 who determined 

that hydromorphone was tenfold more potent 

than morphine. Although Rapp and colleagues did not 

specifically study the effects of age, one would expect this 

ratio to be independent of age in the immediate postoperative 

period. Because morphine has an active metabolite 

that accumulates and hydromorphone does not, the 

apparent potency of morphine relative to hydromorphone 

may increase with chronic administration. 

Lui and colleagues 114 compared epidural hydromorphone 

to intravenous hydromorphone, both administered 

by PCA in a double-blind/double-dummy protocol. They 

found more pruritus in patients receiving epidural hydromorphone, 

but no differences in postoperative analgesia, 

bowel function, or patient satisfaction. Overall, hydromorphone 

in the epidural group was half of that in the 

intravenous group, indicating that hydromorphone is 

acting spinally when administered via the epidural route. 

Hydromorphone and morphine both reach their peak 

concentrations in the cervical cerebrospinal fluid about 

60 minutes after epidural administration, 115 suggesting 

they have similar potential for delayed ventilatory depression 

after epidural administration. In a study of obstetric


patients, Halpern and colleagues 116 found 0.6 mg of hydromorphone 

to be clinically indistinguishable from 3 mg 

of morphine, consistent with the 1 : 5 relative potency 

reported for intravenous hydromorphone and morphine 

in the postoperative period. 

Fentanyl 

Fentanyl is among the “cleanest” opioids in terms of 

pharmacology. It has a rapid onset, predictable metabolism, 

and inactive metabolites. It is (obviously) the first of 

the “fentanyl” series of opioids, notable for their rapid 

metabolism and selective µ potency. It is the only one of 

the opioids that is available for transdermal and transmucosal 

delivery, although these methods of administration 

are being investigated for sufentanil as well. 

Bentley et al. 117 studied aging and fentanyl pharmacokinetics 

in young and elderly groups of patients. They 

found that fentanyl clearance was decreased among the 

elderly, resulting in a prolonged half-life. 

Scott and Stanski 62 used high-resolution arterial sampling 

during and after a brief fentanyl infusion to characterize 

the influence of age on the pharmacokinetics 

of fentanyl. These investigators did not find any effect of 

age on the pharmacokinetics of fentanyl or alfentanil, 

except for a small change in rapid intercompartmental 

clearance. 

The minimal influence of age on the pharmacokinetics 

of fentanyl was subsequently confirmed by Singleton and 

colleagues. 118 These investigators found no change in the 

dose-adjusted concentration of fentanyl between young 

and elderly patients, except for a transient increase in 

concentration in elderly individuals at 2 and 4 minutes 

after the start of the infusion. These findings are consistent 

with the decreased rapid intercompartmental clearance 

reported by Scott and Stanski. 

Scott and Stanski used the EEG as a measure of drug 

effect to estimate the potency of fentanyl. 62,119 They 

observed a decrease of approximately 50% in the dose 

required for 50% of maximal EEG suppression (C 50 ) 

from age 20 to age 85, as shown in Figure 15-9. Because 

the pharmacokinetics of fentanyl seem nearly unchanged 

by age, it is likely that elderly patients require less fentanyl 

because of intrinsic increased sensitivity to opioids. 

Put another way—the elderly brain is twice as sensitive 

to opioids as a younger brain. This predicts that elderly 

patients require half of the fentanyl that younger patients 

require. Because the pharmacodynamics of fentanyl (i.e., 

the C 50 ) is affected by age, and not the pharmacokinetics, 

the offset of fentanyl drug effect in elderly patients who 

receive an appropriately reduced dose of fentanyl should 

be as fast as it is in younger patients. 

The 50% reduction in fentanyl suggested by Scott and 

Stanski’s integrated pharmacokinetic/pharmacodynamic 

model is in reasonable agreement with an analysis by 

C 50 (ng/ml) 

14 

12 

10 

8 

6 

4 

2 

0 

20 30 40 50 60 70 80 90 

Age (years) 

Figure 15-9. The influence of age on the 50% maximal effective 

dose (C 50 ) of fentanyl, as measured by electroencephalogram 

depression. Although there is considerable variability, overall 

there is about a 50% reduction in C 50 from age 20 to age 80, 

reflecting increased brain sensitivity. This has been shown for 

alfentanil 62 and remifentanil, 64 and appears to be a class effect 

of opioids. (Adapted with permission from Scott JC, Stanski 

DR. Decreased fentanyl/alfentanil dose requirment with 

increasing age: A pharmacodynamic basis. J Pharmacol Exp 

Ther 240:159–166, 1987.) 

Martin and colleagues 120 of intraoperative fentanyl utilization. 

Using the automated electronic record system in 

place at Duke University Hospital, they found that intraoperative 

doses of fentanyl decreased by about 10% per 

decade after age 30. Apparently, clinicians have integrated 

this information into their practice appropriately, 

at least at Duke University Hospital. 

Other Fentanyl Delivery Systems 

Fentanyl is also available in two unique dosage forms: 

oral transmucosal fentanyl citrate and transdermal fentanyl. 

Holdsworth and colleagues 121 studied pharmacokinetics 

and tolerability of a 20-cm 2 transdermal fentanyl 

patch in young and elderly subjects. Plasma fentanyl concentrations 

were nearly twofold higher in the elderly subjects 

compared with younger subjects, reflecting either 

increased absorption or decreased clearance. Given that 

fentanyl clearance seems unchanged in the elderly, the 

likely explanation is that transdermal fentanyl absorption 

is more rapid in elderly patients, possibly because the skin 

is thinner and poses less of a barrier to fentanyl absorption. 

The increased concentrations in elderly subjects 

were associated with increased adverse events—so much 

so that the patch was removed for the study in every 

elderly subject, whereas none of the patches were 

removed in younger subjects. 

Davis and colleagues 122 also noted that the time course 

of absorption of fentanyl through the skin is delayed in 

the elderly, with subcutaneous fat acting as secondary 

reservoir leading to prolonged release even after the 

removal of the patch.


Kharasch and colleagues 123 examined the influence of 

age on the pharmacokinetics and pharmacodynamics of 

oral transmucosal fentanyl citrate (the fentanyl “lollipop”). 

They found no change in the pharmacokinetics of 

fentanyl with age, including the absorption characteristics 

of the buccal mucosa. Perhaps unexpectedly, they also 

found no increase in sensitivity to fentanyl, as measured 

by pupillary miosis. Thus, in their view, the data do not 

support reducing the dose of oral transmucosal fentanyl 

citrate in elderly patients. 

Alfentanil 

The relationship between opioids and age becomes more 

complex when we consider alfentanil. Scott and Stanski 62 

reported similar findings for alfentanil as previously 

described for fentanyl. In particular, they did not find any 

effect of age on the pharmacokinetics of alfentanil, except 

for a small change in the terminal half-life. Shafer et al. 124 

also reported no relationship between age and alfentanil 

pharmacokinetics. Sitar and colleagues 125 reported a 

modest decrease in alfentanil clearance and central compartment 

volume in elderly subjects. In a study that used 

historical control data, Kent and colleagues 126 also 

reported a modest decrease in alfentanil clearance with 

advancing age. Lemmens et al. 127 observed that the pharmacokinetics 

of alfentanil in men (as studied exclusively 

by Scott and Stanski) were unaffected by age, whereas 

the pharmacokinetics in women showed a clear negative 

correlation between age and clearance. 

In an effort to sort out these modestly conflicting 

results, Maitre et al. 128 pooled alfentanil concentration 

data from multiple prior studies and performed a population 

pharmacokinetic analysis to estimate the influence 

of age and gender on the pharmacokinetics of alfentanil. 

Maitre et al. found that clearance decreased with age, and 

that the volume of distribution at steady state increased 

with age, the net effect being a longer terminal half-life 

with increasing age. That might sound like the end of the 

story, except that Raemer and colleagues 129 prospectively 

tested the Maitre et al. pharmacokinetics in two groups 

of patients, young women and elderly men, using computer-controlled 

drug administration. In this prospective 

test, the pharmacokinetics reported by Maitre et al. did 

not accurately predict the observed plasma alfentanil 

concentrations. However, pharmacokinetics reported by 

Scott and Stanski, which predict no influence of age or 

gender on alfentanil pharmacokinetics, accurately predicted 

the concentrations in both young women and 

elderly men. From these results, we can conclude that 

pharmacokinetics of alfentanil do not change in a clinically 

significant manner with age. 

Although they found no change in pharmacokinetics 

with age, Scott and Stanski demonstrated that the C 50 for 

EEG depression with alfentanil decreased by 50% in 

elderly subjects, nearly identical to the increased potency 

of fentanyl in elderly subjects. 62 This would suggest that, 

based on pharmacokinetic alterations with age, the dose 

of alfentanil in elderly patients should be about half of 

the dose that would be used in younger patients. Unfortunately, 

subsequent studies by Lemmens et al., 130–132 

based on clinical endpoints, found no influence of age on 

the pharmacodynamics of alfentanil. However, Lemmens 

et al. 133 observed that the alfentanil dose required to 

maintain adequate anesthesia, when administered by 

target-controlled infusion, was decreased by approximately 

50% in elderly subjects. Thus, Lemmens et al. saw 

a similar change in dose-response relationship, in that the 

elderly required half as much opioid as younger subjects, 

but could not explain it as a pharmacodynamic difference. 

However, it is a bigger difference in concentration than 

any of the pharmacokinetic studies would have predicted, 

and there was no control group—the control group was 

a historical control group. 

Where this leaves us is that there are many studies 

suggesting that the alfentanil dose in elderly subjects is 

about half of the dose in younger subjects. The available 

data suggest that the change is probably pharmacodynamic, 

but there may be a pharmacokinetic component 

to the increased sensitivity as well. If the change is mostly 

pharmacodynamic, perhaps, with a modest change in terminal 

half-life in elderly subjects, then the offset of alfentanil 

should be as fast in older subjects as it is in younger 

subjects, provided the dose has been appropriately 

reduced. 

Sufentanil 

Sufentanil is the most potent of the available opioids, 

with potency approximately tenfold greater than fentanyl. 

134 Age has, at most, only a modest influence on 

sufentanil pharmacokinetics. Helmers and colleagues 135 

found no change in sufentanil pharmacokinetics between 

young and elderly subjects. Similarly, Gepts and colleagues 

136 found no effect of age on sufentanil pharmacokinetics 

in a complex population analysis. Matteo and 

colleagues 137 found that the central compartment volume 

of sufentanil was significantly decreased in elderly 

patients. This modest pharmacokinetic difference in 

elderly subjects would be expected to increase the effects 

of sufentanil in the first few minutes after a bolus dose 

and not subsequently. However, the elderly patients in 

Matteo’s study were far more sensitive to sufentanil than 

the younger subjects. Six of seven elderly patients required 

naloxone at the end of this study, whereas only one of 

seven young patients required naloxone. Matteo et al. 

concluded that elderly patients had increased sensitivity 

to a given concentration of sufentanil, similar to the 

increased sensitivity to fentanyl and alfentanil in elderly 

patients described by Scott and Stanski.


Thus, based on the twofold increase in brain sensitivity 

to opioids demonstrated for fentanyl and alfentanil in 

elderly patients, one might expect similar increase in 

brain sensitivity to sufentanil in elderly patients. Thus, it 

is surprising that Hofbauer and colleagues 138 did not 

observe any influence of age on the sufentanil requirement 

of mechanically ventilated patients in the intensive 

care unit. 

Remifentanil 

Remifentanil has the fastest and most predictable metabolism 

of any of the available opioids. Remifentanil was 

introduced into clinical practice under Food and Drug 

Administration guidelines that mandated explicit pharmacokinetic 

and pharmacodynamic analysis for special 

populations, including elderly subjects. Thus, the influence 

of age on remifentanil pharmacokinetics and pharmacodynamics 

was established in high-resolution trials about 

3 times larger than the trials for fentanyl, alfentanil, or 

sufentanil. The pharmacokinetic and pharmacodynamic 

models for remifentanil were reported by Minto and colleagues. 

64 In a companion article, Minto et al. 139 used 

computer simulation to examine the implications of the 

complex age-related changes on remifentanil dosing. The 

pharmacokinetics of remifentanil change with age, as 

shown in Figure 15-10. With advancing age, V 1 , the volume 

of the central compartment, decreases about 20% from 

Figure 15-10. The influence of age on remifentanil pharmacokinetics. 

With advancing age, the volume of the central compartment 

decreases by 50% from age 20 to age 80, and the clearance 

decreases by 66%. (Adapted with permission from Minto 

et al. 64 ) 

Figure 15-11. The influence of age on remifentanil pharmacodynamics. 

With advancing age, the 50% effective concentration 

(EC 50 ) declines, reflecting a nearly identical increase in intrinsic 

potency as seen with fentanyl and alfentanil. Additionally, halftime 

of blood–brain equilibration (t 1/2 k e0 ) increases. (Adapted 

with permission from Minto et al. 64 ) 

age 20 to 80. Concurrently, clearance decreases about 

30% from age 20 to age 80. Figure 15-11 shows the agerelated 

changes in remifentanil pharmacodynamics. As 

also observed for fentanyl and alfentanil, the C 50 for EEG 

depression is reduced by 50% in elderly subjects, suggesting 

that remifentanil has about twice the intrinsic potency 

in elderly subjects as in younger subjects. The t 1/2 k e0 , halftime 

of plasma–effect-site equilibration, is also increased 

in elderly subjects. In the absence of other changes, this 

would mean that the onset and offset of remifentanil drug 

effect will be slower in elderly patients. 

Figure 15-12 uses computer simulations to examine the 

time course of blood concentration (solid lines) and 

effect-site concentration (dashed lines) after a unit bolus 

of remifentanil. The blood concentrations are higher in 

elderly subjects because of the smaller central compartment 

concentration. However, the slower t 1/2 k e0 in elderly 

subjects results in less-rapid equilibration. As a result, the 

effect-site concentrations in elderly individuals do not 

increase higher than the effect-site concentrations in 

young individuals. However, the onset and offset are 

slower in elderly individuals. For example, in a young 

individual, the peak drug effect is expected about 90 

seconds after a bolus injection. In an elderly individual, 

the peak effect is expected about 2–3 minutes after bolus 

injection. 

Figure 15-13 shows the influence of age and weight on 

remifentanil dosing. As seen in the top graph of Figure


Figure 15-12. Simulations showing the effect-site concentration 

from identical bolus doses in a 20-, 50-, and 80-year-old 

subject. The concentrations are highest in the 80-year-old subject 

because of the reduced size of the central compartment. 

However, because of the slower blood–brain equilibrium in the 

80-year-old subject, the peak effect-site concentration is almost 

identical in the three simulations. Thus, the smaller V 1 is offset 

by the slower plasma–effect-site equilibration. However, a bolus 

of remifentanil takes about a minute longer to reach peak 

effect-site concentrations in elderly subjects. (Adapted with 

permission from Minto et al. 139 ) 

15-13, elderly subjects need about half of the bolus dose 

as younger subjects to achieve the same level of drug 

effect. This is not because of the change in pharmacokinetics. 

As shown in Figure 15-12, the peak effect-site 

levels after a bolus of remifentanil are nearly identical in 

young and elderly subjects. Rather, the remifentanil bolus 

is reduced in elderly subjects because of the increased 

sensitivity of the elderly brain to opioid drug effect, 

exactly as reported for fentanyl and alfentanil. The bottom 

graph in Figure 15-13 shows that elderly subjects require 

about one third as rapid an infusion as younger subjects. 

This reflects the combined influences of the increased 

sensitivity and the decreased clearance in elderly 

individuals. 

As seen in Figure 15-13, the influence of weight on 

remifentanil dosing is considerably less than the influence 

of age. We point this out because anesthesiologists reflexively 

adjust remifentanil infusions to body weight, but 

seem reluctant to make an adequate reduction in infusion 

rate for elderly individuals. 

Figure 15-14 shows the time required for decreases in 

effect-site concentration of 20%, 50%, and 80% as a function 

of remifentanil infusion duration. These would be the 

“20% effect-site decrement time,” the “50% effect-site 

decrement time,” and the “80% effect-site decrement 

Figure 15-13. The influence of age and weight on remifentanil 

bolus dose and infusion rates. Bolus doses should be reduced 

by 50% in elderly subjects, reflecting the increased brain sensitivity. 

Infusion rates should be reduced by 66%, reflecting the 

combined effects of increased brain sensitivity and decreased 

clearance. LBM = lean body mass. (Adapted with permission 

from Minto et al. 139 ) 

time,” respectively. For each decrement time, the expected 

relationship is shown for a 20-year-old patient and an 

80-year-old patient. Figure 15-14 suggests that elderly 

patients can be expected to recover from remifentanil 

Figure 15-14. The 20%, 50%, and 80% effect-site decrement 

curves for 20- and 80-year-old subjects. Provided remifentanil 

dose is adequately reduced, as shown in Figure 15-13, there 

should be little difference in the awakening time as a function 

of age.


about as fast as younger subjects, provided the dose has 

been appropriately reduced (e.g., Figure 15-13). 

The unique features of remifentanil are its rapid clearance 

and rapid k e0 , resulting in a rapid onset and offset 

of drug effect. It is tempting to speculate that these characteristics 

will make remifentanil an easy drug to titrate 

and that clinicians will not need to consider patient 

covariates such as advanced age when choosing a dosing 

regimen. However, the rapid onset of drug effect may be 

accompanied by rapid onset of adverse events such as 

apnea and muscle rigidity. The rapid offset of drug effect 

can result in patients who are in severe pain at a time 

when the anesthesiologist is ill-equipped to deal with the 

problem, for example, when the patient is in transit to the 

recovery room. It is thus important that anesthesiologists 

understand the proper dose adjustment required for the 

elderly. By adjusting the bolus and infusion doses, the 

anesthesiologist can hope to avoid the peaks and valleys 

in remifentanil concentration that might expose elderly 

patients to risk. When the proper adjustment is made, the 

variability in remifentanil pharmacokinetics is considerably 

less than for any other intravenous opioid. This 

makes remifentanil the most predictable opioid for treatment 

of the elderly. 

Methadone 

Methadone has several distinguishing characteristics, 

including having the longest terminal half-life and being 

supplied as a racemic mixture with surprising stereospecific 

pharmacology. As shown in Table 15-1 and as evident 

in Figure 15-1, the terminal half-life of methadone is 

approximately 1 day. 66 As a result, it will take nearly a 

week of methadone dosing to reach steady state. When 

methadone is used as a chronic analgesic, particularly in 

elderly patients, the patient and physician must be made 

aware that steady state will not be reached for several 

days, requiring vigilance for accumulation to toxicity 

during the “run-in” titration of methadone for analgesia. 

Also, adequate arrangements for rescue analgesia must 

be available during the period before steady-state 

levels. 

Methadone’s other unique feature is that it is supplied 

as a racemate with two enantiomers. l-Methadone is an 

opioid agonist, whereas d-methadone is an N-methyl-Daspartate 

(NMDA) antagonist. 140 The potency of the d- 

methadone in blocking NMDA is such that, at clinically 

used doses, it may be effective in attenuating opioid tolerance 

and preventing central sensitization (hyperalgesia). 

141,142 There are no specific studies examining the 

pharmacokinetics and pharmacodynamics of methadone 

in elderly subjects. However, as the increased brain sensitivity 

to opioid drug effect seems to be a class effect for 

opioids, it seems prudent to reduce methadone doses by 

about 50% in elderly patients compared with younger 

patients. Additionally, the NMDA blocking activity of d- 

methadone may provide some analgesic synergy between 

the enantiomers. Provided methadone is titrated in a 

manner that is mindful of the long half-life and the potential 

for accumulation, methadone’s rapid onset and sustained 

effect make it a rational choice for postoperative 

analgesia. 

Patient-Controlled Anesthesia 

PCA devices are very effective means to provide postoperative 

analgesia in elderly patients. Lavand’Homme and 

De Kock 143 have reviewed the use of PCA in the elderly. 

They observed that poor pain management places elderly 

patients at risk of confusion and outright delirium, and 

this may be associated with poorer clinical outcomes. 

They emphasized that increased monitoring and individualization 

of dosage are essentials in PCA management 

of elderly patients. They also observed that elderly 

patients may need additional time to become familiar 

with PCA devices and that the devices will become ineffective 

if elderly patients become confused or agitated. 

Macintyre and Jarvis 144 examined morphine PCA in 

elderly patients and observed that age is the best predictor 

of postoperative morphine requirements. They found 

that the average PCA morphine use in the first 24 hours 

after surgery was approximately 100 − age. However, they 

also emphasized that the dose needed to be individualized, 

because there was tenfold variation in the dose in 

each age category. 

This is similar to the results of Woodhouse and 

Mather. 145 They found that elderly patients required significantly 

less fentanyl and morphine administered by 

PCA following surgery. They also identified a similar 

trend for meperidine, but it was less steep and characterized 

by higher variability. As seen in Figure 15-15, elderly 

patients required about half as much morphine and fentanyl 

as younger subjects, consistent with the “50% reduction” 

suggestion at the beginning of the chapter. 

Gagliese and colleagues 146 also found an approximately 

50% reduction in PCA opioid use in elderly patients. In 

their study, patients in the younger group (average age = 

39) expected more severe pain than those in the older 

group (average age = 67). However, both groups obtained 

similar efficacy from their PCA devices and expressed 

similar levels of satisfaction with PCA as a means of managing 

postoperative analgesia. The average 24 hour dose 

of morphine (or morphine equivalents) in the younger 

patients was 67 mg at the end of day one and 44 mg at the 

end of day two. In the older patients, the average dose was 

39 mg at the end of day one and 28 mg at the end of day 

two. In an accompanying editorial, Ready 147 emphasized 

that patients must be able to understand and participate 

in their care, emphasizing the need to individualize therapy


sic therapy, be combined with PCA to provide adequate 

analgesia at the lowest possible opioid dose in elderly 

patients. Beattie et al. 148 have reported that ketorolac 

effectively reduces morphine doses in elderly subjects. In 

this case, the reduced opioid requirement must be balanced 

against the risk of gastric bleeding and fluid retention 

induced by ketorolac. However, in appropriate 

patients, one or two doses of ketorolac are associated 

with only modest risk and would be expected to provide 

significant synergy with morphine. 149,150 

Suggested Guidelines for Chronic Opioids 


The subject of opioids in the management of chronic pain 

in the elderly has been extensively reviewed. 151–153 A few 

basic principles will be emphasized here: 

Figure 15-15. Twenty-four-hour cumulative patient-controlled 

analgesia opioid administration as a function of age. Morphine 

and fentanyl both show the expected reduction in dose of 

about 50%, as predicted by the pharmacokinetic/pharmacodynamic 

modeling. Meperidine (pethidine) is more variable, 

perhaps reflecting its more complex pharmacology, or the 

stimulating effects of normeperidine. (Reprinted with permission 

from Woodhouse and Mather. 145 Copyright ©Blackwell 

Publishing.) 

for elderly patients in whom a cognitive assessment might 

be appropriate before using PCA. 

It is reasonable that other interventions, such as nerve 

blocks, infusions of local anesthetic, and adjuvant analge- 

1. In general, opioids should be reserved for those 

elderly patients in whom less-toxic alternatives, such as 

acetaminophen and nonsteroidal antiinflammatory drugs, 

have proven ineffective. 

2. It is best to start with the weaker opioids, such as 

codeine, and titrate to effect. The stronger opioids should 

be reserved for patients whose symptoms are inadequately 

treated by weaker opioids. 

3. Careful monitoring during the initial dose titration 

is absolutely essential, particularly with opioids or delivery 

systems associated with long half-lives and time to 

steady state, such as methadone, oral sustained-release 

preparations, and transdermal fentanyl. 

4. Opioid-induced constipation may be reduced by the 

use of a peripheral opioid antagonist, such as alvimopan 

154 and methylnaltrexone. 155 Elderly patients are at 

increased risk of drug interactions. The risk of drug interactions 

particularly precludes the use of chronic meperidine 

in elderly patients. However, opioids should be used 

with great caution if combined with any drugs that 

decrease consciousness (e.g., benzodiazepines). Figure 

15-16 shows the interaction between remifentanil and 

propofol on ventilation in healthy volunteers as reported 

by Nieuwenhuijs and colleagues. 156 Whereas propofol and 

remifentanil individually have modest effects on ventilation, 

when combined (solid triangles), they demonstrate 

profound depression of ventilation. This effect will be 

exaggerated in elderly patients because of the increased 

sensitivity to opioid drug effects. 

5. Elderly patients are at increased risk of confusion in 

response to opioids. 

6. Rotation of opioids may permit lower doses to be 

used, because of the incomplete cross-tolerance and individual 

differences in analgesic versus toxicity profiles 

among individuals.


Ventilation (L/min) 

35 

30 

25 

20 

15 

10 

5 

0 

35 40 45 50 55 60 65 70 

P ET CO 2 (mmHg) 

Conclusion 

Opioids are appropriate for both acute and chronic pain 

in elderly patients, particularly when nonopioid analgesics 

have failed to provide adequate pain relief. Elderly 

patients, on average, need about half the dose of opioids 

as younger patients to achieve the same level of analgesic 

effect. The biologic basis for the increased brain sensitivity 

(pharmacodynamic increased potency) to opioids 

in elderly patients is not completely understood. Elderly 

patients have factors that place them at increased risk 

of opioid toxicity, including increased pharmacologic 

variability, frequent polypharmacy, noncompliance with 

dosage regimens, and impaired renal and hepatic 

function. 

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propofol (1.5 µg/ml) 

remifentanil (1 ng/ml) 

remifentanil + propofol 

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Figure 15-16. The interaction between remifentanil and propofol 

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16 

Intravenous Hypnotic Anesthetics 

Matthew D. McEvoy and J.G. Reves 

This chapter discusses the pharmacology of frequently 

used intravenous hypnotic agents in the geriatric patient. 

The focus of this chapter is the changes in pharmacokinetics 

and pharmacodynamics in the geriatric patient 

specific to propofol, thiopental, midazolam, and etomidate, 

the four most popular intravenous agents for sedation, 

induction, and maintenance of general anesthesia. 

Propofol 

Propofol was first investigated in Europe in the 1980s. 

Initially the drug was suspended in a solvent that caused 

anaphylactoid reactions in some patients. It was reformulated 

in a different preparation and it has gained widespread 

use ever since. Because of its quick onset of action, 

fairly predictable dose-response, and quick termination 

of action, propofol is only second to thiopental in use for 

the intravenous induction of general anesthesia. 1 Propofol 

is also the focus of a tremendous amount of research 

in target-controlled infusion techniques, both in the operating 

room (OR) and in non-OR anesthesia. 

Pharmacology: Structure/Action 

Propofol (2,6-diisopropylphenol) is a hypnotic drug in 

the class of the alkylphenols that principally works at the 

gamma-aminobutyric acid-A (GABA A ) receptor site in 

the central nervous system (CNS). 2 However, it has also 

been postulated in recent years that propofol might have 

additional action at excitatory amino acid receptors. 2,3 

Propofol is composed of a phenol ring with two isopropyl 

groups attached to it. It is not water soluble and is thus 

prepared in an oil-water emulsion consisting of soybean 

oil, egg lecithin, and glycerol. 4 This is important because 

this preparation can support the growth of bacteria, even 

though it contains disodium edetate to retard bacterial 

growth. Because of this unique preparation, propofol is 

not considered to be antimicrobially preserved under 

United States Pharmacopeia specifications. Thus, the 

current recommendations are that sterile technique 

should be used when handling and administering this 

drug, as with all intravenous anesthetics, and that any 

propofol withdrawn from a vial should be used within 

6 hours and any vial that is spiked and used as an 

intravenous infusion should be completely used within 

12 hours. Any amount remaining after those times should 

be discarded. 5,6 


Central Nervous System Effects 

Propofol has numerous effects on various organ systems 

throughout the body. Like thiopental, it has favorable 

effects on CNS parameters, as it lowers cerebral metabolic 

rate (CMRO 2 ), cerebral blood flow (CBF), and 

intracranial pressure (ICP) (Table 16-1). 7 If a large bolus 

is given, propofol does have the ability to lower the mean 

arterial pressure (MAP) considerably, possibly lowering 

cerebral perfusion pressure (CPP) below a critical level 

(

230 M.D. McEvoy and J.G. Reves 

Table 16-1. Cardiovascular, respiratory, and cerebral effects of several intravenous hypnotic agents. 

Cardiovascular* Respiratory* Cerebral* 

Agent HR MAP Vent B’dil CBF CMRO 2 ICP 

Propofol 0/↓↓ ↓↓↓ ↓↓/↓↓↓ ? ↓↓↓ ↓↓↓ ↓↓↓ 

Thiopental ↑↑/↑ ↓↓/↓↓↓ ↓↓/↓↓↓ ↓ ↓↓↓ ↓↓↓ ↓↓↓ 

Etomidate 0 0/↓ ↓/↓↓ 0 ↓↓↓ ↓↓↓ ↓↓↓ 

Midazolam ↑ ↓↓ ↓↓/↓↓↓ 0 ↓↓ ↓↓ ↓↓ 

Source: Modified with permission from Morgan GE Jr, Mikhail MS, Murray MJ. Clinical Anesthesiology. 3rd ed. New York/Stamford, CT: McGraw- 

Hill/Appleton & Lange; 2002. 

0 = no change, ↑/↓ = minimal change in corresponding direction, ↑↑/↓↓ = moderate change in corresponding direction, ↑↑↑/↓↓↓ = marked change 

in corresponding direction, HR = heart rate, MAP = mean arterial pressure, Vent = ventilation, B’dil = bronchodilation, CBF = cerebral blood 

flow, CMRO 2 = cerebral metabolic rate, ICP = intracranial pressure. 

*Where there is a difference between the young adult and the geriatric patient, the first set of arrows indicates the response in the young adult 

and the second set of arrows indicates the response in the geriatric patient. 

EEG stage is regained. 10 The EEG changes described 

above cause a shorter duration of seizure in the electroconvulsive 

therapy (ECT) patient, but they also allow for 

a blunted hypertensive and hyperdynamic response that 

is often seen in these patients. 11 Methohexital will allow 

for longer seizure duration, but it does not block the 

hypertensive response to ECT as much and thus it is not 

as ideal in the geriatric patient who is likely to have 

cardiac disease. Although propofol often allows for seizures 

of a clinically acceptable duration, 11 many psychiatrists 

prefer methohexital for ECT. 

The brain becomes more sensitive to propofol with 

increasing age. Schnider et al. 12 reported that geriatric 

patients were approximately 30% more sensitive to the 

pharmacodynamic effects of propofol than younger 

subjects, as measured by EEG changes. This was found 

to be true for both induction doses and infusions. Thus, 

it seems that increasing age causes changes in the brain 

that increase the effective potency of propofol for the 

geriatric patient. 

Respiratory Effects 

Propofol causes dose-related depression of ventilation 

and it is thought to produce some bronchodilation, 

although this is controversial (Table 16-1). 13,14 In standard 

induction doses, propofol causes apnea. 15 However, when 

compared with thiopental, respirations are lost later and 

recovered earlier. 16 With intravenous infusions for sedation, 

propofol causes increasing levels of respiratory 

depression, mainly by affecting the tidal volume. Furthermore, 

airway reflexes are depressed more so with propofol 

than with equivalent doses of thiopental or etomidate, 

and this effect is greatly enhanced by the addition of 

opioids. 17 Also, although propofol does not inhibit hypoxic 

pulmonary vasoconstriction, it does seem to blunt both 

the hypoxic and hypercapnic ventilatory responses. 16,18–20 

All of these changes described above have particular 

relevance for the elderly patient. Because of increases in 

closing capacity with increasing age, which will exceed 

functional residual capacity (FRC) even in the upright 

position in a 65-year-old individual, desaturation can 

occur at a faster rate. In the elderly, this occurs as a result 

of an increase in shunt fraction rather than a reduced 

FRC, as is seen with the obese or in patients with restrictive 

lung disorders. 21 The elderly also have a decreased 

cough reflex and thus a decreased ability to clear secretions. 

22 This inherently decreased cough reflex in the 

elderly patient combined with the suppression of this 

reflex from propofol puts the elderly person at higher risk 

for aspiration during its use. Furthermore, the elderly 

patient already has a blunted hypoxic and hypercapnic 

ventilatory response compared with the average adult 

patient. 22 These changes call for great vigilance when 

administering propofol to an elderly patient for minimal 

alveolar concentration (MAC) anesthesia or even light 

sedation. Ventilation should be closely monitored, particularly 

if supplemental oxygen is used, because the 

hypercapnic ventilatory response will become the primary 

regulator of respiration. This is important because supplemental 

oxygen could prevent hypoxemia, but allow for a 

progressive hypercapnia that could be dangerous to the 

patient. Finally, all of these effects are increased with the 

concurrent use of opioids, thus requiring even greater 

attention in operative and procedural situations when the 

elderly patient is maintaining oxygenation and ventilation 

through spontaneous respirations without a secure airway 

or end-tidal carbon dioxide monitoring. However, all of 

the evidence cited thus far would suggest that increased 

pharmacodynamic sensitivity in the elderly patient moves 

in a parallel manner for respiratory depression and sedation/hypnosis; 

that is, the patient is not fully awake and 

merely experiencing decreased respiratory drive. Thus, 

in the spontaneously ventilating patient, the gradual

16. Intravenous Hypnotic Anesthetics 231 

titration of propofol matched with a vigilance attentive to 

signs of adequate respiration and level of sedation should 

provide for a safe and effective anesthetic. 

Cardiovascular Effects 

Propofol causes little change in heart rate but can cause 

profound changes in MAP when given in induction bolus 

doses (Table 16-1). 23 These changes are caused by a reduction 

in systemic vascular resistance (via inhibition of sympathetic 

vasoconstriction) and preload, as well as through 

direct effects on myocardial contractility. This hypotension 

is more pronounced than that which is seen with the 

administration of thiopental, etomidate, or midazolam. In 

the normal adult patient, this hypotension is well tolerated 

and it is readily reversed during the stimulation of 

laryngoscopy and intubation. However, studies have 

shown that the degree of hypotension is increased and an 

adequate hemodynamic response to a bolus induction is 

decreased in the geriatric patient. This occurs by several 

mechanisms. First, propofol impairs the arterial baroreceptor 

reflex to hypotension, which is already decreased 

in the geriatric patient. 24 Second, the geriatric patient is 

more likely to have ventricular dysfunction. A decrease 

in preload in these patients may result in a significant 

decrease in cardiac output. Third, these patients are often 

taking beta-blockers and diuretics or other therapies that 

cause hypovolemia in the perioperative period. The 

former will reduce the magnitude of any baroreceptormediated 

reflex tachycardia to a decrease in blood pressure, 

whereas the latter will tend to make the patient 

more sensitive to changes in systemic vascular resistance 

and preload secondary to being relatively intravascularly 

hypovolemic. 24 Finally, it is possible for a profound 

decrease in preload to result in a vagally mediated reflex 

bradycardia. 25 Practically speaking, these concerns can be 

applied clinically in two general categories. First, for the 

geriatric patient with significant cardiac disease, it is best 

to avoid a rapid bolus induction with propofol. Second, 

many of the untoward effects noted above can be greatly 

minimized if a slower infusion induction is performed 

with laryngoscopy being performed after reaching a 

pharmacodynamic endpoint, such as a bispectral index 

(BIS) value of less than 60 (see discussion below). 26 

Other Effects 

Two unique beneficial effects of propofol are noteworthy. 

Propofol has both antiemetic and antipruritic properties. 

27,28 Thus, its intraoperative and perioperative use has 

the potential to reduce the need for traditional antiemetic 

and possibly antipruritic medications in the postoperative 

period. This is particularly important in the geriatric 

patient who may be more susceptible to the untoward 

effects of drugs that work at cholinergic and dopaminergic 

sites in the normal treatment of nausea and pruritus. 

Metabolism and Disposition 

(Pharmacokinetics) 

The pharmacokinetics of propofol involve a very large 

volume of distribution, rapid redistribution, and rapid 

elimination via hepatic and extrahepatic routes. Because 

of high lipid solubility, it has an onset of action of one 

arm-to-brain circulation time (almost as fast as thiopental). 

Rapid awakening from a single bolus is the result of 

extensive redistribution to non-CNS sites throughout the 

body. Its initial distribution half-life in a healthy adult 

patient is approximately 2 minutes. 29,30 

There are various changes in the pharmacokinetics of 

propofol in the elderly patient. The central volume of 

distribution is less, systemic clearance is reduced, and 

intercompartmental clearance is reduced. During a propofol 

infusion, the plasma concentration of the drug is 

about 20% higher in the elderly patient as compared with 

the average adult. 31 Furthermore, the context-sensitive 

half-time changes with increasing age. Studies have shown 

that the time required for a 50% reduction in effect-site 

concentration (50% effect-site decrement time) is significantly 

prolonged with advancing age in an exponential 

manner. For propofol infusions less than 1 hour, there 

is little difference between the young adult patient and 

the elderly patient in recovery time. However, after a 4- 

hour infusion, there is a doubling of the 50% effect-site 

decrement time in an 80-year-old versus a 20-year-old 

patient, and this difference becomes even greater with 

infusions of 10 hours and longer. 31 This fact is of particular 

importance because this assumes that there have 

already been dosage adjustments for other pharmacokinetic 

parameters such that the plasma concentration is 

the same in both patients. Thus, even at reduced infusion 

rates, the elderly patient will take longer to emerge than 

the young patient. 

Indications 

Propofol, as noted above, is routinely used for induction 

and maintenance phases of general anesthesia, as well as 

for various levels of sedation in OR, and non-OR anesthesia, 

1 as well as in the intensive care unit. 

Dosing in the Elderly 

When the pharmacokinetic and pharmacodynamic 

changes are considered together, the current literature 

suggests a 20% reduction in the induction dose of propofol, 

if given as a bolus. Practically, this has been reported 

as a reduction of the bolus dose from 2.0–2.5 to 1.5– 

1.8 mg/kg. 32 Of note, it is the authors’ clinical experience 

that if the induction dose is titrated to a neurologic endpoint 

(such as BIS or PSA4000) or given slowly in order 

to account for the effect-site hysteresis time (k e0 ), this


Figure 16-1. Propofol infusion rate 

required to maintain 1 µg/mL plasma 

level of propofol in patients of various 

ages. These dosing guidelines take into 

account the pharmacokinetic changes 

with aging. This correlates with a mild 

level of sedation. (Reprinted with permission 

from Schüttler and Ihmsen. 29 ) 

dose is reduced to as low as 0.8–1.2 mg/kg in the elderly, 

which corresponds with the findings of Kazama et al. 26 

Furthermore, numerous reports have shown that there is 

less hemodynamic instability if this bolus is given over a 

longer period of time in the elderly patient than as one 

fast bolus. 26,29,31 

Dosing requirements during an infusion are even less 

for the elderly patient. Schüttler and Ihmsen 29 have shown 

that for continuous low plasma level infusions, such as 

those used during the maintenance phase of an anesthetic 

for sedation (plasma concentration 1 µg/mL), a 75-yearold 

patient will require approximately 30% less drug than 

a 25-year-old patient to maintain the same level of drug 

concentration. However, this only takes into account the 

pharmacokinetic changes with age (Figure 16-1). 29 The 

age-related decline in the amount of propofol required 

for the same level of anesthesia becomes even more profound 

when one considers the pharmacodynamic data 

along with the pharmacokinetic data. For a surgical level 

of anesthesia, Shafer proposes an age-adjusted dosing 

guideline based on the compilation of several pharmacokinetic 

and pharmacodynamic studies (Figure 16-2). 12,32 

This pharmacodynamic change is also illustrated in Figure 

16-3, which shows that a 75-year-old patient will require 

350 

1.0 

Unconscious 

Infusion Rate (mg/kg/min) 

300 

250 

200 

150 

25 years old 

50 years old 

75 years old 

Probability of Unconsciousness 

0.8 

0.6 

0.4 

0.2 

75 

50 25 

100 

0 

Conscious 

0 10 20 30 40 50 60 

Time (min) 

Figure 16-2. Propofol infusion rate required to maintain 

adequate surgical anesthesia in patients of various ages. These 

dosing guidelines account for the changes with age in propofol 

pharmacokinetics and pharmacodynamics. (Reprinted with 

permission from Shafer. 32 ) 

0 2 4 6 8 

Plasma Propofol Concentration (µg/mL) 

Figure 16-3. Effect of age on propofol pharmacodynamics. This 

logistic regression shows the age-related probability of being 

asleep after a 1-hour infusion of propofol. A 75-year-old patient 

is 30%–50% more sensitive to propofol than is a 25-year-old 

patient. (Reprinted with permission from Schnider et al. 12 )


Figure 16-4. Context-sensitive half-time of propofol in patients of various ages. Altered pharmacokinetics in the elderly become 

clinically significant after a 1-hour infusion. (Reprinted with permission from Schüttler and Ihmsen. 29 ) 

a 50% lower propofol plasma concentration than a 25- 

year-old patient in order to have the same likelihood of 

being asleep after a 1-hour infusion. 12 Additionally, as 

aforementioned, it must be noted that a prolonged propofol 

infusion should be stopped earlier in the elderly 

patient in order to have recovery at the same time as the 

younger patient (Figure 16-4). 29 

Adverse Effects and Contraindications 

The major adverse effect of propofol, a significant 

decrease in blood pressure, has been mentioned already. 

If proper dosage adjustments are made, propofol is a 

well-tolerated induction and infusion medication in the 

elderly. However, in the patient with significant ventricular 

dysfunction or hemodynamic instability, it may be best 

to use etomidate or thiopental for bolus induction. It is 

also of note that propofol routinely causes pain on intravenous 

injection. However, this is normally brief and well 

tolerated if it is injected into a briskly running intravenous 

line. 

Future Considerations 

The dosing adjustments mentioned above are well supported 

in the pharmacokinetic and pharmacodynamic 

literature. 12,29–32 Clinical application of some of the mathematical 

models that have been simulated has proven 

successful for the authors without the use of targetcontrolled 

infusion pumps. The authors have confirmed a 

less profound hemodynamic change when several models 

have been tested. In our experience, many geriatric 

patients can be induced (as measured by a BIS of less 

than 60) with 0.8–1.2 mg/kg propofol over a 180- to 240- 

second time frame with a less than 10% change from 

baseline heart rate and blood pressure. This is done 

through the application of several pharmacokinetic 

and pharmacodynamic models mentioned above. For 

instance, slightly modifying models proposed by Schüttler, 

Schnider, and Kazama, we induce many geriatric 

patients at an initial rate of 400 µg/kg/min propofol with 

1–2 µg/kg fentanyl given 2–3 minutes before the start of 

the infusion. When the BIS reaches 70 (usually within 

90–150 seconds), the neuromuscular blocker (NMBD) of 

choice (normally cisatracurium or rocuronium) is given 

while the propofol infusion is continued. When sufficient 

time has passed for the NMBD to have taken effect and 

the BIS is


Of further consideration with the use of propofol in the 

geriatric patient is the possible benefit of its antiinflammatory 

and antioxidant properties. 33,34 New research is 

being conducted which may show that a propofol infusion 

for the maintenance of anesthesia decreases the 

magnitude of the rise of inflammatory markers in the 

elderly patient compared with volatile agents. This is of 

profound importance when it is viewed in light of the 

research showing that increases in inflammatory markers, 

such as interleukin-6, tumor necrosis factor-alpha, C- 

reactive protein, and myeloperoxidase, are associated 

with increased rates of cardiovascular mortality and 

morbidity. 35,36 

Thiopental 

Barbituric acid, a combination of urea and malonic acid 

that is lacking in sedative properties, was first synthesized 

in 1864 by J.F.W. Adolph von Baeyer, a Nobel prizewinning 

organic chemist. 37 The thiobarbiturates were first 

described in 1903. However, because of fatal experiments 

in dogs, their use was not further explored until the 

1930s. 38–40 In 1935, Tabern and Volwiler synthesized a 

series of sulfur-containing barbiturates, of which thiopental 

became the most widely used. Thiopental was introduced 

clinically by Ralph Waters and John Lundy, and 

became preferred clinically because of its rapid onset of 

action and short duration, without the excitatory effects 

of hexobarbital. 41 


Thiopental is a hypnotically active drug that works at 

GABA A receptor sites in the CNS. 42 Thiopental is in the 

class of thiobarbiturates, which is defined by having a 

sulfur substituted at the position C2. Substitutions at the 

5, 2, and 1 positions of the barbiturate ring confer different 

pharmacologic activities to the barbiturate nucleus. 

Substitutions at position 5 with either aryl or alkyl groups 

produce hypnotic and sedative effects. A phenyl group 

substitution at C5 produces anticonvulsant activity. An 

increase in length of one or both side-chains of an alkyl 

group at C5 increases hypnotic potency. Substitution of a 

sulfur at position 2 produces a more rapid onset of action, 

as seen with thiopental. 43 


Thiopental produces sedation and sleep. Sufficient doses 

produce a CNS depression that is attended by loss of 

consciousness, amnesia, and respiratory and cardiovascular 

depression. The response to pain and other noxious 

stimulation during general anesthesia seems to be 

obtunded. However, the results of pain studies reveal 

that barbiturates may actually decrease the pain threshold 

in low doses, such as with small induction doses of 

thiopental or after emergence from thiopental when the 

blood levels are low. 44 The amnesic effect of barbiturates 

has not been well studied, but it is decidedly less pronounced 

than that produced by benzodiazepines or 

propofol. 45 


Barbiturates, similar to other CNS depressants, have 

potent effects on cerebral metabolism. Several studies in 

the 1970s demonstrated the effect of barbiturates as a 

dose-related depression of the CMRO 2 , which produces 

a progressive slowing of the EEG, a reduction in the rate 

of adenosine triphosphate consumption, and protection 

from incomplete or focal cerebral ischemia. 46,47 When the 

results of the EEG became isoelectric, a point at which 

cerebral metabolic activity is approximately 50% of 

baseline, no further decrements in CMRO 2 occurred. 48 

These findings support the hypothesis that metabolism 

and function are coupled. However, it must be noted that 

it is the portion of metabolic activity concerned with 

neuronal signaling and impulse traffic that is reduced by 

barbiturates, not that portion corresponding to basal 

metabolic function. The only way to suppress baseline 

metabolic activity concerned with cellular activity is 

through hypothermia. Thus, the effect of barbiturates on 

cerebral metabolism is maximized at a 50% depression 

of cerebral function in which less oxygen is required as 

CMRO 2 is diminished, leaving all metabolic energy to be 

used for the maintenance of cellular integrity. 48 This may 

be of importance to the elderly patient undergoing neurosurgery 

for aneurysm clipping or carotid endarterectomy 

in which focal ischemia may occur. 

With the reduction in CMRO 2 , there is a parallel reduction 

in cerebral perfusion, which is seen in decreased 

CBF and ICP (Table 16-1). With reduced CMRO 2 , cerebral 

vascular resistance increases and CBF decreases. 49 

However, for thiopental, the ratio of CBF to CMRO 2 is 

unchanged. Thus, the reduction in CBF after the administration 

of barbiturates causes a concurrent decrease in 

ICP. Furthermore, even though the MAP decreases, barbiturates 

do not compromise the overall CPP, because the 

CPP = MBP – ICP. In this relationship, ICP decreases 

more relative to the decrease in MAP after barbiturate 

use, thus preserving CPP. This is in contrast to propofol, 

which has a greater likelihood in the elderly patient of 

decreasing MAP to an extent that may compromise CPP, 

as noted above. 50 

Onset of Central Nervous System Effects 

Barbiturates produce CNS effects when they cross the 

blood–brain barrier. There are several well-known factors


that help to determine the rapidity with which a drug 

enters the cerebral spinal fluid (CSF) and brain tissue. 

These factors include the degree of lipid solubility, degree 

of ionization, level of protein binding, and the plasma 

drug concentration. Drugs with high lipid solubility and 

low degree of ionization cross the blood–brain barrier 

rapidly, producing a fast onset of action. Approximately 

50% of thiopental is nonionized at physiologic pH, which 

accounts in part for the rapid accumulation of thiopental 

in the CSF after intravenous administration. Protein 

binding also affects the onset of action in the CNS. 

Barbiturates are highly bound to albumin and other 

plasma proteins. Because only unbound drug (free drug) 

can cross the blood–brain barrier, an inverse relationship 

exists between the degree of plasma protein binding 

and the rapidity of drug passage across the blood–brain 

barrier. 

The final factor governing the rapidity of drug penetration 

of the blood–brain barrier is the plasma drug concentration. 

Simply because of concentration gradient, 

higher levels of drug concentrations in the plasma produce 

greater amounts of drug that diffuses into the CSF and 

brain. The two primary determinants of the plasma concentration 

are the dose administered and the rate (speed) 

of administration. The higher the dose and the more rapid 

its administration, the more rapid is the effect. This is of 

particular importance in the elderly patient who may 

have a reduced central volume of distribution and thus 

require a reduced dose of thiopental in order to reach the 

same plasma concentration as a younger adult. 51 

Cardiovascular System 

Cardiovascular depression from barbiturates is a result 

of both central and peripheral (direct vascular and 

cardiac) effects. 52 The hemodynamic changes produced 

by barbiturates have been studied in healthy subjects and 

in patients with heart disease. The primary cardiovascular 

effect of barbiturate induction is peripheral vasodilation 

that results in a pooling of blood in the venous system. A 

decrease in contractility is another effect, which is related 

to reduced availability of calcium to the myofibrils. There 

is also an increase in heart rate. Mechanisms for the 

decrease in cardiac output include (1) direct negative 

inotropic action, (2) decreased ventricular filling because 

of increased capacitance, and (3) transiently decreased 

sympathetic outflow from the CNS. The increase in heart 

rate (10%–36%) that accompanies thiopental administration 

probably results from the baroreceptor-mediated 

sympathetic reflex stimulation of the heart in response to 

the decrease in output and pressure. Thiopental produces 

dose-related negative inotropic effects, which seem to 

result from a decrease in calcium influx into the cells with 

a resultant diminished amount of calcium at sarcolemma 

sites. The cardiac index is unchanged or is reduced, and 

the MAP is maintained or is slightly reduced. 52 Thiopental 

infusions and lower doses tend to be accompanied by 

smaller hemodynamic changes than those noted with 

rapid bolus injections. 26 

The increase in heart rate encountered in patients with 

coronary artery disease anesthetized with thiopental 

(1–4 mg/kg) is potentially deleterious because of the 

obligatory increase in myocardial oxygen consumption 

(MVO 2 ) that accompanies the increased heart rate. 

Patients who have normal coronary arteries have no difficulty 

in maintaining adequate coronary blood flow to 

meet the increased MVO 2 . 53 When thiopental is given to 

hypovolemic patients, there is a significant reduction in 

cardiac output (69%) as well as a substantial decrease in 

blood pressure. 38–41 Patients without adequate compensatory 

mechanisms, therefore, may have serious hemodynamic 

depression with thiopental induction. All of these 

concerns are of particular importance in geriatric patients, 

because they are more likely to have clinically significant 

coronary artery disease, they are more likely to be intravascularly 

hypovolemic, and their compensatory mechanisms 

to maintain heart rate and blood pressure may be 

reduced because of age-related alterations and pharmacologic 

treatments such as beta-blockers or calcium 

channel blockers. Thus, it is of prime importance in the 

elderly patient to understand proper dose reduction (discussed 

below) and the effects of the rate of administration 

of an induction bolus. If these are not heeded, it 

becomes common to have significant hypotension in the 

geriatric patient with the need to administer vasopressors 

after induction, a practice that can be avoided if a proper 

understanding of the above principle is gained. 

Respiratory System 

Barbiturates produce dose-related central respiratory 

depression. There is also a significant incidence of transient 

apnea after their administration for induction of 

anesthesia. 16 The evidence for central depression is a correlation 

between EEG suppression and minute ventilation. 

54 With increased anesthetic effect, there is diminished 

minute ventilation. The time course of respiratory depression 

has not been fully studied, but it seems that peak 

respiratory depression (as measured by the slope of CO 2 

concentration in the blood) and minute ventilation after 

delivery of thiopental 3.5 mg/kg occurs 1–1.5 minutes 

after administration. These parameters return to predrug 

levels rapidly, and within 15 minutes the drug effects are 

barely detectable. 55 Of note, respirations are lost sooner 

and return later than that seen with propofol. Patients 

with chronic lung disease are slightly more susceptible 

to the respiratory depression of thiopental. The usual 

ventilatory pattern with thiopental induction has been 

described as “double apnea.” The initial apnea that occurs 

during drug administration lasts a few seconds and is


succeeded by a few breaths of reasonably adequate tidal 

volume, which is followed by a longer apneic period. 

During the induction of anesthesia with thiopental, ventilation 

must be assisted or controlled to provide adequate 

respiratory exchange. This is of particular concern 

in the elderly patient who will have an increased closing 

capacity, which will produce a shorter time to becoming 

hypoxemic, as compared with the young adult patient. 22 



Thiopental pharmacokinetics have been described in both 

physiologic and compartmental models. These models 

basically describe a rapid mixing of the drug with the 

central blood volume followed by a quick distribution 

of the drug to the highly perfused, low-volume tissues 

(i.e., brain) with a slower redistribution of the drug to lean 

tissue (muscle). In these models, adipose tissue uptake 

and metabolic clearance (elimination) have only a minor 

role in the termination of the effects of the induction dose 

because of the minimal perfusion ratio compared with 

other tissues and the slow rate of removal, respectively. 

Both of these pharmacokinetic models describe rapid 

redistribution as the primary mechanism that terminates 

the action of a single induction dose. 32,56 

Awakening may be delayed in older patients mainly 

because of a decreased central volume of distribution 

relative to younger adults. 57 The initial volume of distribution 

is less in elderly patients when compared with that 

in young patients (80-year-old versus 35-year-old), which 

explains a 50%–75% lower dose requirement for the 

onset of EEG and hypnotic effects. 51,57 However, except 

in disease states, the clearance of thiopental is not reduced 

in the elderly, and thus, awakening should only be prolonged 

in the elderly with a bolus administration and not 

with a constant infusion. 

Indications 

Thiopental is an excellent hypnotic for use as an intravenous 

induction agent. 1 The prompt onset (15–30 seconds) 

of action and smooth induction noted with its use make 

thiopental superior to most other available drugs. The 

relatively rapid emergence, particularly after single use 

for induction, has also been a reason for the widespread 

use of thiopental in this setting. Thiopental does not 

possess analgesic properties and therefore it must be 

supplemented with analgesic drugs in order to obtund 

reflex responses to noxious stimuli during anesthesia 

induction and surgical procedures. Thiopental can be 

used to maintain general anesthesia, because repeated 

doses reliably sustain unconsciousness and contribute 

to amnesia. However, the ease of use of propofol for 

light sedation and total intravenous anesthesia has supplanted 

the use of thiopental for this purpose and relegated 

it mainly for use in the induction portion of an 

anesthetic. 


Numerous studies have shown that the brain of the 

elderly patient is not intrinsically more sensitive to the 

effects of thiopental than that of the younger patient. 51 

Further studies concluded that the need for a reduction 

in the induction dose of thiopental in the elderly is 

attributable to a reduction in the central volume of distribution. 

58 Shafer 32 collated the results of several studies 

to suggest that the optimal dose in an 80-year-old patient 

is 2.1 mg/kg, which is approximately 80% of the dose 

needed for a young adult. However, it should again be 

noted that slower bolusing of the induction dose will 

generally result in less-acute hemodynamic alterations. 

Furthermore, monitoring of an EEG-related endpoint 

during a slow induction can guide the amount of drug 

given and may allow for a more individualized dosing 

regimen. 59 


The effects of barbiturates on various organ systems have 

been studied extensively. There are several side effects 

that occur in unpredictable, varying proportions of 

patients, whereas the cardiovascular and pulmonary are 

dose-related. 60 The complications of injecting barbiturates 

include a garlic or onion taste (40% of patients), 

allergic reactions, local tissue irritation, and rarely, tissue 

necrosis. An urticarial rash may develop on the head, 

neck, and trunk that lasts a few minutes. More severe 

reactions such as facial edema, hives, bronchospasm, and 

anaphylaxis can occur. Treatment of anaphylaxis is to 

stop any further administration of the drug, administer 

1-mL increments of 1 : 10,000 epinephrine with boluses of 

intravenous fluids, give inhaled bronchodilators, such as 

albuterol, for bronchospasm, and then administer histamine 

antagonists, such as Benadryl and Pepcid. 

Studies have shown pain on injection to be 9% and 

phlebitis to be approximately 1% with thiopental use. 61 

Tissue and venous irritation are more common if a 5% 

solution is used rather than the standard 2.5% solution. 

Rarely, intraarterial injection can occur. The consequences 

of accidental arterial injection may be severe. The degree 

of injury is related to the concentration of the drug. 

Treatment consists of (1) dilution of the drug by the 

administration of saline into the artery, (2) heparinization 

to prevent thrombosis, and (3) brachial plexus block. 

Overall, the proper administration of thiopental intravenously 

into a briskly running IV is remarkably free of 

local toxicity. 60 However, it should be noted that thiopental 

can precipitate if the alkalinity of the solution is


decreased, which is why it cannot be reconstituted with 

lactated Ringer’s solution or mixed with other acidic 

solutions. Examples of drugs that are not to be coadministered 

or mixed in solution with the barbiturates are 

pancuronium, vecuronium, atracurium, alfentanil, sufentanil, 

and midazolam. Studies have shown that in rapidsequence 

induction, the mixing of thiopental with 

vecuronium or pancuronium results in the formation of 

precipitate that may occlude the intravenous line. 62 

Midazolam 

The first benzodiazepine found to have sedative-hypnotic 

effects was chlordiazepam (Librium) in 1955. 63 Diazepam 

(Valium) was synthesized in 1959 and became the first 

benzodiazepine used for sedation and anesthesia induction. 

Subsequently, a number of benzodiazepines have 

been produced including lorazepam and the antagonist 

flumazenil. The benzodiazepines produce many of the 

elements important in anesthesia. They produce their 

actions by occupying the benzodiazepine receptor, which 

was first presented in 1971. 62 In 1977, specific benzodiazepine 

receptors were described when ligands were found 

to interact with a central receptor. 64 The most frequently 

used benzodiazepine in the elderly is midazolam. Fryer 

and Walser’s 1976 synthesis of midazolam (Versed) produced 

the first clinically used water-soluble benzodiazepine 

65 and it also was the first benzodiazepine that was 

produced primarily for use in anesthesia. 66 


Midazolam is water soluble in its formulation, but highly 

lipid soluble at physiologic pH. 67 Midazolam solution 

contains 1 or 5 mg/mL midazolam with 0.8% sodium 

chloride and 0.01% disodium edetate, with 1% benzyl 

alcohol as a preservative. The pH is adjusted to 3 with 

hydrochloric acid and sodium hydroxide. The imidazole 

ring of midazolam accounts for its stability in solution 

and rapid metabolism. The high lipophilicity accounts for 

the rapid CNS effect, as well as for the relatively large 

volume of distribution. 68 



All benzodiazepines have hypnotic, sedative, anxiolytic, 

amnesic, anticonvulsant, and centrally produced musclerelaxant 

properties. The drugs differ in their potency and 

efficacy with regard to each of these pharmacodynamic 

actions. The binding of benzodiazepines to their respective 

receptors is of high affinity, is stereospecific, and is 

able to fully saturate the receptors; the order of receptor 

affinity (thus potency) of the three agonists is lorazepam 

> midazolam > diazepam. Midazolam is approximately 

three to six times as potent as diazepam. 69 

The mechanism of action of benzodiazepines is reasonably 

well understood. 70–72 The interaction of ligands with 

the benzodiazepine receptor represents an example in 

which the complex systems of biochemistry, molecular 

pharmacology, genetic mutations, and clinical behavioral 

patterns are seen to interact. Through recent genetic 

studies, the GABA A subtypes have been found to mediate 

the different effects (amnesic, anticonvulsant, anxiolytic, 

and sleep). 73 Sedation, anterograde amnesia, and anticonvulsant 

properties are mediated via a1 receptors, 73 and 

anxiolysis and muscle relaxation are mediated by the a2 

GABA A receptor. 73 The degree of effect exerted at these 

receptors is a function of plasma level. By using plasma 

concentration data and pharmacokinetic simulations, it 

has been estimated that a benzodiazepine receptor occupancy 

of less than 20% may be sufficient to produce the 

anxiolytic effect, whereas sedation is observed with 30%– 

50% receptor occupancy and unconsciousness requires 

60% or higher occupation of benzodiazepine agonist 

receptors. 73 

Agonists and antagonists bind to a common (or at least 

overlapping) area of the benzodiazepine portion of the 

GABA A receptor by forming differing reversible bonds 

with it. 74 The effects of midazolam can be reversed by use 

of flumazenil, a benzodiazepine antagonist that occupies 

the benzodiazepine receptor, but produces no activity 

and therefore blocks the actions of midazolam. The duration 

of reversal is dependent on the dose of flumazenil 

and the residual concentration of midazolam. 

The onset and duration of action of a bolus intravenous 

administration of midazolam depends largely on the dose 

given and time at which the dose is administered; the 

higher the dose given over a shorter time (bolus), the 

faster the onset. Midazolam has a rapid onset (usually 

within 30–60 seconds) of action. The time to establish 

equilibrium between plasma concentration and EEG 

effect of midazolam is approximately 2–3 minutes and is 

not affected by age. 75 Like onset, the duration of effect is 

related to lipid solubility and blood level. 76 Thus, termination 

of effect is relatively rapid after midazolam administration. 

But some physicians have a general sense that 

midazolam is associated with the production of confusion 

even after the termination of sedation. This has been 

reported in prior studies and case reports. 77,78 However, a 

more recent study suggests that this might not be the case, 

particularly at lower doses. 79 Taken together, these data 

seem to suggest that single, lower doses of midazolam 

(0.03 mg/kg) will not cause confusion, whereas higher 

doses (0.05–0.07 mg/kg) plus an infusion of midazolam 

will have a greater association with confusion in the geriatric 

patient, as opposed to that seen with the use of a 

low-dose propofol infusion.



Midazolam, like most intravenous anesthetics and other 

benzodiazepines, produces dose-related central respiratory 

system depression. The peak decrease in minute ventilation 

after midazolam administration (0.15 mg/kg) is 

almost identical to that produced in healthy patients 

given diazepam (0.3 mg/kg). 80 Respiratory depression is 

potentiated with opioids and must be carefully monitored 

in elderly patients getting both. The peak onset of ventilatory 

depression with midazolam (0.13–0.2 mg/kg) is rapid 

(about 3 minutes), and significant depression remains for 

about 60–120 minutes. 56,81 The depression is dose-related. 

The respiratory depression of midazolam is more pronounced 

and of longer duration in patients with chronic 

obstructive pulmonary disease, and the duration of ventilatory 

depression is longer with midazolam (0.19 mg/kg) 

than with thiopental (3.3 mg/kg). 56 

At sufficient doses, apnea occurs with midazolam as 

with other hypnotics. The incidence of apnea after thiopental 

or midazolam when these drugs are given for 

induction of anesthesia is similar. In clinical trials, apnea 

occurred in 20% of 1130 patients given midazolam for 

induction and 27% of 580 patients given thiopental. 67 

Apnea is related to dose and is more likely to occur in 

the presence of opioids. Old age, debilitating disease, and 

other respiratory depressant drugs probably also increase 

the incidence and degree of respiratory depression and 

apnea with midazolam. 


Midazolam alone has modest hemodynamic effects. The 

predominant hemodynamic change is a slight reduction 

in arterial blood pressure, resulting from a decrease in 

systemic vascular resistance. The hypotensive effect is 

minimal and about the same as seen with thiopental. 82 

Despite the hypotension, midazolam, in doses as high as 

0.2 mg/kg, is safe and effective for induction of anesthesia 

even in patients with severe aortic stenosis. The hemodynamic 

effects of midazolam are dose-related: the higher 

the plasma level, the greater the decrease in systemic 

blood pressure 83 ; however, there is a plateau plasma drug 

effect above which little change in arterial blood pressure 

occurs. The plateau plasma level for midazolam is 

100 ng/mL. 83 Heart rate, ventricular filling pressures, and 

cardiac output are maintained after induction of anesthesia 

with midazolam. 

The stresses of endotracheal intubation and surgery 

are not blocked by midazolam. 84 Thus, adjuvant anesthetics, 

usually opioids, are often combined with benzodiazepines. 

The combination of benzodiazepines with opioids 

and nitrous oxide has been investigated in patients with 

ischemic and valvular heart diseases. 85–88 Whereas the 

addition of nitrous oxide to midazolam (0.2 mg/kg) has 

trivial hemodynamic consequences, the combination of 

benzodiazepines with opioids does have a synergistic 

effect. 89 The combination of midazolam with fentanyl 86 or 

sufentanil 88 produces greater decreases in systemic blood 

pressure than does each drug alone. 



Biotransformation of all benzodiazepines occurs in the 

liver. The two principal pathways involve either hepatic 

microsomal oxidation (N-dealkylation or aliphatic 

hydroxylation) or glucuronide conjugation. 90,91 The difference 

in the two pathways is significant, because oxidation 

is susceptible to outside influences and can be 

impaired by certain population characteristics (specifically 

old age), disease states (e.g., hepatic cirrhosis), or 

the coadministration of other drugs that can impair oxidizing 

capacity (e.g., cimetidine). Of the two, conjugation 

is less susceptible to these factors. 90 Midazolam undergoes 

oxidation reduction, or phase I reactions, in the 

liver. 92 The cytochrome P450 3A4 is primarily responsible 

for metabolism. 93 The fused imidazole ring of midazolam 

is oxidized rapidly by the liver, which accounts for 

the high rate of hepatic clearance. Neither age nor 

smoking decreases midazolam biotransformation. 94 

Chronic alcohol consumption increases the clearance of 

midazolam. 95 

The metabolites of the benzodiazepines can be important. 

Midazolam is biotransformed to hydroxymidazolams, 

which have activity, and when midazolam is given in 

prolonged infusions these metabolites can accumulate. 96 

These metabolites are rapidly conjugated and excreted in 

the urine. The 1-hydroxymidazolam has an estimated 

clinical potency 20%–30% of midazolam. 97 It is primarily 

excreted by the kidneys and can cause profound sedation 

in patients with renal impairment. 98 Overall, the metabolites 

of midazolam are less potent and normally more 

rapidly cleared than the parent drug, making them of 

little concern in patients with normal hepatic and renal 

function. However, they may be a consideration in elderly 

patients with impaired renal function. 

Midazolam is classified as a short-lasting benzodiazepine. 

The plasma disappearance curves of midazolam can 

be fitted to a two- or three-compartment model. The 

clearance rate of midazolam ranges from 6 to 11 mL/kg/ 

min. 94 Although the termination of action of these drugs 

is primarily a result of redistribution of the drug from 

the CNS to other tissues after bolus or maintenance use 

for surgical anesthesia, after daily (long-term) repeated 

administration or after prolonged continuous infusion, 

midazolam blood levels will decrease more slowly. 

Factors known to influence the pharmacokinetics of 

benzodiazepines are age, gender, race, enzyme induction, 

and hepatic and renal disease. Age reduces the clearance


of midazolam to a modest degree. 99 Among the pharmacokinetic 

parameters of midazolam that vary significantly 

with age, it is clearance which does so most consistently. 100 

In healthy adults, midazolam clearance is high, approximating 

50% of hepatic blood flow. 101 However, with 

advanced age, there is a loss of functional hepatic tissue 

and a decrease in hepatic perfusion such that clearance 

is reduced in the elderly by as much as 30% from that of 

a young adult. 39 As a result of the normal decline in lean 

tissue mass and concomitant increase in percent body fat 

in the aged, a slight increase is also observed in volume 

of distribution. 102 Moreover, according to one study, 

advanced age is in itself enough to cause the mean elimination 

half-life of midazolam to double. 38 Neither oral 

bioavailability nor midazolam protein binding are affected 

by age, despite reduced hepatic albumin synthesis and 

lower serum albumin concentrations in the elderly. 39,100 

Midazolam pharmacokinetics are affected by obesity. 

The volume of distribution is increased as drug goes from 

the plasma into the adipose tissue. Although clearance is 

not altered, elimination half-lives are prolonged, because 

of the delayed return of the drug to the plasma in obese 

persons. 99 This can be of concern in elderly obese patients. 

Although the pharmacokinetics of midazolam are clearly 

affected by age, they are, with the exception of total clearance, 

not consistently altered to statistical significance. 39,98 

These pharmacokinetic changes with age do not explain 

the increased sensitivity of the elderly to midazolam discussed 

above. There are pharmacodynamic factors that 

are yet to be fully understood that make midazolam more 

potent in the elderly than the young. 

Indications 

Intravenous Sedation 

Midazolam is used for sedation as preoperative premedication, 

intraoperatively during regional or local anesthesia, 

and postoperatively for sedation. The anxiolysis, 

amnesia, and elevation of the local anesthetic seizure 

threshold are desirable benzodiazepine actions for re - 

gional anesthesia. It should be given by titration for this 

use; endpoints of titration are adequate sedation or dysarthria 

and maintained ventilation. The onset of action is 

relatively rapid with midazolam, usually with peak effect 

reached within 2–3 minutes of administration. The duration 

of action depends primarily on the dose used. There 

is often a disparity in the level of sedation compared with 

the presence of amnesia (patients can be seemingly conscious 

and coherent, yet they are amnesic for events and 

instructions). The degree of sedation and the reliable 

amnesia, as well as preservation of respiratory and hemodynamic 

function, are better overall with midazolam than 

with other sedative-hypnotic drugs used for conscious 

sedation. When midazolam is compared with propofol for 

sedation, the two are generally similar except that emergence 

or wake-up is more rapid with propofol and amnesia 

is more reliable with midazolam. Propofol requires closer 

medical supervision because of its respiratory depression 

and hypotension. 103,104 Despite the wide safety margin 

with midazolam, respiratory function must be monitored 

when it is used for sedation to prevent undesirable 

degrees of respiratory depression. This is especially true 

in the geriatric patient. There may be a slight synergistic 

action between midazolam and spinal anesthesia with 

respect to ventilation. 103 Thus, the use of midazolam 

for sedation during regional and epidural anesthesia 

requires vigilance with regard to respiratory function, as 

when these drugs are given with opioids. Sedation for 

longer periods, for example, in the intensive care unit, is 

accomplished with benzodiazepines. Prolonged infusion 

will result in accumulation of drug and, in the case of 

midazolam, significant concentration of the active metabolite. 

The chief advantages are the amnesia and hemodynamic 

stability and the disadvantage, compared with 

propofol, is the longer dissipation of effects when infusion 

is terminated. 

Induction and Maintenance of Anesthesia 

With midazolam, induction of anesthesia is defined as 

unresponsiveness to command and loss of the eyelash 

reflex. When midazolam is used in appropriate doses, 

induction occurs less rapidly than with thiopental or 

propofol, 67 but the amnesia is more reliable. Numerous 

factors influence the rapidity of action of midazolam. 

These factors are dose, speed of injection, degree of 

premedication, age, American Society of Anesthesiologists 

(ASA) physical status, and concurrent anesthetic 

drugs. 67,105 In a well-premedicated, healthy patient, midazolam 

(0.2 mg/kg given in 5–15 seconds) will induce anesthesia 

in 28 seconds. Emergence time is related to the dose 

of midazolam as well as to the dose of adjuvant anesthetic 

drugs. 67 Emergence is more prolonged with midazolam 

than with propofol. 106,107 This difference accounts for some 

anesthesiologists’ preference for propofol induction for 

short operations. The best method of monitoring depth 

with midazolam is use of the EEG-BIS. 108 

The amnesic period after an anesthetic dose is about 

1–2 hours. Infusions of midazolam have been used to 

ensure a constant and appropriate depth of anesthesia. 109 

Experience indicates that a plasma level of more than 

50 ng/mL when used with adjuvant opioids (e.g., fentanyl) 

and/or inhalation anesthetics (e.g., nitrous oxide, volatile 

anesthetics) is achieved with a bolus loading dose of 

0.05–0.15 mg/kg and a continuous infusion of 0.25-1 µg/ 

kg/min. 110 This is sufficient to keep the patient asleep and 

amnesic but arousable at the end of surgery. Lower infusion 

doses almost certainly are required in elderly patients 

and with certain opioids.


Percent of Patients Demonstrating 

No Response Verbal Command 

100 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

Age 

80 

70 

60 

50 

40 

0 200 400 600 800 1000 1200 

Steady-State Plasma Midazolam Concentration (ng/ml) 

Figure 16-5. Response curves to verbal commands in patients 

of various ages at varying plasma levels of midazolam. This 

demonstrates a pharmacodynamic change associated with aging 

in response to midazolam. (Reprinted with permission from 

Jacobs et al. 112 ) 

Effects of Age on Pharmacology 

Elderly patients require lower doses of midazolam than 

younger patients to reach various standard clinical endpoints 

of sedation, such as response to verbal command 

(Figure 16-5). 111,112 The usual induction dose of midazolam 

in elderly premedicated patients is between 0.05 and 

0.15 mg/kg. Some studies show that patients older than 

55 years and those with ASA physical status higher than 

3 require a 20% or more reduction in the induction dose 

of midazolam. 67 However, Shafer, who collated the results 

of numerous pharmacokinetic and pharmacodynamic 

studies, recommends a 75% reduction in dose from the 

20-year-old to the 90-year-old. Thus, there is definitely a 

graded decrease in the amount of drug needed as a result 

of aging. 32 Furthermore, when midazolam is used with 

other anesthetic drugs (coinduction), there is a synergistic 

interaction, 110,113,114 and the induction dose is less than 

0.1 mg/kg. The synergy is seen when midazolam is used 

with opioids and/or other hypnotics such as thiopental, 

propofol, and etomidate. 

Awakening after midazolam anesthesia is the result of 

the redistribution of drug from the brain to other, less 

well-perfused tissues. The emergence (defined as orientation 

to time and place) of young, healthy volunteers 

who received 10 mg of intravenous midazolam occurred 

in about 15 minutes, 113 and, after an induction dose of 

0.15 mg/kg, it occurred in about 17 minutes. 78 The effect 

of age on emergence has not been studied, but it likely is 

prolonged compared with younger patients because of 

greater potency in the elderly. 


Midazolam is a remarkably safe drug. It has a relatively 

high margin of safety, especially compared with barbiturates 

and propofol. It is also free of allergenic effects and 

does not suppress the adrenal gland. 114 The most significant 

problem with midazolam is respiratory depression. 

It is free of venous irritation and thrombophlebitis, 

problems related to aqueous insolubility and requisite 

solvents in other drug formulations. 67 When used as a 

sedative or for induction and maintenance of anesthesia, 

midazolam can produce an undesirable degree or prolonged 

interval of postoperative amnesia, sedation, and, 

rarely, respiratory depression. These residual effects can 

be reversed with flumazenil. 

Etomidate 


Etomidate is a hypnotic drug that is structurally unrelated 

to all other induction medications. It contains a 

carboxylated imidazole ring that provides water solubility 

in an acidic milieu and lipid solubility at physiologic 

pH. It is dissolved in propylene glycol, which often causes 

pain on injection. Etomidate works by depressing the 

reticular activating system and it enhances the inhibitory 

effects of GABA by binding to a subunit of the GABA A 

receptor and thereby increasing its affinity for GABA. 

However, unlike the barbiturates, which have global 

depressant effects on the reticular activating system, 

etomidate has some disinhibitory effects, which accounts 

for the 30%–60% rate of myoclonus with administration. 

Interestingly, one study has shown that this unwanted 

side effect can be reduced with pretreatment, similar to 

a defasciculating dose of NMBDs. 115 



Etomidate induces changes in CBF, metabolic rate, and 

ICP to the same extent as thiopental and propofol. 

However, because this is not the result of a large reduction 

in arterial blood pressure, CPP is well maintained. 115 

This is of particular importance in the elderly person who 

is at risk for ischemic stroke secondary to carotid occlusion. 

Etomidate has EEG changes similar to thiopental 

with a biphasic pattern of activation followed by depression. 

However, etomidate has been shown to activate 

somatosensory evoked potentials. 50 Of note, etomidate 

does have a higher rate of postoperative nausea and vomiting 

associated with it than with the other intravenous 

induction drugs. 116 Finally, there are no pharmacodynamic 

changes with age with respect to etomidate as measured 

by EEG. 115 


Unlike propofol, etomidate has minimal effects on the 

cardiovascular system. There is a slight decline in the


arterial blood pressure secondary to a mild reduction 

in the systemic vascular resistance. Etomidate does not 

seem to have direct myocardial depressant effects, 

because myocardial contractility, heart rate, and cardiac 

output are usually unchanged. 117 Etomidate does not 

cause histamine release. These aspects of the pharmacodynamics 

of etomidate make it very useful in the patient 

with compromised intravascular volume, coronary artery 

disease, or reduced ventricular function, as is often 

encountered in the elderly patient. 


Etomidate causes less respiratory depression than benzodiazepines, 

barbiturates, or propofol in induction doses. 

In fact, even an induction dose of etomidate often does 

not cause apnea. 118 This fact, combined with its minimal 

cardiovascular effects, makes etomidate a very useful 

drug in the setting of a hemodynamically brittle elderly 

patient with a possible difficult airway and little respiratory 

reserve. 

Endocrine Effects 

Induction doses of etomidate temporarily inhibit the synthesis 

of cortisol and aldosterone. 119 However, with a 

single bolus dose there is little clinical significance. Alternatively, 

long-term infusions or closely repeated exposures 

can lead to adrenocortical suppression, which may 

be associated with an increased susceptibility to infection 

and an increased mortality rate in the critically ill 

patient. 120 



Etomidate is used only in intravenous formulations and 

is generally used for the induction of general anesthesia. 

Etomidate is similar to thiopental in its distribution and 

onset of action. Although it is highly protein bound, 

etomidate has a very rapid onset of action because of its 

high lipid solubility and its large nonionized fraction. 

Redistribution to noncentral compartments is responsible 

for its rapid offset of action. Hepatic microsomal 

enzymes as well as plasma esterases rapidly hydrolyze 

etomidate to its nonactive metabolites. This rate of biotransformation 

is five times greater than that of thiopental, 

but less than that of propofol. 

The volume of distribution is slightly larger than that 

of the barbiturates and the elimination clearance is 

greater. However, the elimination clearance is still less 

than propofol. Thus, the elimination half-life of etomidate 

is faster than thiopental, but longer than propofol. Both 

of these parameters are decreased in the elderly, which 

causes a higher plasma concentration of etomidate for 

any given dose. Furthermore, to our knowledge, no study 

has ever shown an increased brain sensitivity to etomidate 

with increasing age. Therefore, like thiopental, any 

dose reduction in the elderly is attributable to pharmacokinetic, 

not pharmacodynamic, changes. 121 

Indications 

Etomidate is used for the intravenous induction of anesthesia. 

1 It can be used with an intermittent bolus technique 

for short procedures. Typically, 25% of the induction 

dose is given every 15–30 minutes to maintain surgical 

anesthesia. Etomidate is not approved in the United 

States for maintenance infusions. 


The standard induction dose of etomidate is intravenous 

0.3–0.4 mg/kg. However, the elderly may only require 

0.2 mg/kg. This change in dosage is attributable only to 

pharmacokinetic parameters, not pharmacodynamic. 121 


Etomidate has a high incidence of side effects, most of 

which are minor. As mentioned above, etomidate has a 

higher rate of postoperative nausea and vomiting than 

either propofol or thiopental. The incidence of myoclonic 

movements on induction is reported to be as high as 

60%. This effect as well as pain on injection can be 

reduced with a slow injection into a rapidly running intravenous 

carrier line, preferably in a large vein. When 

etomidate is injected into veins in the hand, the incidence 

of pain is reported to exceed 40%. Furthermore, because 

of the propylene glycol solvent, studies have shown that 

10%–20% of patients experience venous sequelae after 

its use. 122 

Summary 

This chapter has surveyed the pharmacology of frequently 

used intravenous hypnotic agents in the geriatric patient. 

There is substantial evidence of significant changes in 

the pharmacokinetic and pharmacodynamic behavior of 

propofol, thiopental, midazolam, and etomidate in this 

population. A few final points remain when considering 

the general changes for each of these hypnotic agents. 

First, practitioners should perform a thorough review of 

the cardiopulmonary status of all geriatric patients, 

because an absence of complaints in a review of systems 

may merely be a function of a sedentary lifestyle. A more 

extensive history may elicit findings that would alter the 

method of induction or the combination/doses of drugs 

used for anesthesia. Second, a full review of the current 

medical management of systemic disease should be


performed, because the elderly population often presents 

for surgery with outpatient polypharmacy. Particular 

attention should be given to current use of antihypertensive, 

diuretic, antidepressant, anti-Parkinsonian, and erectile 

dysfunction agents, with vigilance given to careful 

blood pressure monitoring when using the induction 

agents reviewed in this chapter in patients who are taking 

one or several of these medications. Third, a thorough 

understanding of the changes in the pharmacokinetics 

and pharmacodynamics of opioids in the geriatric patient 

is critical when combining them for sedation or general 

anesthesia in this population. Finally, unless a rapid 

sequence induction is indicated, a slow and careful titration 

of the induction of anesthesia using smaller doses of 

hypnotic agents and some form of an EEG monitor will 

prevent overdosing, subsequent hypotension, and delayed 

awakening in this population. 

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injection of diazepam, flunitrazepam, thiopentone 

and etomidate. Acta Anaesthesiol Scand 1980;24:227.

17 

Inhalational Anesthetics 

Gary R. Haynes 

General anesthesia with inhalational anesthetic agents is 

the most common method of surgical anesthesia. Although 

regional and neuroaxial anesthetics are preferred in some 

circumstances, the use of general anesthesia with in - 

halational agents remains widespread. Total intravenous 

anesthesia has greater acceptance in Europe where it 

accounts for approximately 40% of general anesthesia 

cases. However, only a small portion of general anesthesia 

cases in the United States use this technique. 

General anesthesia in older adults with inhalational 

agents compares favorably to intravenous anesthesia. 1 

However, there are many gaps in our knowledge of volatile 

anesthetic drug effects in the elderly. Many of the 

most comprehensive studies on inhalational anesthetics 

were done in young adults. Clinical drug trials demonstrating 

their safety, dosing, and efficacy frequently involve 

younger patients. When clinical trials enroll subjects over 

a range of ages, they frequently do not stratify patients 

into age groups. Consequently, it is often impossible to 

make statements describing any differences between 

younger and older patients. 

The focus of past clinical studies investigating inhalational 

anesthetic agents was their immediate effects and 

short-term outcomes. The control of cardiovascular 

responses and time for emergence from general anesthesia 

are typical examples. There is only limited information 

on the immediate perioperative outcome of elderly 

patients and even fewer reports regarding their long-term 

outcomes. When the concern is the elderly patient, there 

are often more questions than answers. 

The Pharmacokinetics of Inhalational 

Agents in the Elderly 

The pharmacokinetic aspects of inhalational anesthetic 

agents include the absorption, distribution, and metabolism 

of these drugs. Profound age-related changes occur 

in the pharmacokinetics of intravenous drugs, so it is 

anticipated that age will also change inhalational anesthetic 

behavior. However, there are few studies describing 

how their pharmacokinetics change with age. 

Advancing age modifies every aspect of systems controlling 

the movement of these drugs. Consequently, the 

assumptions based on the behavior of inhaled anesthetics 

in younger patients may not hold when administered to 

older individuals. Some insight comes from the results of 

studies in middle-aged adults or from studies in the 

elderly conducted for some purpose other than examining 

pharmacokinetics. 

The pharmacokinetics of volatile anesthetics can be 

studied in one of two ways. Under laboratory conditions, 

subanesthetic doses of several agents can be administered 

in combination to a single subject. This approach 

has the advantage of limiting the variability between individuals 

while measuring the kinetics of each drug. The 

drawback of this method is the inability to measure the 

pharmacologic effect specific to each drug. 2,3 The other 

method is to administer a single agent and track it in an 

individual subject. These studies require validation in 

many subjects. Frequently, the design of such studies does 

not address the issue of age. 

Influence of the Aging Pulmonary System 

Uptake of anesthetics begins when the fresh gas inflow 

from the anesthesia machines carries a volatile agent into 

the patient. The uptake of an inhalational agent is simply 

the difference between the inspired and expired concentrations 

multiplied by the alveolar ventilation. 

The total gas flow passing through the vaporizer determines 

the rate of inhalational agent consumption. 4 In 

young subjects, saturation is most rapid with desflurane. 

Saturation is next most rapid with sevoflurane. High fresh 

gas flow (>3 L/min) will consume volatile agents more 

rapidly than when using low flows, and anesthetic drug 

cost can be reduced by using a low-flow technique. 

246

17. Inhalational Anesthetics 247 

With the low-flow technique, fresh gas flow rate is reduced 

to less than half the patient’s minute ventilation, usually 

to less than 3.0 L/min. Monitoring of inspired and expired 

gas concentrations is mandatory. At a low flow rate, 

consumption of an insoluble agent, such as desflurane, 

depends on fresh gas flow whereas halothane does not. 

Consumption of isoflurane and enflurane vary with 

minimal and low fresh gas flow rates. 5 

Do anesthetic agents control the response to surgical 

stimulation in the same manner at low flows? The partial 

pressure of agents in pulmonary arterial blood that have 

a low blood/gas solubility should change rapidly with 

changes in vaporizer settings. Desflurane provides faster 

control of hemodynamic responses at 1 and 3 L/min flows, 

and its use requires fewer incremental increases to control 

acute responses to surgical stimulation. At fresh gas flow 

rates of 1 L/min, more interventions are necessary to 

control blood pressure in older patients receiving isoflurane 

compared with desflurane. 6 

The respiratory changes characterizing advanced 

age have been thoroughly reviewed by others. 7–11 The 

principal anatomic changes include lung atrophy and a 

loss of pulmonary elasticity. There is a loss of alveolar 

walls, a depletion of the connective tissue elastin, and an 

increase in interstitial fibrous tissue. The histopathologic 

change in the senescent lung is sometimes termed “senile 

emphysema,” and it refers to the atrophic changes and 

dilatation of the alveoli that mimic mild emphysema 

(Figure 17-1). 

The destruction of alveolar walls results in small alveoli 

coalescing to form larger sacs. Consequently, the lungs 

have less elasticity and less natural recoil to hold small 

airways open as lung volumes change with respiration. 12,13 

Airways from the level of bronchioles to the alveolar 

ducts lack a cartilaginous support. Without a semirigid 

structure to keep them open during passive exhalation, 

these airways depend on the elastic recoil of the lung 

parenchyma to prevent collapse at low lung volumes 

(Figure 17-2). There is an age-related decrease in the 

diameter of small bronchioles from the fourth decade 

that is consistent with decreased compliance. 14 In the 

older patient, these dependent airways close at a higher 

lung volume than in younger subjects. The physiologic 

consequence of these changes is increasing ventilationperfusion 

(V/Q) mismatching with advancing age. 

A progressive hypoxemia develops as the number of 

alveoli gradually decreases and anatomic dead space 

increases. 15 

The increased closing volume makes it more likely an 

older patient will experience hypoxia at some time in the 

perioperative period. Older patients experience hemoglobin 

desaturation at a faster rate because of greater 

V/Q mismatching. In the operating room, the transfer of 

oxygen is not as efficient when using positive pressure 

ventilation in the supine position as it is when breathing 

spontaneously. The combination of altered ventilatory 

response to hypoxia, sedation from residual inhalational 

agents, and analgesics increases the risk of hypoxia after 

general anesthesia. The likelihood of hypoxia is further 

compounded if pulmonary disease is superimposed on 

age-related changes. 

An age-related mismatching of pulmonary ventilation 

and perfusion may influence the uptake of volatile anesthetic 

agents. Areas of the lung that are well ventilated 

but with less perfusion will contribute more anesthetic 

gas and can be expected to cause a more rapid increase 

in the ratio of alveolar (F A ) to inspired (F I ) agent concentrations. 

However, there is little evidence to confirm this. 

A 

B 

Figure 17-1. Histologic sections of normal lung from a nonsmoking (A) 22-year-old homicide victim, and (B) a 75-year-old individual 

(hematoxylin and eosin stain, 2×).

248 G.R. Haynes 

14 

12 

A 

110 

100 

B 

Pst(I), H 2 O 

10 

8 

6 

4 

Arterial PaO2 (mmHg) 

90 

80 

70 

2 

Age vs Pst(I) 

95% C.I. 

60 

0 

0 10 20 30 40 50 60 70 

Age, years 

Figure 17-2. (A) The change in static recoil of the lung measured 

at 60% of total lung capacity. The decrease in recoil with 

age is apparent. Atrophy of pulmonary parenchyma results in 

less elastic recoil to hold open small airways at low tidal volumes. 

(Data from Turner et al. 13 ) (B) Increasing ventilation-perfusion 

50 

0 20 30 40 50 60 70 80 

Age, years 

mismatching occurring with age leads to lower resting PaO 2 . 

The resting arterial tension was determined by the equation 

PaO 2 (mm Hg) = 143.6 − (0.39 × age) − (0.56 × BMI) − (0.57 × 

Paco 2 ), assuming a BMI of 25 and Paco 2 of 40 mm Hg. 

(Data from Cerveri et al. 15 ) 

In the absence of grossly abnormal pulmonary function, 

the small increase in the F A /F I ratio caused by a progressive 

V/Q mismatch is probably offset by a lower metabolic 

rate, and hence lower ventilation and perfusion per 

kilogram body weight in the elderly. It is difficult to demonstrate 

any difference in anesthetic uptake attributable 

to age alone in normal patients (Edmond Eger, personal 

communication, 2005). However, patients with chronic 

pulmonary obstructive disease from emphysema, chronic 

bronchitis, or asthma will have a slower increase in the 

alveolar concentration (F A ) of volatile anesthetic agents 


There is no evidence that an obstruction to diffusion 

of anesthetic agents develops with age. Alveolar thickening 

from unusual disorders such as idiopathic pulmonary 

fibrosis or common problems such as lung congestion 

from cardiac failure should slow diffusion of anesthetic 

gases, but it is not likely that this results in a slower 

increase in the partial pressure of the inhalational agent 

in pulmonary venous blood. 

Any change in V/Q mismatching has a more pronounced 

effect on inhalational agents with low blood/gas 

partition (B/G) coefficients. 16 This includes sevoflurane, 

desflurane, and the inorganic compound nitrous oxide 

(Table 17-1). Lu et al. 17 measured sevoflurane concentration 

in arterial and jugular venous blood samples in 

patients during cardiac surgery. Their study population 

consisted of 10 patients between the ages of 51 and 73 

years who received a constant 3.5% inspired sevoflurane 

concentration for 1 hour. It took 40 minutes before the 

concentration of sevoflurane in venous blood became 

equal to the arterial blood. The arterial sevoflurane concentration 

was also approximately 40% less than the endtidal 

expired sevoflurane. Thus, the end-tidal sevoflurane 

concentration did not reliably reflect the parallel concentration 

of sevoflurane in the brain. The equilibration 

between arterial blood and brain tissues takes four times 

longer than predicted and sevoflurane uptake in the brain 

takes approximately 1 hour. 17 As a result of the changes 

showing slower uptake, it should also be anticipated there 

F A /F I 

1.0 

0.8 

0.6 

0.4 

0.2 

Normal 

Obstructive pulmonary disease 

0.0 

0 5 10 15 20 25 30 35 

Time (min) 

Figure 17-3. The effect of pulmonary disease on the increase 

of alveolar concentration (F A ) compared with inspired concentration 

(F I ) versus time. The increase in F A /F I is slower in subjects 

with pulmonary disease. (Adapted with permission from 

Gloyna DF. Effects of inhalation agents. In: McLeskey CH, ed. 

Geriatric Anesthesiology. Baltimore: Williams & Wilkins; 

1997.)


Table 17-1. Physical properties of inhalational agents including nitrous oxide. 

Molecular Boiling* Vapor 

Partition coefficient 

Recovered as 

Agent weight*† (g) point (°C) pressure*‡ Oil/gas* Blood/gas* Fat/blood§ metabolites (%) 

Halothane 197.4 50 243 224 2.3 51 11–25 

F CI 

Br 

F 

F 

Enflurane 184.5 57 172 98.5 1.91 36 2.4 

F 

F F 

F 

F O 

CI 

Isoflurane 184.5 49 238 90.8 1.4 45 0.2 

CI F 

F 

O 

F F 

F 

Desflurane 168 24 669 19 0.45 27 0.02 

F 

F O 

F 

F 

F F 

Sevoflurane 200 59 157 53.4 0.60 48 5.0 

F 

F 

F 

F O 

F 

F F 

Nitrous oxide 44 −88 38,770 1.4 0.47 2.3 0 

O 

I N 

N 

Note: Values are based on measurement at 37°C unless otherwise noted. 

*Data from Stevens WC, Kingston HGG. Inhalational Anesthesia. In: Barash PG, ed. Clinical Anesthesia. Philadelphia: JB Lippincott; 1989:295. 

†Data from Eger EI, Weiskopf RB, Eisenkraft JB. The Pharmacology of Inhaled Anesthetics. The Dannemiller Memorial Educational Foundation; 

2002. 

‡At 20°C, in mm Hg. 

§Data from Eger EI. Uptate and Distribution. In: Miller RD, ed. Anesthesia. Philadelphia: Elsevier Churchill Livingstone; 2005:132. 

Data from Carpenter et al. 73 

For individuals aged 30–60 years. 

will be slower elimination of inhalational anesthetics 

from altered pulmonary function. 18 

Alveolar ventilation does not change with age. However, 

there are changes that lead to degrees of V/Q mismatching 

and changes in the control of minute ventilation in 

response to hypoxia and hypercarbia. The normal partial 

pressure of carbon dioxide in arterial blood is 4.6–5.3 kPa 

(34.5–39.8 mm Hg) in older patients. 19,20 With advancing 

age, the control of ventilation is less sensitive. The normal 

response to hypercarbia is an increase in the minute ventilation. 

In young individuals, there is a profound response, 

about 2–5 L/min per torr carbon dioxide. 21,22 Where the 

response to rebreathing carbon dioxide is 3.4 L/min in 

men whose average age is 26 years, the response is only 

1.8 L/min in men who are about 70 years of age. 23 The 

likelihood of respiratory acidosis from impaired ventilation 

after general anesthesia is therefore greater but it is 

not documented. 

The ventilatory response to hypoxia greatly diminishes 

with advanced age. 23 When combined with the sedative 

effect of inhalational anesthetics, the profoundly impaired 

drive to increase minute ventilation in response to hypoxia 

leaves the elderly patient at risk for hypoxia. This may 

contribute to the numerous instances of respiratory complications 

in the recovery period including hypoxia 

hypoventilation, and atelectasis. 24 Therefore, less-soluble 

inhalational anesthetic drugs for elderly patients are reasonable 

choices. Transporting elderly patients with supplemental 

oxygen from the operating room to the 

postanesthesia care unit (PACU) is prudent. Generous 

use of supplemental oxygen and close monitoring while 

in the PACU are imperative.


Influence of the Aging Cardiovascular System 

The major cardiovascular changes occurring with age 

include impaired pump function and atherosclerotic 

changes in the vasculature. These changes occur independently 

of diseases that can affect the heart and peripheral 

vasculature. The most common cardiovascular problems 

are hypertension, arteriosclerosis, atherosclerotic vascular, 

and coronary disease. Angina pectoris and myocardial 

ischemia leading to myocardial infarction are frequent 

myocardial events. 25 Heart failure is a common problem 

in the elderly. The incidence of heart failure in the elderly 

is 20–30 cases per 1000 persons older than 80 years of 

age. 26 Approximately half of congestive heart failure 

cases occur in patients with preserved systolic function, a 

problem now recognized as diastolic dysfunction. 27 

Aside from being the frequent target of disease, the 

cardiovascular system experiences a decline in function 

with age. One general measure of cardiac function, the 

maximum oxygen transport or VO 2-max , decreases at the 

rate of approximately 1% per year after age 30. 28–30 It is 

tempting to rely on cardiac output as a way of assessing 

the effect of age. However, changes in cardiovascular 

function are variable and not easily attributed to a single 

cause. Cardiac output has several determinants, and, as a 

single index, it is not an adequate measure to understand 

anesthetic effects in the elderly. 

In healthy older subjects, the peripheral flow of blood 

decreases and peripheral vascular resistance increases in 

comparison to younger counterparts. Physical conditioning 

does not alter these changes 31 (Figure 17-4). Increasing 

vascular resistance may explain some decrease in 

A 

Femoral Blood Flow (ml/min) 

600 

500 

400 

300 

200 

r = –0.40 

P < 0.001 

B 

Femoral Vascular 

Resistance (U) 

0.7 

0.6 

0.5 

0.4 

0.3 

0.2 

r = 0.47 

P < 0.001 

C 

100 

10 20 30 40 50 60 70 80 

8 

Young (20–35 years) 

Older (55–75 years) 

0.1 

10 20 30 40 50 60 70 80 

Age (years) 

6 

Cardiac output (L/min) 

4 

2 

0 

Sedentary 

Physically active 

Endurance trained 

Figure 17-4. Cardiovascular changes 

occurring with age in healthy male 

subjects. Femoral blood flow decreases 

(A) and peripheral vascular resistance 

increases (B) with age. The effect of age 

on these variables is not influenced by 

exercise conditioning. (C) Age-related 

changes in cardiac output are minor. 

(A and B reprinted with permission, 

and C data from Dienno FA, Seals DR, 

DeSouza CA, Tanaka H. Age-related 

decreases in basal limb blood flow in 

humans: time course, determinants 

and habitual exercise effects. J Physiol 

2001;531:573–579.)


cardiac output, but decreases in cardiac output may also 

result from decrement in the chronotropic response, systolic, 

and diastolic function. There is general agreement 

that the maximum heart rate response decreases with age. 

The maximum cardiac stroke volume does not change 

very much as a result of age alone, but it may decrease 

for several reasons, such as ventricular hypertrophy, stiffening 

of the ventricular wall, lower preload, and higher 

afterload. By carefully matching the physical abilities of 

older master athletes with younger competitive runners, 

Hagberg et al. 32 demonstrated that the decrease in 

VO 2-max occurring with age is attributable only to a 

decreased maximal heart rate. There was no change in the 

stroke volume and arterial-venous oxygen difference to 

account for lower cardiac output. 32 The influence of age 

on cardiac function is seen when normal subjects are 

stressed. The cardiac output is maintained by increasing 

the end-diastolic volume, and thus the stroke volume, to 

compensate for less ability to increase the heart rate 


SLOPE COEFFICIENT OF AGE REGRESSION 

1.0 

.80 

.60 

.40 

.20 

0 

–.20 

–.40 

–.60 

EDV 

ESV 

SBP 

CD 

EF 

Figure 17-5. The action of increasing workload on cardiac function 

as a function of advancing age. Each point is the slope of 

a coefficient for each physiologic parameter measured in a 

group of normal subjects ranging in age from 25 to 79 years. The 

subjects performed stationary bicycle work while hemodynamic 

measurements were taken and worked to the point of exhaustion. 

An increase or decrease in the slope coefficient with 

increasing workload indicates an increasing or decreasing effect 

of age. CO = cardiac output, EDV = end-diastolic volume, 

ESV = end-systolic volume, SBP = systolic blood pressure, 

EF = ejection fraction, HR = heart rate. (Reprinted with permission 

from Rodeheffer RJ, Gerstenblith G, Becker LC, Fleg JL, 

Weisfeldt ML, Lakatta EG. Exercise cardiac output is maintained 

with advancing age in healthy human subjects, cardiac 

dilatation and increased stroke volume compensate for a diminished 

heart rate. Circulation 1984;69:203–213.) 

HR 

REST 25 50 75 100 

WATTS 

Cardiac output is determined by the heart rate and 

stroke volume. Altered uptake and distribution of inhalational 

anesthetic agents result when cardiac pump function 

decreases. Patients with decreased cardiac output 

have a slower systemic circulation time that is matched 

with a slower circulation through the pulmonary circuit. 

During general anesthesia, slower pulmonary circulation 

provides more time for volatile anesthetic agents to 

diffuse into the blood. Pulmonary venous blood can attain 

a higher partial pressure of anesthetic gas under these 

circumstances than anticipated. Thus, the effect of lower 

cardiac output is greater delivery of anesthetic drug to 

the myocardium and the central nervous system. Generally, 

this effect occurs with the more soluble anesthetics 

such as halothane and enflurane. The action of low cardiac 

output increasing uptake is attenuated by anesthetics 

with a lower B/G solubility. This favors the use of lowsolubility 

agents such as desflurane and sevoflurane. 

A slower systemic circulation also slows delivery of 

anesthetic agents to target tissues including the central 

nervous system (Figure 17-6). The clinical result is a slower 

onset of anesthesia. However, with the most soluble inhalational 

agents, a lower cardiac output means arterial blood 

will convey a higher partial pressure of anesthetic agent to 

the central nervous system, and, consequently, with greater 

drug delivery, the anesthetic effect may be more profound. 

Low cardiac output in patients with cardiac disease exaggerates 

this effect. Volatile anesthetic agents can cause a 

cycle of myocardial depression leading to increased uptake, 

increased alveolar concentration, and further depression 

of cardiac output. Therefore, the potential cardiac depressant 

effect of volatile anesthetics is significant. 

Anesthetics may decrease stroke volume by depressing 

contractility or slowing the rate. Bradycardia is encountered 

in many clinical situations and it is often a simple 

problem to treat. An advantage of newer volatile anesthetics 

is that they generally cause little change in heart 

rate or they tend to increase it slightly at higher concentrations 

(Figure 17-7). In younger patients, tachycardia results 

from abrupt increases in desflurane administration above 

1 minimal alveolar concentration (MAC) (Figure 17-8). A 

similar but less-pronounced response also occurs with isoflurane. 

33 Suddenly increasing the administration of this 

agent has no advantage because the drug’s low solubility 

will result in a rapid change of its partial pressure in blood. 

The depression of myocardial contractility by anesthetic 

agents is a more important consideration. Global cardiac 

depression is most likely with halothane, enflurane, and to 

some extent, isoflurane. These drugs are more soluble in 

blood than either desflurane or sevoflurane, and can have 

a greater effect for this reason (Table 17-2). 

Predicting how patients with combined pulmonary and 

cardiac disease will respond during general anesthesia 

with volatile anesthetics is difficult. Clinicians can expect 

slower induction and longer emergence from inhalational


Reduced cardiac output 

CNS 

Anesthetic 

concentration 

Normal cardiac output 

Time 

Figure 17-6. Reduced cardiac output results in slower pulmonary 

circulation and allows for the diffusion of more anesthetic 

agent into the blood. This results in a more rapid increase in the 

partial pressure of agent in the blood, greater delivery to the 

central nervous system, and a more profound onset of anesthesia. 

This is more likely with the very soluble anesthetic agents. 

However, the onset of action may be delayed compared with 

patients with normal cardiac output. (Reprinted with permission 

from Gloyna DF. Effects of inhalation agents. In: McLeskey 

CH, ed. Geriatric Anesthesiology. Baltimore: Williams & 

Wilkins; 1997. Data from Musnon ES, Eger EI II, Bowers DL. 

The effects of changes in cardiac output and distribution on the 

rate of cerebral anesthetic equilibration. Calculations using a 

mathematical model. Anesthesiology 1968;29(3):533–537.) 

anesthesia. It is also likely these patients will have greater 

hemodynamic instability during anesthesia. 

Influence of Body Composition Changes 

A primary factor influencing inhalational agent pharmacokinetics 

is the change in body composition. These 

include a reduction in the skeletal muscle mass and an 

increase in the total body fat content. 34 Although there is 

considerable variation, the general trend is for an increase 

in the percentage of body fat (Figure 17-9). The change 

in body composition is greater for men, with about 25% 

of their total body mass being fat. For older women, the 

total body fat content averages 35%. 35 As total body fat 

increases with age, the proportion of total body water 

also decreases. 

A 140 

B 140 

Heart Rate (beats/min) 

120 

100 

80 

DES - O 2 

DES - N 2 O 

Heart Rate (beats/min) 

120 

100 

80 

Isoflurane-O 2 1st hour 

Isoflurane-O 2 5th hour 

60 

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 

Total MAC equivalent 

60 

0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.8 

Total MAC equivalent 

Figure 17-7. (A) Hemodynamic effects of desflurane (DES) 

during controlled ventilation in young volunteer subjects. The 

subjects received no other drugs. MAC = minimal alveolar concentration. 

(Data from Cahalan MK, Weiskopf RB, Eger EI II, 

et al. Hemodynamic effects of desflurane/nitrous oxide anesthesia 

in volunteers. Anesth Analg 1991;73:157–164.) (B) Hemodynamic 

effects of isoflurane during controlled ventilation in 

young volunteer subjects. Measurements were made during the 

first and fifth hours of continuous anesthesia and demonstrate 

small changes occurring in the heart rate response with prolonged 

anesthesia. (Data from Stevens et al. 38 )


Figure 17-8. A transient increase in heart rate, blood pressure, 

and sympathetic activity occurs with isoflurane and desflurane 

when the concentrations are increased rapidly to more than 1 

minimal alveolar concentration. Several interventions have 

been described to effectively counter this occurrence, including 

avoiding the “over pressuring” technique. HR = heart rate, 

MAP = mean arterial pressure. (Reprinted with permission 

from Weiskopf et al. 33 ) 

Fat tissue has a great capacity to retain lipid-soluble 

drugs. For those inhalational agents with greater lipid 

solubility, the volume of distribution increases (Tables 

17-1 and 17-3). Fat acts as a reservoir for volatile agents, 

resulting in the accumulation of inhalational agents 

during maintenance and delaying emergence. Depending 

on many variables, including the lipid solubility of the 

agent, less blood flow to fat tissue than other tissues, and 

the duration of anesthesia, an increase in the proportion 

of body fat may prolong emergence. Although the changes 

in body fat composition are greater in men, and women 

have a greater percent body fat at all ages, there is no 

indication of a gender difference with the pharmacokinetics 

of inhalational anesthetic agents. 

The lipid-soluble drugs redistribute slowly from 

fat tissue so their effect may be prolonged. The loss of 

skeletal muscle mass has a significant impact on drug 

pharmacokinetics because this tissue receives a large 

portion of the blood supply. As the body fat content 

increases, a smaller part of each circulating blood volume 

perfuses this tissue and it diminishes the volume of distribution 

for the agents that are not very lipid soluble. 

Most body fat resides in subcutaneous and abdominal 

areas. However, body fat may be heterogeneous and 

various anatomic fat stores may differ in their capacity to 

act as a reservoir for lipid-soluble drugs. 36 Subcutaneous 

fat that develops from excessive eating may function differently 

from the epicardial or mesenteric fat that is 

present even in very lean individuals. How this might 

affect the uptake and retention of lipid-soluble inhalational 

agents is yet to be determined. 

The steady-state volume of distribution, V dss , is greatest 

for isoflurane and least with desflurane 37 (Table 17-3). The 

movement of volatile agent from the central to peripheral 

compartments is fastest for desflurane and intermediate 

for sevoflurane, whereas isoflurane is the slowest. 

Table 17-2. The influence of halothane or enflurane on myocardial contractility, E ES , 

in a canine model and during coronary artery bypass surgery. 

Canine model 

Halothane (n = 7) Enflurane (n = 7) CABG surgery 

Control 10.1 ± 0.6 15.2 ± 0.4 Control 11.5 ± 2.0 

1% 6.7 ± 0.4 12.3 ± 0.6 60% N 2 O 9.0 ± 2.2 

2% 4.2 ± 0.5 9.3 ± 0.5 0.5% halothane 8.1 ± 2.4 

Source: Data from Van Trigt P, Christian CC, Fagraeus L, et al. Myocardial depression by anesthetic 

agents (halothane, enflurane, and nitrous oxide): quantitation based on end-systolic 

pressure-dimension relations. Am J Cardiol 1984;53:243–247. 

E ES (mm Hg/mm) = slope of the end-systolic pressure-diameter relation, a sensitive index of contractility 

unaffected by volume loading; CABG = coronary artery bypass graft.


A 

Figure 17-9. The change in body composition occurring 

with age. Data from the Fels Longitudinal Study including 

men (A) (n = 102) and women (B) (n = 108) for 

subjects not selected because of any known criteria 

related to body composition. Women have a greater 

percent of body fat than men at all ages. Men have an 

increasing trend in body weight and percent body fat. 

Women tend to lose fat-free mass as they become older. 

(Data from Guo et al. 34 ) 

B 

It is not just the greater solubility of isoflurane that 

accounts for its V d being six times that of desflurane. Isoflurane 

increases blood flow to tissues such as skeletal 

muscle, a tissue with large storage capacity. 37,38 

The partial pressure of anesthetic permitting wakefulness, 

the MAC-awake value, determines the emergence 

from general anesthesia. The MAC-awake value for all 

volatile anesthetics is about one third the MAC value. A 

slow, continued release of volatile agent from fat tissue 

can maintain a partial pressure of agent in the blood 

causing excessive sedation, respiratory depression, and 

contribute to postanesthesia delirium. This action may 

Table 17-3. Pharmacokinetics of newer volatile anesthetic agents. 

Agent MAC B/G* FGF† k 3 12 (min −1 ) Cl 12 ‡ (mL vapor kg −1 min −1 ) V dss ‡ (mL vap /kg bw ) 

Sevoflurane 2.1 0.69 2 0.117 (0.070–0.344) 13.0 (9.8–22.4) 1748 (819–8997) 

Isoflurane 1.2 1.4


contribute to a greater incidence of postoperative complications 

and prolonged stays in the PACU. 

The increasing proportion of body fat suggests an 

advantage with the less-soluble volatile anesthetic drugs. 

Emergence from general anesthesia has been studied by 

comparing desflurane and isoflurane anesthesia in elderly 

patients. Compared with isoflurane anesthesia, signs of 

early recovery and endotracheal tube removal occurred 

in approximately half the time with desflurane. Emergence 

was also faster than with intravenous anesthesia. 39 

For short procedures (less than 2 hours), patients reached 

signs of early recovery and experienced endotracheal 

tube removal sooner with desflurane compared with 

sevoflurane. 40 

Influence of Renal Changes 

Renal atrophy occurs with age, mainly through the loss 

of cortical nephrons. The kidney loses about 20% of its 

mass by age 80, and functional changes accompany renal 

atrophy. The majority of subjects experience a decrease 

in renal blood flow, glomerular filtration rate (GFR), and 

creatinine clearance. The reduction in renal blood flow 

probably results from cardiovascular changes in addition 

to renal changes. 41 However, the Baltimore Longitudinal 

Study of Aging showed that a decline in the GFR is not 

inevitable because 30% of healthy individuals have no 

decrease in GFR with age. 42 The plasma creatinine level 

varies with the muscle mass and with age-related changes 

in body composition accompanying the aging process. 

Thus, it is better to evaluate renal function in the elderly 

using the Cockroft-Gault formula [(140 − age) × weight 

(kg)/Cr × 72] than simply using the plasma creatinine 

value 43 (Figure 17-10). 

All volatile anesthetic agents in clinical use are fluorinated 

ether compounds. The constellation of renal 

changes may place the older patient at greater risk for 

fluoride toxicity 44 (Table 17-1). Inorganic free fluoride 

ions form during metabolism of these agents by the 

hepatic cytochrome P-450 enzyme system. Toxic levels of 

free fluoride produce a high output, vasopressin-resistant 

form of acute renal failure. 45 This disorder was first 

reported with methoxyflurane in 1966. 

The only inhalation agents used today that can produce 

enough fluoride to be of concern are enflurane, isoflurane, 

and sevoflurane. 46–48 The threshold fluoride level for 

causing mild defects in renal concentrating ability is 

50 µmol/L. 49 Experiments with cultured collecting duct 

cells indicate mitochondria may be the target of the free 

fluoride ion. 50 

Whether fluoride toxicity results from the use of 

modern inhalational anesthetics is in doubt. Concern surrounded 

the use of sevoflurane because about 5% of it is 

metabolized by the cytochrome P-450 2E1 isoform. 51 Of 

that, 3.5% appears in the urine as free fluoride ion. 52 This 

is less than the fluoride production from methoxyflurane 

metabolism but more than that seen with either enflurane 

or isoflurane. 

The likelihood of fluoride toxicity has been questioned 

because fluoride levels in excess of 50 µg/L were reached 

in studies comparing sevoflurane and enflurane administration 

in humans, yet they did not demonstrate nephrotoxicity. 

53 The mean fluoride level in patients receiving 

sevoflurane was 47 µmol/L, twice the 23 µmol/L level in 

Figure 17-10. The relationship between serum creatinine and 

creatinine clearance by age. The glomerular filtration rate 

(GFR) decreases in the majority of individuals after age 30 but 

a decline in GFR is not inevitable. The graphs are standardized 

for a 70-kg male with values calculated using the Cockroft- 

Gault formula. (Data from Hughes et al. 35 )


patients that received prolonged enflurane anesthesia. 

More than 40% of subjects having prolonged sevoflurane 

anesthesia had plasma fluoride levels greater than 

50 µmol/L, with no impairment of renal concentrating 

ability. The results of this study should be cautiously 

extrapolated to the elderly because it included only young 

volunteers in their mid-twenties. 54 Neither enflurane nor 

halothane produced a further decrease of renal function 

in patients with moderate renal insufficiency. 55 At this 

time, enflurane is infrequently used for general anesthesia. 

There are no clinical reports that actively assert that 

enflurane should be avoided in elderly patients with renal 

insufficiency. 

A toxic fluoride threshold more likely will be met with 

prolonged exposure to isoflurane than halothane. The 

peak plasma level of fluoride occurs 24 hours after an 

average 10-hour administration of isoflurane. This is 

equivalent to 19.2 MAC hours of isoflurane exposure. 

With this level of exposure, 40% of patients studied had 

fluoride levels slightly greater than 50 µmol/L. In contrast, 

similar exposure to halothane produced lower fluoride 

levels with the highest plasma levels occurring at the end 

of the surgical cases. Among elderly patients with renal 

insufficiency, no further deterioration of renal function 

resulted with the use of isoflurane, enflurane, or sevoflurane 

anesthesia. 56 Desflurane poses very little risk to 

patients with renal insufficiency because so very little of 

it is metabolized. 57 

Sevoflurane breaks down in the alkaline environment 

of the carbon dioxide absorber to form fluoromethyl-2,2- 

difluoro-1-(trifluoromethyl)vinyl ether, or Compound A. 

This happens particularly at low total gas flows. Similar to 

free fluoride ion, compound A is also nephrotoxic. The 

production of Compound A is increased with greater production 

and absorption of carbon dioxide because 

the degradation of sevoflurane increases with absorber 

temperature. 58–60 The combination favoring production of 

Compound A includes not only increased CO 2 absorption 

but also absorber temperature, decreased CO 2 washout, 

and high levels of sevoflurane. 23,61,62 Compound A is clearly 

nephrotoxic in the laboratory, but it is not certain whether 

any instances of renal failure occurred from using sevoflurane. 

In patients with normal renal function and ranging 

in age from 30 to 69 years, Compound A accumulated 

during anesthesia with 1 LPM gas flows. Yet, there was no 

difference detected in clinical or biochemical markers of 

renal function when those patients were compared with 

subjects receiving isoflurane anesthesia. 63 Compound A 

does not accumulate in breathing circuits or carbon 

dioxide absorbers when gas flows are 5 L/min, but because 

of the potential for Compound A formation, sevoflurane 

is not recommended for use at less than 2 LPM fresh gas 

flow. 64 Nevertheless, no differences in biochemical markers 

were noted among patients receiving sevoflurane at lowflow 

(1 L/min), high-flow (5–6 L/min), or low-flow isoflurane 

anesthesia, and no evidence of renal toxicity exists. 65 

Furthermore, in older patients with moderately impaired 

renal function, sevoflurane anesthesia does not cause 

apparent injury to the renal tubules, 66 and low-flow anesthesia 

with sevoflurane does not result in any greater 

change in blood urea nitrogen, creatinine, or creatinine 

clearance than isoflurane. 67 

Influence of Hepatic Changes 

There is a similar atrophy of the liver that is accompanied 

by a reduction in hepatic blood flow. 68–70 Decreased 

hepatic blood flow results in diminished metabolism of 

drugs that rely on hepatic clearance. The decrease in 

hepatic blood flow seems responsible for the decreased 

hepatic metabolism of drugs and not changes in hepatic 

enzyme activity. 71 

The newer inhalational agents are not extensively 

metabolized. Of all the volatile agents, halothane is the 

most extensively transformed with approximately 20% of 

it metabolized in the liver. 72 The other agents in common 

use are metabolized to a much lesser extent. Approximately 

5% of sevoflurane, 2.4% of enflurane, 0.2% of 

isoflurane, and 0.02% of desflurane are metabolized 16,73–75 

(Table 17-1). Metabolism of halothane, isoflurane, and 

desflurane produces trifluoroacetic acid. The amount of 

this metabolite produced is lowest with desflurane. 72,76–79 

The hepatic-function changes associated with aging 

are probably important only for halothane and sevoflurane 

because the other agents undergo only minimal 

transformation. The loss of hepatic tissue with age may 

be associated with decreased metabolism of the volatile 

agents, but this is not documented. If decreased metabolism 

of these drugs occurs, it is probably not clinically 

significant. 

Volatile anesthetic agents have a variable effect on 

liver function. Sevoflurane decreases production of fibrinogen, 

transferrin, and albumin in cultured hepatocytes 

more than exposure to halothane, isoflurane, or enflurane 

does. 80 However, enflurane causes greater depression of 

albumin synthesis than sevoflurane. The effects of desflurane 

on hepatic synthesis are not known. It is not anticipated 

that it would have much effect because so little of 

it is metabolized. 81 

Many drugs bind to plasma proteins, and several intravenous 

anesthetic drugs are carried in the blood bound 

to plasma proteins. Albumin is a carrier for many drugs, 

and low blood concentrations of albumin are frequently 

encountered in elderly patients. This probably contributes 

to the exaggerated effects of many drugs in older 

subjects because of the greater fraction of unbound free 

drug. There is no evidence suggesting that volatile agents 

rely on protein binding for transport or that the increased 

sensitivity to volatile anesthetics works through this 

mechanism.


The Pharmacodynamics of Inhalational 

Agents in the Elderly 

The introduction of halogenated ethers with progressively 

lower solubility characterizes the era of modern 

agents. As the solubility of newer agents approaches that 

of nitrous oxide, the result is a more rapid uptake and 

faster elimination of the drug. Theoretically, low solubility 

and faster uptake also allow greater control of anesthetic 

blood levels during the maintenance phase of anesthesia. 

Faster elimination with low-solubility agents should 

provide for a rapid emergence from anesthesia. Inhalational 

agents used for general anesthesia include isoflurane, 

sevoflurane, desflurane, halothane, and enflurane. 

For practical purposes, the first three warrant most consideration 

because they represent the majority of volatile 

agents used. The properties of the inhalational agents are 

found in Table 17-1. 

Aging and the Minimal Alveolar 

Concentration 

The classic expression of pharmacodynamic effect for volatile 

anesthetic agents is the MAC. MAC is the minimal 

alveolar concentration of a volatile drug at 1 atm that prevents 

movement in 50% of subjects following surgical incision. 

82 The concentrations of volatile agents defined by 

MAC values are usually not enough for adequate anesthesia 

during surgical cases. Frequently, about 1.3 times MAC, 

or essentially an ED 95 dose of anesthetic, is needed. 83 

For adult subjects, the MAC is 1.15% for isoflurane, 6% 

for desflurane, and 1.85% for sevoflurane. As patients 

age, MAC decreases for all the volatile drugs, generally 

occurring at approximately 6% per decade. 84 The decrease 

in drug requirement does not follow a linear relationship 

but accelerates after 40–50 years of age. This phenomenon 

also applies to intravenous anesthetic drugs in which 

the pharmacokinetics of injected drugs changes substantially 

with age. 85 Guedel 86 was the first to note that inhalational 

anesthetic requirements decrease with age. This 

has subsequently been documented for halothane, 87 isoflurane, 

88 enflurane, desflurane, 89,90 and sevoflurane. 91 The 

mathematic relationship of MAC, age, end-expired concentration 

of anesthetic agent, and the contribution by 

nitrous oxide has been determined. 92 A nomogram for 

estimating age-related changes in MAC is available 

(Figure 17-11). 

Martin et al. 93 reviewed the use of the most common 

anesthetic drug combinations for general anesthesia. 

Age (yr) 

100 

90 

80 

70 

60 

50 

40 

30 

20 

10 

1 

Sevoflurane in 87% nitrous oxide for a 3-yr-old 

© JGC lerou, 2003 

Total MAC 

(MAC units) 

1.8 

1.6 

1.4 

1.2 

1.0 

0.8 

Turning axis 

0.6 

0.4 

0.2 

Sevoflurane 

Enflurane 

Desflurane 

Isoflurane 

Halothane 

0% 50% 67% nitrous oxide 

End-expired concentration (% atm) 

Desflurane Other agents 

0.0 

20 19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 

0.2 

0.4 

0.6 

0.8 

1.0 

1.2 

1.4 

1.6 

1.8 

2.0 

2.2 

2.4 

2.6 

2.8 

3.0 

3.2 

3.4 

3.6 

3.8 

4.0 

End-expired concentration of halothane, isoflurane, 

enflurane or sevoflurane 

Figure 17-11. Nomogram relating age, total minimal alveolar 

concentration (MAC) expressed in MAC units, and end-expiratory 

concentrations of volatile agent and nitrous oxide. A result 

is found by drawing two straight lines. Example (dotted lines): 

if the measured end-expired concentrations of sevoflurane and 

nitrous oxide are 1.8% and 67% (at 1 atm), respectively, then 

the total age-related MAC is 1.3 in a 3-year-old. Reverse 

example: a total MAC of 1.3 in a 3-year-old, when using sevoflurane 

and nitrous oxide 67% in oxygen, requires an endexpired 

sevoflurane concentration of 1.8%. (Reprinted with 

permission from Lerou. 92 )


Isoflurane 

Residual 

0.02 

0.00 

–0.02 

–0.04 

–0.06 

–0.08 

–0.10 

–0.12 

30 40 50 60 70 80 

Age 

Group 

IFNPM 

IFNT 

IFNTM 

Figure 17-12. The trend in reduction of isoflurane concentration 

with age. Compared with maximum values at age 30, there 

is an 11%–16% reduction in isoflurane requirement by age 80. 

IFNTM, isoflurane, fentanyl, nitrous oxide, thiopental, midazolam; 

IFNPM, isoflurane, fentanyl, nitrous oxide, propofol, 

midazolam; IFNT, isoflurane, fentanyl, nitrous oxide, thiopental. 

(Reprinted with permission from Martin et al. 93 ) 

When controlling for the synergistic interaction of intravenous 

and inhalational agents, the authors demonstrated 

a decrease in drug requirements for 80-year-old patients. 

The decrease was not the same for drugs of different 

classes. The utilization of intravenous drugs decreased 

30%–50%, whereas the requirement for isoflurane 

decreased only 11%–26% (Figure 17-12). Although older 

patients do not require as much anesthetic drug, there is 

little known that explains the decreased requirement of 

inhalational anesthetics. 

MAC is a value that provides a way to compare 

the potency of inhalational anesthetic agents on a specific 

endpoint. Depth of anesthesia is one endpoint of interest. 

Other endpoints have received less attention in the aged 

patient. This is generally one third the MAC value except 

in the case of halothane, for which MAC awake is 0.55 MAC. 

MAC awake decreases with age. 94 The MAC-BAR is the 

MAC of agent that inhibits a sympathetic nervous system 

response such as tachycardia or hypertension when subjects 

are stimulated. It is expressed as a multiple of the 

MAC (Table 17-4). However, there is no information on 

the concentration of volatile agent needed to attenuate 

autonomic reflexes (MAC-BAR) with increasing age. 

There are several possible explanations of how 

age decreases the inhalational anesthetic requirements. 

Several changes contribute to this change: an increase in 

body fat; reductions in metabolism, reduced cardiac 

output, decreased drug clearance; and atrophy of organ 

systems, particularly the central nervous system. 95 A combination 

of factors probably accounts for the decreased 

dose of hypnotic drugs needed for loss of consciousness 

and shifting the electroencephalogram pattern. 96–98 Several 

factors associated with increasing and decreasing MAC 

are listed in Tables 17-5 and 17-6. Factors not associated 

with a change in MAC are listed in Table 17-7. 

Drugs frequently used in the elderly influence the 

effective dose of volatile agents. These include calcium 

channel blockers 99 and clonidine. 100 Some drugs may 

affect MAC by depletion of neurotransmitters. 101,102 Benzodiazepines 

and opioids have an additive effect with 

volatile anesthetic agents. 43 

Slow emergence and prolonged sedation in the recovery 

room are usually regarded as detrimental for elderly 

patients. Postoperative sedation occurs in approximately 

10% of elderly general surgery patients. Among elderly 

patients, the incidence of postoperative sedation after 

general anesthesia can be as high as 61% for those having 

emergency surgery. Intraoperative hypotension and anesthetic 

drugs contribute to postoperative sedation and 

longer hospitalization. 103 

The physical properties of the inhalational anesthetics 

contribute to the speed of action and resolution of these 

Table 17-4. Clinical properties of volatile anesthetic agents in routine use. 

MAC [atm, (%)] at various ages* 

MAC‡§ 

2–5 years† 36–49 years† 65 years† MAC awake MAC awake /MAC MAC-BAR 

N 2 O 1.04 0.68 0.64 — 

Halothane 0.0041 0.55 1.3 

Isoflurane 0.0160 (1.6) 0.0115 (1.15) 0.0105 (1.05) 0.0049 0.38 1.3 

Desflurane 0.0854 (8.54) 0.0600 (6) 0.0517 (5.17) 0.025 0.34 1.45 

Sevoflurane 0.0250 (2.5) 0.0185 (1.85) 0.0177 (1.77) 0.0062 0.34 2.24 

MAC = minimal alveolar concentration. 

*Data from Eger EI II, Eisenkraft JB, Weiskopf RB. The Pharmacology of Inhaled Anesthetics. Dannemiller Memorial Educational Foundation; 

2002:7–19. 

†Volatile agent delivered in oxygen without nitrous oxide. 

‡Values for subjects aged 20–60 years. 

§Data from Stevens WC, Kingston HCG. Inhalation anesthesia. In: Barash PG, et al. Clinical Anesthesia. 3rd ed. Philadelphia: Lippincott-Raven; 

1997:359–383.


Table 17-5. Factors that increase minimal alveolar concentr - 

ation. 

Increased central neurotransmitters 

• Monoamine oxidase inhibitors 

• Acute dextroamphetamine use 

• Cocaine ingestion 

• Ephedrine 

• Levodopa 

Hyperthermia 

Chronic ethanol abuse 

Hypernatremia 

Source: Modified with permission from Ebert TJ, Schmid PG. Inhalation 

anesthesia. In: Barash PG, Cullen BF, Stoelting RK, eds. Clinical 

Anesthesia. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 

1997:389. 

drugs. The blood level of agents with low blood/gas 

and blood/lipid solubility changes rapidly in response to 

varying the administered dose. At the conclusion of 

general anesthesia, the resolution of the hypnotic effect 

resolves faster with these agents. Faster emergence from 

general anesthesia is an important way to minimize postoperative 

complications in the elderly. Reports indicate 

faster emergence from anesthesia and shorter time spent 

in the PACU with desflurane. 29 

Table 17-6. Factors that decrease minimal alveolar 

concentration. 

Metabolic acidosis 

Hypoxia (PaO 2 < 38 mm Hg) 

Hypotension (mean arterial pressure < 50 mm Hg) 

Decreased central neurotransmitters (alpha methyldopa, reserpine, 

chronic dextroamphetamine use, levodopa) 

Clonidine 

Hypothermia 

Hyponatremia 

Lithium 

Hypoosmolality 

Pregnancy 

Acute ethanol use 

Ketamine 

Pancuronium 

Physostigmine (10 times clinical doses) 

Neostigmine (10 times clinical doses) 

Lidocaine 

Opioids 

Opioid agonist-antagonist analgesics 

Barbiturates 

Chlorpromazine 

Diazepam 

Hydroxyzine 

∆-9-Tetrahydrocannabinol 

Verapamil 

Source: Modified with permission from Ebert TJ, Schmid PG. Inhalation 

anesthesia. In: Barash PG, Cullen BF, Stoelting RK, eds. Clinical 

Anesthesia. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 

1997:389. 

Table 17-7. Factors that do not reduce minimal alveolar 

concentration. 

Duration of anesthesia 

Type of stimulation 

Gender 

Hypocarbia (Paco 2 to 21 mm Hg) 

Hypercarbia (Paco 2 to 95 mm Hg) 

Metabolic alkalosis 

Hyperoxia 

Isovolemic anemia (hematocrit to 10%) 

Arterial hypertension 

Thyroid function 

Magnesium 

Hyperkalemia 

Hyperosmolality 

Propranolol 

Isoproterenol 

Promethazine 

Naloxone 

Aminophylline 

Source: Modified with permission from Stevens WC, Kingston HG. 

Inhalational anesthesia. In: Barash PG, ed. Clinical Anesthesia. 

Philadelphia: JB Lippincott; 1992:443.) 

Cardiovascular Actions of Inhalational Agents 


The elderly patient’s heart and vascular system are 

anatomically and functionally different from younger 

patients. The most striking are a decrease in the maximum 

heart rate response to exercise, decreased sensitivity 

to catecholamines, increased pulmonary artery, and left 

ventricular diastolic filling pressures. 104–107 Determining 

whether these changes are a direct result of aging and if 

they can be modified are current issues. Both mechanisms 

of aging in the cardiovascular system and lifestyle 

undoubtedly have a role in these changes. 108 

The physiologic response of elderly patients during 

anesthesia must be evaluated carefully because impressions 

about how elderly patients will respond may be 

incorrect. For example, Joris et al. 109 found that cardiac 

index decreases significantly in young patients when 

abdominal insufflation impairs venous return to the right 

side of the heart. Because cardiovascular changes inevitably 

occur with age, it is reasonable to expect greater 

hemodynamic changes in elderly patients. However, the 

response of elderly patients may be better than expected. 

In patients over age 75 years, the cardiac function 

decreased with induction of general anesthesia with 

isoflurane and nitrous oxide. But during laparoscopic 

cholecystectomy, the cardiac performance increased and 

blood pressure returned to preanesthetic levels with the 

onset of surgery. Surprisingly, elderly patients tolerated 

the decreased preload and increased afterload from 

abdominal insufflation rather well. 110 

Hemodynamic changes during general anesthesia in 

sicker American Society of Anesthesiologists (ASA)


physical status 3 and 4 patients are similar to changes 

in healthier ASA 1 and 2 patients. 111–117 Inhalation 

anesthesia produces a dose-dependent decrease in 

blood pressure and depression of the cardiovascular 

system. 118–121 Volatile anesthetics reduce blood pressure 

by reducing cardiac output and vasodilatation. 

Inhalation anesthetics affect cardiac systolic function. 

Depression of myocardial contractility in the elderly 

varies with the inhalational agent. Isoflurane does 

not maintain the cardiac output in older patients as 

it does in younger individuals during anesthesia. 120 

The addition of nitrous oxide to isoflurane helps maintain 

the cardiac index; however, its ability to maintain 

myocardial contractility is inconsistent. There are reports 

suggesting nitrous oxide both helps maintain 122 and 

depresses 123 myocardial contractility when combined with 

halothane. 

Inhalational anesthetics also affect diastolic function. 

Myocardial relaxation has two components: an energydependent 

active component and a passive component, 

influenced by myocardial stiffness. In patients over the 

age of 60, halothane and isoflurane decrease the early, 

energy-dependent component of left ventricle relaxation, 

and the effect is greater with isoflurane. 124 

The cardiac status of the elderly patient is a significant 

factor in determining the response to inhalational anesthetics. 

For instance, healthy elderly surgical patients with 

well-controlled hypertension tolerate inhalational induction 

of general anesthesia with sevoflurane. Whether 

receiving sevoflurane as a rapidly delivered bolus (8% for 

3 minutes) or in a graded manner (8% initially with 2% 

incremental decreases until reaching 2%), patients with 

good pump function tolerate the induction with no change 

in heart rate, no electrocardiographic evidence of ischemia, 

and moderate decreases in blood pressure. The 

decrease in blood pressure when using incremental 

decreases of sevoflurane compared with maintaining the 

same concentration throughout the induction was less 

than that encountered when using low-dose sevoflurane 

and propofol in combination. 125 

Blood pressure decreases significantly with the ad - 

ministration of inhalational anesthetics to patients with 

diminished cardiac function. 126 In patients with congestive 

heart failure, blood pressure and cardiac index 

decrease during isoflurane anesthesia. The decrease is 

greater with halothane in those patients with poor left 

ventricle function. 127 The catecholamine blocking effect 

of the inhalational agents may have a role in the hypotension 

encountered in these settings. 

The inhalational anesthetics have a variable effect on 

heart rate. Isoflurane decreases systemic blood pressure 

in both young and old subjects. However, isoflurane 

decreases the cardiac index and heart rate in elderly subjects 

whereas it increases the heart rate and leaves the 

cardiac index unchanged in young individuals. Thus, isoflurane 

seems to maintain the cardiac index in younger 

patients through increases in heart rate whereas this does 

not happen in older patients. Sevoflurane produces a 

dose-dependent increase in heart rate when given to 

normal, healthy volunteers. 128 In contrast, the heart rate 

shows no significant change during induction with either 

4% or 8% sevoflurane. 129 Halothane and enflurane have 

little effect on heart rate in elderly patients. 130 There is no 

difference in the heart rate during the initial period after 

induction of anesthesia when using halothane. With isoflurane 

anesthesia, elderly patients have a lower heart 

rate compared with younger subjects. 120,131 

Inhalational anesthetics also influence the cardiovascular 

system indirectly through actions on the autonomic 

nervous system. Rapid increases above 1 MAC in 

the inspired concentration of isoflurane and desflurane 

trigger transient sympathetic stimulation. There is a 

brief period of hypertension and tachycardia that is more 

pronounced with desflurane. 33 This action is apparently 

mediated through rapidly adapting airway receptors. 

Fentanyl and alpha- and beta-adrenergic blocking drugs 

easily block the effect. 132,133 Although this phenomenon 

was studied in subjects in their early twenties, elderly 

patients have a higher state of sympathetic nervous 

system activity and it is likely this action may be more 

pronounced. 

Inhalational anesthetics may have a delayed inhibition 

of hemodynamic control. Patients having a carotid endarterectomy 

with isoflurane anesthesia required more 

phenylephrine for blood pressure support and needed 

more labetalol during emergence to manage hypertension 

than did patients receiving propofol for general 

anesthesia. More significantly, although there was no difference 

in hemodynamic stability between patients anesthetized 

with isoflurane or propofol, patients anesthetized 

with isoflurane experienced significantly more frequent 

myocardial ischemia. 134 

Volatile anesthetics typically cause peripheral vasodilatation. 

The expected consequence is greater blood 

flow if cardiac output can be maintained or increased. 

However, there is a distinct, age-related difference in 

peripheral blood flow between young (18–34 years) 

and healthy elderly (60–79 years) subjects during the 

induction of general anesthesia. When receiving either 

isoflurane or halothane in combination with 66% nitrous 

oxide, there is a slight difference in changes of heart rate 

or mean blood pressure between the age groups. The 

perfusion of skin and muscle, assessed by forearm 

blood flow, decreases along with the mean arterial blood 

pressure during anesthesia with halothane, and there 

is no age-related difference. However, with isoflurane 

anesthesia, the peripheral perfusion is maintained in 

young patients even though the blood pressure de - 

creases whereas the perfusion decreases in the elderly 

(Figure 17-13). 135


Heart rate during induction of anesthesia, isoflurane 

plus 66% nitrous oxide 

120 

Heart rate during induction of anesthesia, halothane 

plus 66% nitrous oxide 

120 

Heart rate (beats/min) 

100 

80 

60 

40 

20 

Heart rate (beats/min) 

100 

80 

60 

40 

20 

0 

Awake Ind + 1 Intub + 

1 

Agnt + 

5 

Agnt + 

10 

Agnt + 

15 

Agnt + 

20 

0 


1 

Agnt + 

5 

Agnt + 

10 

Agnt + 

15 

Agnt + 

20 

Mean arterial blood pressure during induction of 

anesthesia, isoflurane plus 66% nitrous oxide 

Mean arterial blood pressure during induction of 

anesthesia, halothane plus 66% nitrous oxide 

160 

160 

Mean arterial BP (mm Hg) 

140 

120 

100 

80 

60 

40 

20 

Mean arterial BP (mm Hg) 

140 

120 

100 

80 

60 

40 

20 

0 

Awake Ind + 1 Intub + Agnt + Agnt + 

1 5 10 

Agnt + 

15 

Agnt + 

20 

0 


1 

Agnt + Agnt + 

5 10 

Agnt + 

15 

Agnt + 

20 

Forearm blood flow during induction of anesthesia, 

isoflurane plus 66% nitrous oxide 

Forearm blood flow during induction of 

anesthesia, halothane plus 66% nitrous oxide 

6 

6 

FBF (ml blood/100 ml tissue/min) 

5 

4 

3 

2 

1 

FBF (ml blood/ 100 ml tissue/min) 

5 

4 

3 

2 

1 

0 


1 

Agnt + 

5 

Agnt + 

10 

Agnt + 

15 

Agnt + 

20 

0 

Awake Ind + 1 Intub + Agnt + 5 Agnt + 

1 

10 

Agnt + 

15 

Agnt + 

20 

Figure 17-13. Heart rate, mean arterial blood pressure, and 

forearm blood flow measured following the induction of general 

anesthesia in healthy young and elderly subjects. Patients 

received isoflurane (0.8%–1.2%) or halothane (0.7%–1.0%) and 

nitrous oxide (66%) after induction with etomidate and endotracheal 

intubation. Little difference in the change of heart rate 

or blood pressure was found between subject groups. Forearm 

blood flow decreased in older and younger patients receiving 

halothane whereas it was much greater in young patients receiving 

iso flurane. Mean values are shown. Light gray bars = young 

(18–34 years), dark gray bars = elderly (60–79 years). Time units 

are in minutes. (Data from Dwyer and Howe. 135 )


Summary 

Much of the clinical literature on inhalational anesthetic 

agents during the past decade focused on trying to demonstrate 

the superiority of one agent over another. The 

clinical issue is not that one agent is clearly better than 

another in all instances. Each agent can control the 

response to surgical stimulation during general anesthesia. 

The issues that matter are which drug is best, given 

the particular disease or pathophysiology of the patient, 

and to what degree do we suppress consciousness 

and autonomic responses. The growing interest in the 

relationship of depth of anesthesia to long-term survival 

raises the possibility that we should use cardiovascular 

drugs as adjuncts to control heart rate and blood 

pressure. 

Because of the limited number of publications describing 

how age affects anesthesia, extracting age-related 

data from studies that compare intravenous and in - 

halational agents is useful. In reviewing the anesthesia 

literature of the past decade, it is apparent there is a 

growing interest in the relationship between aging and 

general anesthesia. However, the limited knowledge 

regarding the influence age has on anesthesia is a cause 

for concern. 

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18 

Relaxants and Their Reversal Agents 

Cynthia A. Lien and Takahiro Suzuki 

Whether or not to maintain neuromuscular block in 

patients, young or elderly, is very much a matter of debate 1 

and is influenced by the type of anesthesia administered 

as well as the planned surgical procedure. Once the decision 

is made to administer a nondepolarizing neuromuscular 

blocking agent to an elderly patient, special 

consideration must be given to the potential for altered 

pharmacologic behavior in this patient population. 

A number of factors that accompany aging may affect 

the effect of nondepolarizing neuromuscular blocking 

agents in the geriatric patient. Because of skeletal muscle 

denervation, geriatric patients have a decrease in generalized 

muscle strength and coordination. Many alterations 

in the neuromuscular junction accompany aging. Additionally, 

decreased total body fluid and lean body mass, 

as well as decreased kidney function, cardiac output, and 

splanchnic blood flow may all affect the pharmacodynamics 

and kinetics of neuromuscular blocking agents. 

An increasing geriatric surgical population, coupled 

with constantly changing surgical trends and practices, 

mandates that nondepolarizing neuromuscular blocking 

agents, as well as anesthetics, are chosen based on 

their specific pharmacodynamic characteristics in aged 

patients. 

Changes in the Structure of the 

Neuromuscular Junction 

In people over the age of 60 years, the neuromuscular 

junction in skeletal muscle undergoes continuous degeneration 

and regeneration. The reorganization is primarily 

mediated through a reduction in the number of motor 

neurons in the spinal cord 2 and the ventral root fibers. 3 

Moreover, the number of motor units composed of a 

motor neuron and the innervated muscle fibers seems to 

decrease with aging. Because reinnervation does not 

compensate for the progressive neurogenic process, 

muscle fibers degenerate and are subsequently replaced 

with fat and fibrous tissue. A 25%–35% decrease in 

muscle mass is typically seen in the elderly 4 and is considered 

to be the result of both a loss of muscle fibers as 

well as a reduction in size of primarily type 2, or fasttwitch, 

fibers. 5 This is accompanied by a 50%–75% 

increase in body fat. 6 The loss of motor units is offset by 

an increase in the size of the motor unit. Because of this, 

an augmented twitch tension is evoked by stimulating a 

single motor nerve 7 in the aged. 

Aging is accompanied by many structural changes at 

the neuromuscular junction. Preterminal axons are 

increased in number and a greater number of the axons 

enter into a single endplate. The distance between the 

preterminal axon and the motor endplate is increased. 

The motor endplate is composed of a greater number of 

smaller conglomerates of nicotinic acetylcholine receptors 

and is lengthened with increasing age. This is accompanied 

by a flattening of the folds of the endplate at the 

neuromuscular junction. 8 

Alterations in muscle anatomy and physiology extend 

beyond the neuromuscular junction in that extrajunctional 

acetylcholine receptors are frequently found in 

aged muscles. 9 This may be the result of a progressive 

denervation that accompanies aging. How these changes 

in the neuromuscular junction influence neuromuscular 

transmission in the elderly is not known. Proliferation of 

acetylcholine receptors, as is observed in disuse atrophy, 

leads to a relative resistance to neuromuscular blocking 

agents. 10 Elderly patients, however, are not resistant to 

the effects of neuromuscular blocking agents. 

In animal experiments, age-related changes in acetylcholine 

storage and release at the neuromuscular junction 

have been found. In the neuromuscular junction of 

the diaphragm of aged rats, the acetylcholine content of 

a single motor nerve terminal is lower than that found in 

young adult rats. However, in these neuromuscular junctions, 

increased numbers of nerve terminals per endplate 

caused by terminal arborization contribute to the release 

266

18. Relaxants and Their Reversal Agents 267 

of greater amounts of acetylcholine for each endplate. 11 

This alteration in transmitter release is likely responsible 

for maintenance of normal neuromuscular transmission 

in the aged rats. Overall, however, advanced age is associated 

with a decrease in the amount of acetylcholine 

released. 8 

Despite all of the changes at the neuromuscular junction, 

changes in the pharmacodynamic behavior of the 

nondepolarizing neuromuscular blocking agents seem to 

be the result of alterations in their pharmacokinetics 

rather than altered interaction of the nondepolarizing 

compound and the motor endplate. 

Dose-Response Relationships 


As the elderly become more sedentary and lose muscle 

mass, one would expect that there would be an upregulation 

of acetylcholine receptors, as is seen with denervation. 

12 These physiologic changes would be expected to 

contribute to a relative resistance to neuromuscular 

blockers. With the decrease in lean body mass 13 and 

volume of distribution 14 that accompany aging, one would 

also expect that the dose required to establish neuromuscular 

block in geriatric patients would be less that that 

required in younger patients. Nondepolarizing neuromuscular 

blocking compounds are bulky, highly charged 

compounds that do not readily leave the central volume. 

This has been confirmed in elderly patients receiving 

either d-tubocurarine or metocurine. 15 Patients, young 

and elderly, received a single intravenous dose of the 

study compound and elderly patients were found to have 

both a decreased initial volume of distribution and volume 

of distribution. Results, with respect to volumes of distribution 

of other nondepolarizing compounds, however, 

are not consistent. Pharmacokinetic study of the 

intermediate-acting agent, vecuronium, in patients over 

the age of 70 years demonstrated that both the initial 

volume of distribution and the volume of distribution 

after a single intravenous dose of 0.1 mg/kg were indistinguishable 

from what was found in younger patients. 16 

The decrease in plasma proteins in the elderly would 

argue that bioavailability of drugs would be increased as 

less would be bound to proteins. However, nondepolarizing 

neuromuscular blocking agents are not highly 

protein bound 17 and the available free fractions of long-, 

intermediate-, and short-acting compounds have been 

shown, in vitro, to be the same in elderly and young 

adults. 18 

With the structural changes in the neuromuscular junction, 

already described in this chapter, it would not be 

unreasonable to expect that sensitivity to nondepolarizing 

compounds would be increased. This, however, has 

Figure 18-1. The relationship between plasma metocurine 

(o-o) and d-tubocurarine (-) in young and elderly patients 

and their depth of neuromuscular block. Values for the young 

are represented by the unfilled symbols (o and ) and those for 

the elderly by the filled symbols (• and ). Differences between 

the young and elderly are not significant for either of the neuromuscular 

blocking agents. (Adapted with permission from 

Matteo et al. 15 Copyright © Lippincott Williams & Wilkins.) 

not been found to be true. Duvaldestin 19 found that, in 

the case of the long-acting nondepolarizing compound 

pancuronium, there was no difference in the plasma 

concentration–response relationships in young and 

elderly patients. Similarly, both metocurine and d- 

tubocurarine have no difference between the plasma concentration–response 

relationships of the elderly and the 

young adult patients (Figure 18-1). 15 Similar results have 

been documented with the intermediate-acting nondepolarizing 

agents. Rupp et al. 20 found that the steady-state 

concentration of vecuronium at 50% neuromuscular 

block was the same in elderly and young adult patients. 

These results indicate that at the same plasma concentration 

of relaxant, elderly and young patients have the same 

degree of neuromuscular blockade, and sensitivity of the 

acetylcholine receptor is, therefore, not increased in geriatric 

patients. 

Although alterations in pharmacokinetics influence 

the onset of effect and duration of action, the dose of re - 

laxant that will generally produce 95% neuromuscular 

block is the same in elderly and young adults. This 

has been shown for the long-acting compounds pancuronium, 

19 pipecuronium, 21 and doxacurium 22 as well 

as the intermediate-acting compounds vecuronium, 23 

rocuronium, 24 and atracurium. 25

268 C.A. Lien and T. Suzuki 

Table 18-1. Onset of maximal block in young and elderly patients following administration of nondepolarizing neuromuscular 

blocking agents. 

Onset (minutes) 

Reference Neuromuscular blocking agent Dose (mg ⋅ kg −1 ) Elderly patients Young adult patients 

26 Succinylcholine 1 1.58 [0.12] 1.18 [0.13] 

Short-acting nondepolarizing neuromuscular blocking agents 

52 Mivacurium 0.15 2.03 (0.53) 2.08 (0.82) 

Intermediate-acting nondepolarizing neuromuscular blocking agents 

26 Vecuronium 0.1 4.92 [0.52] 3.70 [0.23] 

59 0.1 3.52 (1.11) 2.57 (0.66)* 

42 Rocuronium 0.6 4.5 (2.4) 4.1 (1.5) 

43 1.0 1.33 (0.43) 1.04 (0.21)* 

26 Cisatracurium 0.1 4.0 3.0* 

50 0.1 3.4 (1.0) 2.5 (0.6)* 

Long-acting nondepolarizing neuromuscular blocking agents 

21 Pipecuronium 0.07 6.9 (2.6) 4.5 (1.5)* 

22 Doxacurium 0.025 11.2 (1.1) 7.7 (1.0)* 

Note: Data are mean (SD) or [SEM]. 

*Statistically significant difference when compared with elderly patients. 

Onset of Neuromuscular Block 

For nondepolarizing neuromuscular blocking agents to 

exert their effect, they must be carried to the neuromuscular 

junction. The rate at which this is done is influenced 

by a number of factors including circulation to the muscles, 

and cardiac output. Once the nondepolarizing muscle 

relaxant arrives at the muscle, it needs to diffuse into the 

neuromuscular junction and bind with the acetylcholine 

receptor to cause neuromuscular blockade. In geriatric 

patients, although there are some differences as to the 

extent (Table 18-1), increased age is generally associated 

with a slower onset of neuromuscular block when doses 

of 2×ED 95 (2 times the dose that causes, on average, 95% 

neuromuscular block) or greater are administered. Differences 

in onset are more apparent when doses not 

causing complete neuromuscular block are examined 26 

(Figure 18-2). With administration of these smaller doses 

of nondepolarizing compound, the time to the actual 

maximal effect can be measured. However, administration 

of the larger doses allows only for the determination 

of the time required to achieve 100% neuromuscular 

block. The greater time required for maximal effect may 

be attributable to a decreased cardiac output, although 

physically active, healthy geriatric patients may not have 

a decline in cardiac function. 27 

In a study in patients over the age of 65 years, receiving 

oxygen-nitrous oxide-isoflurane anesthesia, cisatracurium 

(0.1 mg/kg) was administered after induction of 

anesthesia and subsequent boluses of 0.025 mg/kg at 

recovery of twitch height to 25% in order to maintain 

neuromuscular block. 28 The authors found that onset of 

block after the administration of cisatracurium was slower 

in elderly individuals than in young adults (3 versus 4 

minutes, respectively). Pharmacodynamic modeling demonstrated 

that the biophase equilibration in the elderly 

was slower than in young adults (0.06 versus 0.071, respectively). 

The authors attributed the slower onset of neuromuscular 

block to the slower biophase equilibration in 

the elderly. The relative contributions of decreased cardiac 

time (sec) 

700 

600 

500 

400 

300 

200 

100 

Vecuronium 0.03 mg/kg 

1-3 yr 

3-10 yr 

20-40 yr 

60-80 yr 

0 

0 10 20 30 40 50 60 70 80 90 

age (yr) 

Figure 18-2. The onset of maximal neuromuscular blocking 

effect of vecuronium 0.03 mg/kg in four different age groups. 

Onset of maximal effect is faster in the children and slowest in 

the most aged subjects. p < 0.00001 by linear regression. 

(Reprinted with permission from Koscielniak-Nielsen et al. 26 

Copyright © Lippincott Williams & Wilkins.)


output and slower biophase equilibration remain to be 

determined. 

The slower onset of maximal clinical effect of nondepolarizing 

neuromuscular blocking agents in geriatric 

patients may result in relative overdosing of the muscle 

relaxant. Unwillingness to wait for onset of maximal 

effect of a given dose causes clinicians to administer 

either additional medication, or a larger dose at the outset 

to speed onset of block. This results in an increase in 

the duration of action of the drug because a larger 

total amount of drug has been administered. Furthermore, 

in the case of those compounds that are eliminated 

through hepatic and renal mechanisms, these larger doses 

and administration of subsequent doses result in cumulation 

so that each subsequent dose lasts longer than 

the previous one. 29 This occurs because after the initial 

dose of nondepolarizing compounds, such as pancuronium 

and vecuronium, recovery of neuromuscular function 

occurs as a result of distribution to sites other than the 

plasma rather than elimination of the relaxant from the 

body. With subsequent doses, the first dose is entering 

into its elimination phase and reentering the plasma. The 

drug effect, therefore, is a combination not only of the 

recently administered relaxant but also of a portion 

of the earlier dose as both contribute to plasma concentration. 

This effect is more pronounced with the longacting 

pancuronium than with the intermediate-acting 

vecuronium. 

Pharmacokinetics and Duration 

of Effect 

Aging, even in healthy elderly patients, is accompanied 

by decreases in hepatic and renal blood flow and 

function. Because the majority of nondepolarizing neuromuscular 

blocking agents are eliminated through some 

combination of these means, alterations in pharmacokinetics 

and duration of effect are to be expected. Alterations 

in the pharmacodynamics of nondepolarizing 

compounds as a result of changes in the pharmacokinetics 

associated with the normal process of aging may 

be difficult to distinguish from concomitant disease 

processes. 

Long-Acting Agents 

Although there may be some differences in the actual 

percent of drug eliminated through splanchnic and renal 

mechanisms, the long-acting nondepolarizing agents 

depend largely on the kidney for their elimination from 

the plasma (Table 18-2). It is not surprising, therefore, 

that these compounds should have a longer duration of 

action in geriatric patients. As has been found in the 

Table 18-2. Means of elimination of nondepolarizing neuromuscular 

blocking agents from the body. 

Neuromuscular blocking agent 

Means of elimination 

Long-acting compounds 

Pancuronium Kidney 85%, liver 15% 

Pipecuronium Kidney 90%, liver 10% 

Doxacurium Kidney 90%, liver 10% 

d-Tubocurarine Kidney 80%, liver 20% 

Metocurine Kidney 98%, liver 2% 

Intermediate-acting compounds 

Vecuronium Kidney 40%–50%, liver 50%–60% 

Rocuronium Kidney 10%, liver 70% 

Atracurium 

Kidney 10%–40%, Hofmann 

elimination 60%–90% 

Cisatracurium 

Kidney 16%, Hofmann elimination 

>75% 

Short-acting compounds 

Mivacurium 

Kidney 95% 

majority of studies with these agents, their prolonged 

duration of action can be attributed to a prolonged elimination 

half-life and a decreased clearance. 

McLeod et al. 30 demonstrated that the clearance of 

pancuronium decreased with increasing age. In a later 

study, Duvaldestin et al. 19 studied the pharmacokinetics 

and dynamics of pancuronium in young adults and those 

older than 75 years. He found that the 10%–75% and 

25%–75% recovery intervals were prolonged by at least 

60% in the elderly. This could be attributed to a slower 

elimination of pancuronium from the plasma in elderly 

patients (Figure 18-3). Not surprisingly, the clearance of 

pancuronium was decreased from 1.8 in young adults to 

1.2 mL/min/kg in patients of advanced age. Because the 

volume of distribution in the elderly was no different 

from that in younger adults, the decrease in clearance 

resulted in a doubling of the elimination half-life from 

107 to 201 minutes. 

Similar results have been found for metocurine and 

d-tubocurarine. 15 In this study, elderly patients were 

defined as being older than 70 years of age and young 

adults were between 29 and 59 years of age. The elderly 

patients had a significantly prolonged 25%–75% recovery 

interval. This could be attributed to a decreased 

volume of distribution and clearance as well as a markedly 

prolonged elimination half-life for both nondepolarizing 

neuromuscular blocking agents. The study results 

are summarized in Table 18-3. 

Doxacurium, similar to the other long-acting neuromuscular 

blocking agents, is eliminated through the 

kidneys and, in patients with renal failure, its clearance 

is significantly decreased 31 and it has a longer duration 

of action. 32 Not surprisingly, therefore, the clinical duration 

of action 33 and interpatient variability 22 is increased 

in elderly patients. In a pharmacokinetic study of the


Figure 18-3. The elimination of pancuronium from the plasma 

after administration of a bolus dose. Pancuronium disappears 

from the plasma significantly more slowly in elderly patients 

than in middle-aged adults. (Reprinted with permission 

from Duvaldestin et al. 19 Copyright © Lippincott Williams & 

Wilkins.) 

relaxant in elderly patients, however, the drug was found 

to not have a decreased clearance or prolonged elimination 

half-life. 22 This negative result may have been the 

result of differences in intraoperative fluid management 

of the young and elderly patients. The elderly patients 

received 1750 mL of intravenous fluid at the start of 

surgery whereas their younger counterparts received 

1063 mL. In addition, the elderly patients sustained, on 

average, 5 times more blood loss than did the younger 

patients so that total fluid replacement in the elderly was 

almost 6 L, whereas in the young it was 2500 mL. These 

differences would increase calculated volumes of distribution 

and lower the plasma concentration of drug measured 

in the elderly. 

Similarly, pipecuronium has a prolonged duration of 

action and decreased clearance in patients with renal 

failure. 34 Despite this, the age-related decreases in renal 

function do not seem to cause the drug to have a prolonged 

duration of action or a decreased clearance. 21 In 

a study of 20 elderly and 10 young adults receiving nitrous 

oxide, fentanyl and droperidol anesthesia, patients 

received 70 µg/kg pipecuronium as a single intravenous 

bolus. The elderly patients developed, on average, a lesser 

degree of neuromuscular block with this dose than did 

the younger patients (95% versus 100%, respectively). 

Clearance of pipecuronium was the same in both groups 

and differences in elimination half-life (181 versus 154 

minutes in the elderly and young, respectively) were not 

statistically different. 

Intermediate-Acting Agents 

In contrast to the dependence of the long-acting nondepolarizing 

compounds on the kidneys for their elimination, 

the intermediate-acting compounds are eliminated 

from the body primarily through other mechanisms 

(Table 18-2). These include hepatic elimination and 

Hofmann degradation. In addition to decreases in renal 

function and blood flow, aging is associated with decreases 

in hepatic blood flow and hepatocellular function. 35–37 

One would, therefore, expect that compounds relying on 

this means for elimination from the body would have 

Table 18-3. Pharmacokinetics of nondepolarizing neuromuscular blocking agents in geriatric patients. 

Neuromuscular blocking agent Patient age t 1/2 β (minutes) Cl (mL ⋅ kg −1 ⋅ min −1 ) V d (L ⋅ kg −1 ) Reference 

Vecuronium Young 78 ± 21 5.6 ± 3.2 0.49 ± 0.02 16 

Elderly 125 ± 55* 2.6 ± 0.6* 0.44 ± 0.01 

Young 70 ± 20 5.2 ± 0.8 0.24 ± 0.04 20 

Elderly 58 ± 10 3.7 ± 1.0* 0.18 ± 0.03* 

Atracurium Young 15.7 ± 2.5 5.3 ± 0.9 0.10 ± 0.01 46 

Elderly 21.8 ± 3.3* 6.5 ± 1.1 0.19 ± 0.06* 

Cisatracurium Young 21.5 ± 2.4 4.6 ± 0.8 0.11 ± 0.01 50 

Elderly 25.5 ± 3.7* 5.0 ± 0.9 0.13 ± 0.02* 

Pancuronium Young 107 ± 24 1.81 ± 0.36 0.27 ± 0.06 19 

Elderly 201 ± 69* 1.18 ± 0.39* 0.32 ± 0.10 

Pipecuronium Young 154 ± 61 2.5 ± 0.7 0.31 ± 0.07 21 

Elderly 181 ± 68 2.4 ± 1.0 0.39 ± 0.13 

d-Tubocurarine Young 173 ± 38 1.71 ± 0.32 0.42 ± 0.06 15 

Elderly 268 ± 51* 0.79 ± 0.18* 0.28 ± 0.04* 

Metocurine Young 269 ± 56 1.1 ± 0.16 0.45 ± 0.04 15 

Elderly 530 ± 83* 0.36 ± 0.08* 0.23 ± 0.03* 

Doxacurium Young 86 ± 50 2.22 ± 1.09 0.15 ± 0.04 22 

Elderly 96 ± 20 2.47 ± 0.69 0.22 ± 0.08* 

t 1/2 β = half-life of elimination, Cl = plasma clearance, V d = volume of distribution. 

*There is a statistically significant difference compared with younger adults.


altered pharmacokinetics. In contrast, clearance by 

Hofmann elimination is independent of end-organ function 

and aging should have little impact on the pharmacokinetics 

of compounds eliminated primarily by this 

means. 

Vecuronium was the first of the intermediate-acting 

nondepolarizing relaxants to be introduced into clinical 

practice. Although it is eliminated primarily in the bile, 38,39 

20%–25% of the relaxant is eliminated unchanged in the 

urine. Whether or not aging affects the pharmacokinetics 

of vecuronium has been much debated. The action of 

vecuronium in the elderly has been studied by four 

different groups of investigators. 16,20,39,40 d’Hollander 

and colleagues examined the rate of recovery from 

vecuronium-induced neuromuscular blockade in patients 

over the age of 60 years. These recovery rates were compared 

with those in patients under the age of 40 and those 

between 40 and 60 years of age. The 10%–25% and 

25%–75% recovery intervals were significantly prolonged 

in the elderly patients compared with recovery intervals 

in younger patients. Additionally, less vecuronium was 

required to maintain 90% neuromuscular block for a 

period of 90 minutes in the elderly patients than it was in 

the younger controls. 39 McCarthy et al. 40 reported very 

similar results. They found that the duration of action was 

significantly prolonged in the elderly (39 versus 28 

minutes) and the clinical duration of action was prolonged 

as well (69 and 45 minutes, respectively) after a 

bolus of 0.08 mg/kg vecuronium. 

Rupp et al. 20 studied the pharmacokinetics and dynamics 

of vecuronium in elderly patients in whom an infusion 

had been discontinued once 70%–80% neuromuscular 

block had been achieved. In this study, patients older than 

70 years had clearance and volume of distribution for 

vecuronium that were approximately 30% less than was 

found in younger adults. Elimination half-life and the 

25%–75% recovery interval were not, in contrast, different 

from what was found in young adult controls. Lien 

et al. 16 used a different study design to determine the 

kinetics and dynamics of vecuronium in elderly patients. 

In this study, patients received a single intravenous bolus 

dose of vecuronium. Recovery was monitored and venous 

blood taken for determination of pharmacokinetics. 

Elderly patients (between 72 and 86 years of age) had 

5%–25% and 25%–75% recovery intervals that were 

approximately 3 times longer than those in young adults. 

Clearance of vecuronium was half as fast in the elderly 

as it was in young adult patients (2.6 versus 5.6 mL⋅kg −1 , 

respectively) and elimination of the compound was 

slower in geriatric patients (78 and 125 minutes for young 

adult and elderly patients, respectively). The authors’ 

conclusion that the prolonged duration of action of 

vecuronium in elderly patients is attributable to its 

decreased clearance in this patient population supports 

the findings of d’Hollander and colleagues 39 and is 

not inconsistent with the decreased clearance found by 

Rupp et al. 20 

Rocuronium is the other intermediate-acting nondepolarizing 

neuromuscular blocking agent that has a steroidal 

structure. Similar to vecuronium, it does not depend 

on the kidney for its primary means of elimination from 

the body. However, although it does not depend on the 

kidney solely for its elimination, clearance of rocuronium 

is decreased and its mean residence time is prolonged in 

patients with renal failure. 41 As with vecuronium, the 

behavior of this compound in aged patients has been 

studied by different groups of investigators. 24,42,43 In the 

case of rocuronium, however, the results are more similar 

across the studies. Baykara et al. 43 reported that the first 

response in the train-of-four response after administration 

of rocuronium, 1 mg/kg, was slower in the elderly 

than in young adults. Bevan et al. 24 found, in a study of 

repeat bolus doses of rocuronium, that the clinical duration 

of action and the 25%–75% recovery intervals were 

prolonged in elderly patients. With repeated doses of 

0.1 mg/kg rocuronium administered at 25% recovery 

of twitch height, the duration of action became longer in 

the elderly patients but did not in the young adult control 

patients. Matteo et al. 42 studied the pharmacokinetics 

and pharmacodynamics of rocuronium in geriatric 

patients following a 0.6 mg/kg dose and found that in 

patients between the ages of 70 to 78 years, clearance was 

decreased by 27%. Not unexpectedly, the 25%–75% 

recovery interval was increased from 13 minutes in the 

young adults to 22 minutes in the elderly patients. 

Atracurium depends on neither the kidney nor the 

liver as its primary means of elimination. Rather, it undergoes 

the base and temperature catalyzed process of 

Hofmann elimination (Table 18-2). This spontaneous 

degradation of the relaxant is not end-organ dependent. 

Therefore, the physiologic changes associated with aging 

should not affect the pharmacokinetics of atracurium and 

its duration of action should be unaffected by advanced 

age. As they had done with vecuronium, d’Hollander and 

colleagues 44 studied atracurium in patients over the age 

of 60 years. In this study, patients received an infusion of 

atracurium to maintain 90% depression of neuromuscular 

function for 90 minutes. The dose of relaxant required 

to maintain this depth of paralysis was calculated in the 

age groups studied (older than 60 years, 40–60 years, and 

younger than 40 years of age). There were no differences 

among the groups in terms of their 10%–25% and 25%– 

75% recovery intervals or the amount of relaxant necessary 

to maintain 90% twitch suppression. 

Slight changes in the pharmacokinetics of atracurium 

in elderly patients, however, have been reported. Kent 

et al. 45 administered 0.6 mg/kg atracurium to elderly 

and young adult patients and found no difference in 

clearance and the volume of distribution between the two 

patient groups. There was, however, a small but significant


difference in the elimination half-life. The elimination 

half-life of atracurium was prolonged by 15% in elderly 

patients, from 20 to 23 minutes. Kitts et al. 46 administered 

an infusion of atracurium to achieve 70% neuromuscular 

block. As described by Kent et al., 45 elimination half-life 

was prolonged in the elderly. Because clearance was not 

affected by advanced age, the increase in elimination 

half-life was attributable to a larger volume of distribution 

in elderly patients. Most recently, Parker et al. 47 

found that elimination half-life was prolonged and clearance 

decreased in elderly patients. The results of Kitts, 

Kent, and Parker support the finding by Fisher et al. 48 that 

in addition to Hofmann elimination, renal and hepatic 

mechanisms contribute to the elimination of the compound. 

Despite these pharmacokinetic differences in 

elderly patients, however, the dynamics of neuromuscular 

blockade with atracurium are not different in the young 

and elderly. 44,46 

Cisatracurium is one of the 10 isomers that comprise 

atracurium. Similar to atracurium, it is eliminated primarily 

through Hofmann elimination. Renal clearance 

accounts for 16% of its elimination from the body. 49 As 

with atracurium, small changes have been found in the 

pharmacokinetics of this compound in elderly patients. 

Ornstein et al. 50 described a prolongation of the half-life 

of 4 minutes (21.5 versus 25.5 minutes in young and 

elderly patients, respectively) and an increase in the 

volume of distribution (108 versus 126 mL⋅kg −1 in young 

and elderly patients, respectively) of cisatracurium in 

elderly patients. Clearance was unchanged by advanced 

age. Sorooshian et al. 28 also found that clearance was 

unaffected by advanced age, whereas volume of distribution 

in the elderly was larger. Both studies found no difference 

in recovery of neuromuscular function after 

administration of 0.1 mg/kg cisatracurium. In a later study, 

Pűhringer et al. 51 also noted the lack of effect of small 

changes in pharmacokinetics of cisatracurium on the 

duration of action of the compound in the elderly. Patients 

received 0.15 mg/kg cisatracurium to induce neuromuscular 

blockade and 0.03 mg/kg boluses to maintain neuromuscular 

blockade. The clinical duration of action after 

the initial dose and the time to return to a train-of-four 

ratio of 0.8 following the last dose of cisatracurium were 

recorded. The recovery parameters were the same in 

young adults and those older than 65 years of age. 

Short Duration of Action 

Mivacurium is the only available nondepolarizing neuromuscular 

blocking agent with a short duration of action. 

Similar to succinylcholine, it is metabolized by plasma 

cholinesterase and is dependent on neither hepatic 

nor renal function for its elimination. Mivacurium has 

been shown to have a prolonged recovery in elderly 

patients. 52 In this study, patients received either a bolus 

of 0.15 mg/kg mivacurium and were allowed to recover 

or, following the bolus, were given an infusion to maintain 

90% suppression of neuromuscular response to stimulation. 

All recovery parameters were prolonged by approximately 

30% in elderly patients. The amount of mivacurium 

required to maintain neuromuscular blockade was also 

reduced (3.7 versus 5.5 µg/kg/min in the elderly and 

young, respectively). Goudsouzian et al. 53 also found that 

elderly patients required a lower infusion rate to maintain 

a stable depth of block. These results suggest that the 

pharmacokinetics of mivacurium are altered in elderly 

patients. The results of Østergaard et al. in a study of the 

kinetics of the compound do not explain the prolongation 

in recovery observed in the elderly. 54 They found that the 

half-life and clearances of the three isomers of mivacurium, 

cis-trans, trans-trans, and cis-cis, were not different 

in elderly patients. The volume of distribution of the 

relaxant, however, was larger in the elderly. 

Plasma cholinesterase activity is reduced in the elderly 55 

and mivacurium requirements are inversely related to 

plasma cholinesterase activity 56 in that patients with 

higher plasma cholinesterase activity require higher 

mivacurium infusion rates to maintain the desired depth 

of block than those patients with lower plasma cholinesterase 

activity. If mivacurium is to be used in geriatric 

patients, one can anticipate that lower infusion rates will 

be required to maintain a stable depth of neuromuscular 

block and, if administered with repeated boluses, longer 

dosing intervals would be appropriate. 

Anticholinesterases 

Because the duration of action of many nondepolarizing 

neuromuscular blocking agents is prolonged in the elderly, 

the impact of aging on the pharmacokinetics and pharmacodynamics 

of their antagonists is of interest. The 

three typically used anticholinesterases, edrophonium, 

neostigmine, and pyridostigmine, have prolonged durations 

of action and decreased clearances in the elderly 

(Table 18-4). The kinetics and dynamics of each in the 

elderly have been studied with vecuronium and many of 

the long-acting neuromuscular blocking agents. 

Edrophonium 

The clearance of edrophonium from the plasma depends 

primarily on the kidneys. Decreases in renal blood flow 

and glomerular filtration rate likely account for the 

altered pharmacokinetics of this compound in the elderly. 

As would be anticipated based on its means of elimination, 

the clearance of edrophonium (1 mg/kg) is decreased 

and its elimination half-life prolonged in the elderly. 57 In 

the study by Matteo et al., 57 edrophonium was administered 

during an ongoing infusion of metocurine that was


Table 18-4. Pharmacokinetics of edrophonium, neostigmine, and pyridostigmine in the elderly and young adults. 

Anticholinesterase Patient group t 1/2 β (minutes) Cl (mL ⋅ kg −1 ⋅ min −1 ) V i (L ⋅ kg −1 ) V d (L ⋅ kg −1 ) 

Edrophonium (1 mg ⋅ kg −1 ) 59 Elderly 84.2 (17)* 5.9 (2)* 0.05 (0.02) 0.72 (0.3) 

Young 56.6 (16) 12.1 (4) 0.2 (0.2) 0.81 (0.3) 

Neostigmine (0.07 mg ⋅ kg −1 ) 60 Elderly 16.7 (0.8) 23.4 (5) 0.068 (0.018)* 0.566 (0.13) 

Young 18.5 (7) 33.5 (4) 0.1 (0.04) 0.549 (0.12) 

Pyridostigmine (0.25 mg ⋅ kg −1 ) 68 Elderly 157 (56) 6.7 (2.2)* 0.085 (0.06) 1.4 (0.4) 

Young 140 (60) 9.5 (2.7) 0.095 (0.046) 1.8 (0.7) 

Note: Data are shown as mean (SD). 

t 1/2 β = half-life of elimination, Cl = plasma clearance, V i = initial volume of distribution, V d = volume of distribution. 

*There is a statistically significant difference compared with younger adults. 

dosed to maintain 90% neuromuscular block before the 

administration of the anticholinesterase. Despite its 

altered pharmacokinetics, dosing adjustments are not 

required for antagonism of residual neuromuscular block. 

This has been demonstrated in two different dosing 

models. McCarthy et al. 58 demonstrated in a doseresponse 

study that the dose of edrophonium required 

to antagonize 90% vecuronium-induced neuromuscular 

block, after a bolus administration of 0.08 mg/kg 

vecuronium, did not differ between the elderly and young 

adult patients. Similarly, Kitajima et al. 59 administered 

edrophonium, 0.75 mg/kg, to antagonize neuromuscular 

block that had been induced with vecuronium, 0.1 mg/kg. 

Edrophonium was administered when the train-of-four 

ratio had returned to 25%. The authors found that there 

was no difference in the time required for the train-offour 

ratio to recover to 75% in elderly patients (over the 

age of 70 years) and young adults. Matteo et al. 57 evaluated 

the ability of 1 mg⋅kg −1 edrophonium to reverse a 

deep, steady-state block produced by continuous infusion 

of metocurine in the elderly and younger adult patients. 

They found that there was no significant difference in the 

time to the maximum effect of the anticholinesterase 

in the two study groups (elderly 2.1 versus younger 

1.7 minutes). In this model, the plasma concentration of 

edrophonium at any given point in recovery was greater 

in the elderly patients than in the young adults. 

Therefore, the change in the pharmacokinetic parameters 

of edrophonium in the elderly has no influence on its 

efficacy in antagonizing residual neuromuscular block in 

this patient population. Because the volume of distribution 

tends to be smaller and the clearance slower, the dose of 

edrophonium does not need to be adjusted to obtain the 

same degree of recovery as in younger adults. 

Neostigmine 

In a study designed similar to the kinetic studies of edrophonium 

in the elderly, 57 Young et al. 60 studied the pharmacokinetics 

and dynamics of neostigmine in this patient 

population. Neostigmine was administered to patients 

receiving a metocurine infusion to maintain 90% neuromuscular 

block. The authors found that there was a slight, 

but not statistically significant, decrease in clearance of 

the anticholinesterase in the elderly and a decreased 

initial volume of distribution. 

Dose-response studies of neostigmine are not as 

consistent as those involving edrophonium. They have 

demonstrated that the dose of neostigmine required for 

antagonism of residual neuromuscular block in elderly 

patients is either similar to, 33 or greater 61 than, that 

required in younger adults. When neostigmine is used to 

antagonize doxacurium-induced block, there is no significant 

difference in the dose of neostigmine required to 

achieve recovery, within 10 minutes, to a train-of-four 

ratio of 0.7 from 25% spontaneous recovery of muscle 

strength (41.6 ± 5.8 in the elderly and 53.6 ± 7.5 µg⋅kg −1 in 

younger adults). 33 Furthermore, in a different study, neostigmine, 

50 µg⋅kg −1 , administered as a bolus at 25% 

recovery of muscle strength after administration of doxacurium, 

accelerated recovery to a train-of-four ratio of 

0.7 to the same degree in both patient populations (12.6 

± 7.3 in the elderly and 12.0 ± 6.7 minutes in younger 

adults). 62 It has also been reported, however, that the 

dose of neostigmine required to antagonize 90% 

vecuronium-induced block is greater in the elderly 

(31 µg⋅kg −1 ) than in younger adults (19 µg⋅kg −1 ). 61 Slower 

spontaneous recovery from vecuronium-induced block in 

geriatric patients during neostigmine-antagonized recovery 

may be a cause of their apparent greater requirement 

for neostigmine. That being said, because of its own 

decreased clearance in the elderly, the duration of action 

of neostigmine is prolonged in elderly patients. 63 In addition, 

the decreased initial volume of distribution of 

neostigmine 60 (Table 18-4) results in a greater plasma 

concentration of the anticholinesterase after bolus administration 

and may contribute to its prolonged duration 

of action. This is potentially advantageous because the


duration of action of many nondepolarizing neuromuscular 

blocking agents is prolonged in the elderly. 

Of note, the values reported for times to recovery to a 

train-of-four ratio of 0.7 are average values. As demonstrated 

by Kirkegaard et al., 64 there is a substantial degree 

of interpatient variability in the time required for neostigmine 

antagonism cisatracurium-induced neuromuscular 

block. This interpatient variability in young adults 

becomes even more pronounced when attempting to 

achieve recovery to a train-of-four ratio of 0.9, which has 

been recommended as the new standard for adequacy of 

recovery. 65 

Pyridostigmine 

Similar to neostigmine, pyridostigmine exhibits a prolonged 

duration of action in the elderly. 63,66 Approximately 

75% of administered pyridostigmine is eliminated 

by the kidney 63 and its clearance is slower in patients with 

renal failure. 67 The reduced plasma clearance of pyridostigmine 

(Table 18-4) caused by age-related deterioration 

in renal function likely accounts for its prolongation 

of action. 

Adverse Effects of Anticholinesterases in 

Geriatric Patients 

The cardiac muscarinic effects of anticholinesterases 

include dysrhythmias, such as bradycardia and conduction 

defects. Especially in the geriatric patient population, 

a large percentage of which has preexisting cardiovascular 

disease, anticholinesterase administration creates a 

greater risk of cardiac dysrhythmias. 68 Of the anticholinesterases, 

neostigmine is more likely to cause dysrhythmias 

than pyridostigmine (35% versus 14%, respectively). 69 

In any patient, antimuscarinic agents, such as atropine or 

glycopyrrolate, are administered with the anticholinesterase 

to counteract the bradycardic effects of the anticholinesterase. 

Depending on the dosing regimen, tachycardia, 

rather than bradycardia, is frequently observed. In 

patients with cardiovascular disease, the resultant increase 

in myocardial oxygen consumption may not be well tolerated 

and may lead to myocardial ischemia. 

In addition, atropine is a tertiary amine and can, therefore, 

cross the blood–brain barrier. In the central nervous 

system, anticholinergic drugs are known to affect the 

central cholinergic pathway where they are a cause of 

deterioration in postoperative cognitive function. 70 Atropine 

has been shown to produce disorientation, hallucinations, 

and memory loss. Glycopyrrolate, which is a 

quaternary amine, does not readily cross the blood–brain 

barrier and postanesthetic arousal times after its administration 

with neostigmine are shorter than those after 

the administration of atropine and neostigmine. 71 

Outcome Studies 

Reports of adverse outcome from residual neuromuscular 

blockade exist. 72–75 One prospective trial of patient 

outcome after general anesthesia and nondepolarizing 

relaxants has been done. 72 In this study, patients undergoing 

gynecologic, general, or orthopedic surgical procedures 

were randomly assigned to receive vecuronium, 

atracurium, or pancuronium. Muscle strength was determined 

in the postanesthesia care unit and patients were 

followed for several days for evidence of postoperative 

pulmonary complications. Elderly patients who received 

pancuronium were more likely to enter the postanesthesia 

care unit with a train-of-four ratio less than 0.7 than 

those receiving either of the intermediate-acting relaxants 

and the younger adult patients, regardless of the 

neuromuscular blocking agent they received. In addition, 

these patients were more likely to develop postoperative 

pulmonary complications than patients who had arrived 

to the postanesthesia care unit with a train-of-four ratio 

≥0.7. This is not unexpected because residual neuromuscular 

block has been found to interfere with the coordination 

of swallowing 76,77 and the response of the carotid 

body chemoreceptor to hypoxia. 78 

Summary 

Although age-related changes in hepatic, renal, and 

cardiac function slow the onset and clearance of many 

nondepolarizing neuromuscular blocking agents in geriatric 

patients, extensive changes at the neuromuscular 

junction do not increase sensitivity to these compounds. 

Decreased clearance mandates that neuromuscular block 

be maintained and subsequent doses administered only 

after documentation of return of muscle strength with a 

monitor of neuromuscular blockade. Except in rare cases, 

the clinician should anticipate having to pharmacologically 

antagonize residual neuromuscular block. 

As the surgical population ages and surgical trends and 

practices evolve, neuromuscular blocking agents, like 

anesthetics, must be specifically chosen based not only on 

their pharmacokinetic and pharmacodynamic properties, 

but also on the basis of patient age. 

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19 

Management of Regional Anesthesia 

Bernadette Veering 

There has been a dramatic increase in the elderly population 

throughout the past century. In one century, the 

number of persons aged 65 years or older has increased 

three times. Patients aged 85 and older are the most 

rapidly growing age group. By 2030, up to 20% of Western 

populations will be more than 65 years of age. 1 This situation 

has led to a progressive increase in the number of 

surgical interventions in elderly people. It has been estimated 

that more than half of the population older than 

65 years will require surgical intervention at least once 

during the remainder of their lives. 2 

Regional anesthesia is frequently used in elderly 

patients, especially during genitourologic and gynecologic 

procedures, orthopedic surgery, cataract extraction, 

and inguinal hernia repairs. Knowledge of the age-related 

effects is important with respect to the design of an 

optimal regional anesthetic regimen in elderly patients. 

Age-Related Changes Relevant to 

Regional Anesthesia 

Anatomic and physiologic changes, associated with 

advancing age, may affect the nerve block characteristics 

and the pharmacokinetics after administration of local 

anesthetics (Figure 19-1). A declining number of neurons, 

deterioration in myelin sheaths in the dorsal and ventral 

roots, changes in the anatomy of the spine, and intervertebral 

foramina may contribute to altered nerve block 

characteristics after a regional anesthetic procedure. 3,4 

Furthermore, the number of axons in peripheral nerves 

decreases with advancing age, and the conduction velocity 

diminishes, particularly in motor nerves. 5,6 With 

increasing age, changes in the connective tissue ground 

substances may result in changes in local distribution, 

i.e., in the distribution rate of the local anesthetic from 

the site of injection (the epidural space) to the sites 

of action. 3 

With aging, the dura becomes more permeable to local 

anesthetics because of enlarged arachnoid villi. 7 Aging is 

possibly associated with a reduction of the total volume 

of cerebrospinal fluid (CSF) and with an increase of its 

specific gravity. 8,9 

Central Neural Blockade 

Epidural Anesthesia 

The spread of analgesia increases with advancing age 

after epidural administration of a fixed dose of a local 

anesthetic solution (Figure 19-2). 10–14 Recently, it was 

demonstrated that the spread of analgesia was also 

greater in elderly patients than in younger patients after 

epidural anesthesia with the relatively new long-acting 

local anesthetics ropivacaine and levobupivacaine. 15,16 

Furthermore, elderly patients have a faster onset of analgesia 

in the caudad segments and the rate of regression 

of analgesia is prolonged. However, the total time for 

recovery from analgesia is not affected by age. The motor 

block profile associated with epidural anesthesia alters 

with age as well. With epidural ropivacaine and bupivacaine, 

an enhanced intensity of motor blockade is shown 

with advancing age. 15 With bupivacaine, the onset of 

motor blockade is faster in the oldest compared with the 

youngest patients. 11 

Elderly patients exhibit anatomic and physiologic 

changes that influence the clinical course during epidural 

anesthesia. (See section on age-related changes relevant 

to regional anesthesia.) In older patients, the longitudinal 

spread of the local anesthetic in the epidural space is 

promoted by sclerosis and calcification of the intervertebral 

foramina and a reduced fatty tissue content of the 

epidural space. A more compliant and less resistant epidural 

space with advancing age may also contribute to 

this enhanced spread in the elderly. 17 The clinical course 

of epidural anesthesia may be further influenced by a 

278

19. Management of Regional Anesthesia 279 

Figure 19-1. Factors that can modify epidural and spinal anesthesia 

in elderly patients. 

shift of the site of action from a predominantly paravertebral 

site in the young to a subdural or transdural site in 

the elderly. Factors causing extensive spread are accelerated 

by arteriosclerosis and diabetes, both of which cause 

premature aging. 18 

Epinephrine is used frequently in the epidural test 

dose as a marker of intravascular injection. A given dose 

of epinephrine will not be totally reliable in older patients, 

because of decreased beta-adrenergic responsiveness. 19 

Patient-controlled epidural analgesia has been shown 

to be effective in elderly patients in the management 

of pain after major surgery. 20 Because elderly patients 

exhibit an increased sensitivity to opioids, 21 it has been 

suggested to reduce the bolus dose and infusion rate 

of opioids up to 50% when administered to the elderly. 

Patient-controlled epidural analgesia technique can 

be used only in elderly patients who can participate in 

self-medication, which excludes those with cognitive 

dysfunction. 22 

Spinal Anesthesia 

Spinal anesthesia is frequently applied for lower abdominal, 

urologic, and lower limb surgery in older patients. 

The effect of age on the clinical profile of spinal anesthesia 

depends on the baricity of the injected solutions. With 

isobaric solutions, the effect of age on the maximal height 

of spinal analgesia is marginal. 23–25 With glucose-free 

0.5% bupivacaine, which acts as a slightly hypobaric solution 

at body temperature, the spread of analgesia is unaltered 

with age. 23,24 However, with a solution of isobaric 

2% mepivacaine, a slightly higher level of sensory analgesia 

has been found. 25 The caudad spread of analgesia 

as well as the development of motor blockade occurs 

more rapidly in older patients during spinal anesthesia 

with glucose-free bupivacaine. 23,24 The effect of age on the 

spread of analgesia is more pronounced when hyperbaric 

solutions are used. 26–28 With a hyperbaric solution of bupivacaine, 

the level of analgesia increases with age, extending 

some 3–4 segments higher in elderly as compared to 

young adult patients. However, because of profound 

interindividual variability, the predictability of the analgesia 

levels that will be reached in an individual patient 

is low. In addition, a quicker onset time of motor block 

has been found in older patients. With both hyperbaric 

and glucose-free bupivacaine solutions, the duration of 

analgesia of the T12 dermatome is prolonged, which 

allows more time for operations on the lower abdominal 

or inguinal region in older patients. Addition of adjuvants 

to spinal solutions may prolong the duration of neural 

blockade. Addition of epinephrine to glucose-free bupivacaine 

solutions increases the duration of analgesia in 

elderly patients. 29 However, addition of clonidine is associated 

with prolongation of motor block. 30 

The effects of hypobaric spinal anesthetic solutions are 

probably less reliable in the elderly because of the higher 

average specific gravity and greater individual variation 

in the volume of CSF. 

Upper level of analgesia 

T-1 

T-2 

T-3 

T-4 

T-5 

T-6 

T-7 

T-8 

T-9 

T-10 

T-11 

T-12 

L-1 

r = 0.63 

p = 0.002 

0 20 40 60 80 

Age (years) 

Figure 19-2. Relationship between the upper level of analgesia 

and age after epidural administration of 0.5% bupivacaine. 

(Reprinted with permission from Veering et al. 11 Copyright © 

Lippincott Williams & Wilkins.)

280 B. Veering 

A 

B 

Figure 19-3. Duration of complete sensory block (CSB) (A) or motor block (CMB) (B) and age. (Reprinted with permission 

from Paqueron et al. 31 Copyright © Lippincott Williams & Wilkins.) 

Peripheral Nerve Blockade 

For peripheral blocks, the major physiologic changes are 

in the response of the nerves themselves to local anesthetics. 

By the age of 90 years, one third of the myelinated 

fibers have disappeared from peripheral nerves. In addition, 

conduction velocity, especially of the motor nerve, 

decreases with age. 6 

After administration of ropivacaine at a brachial plexus 

block, the duration of sensory block and motor block is 

greater than in younger patients (Figure 19-3). 31 Onset 

time of complete motor block is shorter in elderly patients. 

Further study is indicated to investigate the effect of age 

on the characteristics of other peripheral blocks. 

Pharmacology 

Regional anesthetic blocks are performed by injecting 

local anesthetic agents close to nerve trunks. Two quite 

separate processes simultaneously occur after injection. 

While there is a vascular uptake of the drug into the systemic 

circulation, which removes the drug from the injection 

site, the drug also diffuses directly to neural structures, 

where the therapeutic action occurs. This is the pharmacodynamic 

part. The uptake into the systemic circulation 

may lead to side effects. 

Pharmacokinetics of Local Anesthetics 

Changes in body composition and characteristics of 

tissues and organs within the body may have an impact 

on the rate and extent of systemic absorption, distribution, 

and elimination of local anesthetics used for regional 

anesthesia. Pharmacokinetic and/or pharmacodynamic 

changes, which may occur with increasing age, could alter 

the clinical profile of local anesthetics after a regional 

anesthetic procedure. 

The effect of age on the pharmacokinetics of local 

anesthetics may be different in females than in males and 

may be influenced by concomitant diseases. 

Systemic Absorption 

Knowledge of the pharmacokinetics of local anesthetics 

is of importance in relation to the clinical profile, in particular, 

the duration of action, and in relation to the risk 

of systemic side effects and toxicity. 32 In this respect, both 

the systemic absorption, i.e., the uptake from the perineural 

site of administration into the blood, and the systemic 

disposition (distribution and elimination) must be considered. 

Peak plasma concentrations of lidocaine and bupivacaine 

after epidural or caudal administration change 

little, if at all, with increasing age. 11,33–35 However, the terminal 

half-life of bupivacaine increases after both epidural 

and subarachnoid administration, suggesting that the 

absorption rate of bupivacaine decreases with advancing 

age. 11,24,26 

Details on the absorption rate cannot be derived from 

the plasma concentration curves, unless a detailed description 

of the disposition is available. A stable isotope 

method allows simultaneous studies of the absorption 

and disposition. 36,37 Local anesthetics exhibit a biphasic 

absorption pattern, a fast initial absorption phase followed 

by a slower absorption phase after epidural and 

subarachnoid administration. 36–38 The initial fast absorption 

rate is a reflection of the high initial concentration 

gradient and the large vascularity of the epidural space. 

With spinal anesthesia, the initial absorption is much 

slower because the subarachnoid space has a poor perfusion. 

The slower second absorption phase is believed to 

occur from slow uptake of local anesthetics. Whereas a 

previous study on the systemic absorption and disposition 

kinetics of bupivacaine after epidural administration 

did not reveal an effect of age on the absorption kinetics, 

12 a recent study demonstrated a significant effect on


the rapid initial absorption kinetics of levobupivacaine 

after epidural administration. 16 After subarachnoid 

administration, the mean absorption has been shown to 

be shorter in elderly patients because of a faster late 

absorption rate. 28 Based on the faster absorption, one 

might expect a shorter duration of spinal and epidural 

anesthesia in older patients; however, this has not been 

demonstrated. 

The epidural absorption studies with bupivacaine and 

levobupivacaine and the spinal absorption study with 

bupivacaine demonstrate an increased sensitivity in the 

elderly that does not seem to be related to the impairment 

of vascular absorption. Therefore, changes in the 

clinical profile with epidural and spinal anesthesia are 

best explained by anatomic considerations and possibly 

pharmacodynamic changes in the elderly rather than by 

pharmacokinetic changes in the elderly. 

Plasma clearance (mL.min –1 ) 

1000 

800 

600 

400 

200 

y = –4.39x + 671.5 

r = –0.57 

p = 0.001 

Systemic Disposition 

20 

Figure 19-4. Relationship between total plasma clearance 

and age. (Reprinted with permission from Veering et al. 11 

Copyright © Lippincott Williams & Wilkins.) 

Age-related changes in drug distribution may result from 

changes in body composition and/or changes in drug 

binding and tissue perfusion. As fatty tissue increases, the 

volume of distribution of lipophilic local anesthetics 

would be expected to increase. 39 Such an increase has 

been demonstrated for lidocaine. 40 However, others 

observed an unchanged volume of distribution of intravenously 

(IV) administered lidocaine. 41,42 

A second factor influencing distribution is the plasma 

binding of drugs. The main binding protein for local anesthetic 

agents is α 1 -acid glycoprotein (AAG), an acute 

phase reactant protein. 43 The plasma protein binding of 

lidocaine tends to increase slightly with age. 44 However, 

age does not influence the serum protein binding of bupivacaine. 

45 This is in keeping with the lack of effect of age 

on AAG concentrations. 46 Any effect of age on AAG 

concentrations is likely to be relatively small, and therefore 

age-related changes in protein binding and in volume 

of distribution of local anesthetic agents that bind to 

AAG are more likely related to other factors. 47,48 

Local anesthetics are predominantly eliminated by 

metabolism. 49 The effect of age on the metabolism and 

excretion of local anesthetics is related to changes in 

hepatic function. Decreases in hepatic mass, hepatic blood 

flow, and hepatic enzyme activity with advancing age may 

result in impairment of metabolism. For local anesthetics 

that exhibit a high rate of hepatic extraction (e.g., lidocaine), 

the rate-limiting step in metabolism is hepatic 

blood flow. 50 Accordingly, the decrease of liver blood flow 

is associated with a decline in clearance of lidocaine with 

advancing age. 51 

There is also a gradual decline in hepatic mass, 52 

and, as a consequence, the clearance of local anesthetics 

with relatively low hepatic extraction ratios, which are 

mostly dependent on metabolizing hepatic enzyme activity, 

may decrease with age. Total plasma clearance of 

bupivacaine has been found to decrease with increasing 

age after epidural and subarachnoid administration 

(Figure 19-4). 11,24,26,28 

Because bupivacaine has a relatively low hepatic extraction 

ratio, the observed age-related decline in clearance is 

likely the result of a change in drug-metabolizing hepatic 

enzyme activity and/or serum protein binding of bupivacaine, 

rather than from an alteration in the liver blood flow. 

However, age has not been shown to affect the protein 

binding of bupivacaine. 45 Therefore, the observed agerelated 

decline in clearance probably reflects a concomitant 

decline in hepatic enzyme activity or capacity. 

The altered pharmacokinetics in elderly patients 

(uncomplicated by disease) seem to be relatively unimportant 

with a single epidural injection. The local anesthetic 

doses need not be modified because of the resulting 

plasma concentrations. 

However, taking into account the age-related decreased 

clearance of lidocaine and bupivacaine, administration of 

multiple intermittent injections or continuous epidural 

infusion of these local anesthetics for prevention of postoperative 

pain might lead to increased accumulation of 

these agents. 34 Consequently, the potential of developing 

side effects, including toxicity, might be enhanced. 

Long-term epidural infusion of bupivacaine for the 

relief of postoperative pain has been shown to result in 

progressively increasing plasma concentrations. 53,54 This 

40 

Age (years) 

60 

80


probably reflects a continuous change in the pharmacokinetics, 

as a result of changes in the degree of protein 

binding. Changes in the protein binding of bupivacaine 

are likely to occur in the postoperative phase, because 

plasma concentrations of AAG increase progressively 

during the first postoperative days. 55 It should be emphasized, 

however, that postoperative increases in total 

plasma concentrations are not accompanied by similar 

increases in the pharmacologically more relevant unbound 

(free) plasma concentrations. 

However, the concentration of free unbound lidocaine 

increases in elderly patients during continuous epidural 

infusion of lidocaine for postoperative pain (Figure 

Total Lidocaine Concentration (mg/L) 

Free-Lidocaine Concentration (mg/L) 

4 

3 

2 

1 

0 

A 0 30 60 90 120 150 180 240 300 min 

0.5 

0.4 

0. 3 

0.2 

0.1 

elder 

middle-age 

0 

B 0 30 60 90 120 150 180 240 300 min 

Figure 19-5. Mean plasma concentrations of total (A) and free 

(B) lidocaine after epidural administration to elderly or middleaged 

male patients. *p < 0.05, compared with the middle-aged 

group. Bars represent standard errors. (Reprinted with permission 

from Fukuda et al. 56 Copyright © 2003. With permission 

from the American Society of Regional Anesthesia and Pain 

Medicine.) 

19-5). 56 The upward trend of free lidocaine concentration 

in elderly patients is not caused by differences in AAG, 

but likely reflects a lower metabolic activity. The ratios of 

the total monoethylglycinexylidide (MEGX)/free lidocaine, 

which reflect the ability to metabolize lidocaine, 

were lower in the elderly group than in the middle-aged 

group. So caution must be exercised during continuous 

epidural infusion of lidocaine in geriatric patients. 

Problems 

Performing epidural and spinal anesthesia may be more 

difficult in elderly patients. It is often not easy to position 

the elderly patient appropriately because of the anatomic 

distortion, particularly curvature or rotation of the spine, 

that is found in many older people. The inability of the 

elderly patient to flex the back as much as the younger 

patient makes axial blockade difficult. Aging is frequently 

accompanied by an increase in the degree of lumbar lordosis 

often attributable to osteoporosis. Calcification of 

the interspinous ligaments and ligamentum flavum, the 

gradual stenosing of the intervertebral foramina in the 

elderly, make needle placement and advancement more 

complicated. 

The most common complication of spinal anesthesia is 

postspinal headache. Although the incidence is largely 

related to the size of the needle used, the incidence is 

decreased with age, possibly because of a decreased elasticity 

of the cranial tissues. 57 Consequently, less CSF leaks 

away from the subarachnoid space in older patients. 

Decreasing pain sensibility with increasing age and a 

decrease in distensibility of pain-sensitive structures in 

the cranium are also considered to contribute. 

Hypotension 

Hypotension is the most common cardiovascular disturbance 

associated with central neural blockade with a 

particularly frequent incidence in the elderly. It occurs 

from decreases in systemic vascular resistance and central 

venous pressure from sympathetic block with vasodilatation 

and redistribution of central blood volume to lower 

extremities and splanchnic beds. 58 Hypotension after 

spinal anesthesia is a common problem, with an incidence 

of 15.3%–33%. 59,60 High levels of analgesia and old 

age seem to be the two main factors associated with the 

development of hypotension. 60 A greater spread of analgesia 

with epidural ropivacaine in elderly patients is 

accompanied with a higher incidence of hypotension and 

bradycardia (Figure 19-6). 15 This problem is a particularly 

important issue in elderly patients with cardiovascular 

disease such as hypertension, because the risk for ischemia 

secondary to hypotension is increased. 61,62 Moreover, 

morbidity and mortality rates in elderly patients

T1 

T2 

T3 

T4 

T5 

T6 

T7 

T8 

T9 

T10 

T11 

T12 

L1 

L2 

L3 


Max. decrease in MAP (mm Hg) 

A 

70 

60 

50 

40 

30 

20 

10 

0 

15 25 35 45 55 65 75 85 

Age (years) 

Figure 19-6. (A) Relationship between the maximum decrease 

of the mean arterial blood pressure (MAP; mm Hg) during 

the first hour after the induction of epidural anesthesia and age. 

(B) Relationship between the maximum decrease of the MAP 

during the first hour after the induction of epidural anesthesia 

Max. decrease in MAP (mm Hg) 

B 

70 

60 

50 

40 

30 

20 

10 

0 

Dermatome 

and the highest level of analgesia for the three age groups 

(• = group 1, 19–40 years; o = group 2, 41–60 years; = group 

3, >61 years). (Adapted with permission from Simon et al. 15 

Copyright © Lippincott Williams & Wilkins.) 

with hypertension might be more frequent than those in 

elderly patients without hypertension because of the 

marked intraoperative hemodynamic lability. 63,64 

Marked hypotension is especially harmful to elderly 

patients with limited cardiac reserve. Structural changes 

in the arterioles and changes in the autonomic nervous 

system with increasing age may contribute to substantial 

hypotension in elderly patients. The elderly have increased 

resting sympathetic nervous system activity and associated 

increased norepinephrine release from nerve terminals. 

65,66 In addition, age-related baroreflex dysfunction 

may compromise arterial pressure homeostasis. 67 Hemodynamic 

instability after spinal anesthesia, therefore, 

might be exaggerated in the elderly because of larger 

decreases in systemic vascular resistance (Figure 19-7). 68 

Transthoracic electrical bioimpedance revealed that 

systolic blood pressure decreased by 25% as early as 6–9 

minutes after the block, indicating that patients should be 

monitored immediately after subarachnoid block. 69 

Treatment of Hypotension in the Elderly 

Common strategies used to prevent or reduce the incidence 

and severity of hypotension include IV fluid bolus 

and the use of vasopressors. Both prophylaxis and therapy 

should aim primarily at stabilizing or replenishing cardiac 

filling. Principally, this can be achieved either by increasing 

blood volume or by counteracting vasodilatation in 

the sympathicolytic regions with vasoconstrictor agents. 

It is common practice to give IV fluids before and during 

30 

Percentage Change from Control 

20 

10 

0 

–10 

–20 

–30 

–40 

–50 

–60 

** 

MAP SVR CO HR SV 9 EDV 

–0.4 

–10 

–10 EF 

–19 

–26 * * 

–33 

** 

** 

** 

* P < 0.05 vs control 

** P < 0.001 vs control 

Figure 19-7. Hemodynamic response to high spinal anesthesia 

in elderly men with cardiac disease. Decrease in systemic vascular 

resistance (SVR) and no decreases in cardiac output (CO) 

were primarily responsible for the large decrease in mean arterial 

blood pressure (MAP). Heart rate (HR) was unchanged; 

therefore, the decrease in cardiac output was attributable to a 

decrease in stroke volume (SV). The decrease in stroke volume 

was less than the decrease in end-diastolic volume (EDV) 

because the ejection fraction (EF) increased. (Reprinted with 

permission from Rooke et al. 68 Copyright © Lippincott Williams 

& Wilkins.)


spinal anesthesia to prevent hypotension. In elderly 

patients, however, fluid preloading is not always effective. 

70,71 Volume loading does not always prevent the 

decrease in systemic vascular resistance caused by spinal 

anesthesia but, in fact, may cause further decreases. 72 

Irrespective of whether crystalloid, colloid, or no prehydration 

is used, a high incidence of hypotension follows 

spinal anesthesia in normovolemic elderly patients undergoing 

elective procedures. Additionally, the attenuated 

physiologic reserve in elderly patients seems to make 

them less able to increase cardiac output in response to 

volume loading. 

Administration of a colloid preload during the induction 

phase of the block, usually about 7 mL/kg, has been 

recommended in elderly patients to compensate for any 

decrease in central venous pressure. 73,74 It should be 

emphasized, however, that rapid volume preloading constitutes 

a potential risk in older patients with limited 

cardiac reserve. At the same time, an alpha agonist should 

be used to reverse any decrease in vascular resistance. 

The degree of hypotension correlates with the level of 

sympathetic block, which is generally two to four segments 

higher than the level of analgesia. 75 From a clinical 

point of view, it is, therefore, important to limit the level 

of sympathetic block. The rationale for combining local 

anesthetics with adjuvant drugs is to use lower doses of 

each agent and to preserve analgesia with fewer side 

effects. A “minidose” of 4 mg of bupivacaine in combination 

with 20 µg of fentanyl provided spinal anesthesia for 

surgical repair of hip fracture in the elderly. 76 The minidose 

combination caused dramatically less hypotension 

than 10 mg of bupivacaine and nearly eliminated the need 

for vasopressor support of blood pressure. 

Changes in the technique of hyperbaric bupivacaine 

spinal anesthesia by injection of hyperbaric bupivacaine 

either at a lower L4-5 interspace than the usual (L3-4) 

lumbar interspace 77 or different periods of sitting after 

injection had little, if any, influence on final analgesia levels 

and on hemodynamic changes in elderly patients. 78 

However, unilateral segmental spinal anesthesia may 

result in more restricted anesthetic spread with less 

hemodynamic variability. Unilaterality can be reliably 

produced with small doses of hyperbaric solutions and by 

prolonged lateral positioning. 79 

Continuous spinal anesthesia (CSA) is a technique that 

allows one to titrate local anesthetic solutions and thus 

reduce the dosage of local anesthetics, providing a more 

adequate analgesia with a lower level of sympathetic 

blockade and minimizing arterial hypotension and bradycardia. 

80 Also, combined spinal-epidural technique 

(CSE) enables smaller intrathecal doses to be used with 

the option of topping up the epidural catheter if the block 

is inadequate. When hemodynamic stability is critical, 

CSE or CSA may be the techniques of choice for lower 

limb surgery in the elderly patients. 

Hypothermia 

As with general anesthesia, advanced age is associated 

with hypothermia during epidural and spinal anesthesia. 

This should be attributed to a variety of factors such as 

a physiologic decrease in basal metabolism, changes in 

the thermoregulatory center, and diminished muscular 

mass. 81–83 Also, elderly patients may be especially at risk 

of hypothermia because low core temperature may not 

initiate autonomic protective responses. 

Advancing age and high-level spinal blockade are 

associated with a significant decrease of thermoregulatory 

threshold (Figure 19-8). 83 The shivering threshold 

is decreased in proportion with the level of spinal blockade 

because the vasomotor tone is inhibited below the 

A 

Figure 19-8. Advanced age (A) and high level of spinal block 

(B) were significant predictors of core hypothermia at admission 

to the postanesthesia care unit by linear regression. 

B 

(Reprinted with permission from Frank et al. 81 Copyright © 

Lippincott Williams & Wilkins.)


level of spinal block. 84,85 So the greater the proportion 

of the body that is blocked, the greater the level of thermoregulatory 

dysfunction that can be expected. Shivering 

and increase in oxygen demand further compromise 

patients, especially those with known cardiovascular 

diseases. 

Controlling and monitoring body temperature in older 

patients and in those with high spinal blocks could 

decrease risk of hypothermia and its complications. 

Sedation 

Prompt and complete postoperative recovery of mental 

function is particularly important in elderly patients if the 

mental condition is already compromised by age-related 

disease or drug therapy. 22 

Elderly people are prone to confusion and are often 

sensitive to low doses of sedative drugs. Geriatric patients 

show an increased responsiveness for benzodiazepine 

compounds. 86 Therefore, smaller doses and more delayed 

increments must be used. Also, caution should be used 

when benzodiazepines are given as premedication in 

geriatric patients. 

The pharmacokinetics and the pharmacodynamics of 

propofol change dramatically with age. 87 Elderly patients 

are more sensitive to the hypnotic and electroencephalographic 

effects of propofol than younger persons. Older 

patients require lower doses for any given effect, in many 

cases as little as 30% of the expected “standard” dose. 

Propofol infusion for sedation during spinal anesthesia 

resulted in a delayed recovery time in elderly patients 

compared with younger patients. 88 Elderly patients may 

require a more prolonged observation period after cessation 

of sedation with propofol. 

Postoperative Cognitive Function 

A proportion of mostly elderly orthopedic patients 

develop early postoperative cognitive dysfunction, confusion, 

and delirium, which are all nonspecific symptoms of 

central nervous system dysfunction. 89–91 This postoperative 

mental condition may persist for several days to 

several weeks and can result in increased morbidity, 

delayed functional recovery, and prolonged hospital stay. 

The mechanism of early postoperative confusion after 

orthopedic surgery and other operations is probably 

multifactorial. 92,93 

In most cases, recovery of cognitive function is prompt 

and complete within 1 week in elderly patients. Neither 

the choice of anesthetic technique nor the modality used 

for the management of postoperative pain seems to be 

an important determinant of postoperative confusion in 

elderly patients. 89,92,93 

The factors that likely explain the development of 

postoperative brain dysfunction are age, hospitalization, 

and extension and duration of surgery. 

Beneficial Aspects of 


The use of both intraoperative and postoperative regional 

analgesic techniques provides physiologic benefits and 

may attenuate the pathophysiology that occurs after 

surgery. 94 Local anesthetic agents have the capability to 

block afferent and efferent signals to and from the spinal 

cord, thus suppressing the surgical stress response (Table 

19-1). 95 The cascade of events unleashed during the stress 

response to surgical events can be blunted with epidural 

anesthesia. 95,96 One such effect is to decrease postoperative 

hypercoagulability. Epidural or spinal analgesia 

and anesthesia attenuates the hypercoagulable perioperative 

state by increasing fibrinolysis and decreasing 

coagulability. 97–99 

Regional anesthesia techniques provide excellent pain 

management, thus sparing the sedative effects of opioids 

and facilitating early postoperative mobilization for a 

faster convalescence. 96,100 

When compared with general anesthesia, intraoperative 

blood loss is reduced by spinal or epidural anesthesia, 

especially in patients undergoing hip replacement 

surgery. 101,102 This is attributed to lower venous pressures 

Table 19-1. Effects of analgesic techniques on postoperative surgical stress responses. 

Type of analgesia Endocrine responses Metabolic responses Inflammatory responses 

Systemic opioid (PCA or intermittent) 

↓ 

NSAID ↓ ↓ 

Epidural opioid 

↓ 

Lumbar epidural local anesthetics 

(lower extremity surgery) 

↓↓↓ 

Thoracic epidural local anesthetics 

(abdominal surgery) 

↓↓ 

Source: Adapted with permission from Kehlet and Holte. 96 Copyright ® The Board of Management and Trustees of the British Journal of 

Anaesthesia. Reproduced by permission of Oxford University Press/British Journal of Anaesthesia. 

PCA = patient-controlled analgesia, NSAID = nonsteroidal antiinflammatory drug, ↓ = small effect, ↓↓ = moderate effect, ↓↓↓ = major effect.


during central neural blockade compared with general 

anesthesia. 

Compared with general anesthesia, epidural 103 and 

spinal anesthesia 104 are not associated with changes in 

arterial blood gases either during or after the operation, 

indicating a preservation of pulmonary gas exchange. 105 

Cardiovascular System 

Thoracic epidural anesthesia (TEA) can produce a selective 

segmental blockade of the cardiac sympathetic nerves 

(T1–T5), with loss of chronotropic and inotropic drive to 

the heart. 58 Animal studies have been performed to test 

whether sympathetic block lessens ischemia. 106,107 Acute 

coronary occlusion during TEA resulted in redistribution 

of flow to the epicardium away from the endocardium, 

affecting beneficially collateral blood flow during myocardial 

ischemia. 106 Under the influence of TEA, the size 

of induced myocardial infarcts was smaller after experimental 

coronary occlusion in dogs. 107 

High TEA in humans improved an ischemia-induced 

left ventricular dysfunction; reduced electrocardio - 

graphic, echocardiographic, and angiographic signs of 

coronary insufficiency decreased the incidence of arrhythmias 

and provided relief of ischemic chest pain. 108–111 

These results show that TEA with an associated cardiac 

sympathetic blockade improves the oxygen supply– 

demand ratio. 112 

Pulmonary System 

Thoracic and lumbar epidural anesthesia are often combined 

with general anesthesia in patients undergoing 

upper abdominal surgery, vascular surgery, and kidney 

surgery. Epidural anesthesia per se has little effect on 

respiration in patients with preexisting lung disease. Most 

of the respiratory changes associated with epidural anesthesia 

are directly attributed to motor block of the muscles 

of respiration. 58 

Perhaps the most profound effect of major abdominal 

and thoracic surgery on pulmonary function is a reduction 

in the functional residual capacity as a result of diaphragmatic 

dysfunction. This is caused by reflex inhibition 

of the phrenic nerve after major surgery, a decreased 

chest wall compliance, and pain-limited inspiration. 113 

Diaphragmatic activity increases after TEA, possibly 

because of the interruption of an inhibitory reflex of 

phrenic nerve motor drive, either related to direct deafferentation 

of visceral sensory pathways, or because 

of a diaphragmatic load reduction caused by increased 

abdominal compliance. 114,115 

Gastrointestinal System 

A TEA over T12 is associated with splanchnic sympathetic 

nervous blockade, which results in reduced inhibitory 

gastrointestinal tone and increased intestinal blood 

flow. 94,116 Blood flow to the bowel is a critical factor for 

gastrointestinal motility. Intestinal sympathectomy also 

results in a contracted bowel because of vagal predominance. 

All these factors result in a faster digestive 

transit. 116,117 In addition, TEA improves microvascular 

perfusion of the small intestine. 118 

Outcome: Regional Versus 


Generally, geriatric patients have a decreased functional 

reserve of organ systems and thus become increasingly 

intolerant to surgical stress. Local anesthetics have the 

capability to block afferent and efferent signals to and 

from the spinal cord, thus suppressing the surgical stress 

response and spinal reflex inhibition of diaphragmatic 

and gastrointestinal function. 

The question often asked is whether these men - 

tioned beneficial aspects of regional anesthesia make 

a difference in the outcome of surgical patients. To 

demonstrate superiority of one anesthetic technique 

over another technique, one needs to look at outcome 

results. 

Discrepancies exist between studies that have evaluated 

the early mortality, i.e., within 1 month, in elderly 

patients, after major orthopedic surgery under either 

regional (epidural or spinal) or general anesthesia (Table 

19-2). Several studies on elderly patients undergoing hip 

Table 19-2. Effect of anesthetic technique on postoperative mortality in elderly patients (age range: 60–90+). 

Mortality (%) 

Author Number of patients (reg/GA) Method 7 days (reg/GA) 30 days (reg/GA) 1 year (reg/GA) 

Sutcliffe 120 383/950 Prospective 9.4/8.8 36.9/32.6 

O’Hara et al. 119 3129/6206 Retrospective 1.6/1.3 5.4/4.4 

Gilbert et al. 123 430/311 Prospective 19.1/16.6 

Urwin et al. 122 1028/1005 Meta-analysis 6.4/9.4* 22.5/21 

Reg = regional anesthesia, GA = general anesthesia. 

*p < 0.05. Advantage regional anesthesia over general anesthesia.


fracture repair failed to reveal advantages of regional 

anesthesia compared with general anaesthesia. 119,120 With 

meta-analysis, it is possible to combine relevant data from 

several existing investigations in order to study the effect 

of specific techniques of anesthesia and to draw conclusions. 

121 A systemic review of randomized trials showed 

that regional anesthesia for hip fracture surgery was associated 

with a reduced early mortality and incidence of 

deep vein thrombosis in comparison with general anesthesia. 

122 The pattern of reduction in early mortality is 

possibly related to a decreased incidence of deep venous 

thrombosis. Long-term morbidity and mortality (2 months 

to 1 year) do not seem to be altered by the anesthetic 

type used during hip repair. 120,123 

Cardiac Outcome 

Cardiac morbidity is the most common cause of death 

after major surgical procedures. The incidence of cardiovascular 

diseases is high in elderly surgical populations 

undergoing peripheral vascular surgery of the lower 

extremity. Because perioperative sympathetic activation 

has a causative role in the development of myocardial 

ischemia and infarction, inhibition of this activation 

would be expected to reduce cardiac morbidity. 

There has been an ongoing discussion as to whether 

regional anesthesia is superior to general anesthesia in 

patients at cardiac risk. Discrepancies exist between 

studies that have evaluated this effect, because most 

studies are insufficiently powered to demonstrate clinically 

and statistically significant benefits. 

The impact of anesthetic choice on cardiac outcome 

was studied in patients undergoing peripheral vascular 

surgery who had a likelihood of associated coronary 

artery disease. 124 In this study, patients were randomly 

assigned to be given general, epidural, or spinal anesthesia. 

There was no significant difference among groups in 

cardiovascular morbidity and overall mortality. In another 

study, patients were randomized to receive general anesthesia 

combined with postoperative epidural analgesia or 

general anesthesia with on-demand narcotic analgesia 

(PCA). 125 The rates of cardiovascular, infectious, and 

overall postoperative complications, as well as duration 

of intensive care unit (ICU) stay, were significantly 

reduced in the general anesthesia–postoperative epidural 

analgesia group. In addition, the incidences of graft occlusion 

were reduced. However, in a comparable study, no 

difference was found in the incidence of cardiac ischemia 

in patients scheduled for elective vascular reconstruction 

of the lower extremities. 126 

However, the need for reoperation for graft failure was 

reduced in the epidural group. Park et al. 127 observed in 

a large, multiinstitutional clinical trial that epidural plus 

general anesthesia and postoperative epidural analgesia 

improved the perioperative cardiac outcome of elderly 

patients undergoing abdominal aortic operations compared 

with that of general anesthesia alone and postoperative 

systemic opioid analgesia. 

Beattie and colleagues 128 performed a meta-analysis to 

determine whether postoperative analgesia continued for 

more than 24 hours after surgery reduces postoperative 

myocardial infarction or in-hospital death. It seemed that 

thoracic epidural analgesia was superior to lumbar epidural 

analgesia in reducing postoperative myocardial 

infarction. These findings suggest that in high-risk cardiac 

patients, thoracic epidural postoperative analgesia is warranted 

and should be used more widely. 

Early administration of continuous epidural analgesia 

was associated with a lower incidence of preoperative 

adverse cardiac events in elderly patients with hip fracture 

who had or were at risk for coronary artery disease. 129 

Although the study group was small, the results war - 

rant further study of preoperative analgesia in this 

population. 

Coagulation 

The risk and incidence of thromboembolic complications 

after lower body complications are lower in patients 

operated on under lumbar epidural and spinal anesthesia 

as compared with those given general anesthesia. 98,130,131 

The mechanism is probably a combination of improved 

lower extremity blood flow, favorable changes in coagulation 

and fibrinolysis, inhibition of thrombocyte aggregation, 

and decreasing blood viscosity. 97–99,132 In addition, the 

systemic absorption of epidurally administered local 

anesthetics, improved pain control, and earlier mobility 

likely decrease the incidence of clot formation. 133 

Pulmonary Outcome 

A major cause of postoperative complications is respiratory 

problems during the early postoperative recovery 

period. 

Decreased intubation times and ICU stays in patients 

with epidural anesthesia and analgesia after major 

abdominal surgery in elderly patients have been 

reported. 129,134 A recent meta-analysis of 48 randomized 

controlled clinical trials assessed improvements in pulmonary 

outcomes comparing systemic opioids, epidural 

opioid, and epidural local anesthetic. 135 Compared with 

those who received systemic opioids, patients who 

received postoperative epidural analgesia with local 

anesthetics had a significant reduction in the incidence 

of pulmonary complications, atelectasis, and pneumonia 

and increase in the postoperative partial pressure of 

oxygen. So continuous epidural local anesthetic or local 

anesthetic–opioid mixtures have been demonstrated to 

improve outcome by controlling postoperative pain, permitting 

earlier extubation, and reducing length of stay.


Gastrointestinal Outcome 

Postoperative ileus is a major surgical morbidity following 

abdominal surgery. As a consequence, the length 

of stay of elderly patients may be prolonged in the 

hospital. Colonic motility is inhibited for 48–72 hours. 

The most frequently accepted theory is that abdominal 

pain activates a spinal reflex arc that inhibits intestinal 

motility. 136–138 

Randomized clinical trials that investigated the recovery 

of gastrointestinal function after abdominal and other 

types of surgery have consistently shown that the use of 

postoperative thoracic epidural analgesia with a local 

anesthetic-based regimen compared with systemic opioid 

analgesia will allow earlier return of gastrointestinal 

function and even discharge from the hospital. 96,117,139 

Conclusion 

This chapter has outlined several aspects of regional 

anesthesia in elderly patients. The general consensus is 

that elderly patients are more sensitive to local anesthetic 

agents and show altered clinical profiles. Older patients 

experience slightly higher levels of sensory and motor 

blockade after epidural and spinal anesthesia and are 

also at somewhat greater risk for arterial hypotension 

because of the sympathicolytic consequences of acute 

peripheral autonomic blockade. Thus, bolus doses of local 

anesthetic should be reduced in elderly patients to limit 

the side effects. 

Regional anesthesia offers several beneficial aspects 

to elderly patients, including reduced blood loss, better 

peripheral vascular circulation, suppression of the surgical 

stress response, and better postoperative pain control. 

The cardiac benefits of regional anesthesia have been 

especially attributed to TEA, particularly in patients 

with ischemic heart disease. Possibly postoperative thoracic 

epidural analgesia reduces cardiac morbidity in 

high-risk cardiac patients. Postoperative epidural analgesia 

can improve outcome after surgery by reducing 

pulmonary complications. Persistent age-related cognitive 

dysfunction seems not to be related to the history of 

an operation under general or regional anesthesia, 

suggesting the existence of other interacting etiologic 

factors. Regional anesthesia may reduce short-term mortality, 

especially in elderly patients undergoing hip fracture 

repair by a decrease in thromboembolism because 

of maintenance of relatively normal fibrinolysis. However, 

no conclusions can be drawn for longer-term mortality. 

There is evidence that epidural anesthesia facilitates 

earlier recovery by reducing ileus in abdominal surgical 

patients. 

Nonetheless, large multicenter prospective randomized 

studies are required in elderly surgical patients to 

more definitively assess the impact of regional anesthesia 

on morbidity and mortality, ICU time, length of hospitalization, 

and cost of health care. 

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11. Veering BT, Burm AGL, Van Kleef JW, et al. Epidural 

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12. Veering BT, Burm AGL, Vletter AA, et al. The effect of 

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20 

Fluid Management 

Jessica Miller, Lee A. Fleisher, and Jeffrey L. Carson 

It is imperative that anesthesiologists are well versed in 

modifications to fluid management for the elderly patient. 1 

This chapter discusses the guiding principles in fluid management 

and the important alterations in kidney function 

and fluid homeostasis in the elderly patient. These concepts 

are built upon to provide recommendations for the 

perioperative period. Preoperative evaluation, assessment, 

and decision making in the intraoperative period 

are discussed below, including methods of monitoring 

intraoperatively, types of fluids to administer, and the 

use of blood transfusions. Special anesthetic challenges 

such as spinal anesthesia and fluid management are also 

included. 

Fluid and Electrolyte Homeostasis 

Understanding changes in fluid and electrolyte balance 

requires examining the major determinants of fluid 

regulation. Total body water decreases with age from 

60%–65% in a young man to 50% by age 80. 2 Total 

body water is distributed as 67% extracellular fluid 

volume and 33% intracellular fluid volume. The cell wall 

separates extracellular fluid from intracellular fluid. 

Extracellular fluid volume is further divided into 75% 

interstitial fluid and 25% plasma. The cells making up the 

walls of arteries and veins and the capillary endothelium 

separate the extracellular compartment into interstitial 

and intravascular fluid. Water moves freely through cell 

walls and vessels. Ions such as sodium can pass freely 

across capillary endothelium, but sodium pumps driven 

by adenosine 5′-triphosphate maintain a concentration 

gradient across cells. Larger molecules such as albumin 

and colloids are unable to move across intact capillary 

endothelium, thus creating a colloid oncotic pressure. 

Movement of fluids between the extracellular and 

intracellular compartment is governed by the Starling 

equilibrium. Starling forces are composed of hydrostatic 

pressure, colloid oncotic pressure, and specific permeability 

coefficients: 

J = K[Pc − Pt − r(C − T)] 

where J = filtration rate out of capillary, K = filtration 

coefficient, Pc = capillary pressure, Pt = tissue fluid pressure, 

C = plasma colloid oncotic pressure, T = tissue 

colloid oncotic pressure, r = reflection coefficient. 

Hydrostatic pressure in the capillaries drives movement 

of fluid from the capillary to the interstitial space. 

Elevated colloid oncotic pressure in intravascular fluid 

opposes hydrostatic pressure to maintain intravascular 

volume and a relatively dry interstitial compartment. 

During surgery, capillary membrane permeability 

increases at the surgical site. Proteins move down 

their concentration gradient into the interstitial fluid, 

thus decreasing colloid oncotic pressure in the intravascular 

space. Administration of fluid in the perioperative 

period also decreases colloid oncotic pressure due to 

hemodilution. 

Perioperative fluid distribution can be understood with 

the Starling equilibrium; however, alterations in endocrine 

and inflammatory mediators also affect fluid homeostasis. 

Surgical trauma results in an increased activity of 

antidiuretic hormone (ADH), aldosterone, and the reninangiotensin 

system. Increased ADH secretion enhances 

water reabsorption in the kidney resulting in lowered 

plasma sodium concentration and a decrease in diuresis. 

Increased aldosterone and renin release results in sodium 

conservation and potassium excretion (Figure 20-1). 3 

Further aspects of the stress response lead to increased 

cortisol secretion. Cortisol may be beneficial in counteracting 

inflammatory mediators and helping to maintain 

capillary integrity. Inflammatory mediators such as interleukin-6, 

tumor necrosis factor, substance P, and bradykinin 

may act as vasodilators and cause further increases in 

capillary permeability. 4 

293

294 J. Miller, L.A. Fleisher, and J.L. Carson 

Figure 20-1. Pathways by which decreased plasma volume leads, 

via the renin-angiotensin system and aldosterone, to increased 

sodium reabsorption and hence decreased sodium excretion. 

GFR = glomerular filtration rate. (Reprinted from Vander et al. 3 

with permission of The McGraw-Hill Companies.) 

These concepts can be applied to perioperative management 

of the elderly patient by understanding the evolution 

of these mechanisms with age. As mentioned, total body 

water decreases in the elderly to approximately 50% of 

body weight by the age of 80 years. Muscle mass is decreased 

by as much as 30% in the 80-year-old patient. The effect 

of a deceased total body water and decreased lean body 

mass results in a larger volume of distribution. Elderly 

patients have subtle alterations in the dynamic renal, 

endocrine, and hormonal elements that work to maintain 

homeostatic balance. These will be discussed in more detail 

below. These alterations in fluid homeostasis are magnified 

by the decrease in arterial distensibility, decreased baroceptor 

reflexes, and more sluggish homeostatic response to 

result in larger alterations in hemodynamic stability. 5 

Aging and Renal Function 

An understanding of changes in renal sodium and water 

excretion is central to understanding fluid and electrolyte 

balance. The aged kidney is able to maintain stable

20. Fluid Management 295 

volume and electrolyte status. Age has been shown 

to have no effect on basal plasma sodium and potassium 

concentrations, or maintenance of normal extracel - 

lular fluid volume. However, the aged kidney has less 

functional reserve and is slower to adapt to acute 

changes. 

Changes in structure and function of the kidney with 

age affect fluid management, electrolyte homeostasis, 

drug metabolism, and pharmacokinetics. These changes 

have been well described; however, the methods of assessment 

of kidney function in aging individuals have received 

more attention recently. Early analysis of aging kidney 

function utilized cross-sectional studies. Attempts were 

made to exclude patients with overt renal disease; 

however, limitations in testing inevitably overlook subclinical 

renal disease. Comparison studies between active 

young individuals were frequently matched with institutionalized 

elderly individuals, thus not representing 

the segments of the elderly population that are residing 

and functioning in the community. 6,7 More recent studies 

have used longitudinal comparison of kidney function in 

carefully selected patients who lacked renal diseases, 

specifically patients who were deemed suitable for kidney 

donation. 8–10 Predictably, these studies showed less 

marked changes in kidney function than previous studies. 

The availability of this more accurate representation of 

changing kidney function is beneficial to overall understanding 

of clinical management; however, the frequent 

presence of comorbid diseases that affect kidney function 

cannot be overlooked in applying these principles to individual 

patient management. 

Alterations in the kidney associated with aging include 

both structural and functional changes. Studies have indicated 

total and cortical renal mass decreases with age. 

Between the ages of 30 and 85 years, renal mass decreases 

by 20%–25%. 2 The decline in renal mass is relatively 

sparing of the medulla, with most loss occurring in the 

cortical area. The number of functioning glomeruli 

decreases proportionally with change in mass; however, 

the size of each remaining glomeruli increases. Global sclerosis 

of the glomeruli increases the proportion of sclerotic 

glomeruli from 5% in middle age to 10%–30% by the 

eighth decade. The length of the proximal convoluted 

tubule decreases in size with age, thus matching the decline 

in glomerular and tubular function seen in aging. 6 

Multiple studies have demonstrated that renal blood 

flow decreases with age. 11–13 Renal blood flow begins to 

decline after the fourth decade of life by approximately 

10% per decade. 14 Further studies also showed a decrease 

in mean blood flow per unit mass with advancing age. 

When correlated with changes in flow rates, it has been 

deduced that the largest decreases in renal perfusion 

occur in the cortex, with relative sparing of flow to the 

deeper regions of the kidney. As flow decreases from the 

cortex, the juxtaglomedullary glomeruli receive more 

perfusion. Their preexisting increased filtration fraction 

compared with the cortex glomeruli may explain the 

increase in filtration fraction with aging. 6 

Glomerular filtration rate (GFR) is the predominant 

measure of renal function. Initial studies assessing nursing 

home residents resoundingly found that GFR decreased 

with age. GFR can be estimated to decrease approximately 

1 mL/min/y. 15 Assessment of GFR in the elderly 

has been repeated using community-dwelling elderly 

in both cross-sectional and longitudinal studies. These 

studies also found a general decline in GFR, but also 

revealed more variations in GFR. Up to 30% of the 

elderly subjects had a stable GFR over a 20-year longitudinal 

study, suggesting that declining GFR is not 

inevitable. 11,15 Only explicit measurement of creatinine 

clearance could identify these patients, thus it should not 

be assumed the elderly patient has a decreased GFR. 

Serum creatinine is relatively constant with age, reflecting 

the decrease in muscle mass with age that parallels 

the decrease in GFR. In clinical practice, a method of 

estimating GFR from creatinine clearance is helpful. 

The most frequently used formula is the Crockroft-Gault 

equation 16 : 

Creatinine clearance = [K (140 − age) (weight in kg)]/ 

[(72) (serum creatinine concentration)] 

K = 1.23 for men, 1.03 for women, 

creatinine clearance in µmoL/min. 

The development of this formula may have been skewed 

by the use of validation on a small number of subjects, 

subjects of only one gender, and institutionalized individuals. 

A recent reevaluation of the accuracy of the 

Crockroft-Gault equation in comparison to a measured 

24-hour creatinine clearance showed only a moderate 

correlation in the equation’s estimates with the measured 

clearance in the elderly subgroup. 17,18 A more comprehensive 

study comparing the validity of several methods 

of estimating GFR found most equations underestimated 

creatinine clearance. In general, it is recommended that 

if an accurate measure of GFR is required, a 24-hour 

creatinine clearance should be measured. There is no one 

estimation method that accurately predicts GFR. For 

purposes needing less accuracy, the Crockroft-Gault 

equation is a reasonable guide. Clinical drug dosing in the 

elderly should maintain careful consideration of drugs 

cleared mainly by renal mechanisms. 

Sodium Handling 

Less is known about the ability of the aged kidney to 

process sodium (Tables 20-1 and 20-2). Studies have concluded 

that age significantly decreases the kidney’s ability 

to conserve sodium. The aged kidney takes a longer 

period of time to reduce urinary excretion of sodium in 

response to a low-sodium diet when compared with a 

young person’s kidney. 8 The decrease in renal blood flow


and GFR does not explain this sluggish response. Other 

elements of the sodium conservation axis, such as the 

renin aldosterone system and atrial natriuretic peptide 

may be responsible. Several studies have shown that the 

renin aldosterone response to acute stimuli is slower with 

advancing age. 14,19,20 

The aged kidney seems to have impaired sodium excretion 

mechanisms. Mechanisms responsible for reduced 

sodium excretion may include a decrease in pressuresensitive 

natriuresis, which may lead to salt-sensitive 

hypertension. An altered response to angiotensin II has 

also been investigated. The administration of sodium-rich 

fluids, dietary indiscretion, and radiocontrast dye must be 

considered with forethought into the possible negative 

effects of the resultant volume load. 

The aged kidney’s ability to alter its response to total 

body sodium is especially critical in the elderly. Older 

patients are more likely to experience confusion and loss 

of thirst sensation in periods of acute illness, which further 

aggravates the body’s sluggish response to altered plasma 

sodium. Other studies have suggested that sodium losses 

have magnified effects on hemodynamic stability. A study 

by Shannon et al. 21 showed that a diuresis of 2 kg resulted 

in a 24 mm Hg decrease in systolic blood pressure upon 

changing from the supine to a standing position, a much 

larger effect than seen in younger patients. 

Investigations into other aspects of fluid homeostasis 

have also been conducted. Studies have concluded that 

substantial declines in plasma renin activity occur with 

aging. 20 Plasma renin is decreased in the resting state, 

and ranges from a 40% to 60% decrease in stimulated 

conditions. Significant and consistent declines in plasma 

renin are found after the sixth decade. The effect of renin 

on angiotensin II release is technically difficult to study. 

Aldosterone is also depleted in elderly patients in the 

stimulated and basal states. 19 Atrial natriuretic peptide 

has shown to be increased in elderly patients with possible 

decreased end-organ responsiveness; at this time its 

full effect is not understood. 

Renal diluting capacity is also shown to be affected by 

aging. A mild defect in renal diluting capacity occurs with 

age, which seems to be related to the decline in GFR. This 

puts the elderly patient at increased risk for dilutional 

hyponatremia in settings of stress, such as surgery, fever, 

Table 20-1. Symptoms of hyponatremia. 

Malaise 

Nausea 

Headache 

Lethargy 

Confusion 

Obtundation 

Stupor 

Seizures 

Coma 

Table 20-2. Symptoms of hypernatremia. 

Polyuria 

Thirst 

Altered mental status 

Weakness 

Neuromuscular irritability 

Focal neurologic deficits 

Seizures 

Coma 

or acute illness. Studies have found the decrease in plasma 

sodium level to be approximately 1 mEq/L per decade 

from a mean of 141 mEq/L in youth. 22 Hyponatremia in 

the inpatient is frequently iatrogenic, because of either 

fluid therapy or medications. Possibilities for medications—such 

as antidepressants, carbamazepine, clofibrate, 

and neuroleptics—to increase the secretion of ADH or 

enhancing the action of ADH at the tubule must also be 

considered. Hyponatremia is not a benign diagnosis 

because some studies have shown a twofold increase in 

mortality over age-matched control subjects. 2,22 

Hypernatremia developing in hospitalized elderly 

patients is most often attributable to surgery or febrile 

illness. Hypernatremia also has implications for mortality 

with a sevenfold increase in mortality compared with 

age-matched controls. 23 

Potassium Management 

Maintaining proper kidney function is crucial to potassium 

homeostasis, because the kidney is the primary 

organ for potassium excretion. Elderly patients are more 

susceptible to hyperkalemia, given the decrease in aldosterone 

and reduction in GFR. Undergoing surgery, tissue 

breakdown, or trauma also increases the risk of hyperkalemia 

especially if acute renal failure is present. Elderly 

patients are at increased risk of gastrointestinal bleeding, 

causing increased potassium levels as a result of red blood 

cell breakdown. Comorbid conditions may be present 

that affect flow to distal tubular sites, thus decreasing the 

amount of sodium available to enable potassium secretion. 

Examples of tubular flow-reducing diseases include 

hypovolemia, postsurgical or gastrointestinal losses, and 

congestive heart failure. 24 

Other risk factors present in elderly patients that 

may contribute to the risk of hyperkalemia include use 

of medications that increase potassium. Many elderly 

patients are prescribed diuretics, which may include the 

potassium-sparing diuretics spironolactone, triamterene, 

and amiloride. Prescription of thiazide diuretics may 

prompt the physician to include potassium supplementation 

as well. Patients may also be managing hypertension 

with salt-lowering diets, which are frequently high in


potassium salts. Angiotensin-converting enzyme inhibitors 

may cause hyperkalemia, because of reductions in 

aldosterone. Similarly, nonsteroidal antiinflammatory 

drugs can also result in a hyporeninemic hypoaldosterone 

state. Beta-blockers inhibit renin release in the kidney to 

cause hyperkalemia. Heparin blocks aldosterone synthesis 

in the adrenal gland, which may rarely cause elevated 

potassium. Trimethoprim-sulfamethazine acts similar to 

amiloride and inhibits the sodium channel in the apical 

membrane of the late distal tubule and collecting duct. 

This leads to a reduction of sodium and hydrogen transport 

into the urine. 24 

Regulation of Urinary Concentration 

Closely related to the kidney’s ability to process sodium 

is the kidney’s ability to alter the concentration of the 

urine produced. A well-designed study by Rowe et al. 25 

demonstrated that elderly patients were less able to significantly 

alter urine flow or urine osmolarity after 12 

hours of dehydration. This study also detailed that the 

differences were not attributable to differences in solute 

intake or correlated to a decreased GFR in the elderly. 

Other contributing factors may include a decrease in the 

efficacy of the countercurrent exchange system resulting 

from a relative increase in the medullary blood flow, or a 

possible defect in solute transport from the tubule to the 

medulla. The role of vasopressin has been investigated 

more recently. 26,27 These studies have shown that the 

osmoreceptor sensitivity is increased with increasing 

age to result in a great amount of vasopressin released 

per increase in osmolarity. This would seem to be compensatory 

for the reduced ability of the kidney to concentrate 

urine. However, the osmoreceptor does not seem 

to have increased sensitivity to changes in volume and 

pressure, such as those induced with orthostatic changes. 

More recent studies have produced conflicting results 

and failed to find a difference in overall ability to excrete 

a water load. 28–30 

Another aspect of water handling is thirst. A study by 

Phillips et al. 31 found that the elderly had less sensation 

of thirst and exhibited less water intake after a 24-hour 

period of dehydration compared with younger individuals, 

despite increases in plasma osmolarity and greater 

decreases in body mass. This defect is attributed to a 

defect in an opioid-mediated thirst center in the central 

nervous system. 

These altered physiologic responses are insignificant in 

maintaining daily homeostasis, but become increasingly 

important when access to free water is controlled. Treatment 

of electrolyte abnormalities is similar, regardless of 

age, but balancing comorbid conditions may complicate 

management. For instance, it has been shown that patients 

with Alzheimer’s disease have a decreased ADH sensitivity. 

Patients treated with thiazide diuretics have impaired 

ability to increase free water clearance during water 

diuresis. It is worth noting that elderly persons may have 

a lag in return to normal mentation after severe electrolyte 

abnormalities, despite clinical normalization of lab 

indicators. 

Acid-Base Abnormalities 

Acid-base balance is well maintained in the elderly 

patient under normal conditions. However, acute illness 

often results in acidosis that may become exaggerated in 

the elderly. The aged kidney has a decrease in ammonia 

generation which acts to buffer about half of the acid 

excreted in the kidney. This increases the frequency of 

severe metabolic acidosis. Coexisting pulmonary disease 

may also limit the ability to excrete carbon dioxide. 

Calcium, Phosphate, Magnesium 

Studies have shown that, at any given plasma level of 

calcium, concentration of parathormone is increased. 

Poor dietary intake, medications, and coexisting disease 

may result in calcium, magnesium, and phosphorus deficiencies. 

The existence of renal disease and impaired 

ability to excrete electrolytes must be considered when 

initiating therapy. 

Nutrition 

Perioperative nutrition affects fluid and electrolyte management 

in the elderly patient. It is also well known that 

a malnourished patient has a much higher likelihood for 

postoperative morbidity and mortality, also increasing 

the chance that the anesthesiologist will be further 

involved in their postoperative critical care management. 

Nutrition strongly affects surgical recovery by delaying 

wound healing, increasing risk of anastomotic breakdown, 

infection, and even possible development of multi– 

organ system failure. Hypoalbuminemia affects plasma 

oncotic pressure, thus altering the distribution of intravascular 

fluids. Electrolyte abnormalities are common in 

the malnourished patient. 

Debate exists about how best to identify and correct 

malnutrition. In theory, elective intervention can be preceded 

by preoperative supplemental nutrition. Parenteral 

nutrition carries the risk of infection, whereas enteral 

nutrition has the risk of aspiration pneumonia and invasive 

surgical placement. In a thorough meta-analysis 

of studies addressing preoperative parenteral nutrition, 

only severely malnourished patients demonstrated fewer 

noninfectious complications. Benefit was demonstrated 

if preoperative parenteral nutrition was provided for 

7 days or more. 32


Preoperative enteral nutrition studies demonstrate 

reduced postoperative mortality and decreased incidence 

of wound infections. 33–36 Difficulties encountered in 

implementing these therapies include the need to place 

nasogastric tubes or feeding tubes. Oral supplementation 

is less predictable in increasing calorie intake because of 

poor appetite, taste barriers, and limitations because of 

cost. 

Postoperative nutrition is more practical because many 

surgeries cannot be delayed. Studies have shown a significant 

increase in morbidity and mortality if a patient 

receives only hypocaloric feeding for more than 14 days. 37 

However, postoperative parenteral nutrition has been 

shown to increase morbidity in some studies mainly 

because of septic complications. Postoperative enteral 

nutrition supplementation has been shown to have very 

positive effects. Two studies of hip fracture repair in 

elderly women showed reduced length of hospital 

stay, shortened time to weight bearing, and more rapid 

return to independent mobility with the use of enteral 

supplementation. 38,39 

Clinical Implications 

The renal response to surgery and anesthesia does not 

seem to significantly alter with age. GFR is known to be 

directly depressed by general anesthesia; however, this 

is not usually clinically significant. Decreases in cardiac 

output and blood pressure, frequently attributable to 

intravascular losses and hypothermia in surgery, will 

decrease renal blood flow. Appropriately assessing and 

maintaining intravascular volume has the most impact on 

renal function in the perioperative period. Recognition 

and treatment of hypovolemia has the potential to reduce 

incidence of organ dysfunction, postoperative morbidity, 

and death. The elderly patient is at much higher risk of 

developing acute renal failure because of the lack of functional 

reserve of the kidney. Incidence of developing 

postoperative renal failure can range from 0.1% to 50% 

after high-risk surgeries such as trauma, thoracic, or cardiovascular 

interventions, depending on the site of 

surgery. Acute tubular necrosis is the most common cause 

of acute perioperative renal failure (Table 20-3). 

Mortality in patients with acute renal failure can 

be greater than 50%, and at least one fifth of all perioperative 

deaths in elderly surgical patients are attributable 

to acute renal failure. Patients with perioperative 

renal failure account for up to 50% of the patients needing 

acute dialysis. 40 Acute renal failure in the elderly increases 

morbidity and mortality, and also burdens the health 

care system with additional costs. Avoidance of complications 

resulting from inappropriate fluid management 

involves intervention at all stages of perioperative 

medicine. 

Table 20-3. Risk factors of acute tubular necrosis. 

Ischemic acute tubular necrosis 

Major surgery 

Trauma 

Severe hypovolemia 

Sepsis 

Extensive burns 

Toxic acute tubular necrosis 

Exogenous: radiocontrast, cyclosporine, antibiotics 

(aminoglycosides), chemotherapy (cisplatin), organic solvents 

(ethylene glycol), acetaminophen, illegal abortifacients. 

Endogenous: rhabdomyolysis, hemolysis, uric acid, oxalate, plasma 

cell dyscrasia (myeloma) 

Preoperative Evaluation 

There are several clinical conditions that merit additional 

attention to fluid balance. Preexisting azotemia prompts 

the clinician to look for correctable conditions before the 

perioperative period. Classification of renal dysfunction 

perioperatively is frequently delineated as prerenal, intrarenal, 

and postrenal. Chronic disorders such as enterocutaneous 

fistulas and chronic diarrhea can produce fluid and 

electrolyte depletion. Patients with chronic fluid imbalances 

may not have the typical signs and symptoms such 

as postural hypotension and tachycardia, making them 

more difficult to diagnose. Other important risk factors for 

elderly patients to develop hypovolemia include female 

sex, age older than 85 years, diagnosis of more than four 

chronic medical conditions, taking more than four medications, 

and being confined to bed 39 (Table 20-4). 

Physical examination remains important in diagnosing 

volume status. The most reliable clinical signs of hypovolemia 

are postural pulse increment and postural hypotension. 

A postural pulse increment of 30 beats/min or more 

has a specificity of 96%. 41 Postural hypotension is defined 

as a decrease in systolic blood pressure of more than 

20 mm Hg after rising from supine to standing position. 

With age, the increment in pulse can be less than 30 in a 

hypovolemic individual; however, there is no absolute 

cutoff level to indicate hypovolemia. Postural hypotension 

can also be found in 11%–30% of normovolemic 

patients older than 65 years. Mild postural dizziness is not 

definitive for hypovolemia; however, inability to stand for 

vital signs because of severe dizziness is a reliable predictor 

of hypovolemia. Skin turgor is less sensitive in elderly 

patients because of a reduction in skin elastin with age. 

Decreased axillary sweating can indicate hypovolemia. 

Invasive measurements of filling pressure and cardiac 

output may also be useful, but must be balanced with the 

inherent risk of invasive monitoring. 


Intrinsic renal failure is common perioperatively with the 

use of aminoglycosides, contrast dyes, and postoperative


Table 20-4. Adjusted odds ratios and 95% confidence intervals for significant risk factors among severe cases of dehydration. 

Strata 

Sex* 

Mobility* 

Age (years)* >85/4 chronic diseases 42.4 (16.8–106.4)‡ 53.6 (21.1–140.2)‡ (7.2–67.6) (3.8–18.6) 

>4 medications 30.7 (12.7–74.0)‡ 26.1 (11.3–61.6)‡ 65.0 (10.3–410.1)‡ 

Mobility: 

Assistance 11.5† 36.0† 

(2.9–45.2) (7.4–174.7) 22.6 (7.5–68.1)‡ — 

Bedridden 1.3 (3.9–17.9)‡ 7.6 (3.6–16.1)‡ — 

Feeding status: 19.0† 10.0† 

Assistance 30.0 (11.9–74.3)‡ 28.8 (11.5–71.6)‡ (3–122.0) (2.7–37) 

Tube 79.00† 17.01† 

(10.4–601.6) (5.4–52.9) 24.8 (9.3–67.1)‡ — 

45.0† 3.0† 

Skilled care level 4.2 (1.9–9.8)‡ 4.3 (1.9–9.4)‡ (6.5–310.9) (1.3–7.2) 

25.8† 5.9† 

Winter 14.8 (6.4–34.9)‡ 12.8 (5.5–28.8)‡ (8.3–74.4) (2.7–13.3) 

*Pooled where appropriate using χ 2 heterogeneity test. All are statistically significant at p = 0.05. Confidence intervals calculated using test-based 

interval estimation. 

†Not pooled based on heterogeneity score. 

‡Pooled, signifi cant with 95% confidence intervals. 

Source: Reprinted with permission from Lavizzo-Mourey et al. 39 Published by Blackwell Publishers Ltd. 

effects of cardiac bypass. Certain surgeries have increased 

risk of postoperative renal failure, such as cardiac or 

aortic surgery, as well as any surgery involving large fluid 

shifts, trauma patients, or the biliary tract. The risk of 

postoperative renal dysfunction in open abdominal aortic 

aneurysm repair is increased in emergency surgery 

and in incidences of increased length of cross-clamp 

duration and sustained hypotension. Dislodgement of 

atheromatous emboli may also occur in aortic repair. 

The mechanism of renal dysfunction after biliary tract 

surgery is unknown, but associated risk factors include 

postoperative sepsis, prior renal insufficiency, and height 

of preoperative bilirubin concentration. Preventing 

muscle compression and breakdown must also be considered 

in lengthy surgeries to decrease myoglobinuria. 

Postrenal azotemia should also be suspected, because 

elderly patients may have prostatic hypertrophy or 

nephrolithiasis. 24,42 

Several papers have addressed the best methods for 

determining the need for fluid administration in perioperative 

patients. These studies link fluid balance with 

its effect on hemodynamic stability. The Starling curve 

describes the effect of volume loading on myocardial 

performance. Starling curves (Figure 20-2) illustrate the 

relationship between preload and cardiac output. Administration 

of a volume of fluid can increase preload and 

thus increase cardiac output. Beyond a certain amount of 

fluid administration, further increases in end-diastolic 

volume can decrease ventricular function and cardiac 

output. 

From a physiologic standpoint, fluid management can 

be guided by physical signs and symptoms of hemodynamic 

stability, or more quantitative methods such as 

information from esophageal Doppler monitors, central 

venous catheters, or pulmonary artery catheters. The 

standard measures of volume status in the anesthetized 

patient are blood pressure, heart rate, oxygen saturation, 

Cardiac output 

Fluid administration 

improves myocardial 

performance 

Fluid volume administered 

Fluid administration 

impairs myocardial 

performance 

Figure 20-2. Effects of perioperative fluid therapy on the 

Starling myocardial performance curve. (Reprinted from Holte 

et al. 3 Copyright © The Board of Management and Trustees of 

the British Journal of Anaesthesia. Reproduced by permission 

of Oxford University Press/British Journal of Anaesthesia.)


and urine output. Interpretation of blood pressure 

and heart rate is frequently altered by many different 

variables in the perioperative patient, including sympathetic 

responses to surgical stimulus, anxiety and pain 

responses, and side effects of medications and anesthetic 

agents. Urine output is unreliable as well. Because of the 

depressive effects of general anesthesia, the common goal 

of 0.5 mL/kg/h of urine production is typically attained 

only with a fluid load. Meanwhile, studies have demonstrated 

that a low intraoperative urinary output did not 

correlate with development of renal failure, as long as 

hypovolemia was avoided. 43 Furthermore, excretion of 

a fluid excess of 1.5–2 L can take up to 2 days in healthy 

volunteers, which is an approximate indicator of the 

increased workload on the kidney with excessive fluid 

administration. 3 

A 2002 study 44 focused on the use of esophageal 

Doppler monitoring to guide fluid administration during 

the intraoperative period for moderate-risk surgical 

patients. The authors hypothesized that appropriate fluid 

resuscitation may decrease the extent of postoperative 

gastrointestinal dysfunction, reduce time to ability to tolerate 

oral intake, and ultimately reduce length of hospital 

stay. This prospective, single-blinded study compared 

fluid administration guided by esophageal Doppler, to 

administration guided by standard cardiovascular variables 

(blood pressure, heart rate, oxygen saturation), 

with significantly more hetastarch in the protocol group 

(847 ± 373 mL) compared with the control group 

(282 ± 470 mL). The study demonstrated a reduction in 

hospital stay in the Doppler-guided protocol group. 

Several studies of perioperative fluid optimization 

targeted repair of proximal femoral fractures. This is a 

common procedure for elderly and frail patients, typically 

straightforward surgically, with outcome determined by 

medical comorbidities. Avoidance of hypovolemia is 

important; however, fluid overload is also of particular 

concern in this patient population with cardiac and pulmonary 

comorbidities. Sinclair et al. 45 conducted a 

randomized controlled trial of proximal femoral fracture 

repairs with fluid administration guided by an esophageal 

Doppler monitor that demonstrated reduction of hospital 

stay. Because of the data obtained from Doppler monitoring, 

the intervention group received a larger volume 

of colloid, with approximately equal amounts of crystalloid 

received in both groups. Venn et al. 46 concluded a 

similar study with fluid management guided by central 

venous pressure (CVP) or esophageal Doppler, also 

demonstrating a reduction in duration of hospital stay 

in patients with fluid optimization guided by quantitative 

strategies. The drawback of both of these studies is the 

small number of participants, only 130 total, which is 

inadequate to detect changes in early mortality or to 

detect particular subgroups that might especially benefit 

from guided fluid administration. 47 

The studies above describe guided fluid administration 

via goals for stroke volume or CVP, and assessment of 

changes in these variables in response to additional fluid 

boluses. Additional studies focused on using quantitative 

data to produce supranormal physiologic parameters and 

assess the effects on outcomes. Shoemaker et al. 48 in 1988 

observed that survivors of high-risk surgery had increased 

hemodynamic and oxygen transport variables. They conducted 

a prospective randomized trial to determine if 

optimization of hemodynamic and oxygen transport 

variables to supranormal values would affect outcome. 

This study demonstrated that optimization to supranormal 

values with the use of pulmonary artery catheter 

data reduced complications, duration of hospitalization, 

decreased time in the intensive care unit (ICU), decreased 

duration of mechanical ventilation, and reduced hospital 

cost. The authors caution that use of supranormal physiologic 

parameters may be inappropriate for the elderly 

patient because of a possible limited capacity for physiologic 

compensation. Scalea et al. 49 showed an improvement 

in survival rate in patients older than 65 years when 

early hemodynamic monitoring was instituted within 2.2 

hours from sustaining diffuse blunt trauma, and using this 

information to augment cardiac output. Although these 

approaches may be appropriate in younger patients with 

sepsis, they may lead to increased morbidity and mortality 

in the presence of multiple comorbidities. Therefore, 

more studies are needed in the elderly before such an 

approach is routinely adopted. 

Discussion about the appropriate fluid to use in volume 

resuscitation continues for all perioperative patients. Use 

of crystalloid is supported by many practitioners for its 

economy. They cite colloid use as having potential alterations 

in coagulation factors and risk of adverse drug reactions. 

Colloid supporters cite the benefit of using a smaller 

amount of fluid to resuscitate a patient, which may lead 

to less tissue edema and fewer adverse consequences, 

such as pulmonary edema and bowel dysfunction. Re - 

cently there have been three meta-analyses focusing on 

the use of colloid versus crystalloid in patients requiring 

volume resuscitation and the effect on mortality (Tables 

20-5 and 20-6). None of these studies has demonstrated 

a mortality benefit with the use of colloid. These conclusions 

have been criticized for their combination of heterogeneous 

populations, use of many types of solutions, 

and varying indications for use. 50–52 The SAFE study, 

which is the largest trial of its kind as of this writing, 

demonstrated no appreciable difference in outcomes 

with the use of either 4% albumin or normal saline for 

intravascular volume resuscitation. 53 The multicenter, 

randomized, double-blind 28-day study included a diverse 

cohort of 6997 ICU patients with analogous baseline 

characteristics. These results demonstrate that albumin 

and saline can be considered clinically comparable 

treatments. The choice of fluid for intravascular volume

Table 20-5. Summary of results of studies comparing colloid versus crystalloid for resuscitation in critically ill patients. 

Review: Colloids versus crystalloids for fluid resuscitation in critically ill patients 

Comparison: 01 colloid vs crystalloid (add-on colloid) 

Outcome: 01 deaths 

Study Colloid n/N Crystalloid n/N Relative risk (fixed) 95% CI Weight (%) Relative risk (fixed) 95% CI 

01 Albumin or PPF 

x Boldt 1986 0/1 0/1 0.0 Not estimable 


Boutros 1979 0/7 2/17 0.2 0.45 [0.02, 8.34] 

x Gallagher 1985 0/5 0/5 0.0 Not estimable 

Goodwin 1983 11/40 3/39 0.4 3.57 [1.08, 11.85] 

Grundmann 1982 1/14 0/6 0.1 1.40 [0.06, 30.23] 

Jelenko 1978 1/7 1/5 0.2 0.71 [0.06, 8.91] 

Lowe 1977 3/77 4/94 0.5 0.92 [0.21, 3.97] 

Lucas 1978 7/27 0/27 0.1 15.00 [0.90, 250.25] 

Metildi 1984 12/20 12/26 1.4 1.30 [0.75, 2.25] 

x Prien 1990 0/6 0/6 0.0 Not estimable 

Rackow 1983 6/9 6/8 0.8 0.89 [0.48, 1.64] 

SAFE 2004 726/3473 729/3460 95.0 0.99 [0.91, 1.09] 

Shah 1977 2/9 3/11 0.4 0.81 [0.17, 3.87] 

x Shires 1983 0/9 0/9 0.0 Not estimable 

Tollofsrud 1995 0/10 1/10 0.2 0.33 [0.02, 7.32] 

Virgilio 1979 1/15 1/14 0.1 0.93 [0.06, 13.54] 

Woittiez 1997 8/15 4/16 0.5 2.13 [0.81, 5.64] 

Zetterstrom 1981a 0/15 1/15 0.2 0.33 [0.01, 7.58] 

Zetterstrom 1981b 2/9 0/9 0.1 5.00 [0.27, 91.52] 

Subtotal (95% CI) 780/3783 767/3793 100.0 1.02 [0.93, 1.11] 

Test for heterogeneity chi-square = 13.88 df = 14 p = 0.4584 

Test for overall effect = 0.41 p = 0.7 

02 Hydroxyethylstarch 



x Dehne 2001 0/45 0/15 0.0 Not estimable 

x Lang 2001 0/21 0/21 0.0 Not estimable 

Nagy 1993 2/21 2/20 12.0 0.95 [0.15, 6.13] 

Prien 1990 1/6 0/6 2.9 3.00 [0.15, 61.74] 

Rackow 1983 5/9 6/8 37.2 0.74 [0.36, 1.50] 

x Sirieix 1999 0/8 0/8 0.0 Not estimable 

Woittiez 1997 13/27 4/16 29.5 1.93 [0.76, 4.90] 

Younes 1998 2/12 3/11 18.4 0.61 [0.12, 3.00] 

Subtotal (95% CI) 23/229 15/145 100.0 1.16 [0.68, 1.96] 



03 Modified gelatin 



Evans 1996 1/11 2/14 27.3 0.64 [0.07, 6.14] 

x Ngo 2001 0/56 0/111 0.0 Not estimable 

Tollofsrud 1995 0/10 1/10 23.3 0.33 [0.02, 7.32] 

x Wahba 1996 0/10 0/10 0.0 Not estimable 

Wu 2001 2/18 3/16 49.4 0.59 [0.11, 3.11] 

Subtotal (95% CI) 3/145 6/201 100.0 0.54 [0.16, 1.85] 



04 Dextran 

Dawidson 1991 1/10 1/10 1.5 1.00 [0.07, 13.87] 

Hall 1978 18/86 16/86 24.7 1.13 [0.62, 2.06] 

Karanko 1987 0/14 1/18 2.0 0.42 [0.02, 9.64] 

x Modig 1983 0/14 0/17 0.0 Not estimable 

x Ngo 2001 0/55 0/111 0.0 Not estimable 

Tollofsrud 1995 0/10 1/10 2.3 0.33 [0.02, 7.32] 

Vassar 1993a 21/89 11/85 17.4 1.82 [0.94, 3.55] 

Vassar 1993b 49/99 20/50 41.1 1.24 [0.83, 1.83] 

Younes 1992 7/35 7/35 10.8 1.00 [0.39, 2.55] 

Subtotal (95% CI) 96/412 57/422 100.0 1.24 [0.94, 1.65] 



0.01 0.1 1 10 100 

favors colloid favors crystalloid 

Source: Reprinted with permission from Alderson. 51 Copyright Cochrane Library. 

CI = confidence interval, PPF = plasma protein fraction, df = degrees of freedom; x = relative risk not estimable.


Table 20-6. Summary of results of studies comparing colloid versus crystalloid for resuscitation in critically ill patients. 

Review: Colloids versus crystalloids for fluid resuscitation in critically ill patients 

Comparison: 02 colloid and hypertonic crystalloid versus isotonic crystalloid 

Outcome: 01 deaths 

Treatment Control Relative risk (fixed) Weight Relative risk (fixed) 

Study n/N n/N 95% CI (%) [95% CI] 

01 Albumin or PPF 

Jelenko 1978 1/7 2/7 100.0 0.50 [0.06, 4.33] 

Subtotal (95% CI) 1/7 2/7 100.0 0.50 [0.06, 4.33] 

Test for heterogeneity chi-square = 0.00 df = 0 


02 Hydroxyethylstarch 

Subtotal (95% CI) 0/0 0/0 0.0 Not estimable 



03 Modified gelatin 

Subtotal (95% CI) 0/0 0/0 0.0 Not estimable 



04 Dextran 

Chavez-Negrete 1991 1/26 5/23 2.9 0.18 [0.02, 1.41] 

Mattox 1991 35/211 42/211 22.6 0.83 [0.56, 1.25] 

Vassar 1990 12/23 13/24 6.8 0.96 [0.56, 1.65] 

Vassar 1991 30/83 34/83 18.3 0.88 [0.60, 1.30] 

Vassar 1993a 21/89 14/84 7.7 1.42 [0.77, 2.60] 

Vassar 1993b 49/99 23/45 17.0 0.97 [0.68, 1.37] 

Younes 1992 7/35 8/35 4.3 0.88 [0.36, 2.15] 

Younes 1994 27/101 40/111 20.5 0.74 [0.49, 1.11] 

Subtotal (95% CI) 182/667 179/616 100.0 0.88 [0.74, 1.05] 



Source: Reprinted with permission from Alderson. 51 Copyright Cochrane Library. 

CI = confidence interval, PPF = plasma protein fraction, df = degrees of freedom. 

0.01 0.1 1 10 100 

resuscitation is ultimately governed by the clinician’s 

preference and the patient’s ability to tolerate the treatment. 

Specific studies addressing the use of colloid versus 

crystalloid exclusively in the elderly population have not 

been performed. 


Postoperative management must include continued vigilance 

in fluid balance. Early resumption of oral intake 

should be encouraged. Fluid losses from all sites must be 

accurately accounted and carefully replaced. Insensible 

losses should be replaced, typically in the range of 500– 

1000 mL/day in afebrile patients. Free water replacement 

is guided by serum sodium concentration. Third space 

losses, such as postoperative ileus, are deposits for extracellular 

fluids. Continued attention to the use of nephrotoxic 

drugs is imperative in maintaining renal function. 

Good urine output postoperatively is a good indication 

of renal function and fluid balance. Creatinine measurements 

and creatinine clearance measurements are useful 

in patients with higher risk of postoperative acute tubular 

necrosis. 

Special Situations: Regional Anesthesia 

Regional anesthesia merits additional consideration when 

attempting appropriate fluid management in the perioperative 

period. Spinal anesthesia inhibits the release of 

norepinephrine of sympathetic efferent nerves at the vascular 

smooth muscle cells, the sinoatrial node, the atrioventricular 

node, and the muscle cells of the heart. The 

degree of sympathetic blockade is determined by the 

spread of local anesthetics in the intrathecal fluid. Studies 

have shown that sympathetic blockade extends several 

dermatomes above the level of sensory blockade, thus 

producing hypotension with even a modest degree of 

sensory inhibition. 54 The response to the effects of sympathetic 

blockade is sensed by the vagus nerve input to the 

baroreflex receptor; however, the subsequent response of


the baroreflex is limited by the amount of vascular bed 

remaining for vasoconstriction. 

Management of fluids during spinal anesthesia in the 

elderly can pose a conflict between competing physiologic 

concerns. The need to avoid hypotension is apparent, but 

the desire to limit fluid overload must also be considered. 

Additionally, it should be considered if the elderly have 

exaggerated responses to spinal anesthesia compared with 

younger patients. Elderly patients have increased sympathetic 

tone at rest, which may cause more dramatic changes 

in hemodynamics if vascular resistance is abruptly altered 

by spinal anesthesia. The aged heart is also less responsive 

to beta receptor stimulation triggered by the baroreflex to 

increase contractility and heart rate. In addition, this population 

may be especially sensitive to acute intravascular 

volume changes, because of a more preload-dependent 

aged ventricle with possible diastolic dysfunction. 

Studies are limited that directly compare young and 

elderly patients. Young patients have an average of 10% 

decreases in vascular resistance and cardiac output. 

Elderly patients with a median block of T4 have an 

average 10% decrease in cardiac output, but a larger 26% 

decrease in systemic vascular resistance. 55 Hypotension 

with spinal anesthesia is prevalent, occurring in up to 

60% of patients with sympathetic blockade higher than 

T7. 56 The appropriate treatment for this hypotension has 

been examined. Crystalloid preloading has been shown 

to have no effect on the incidence of hypotension in 

spinal anesthesia. Treatment with a vasopressor is appropriate 

if systolic blood pressure decreases by more than 

25% of baseline, or below 90 mm Hg. Ephedrine is often 

used; however, it may be less effective in the elderly 

patient. A pure vasoconstrictor may seem appropriate 

because the primary mechanism of hypotension is 

decreased systemic vascular resistance. This may have 

adverse effects on coronary vascular resistance and afterload. 

Epinephrine can also be considered in small doses 

to provide some vasoconstriction, with minimal effect on 

blood pressure. Excessive tachycardia should be avoided. 

Fluid overload should also be avoided to reduce risk of 

adverse outcomes such as pulmonary edema, congestive 

heart failure, bowel dysfunction, and prolonged fluid 

retention. If hypotension is minimized, cardiac performance 

is minimally affected by spinal anesthesia and safe 

for patients with preexisting cardiac disease as well. 55 

Currently, there is no best way to approach fluid management 

with regional anesthesia, and either additional fluid 

administration or use of vasopressors is appropriate. 

Perioperative Transfusion in the Elderly 

A discussion of fluid management should also take into 

account the need for repletion of blood products and 

the effect on fluid requirements. Blood transfusion is an 

extensively studied and discussed topic of medical care. 

Approximately 12 million units of red blood cells are 

transfused each year. Each unit of blood costs about $217 

per patient, for a total cost of more than $2 billion a year. 

A large majority, 60%–70% of transfusions, occur in the 

perioperative period. 57 The need for rational decision 

making concerning blood transfusion is obvious. The 

following discussion will focus on transfusion of red 

blood cells. 

Administration of blood-component therapy in a 

patient of any age must take into account the indications 

for the treatment, the risks, and the benefits of treatment. 

The objective of red blood cell transfusion is improvement 

of inadequate oxygen delivery. The use of perioperative 

transfusion assumes that surgical patients 

experience adverse outcomes as a result of diminished 

oxygen-carrying capacity, and that transfusion can prevent 

these adverse outcomes. The most serious effect of anemia 

and reduction of oxygen-carrying capacity is myocardial 

ischemia. Younger patients with less comorbidity may 

tolerate altered perfusion to less vessel-rich organs well; 

however, the elderly patient may have more significant 

long-term morbidity. 

The decision to transfuse a patient in the periopera - 

tive period requires consideration of several factors. The 

National Heart, Lung, and Blood Institute Consensus 

Conference recommends considering the following: duration 

of anemia, intravascular volume, hemodynamic stability, 

extent of operation, probability for massive blood 

loss, and comorbidities such as impaired pulmonary 

function, decreased cardiac output, myocardial ischemia, 

cerebrovascular or peripheral vascular disease. 58 

Correlations between acute changes in intravascular 

volume and hemodynamic stability have been defined 

previously. The American College of Surgeons has classified 

hypovolemia caused by blood loss according to signs 

and symptoms. 59 Class I hemorrhage is a loss of up to 

15% of blood volume and usually causes vasoconstriction 

and mild tachycardia. Class II hemorrhage is attributable 

to a loss of 15%–30% of blood volume, and produces 

tachycardia and decreased pulse pressure. Patients who 

are awake may exhibit anxiety or restlessness. Class III 

hemorrhage is attributable to 30%–40% of blood volume 

loss, and causes marked tachycardia, tachypnea, hypotension, 

and altered mental status. Class IV hemorrhage, 

occurring after loss of more than 40% of blood volume, 

results in marked tachycardia, hypotension, narrow pulse 

pressure, decreased urine output, and markedly depressed 

mental status. 

Use of physical signs may be helpful perioperatively, 

but may not be as reliable for the anesthetized patient. 

Measurements of vital signs that typically indicate anemia 

or hypovolemia may be altered by the depressant effects 

of general anesthetics. Signs of organ ischemia under 

anesthesia can be subtle. Intraoperative myocardial


ischemia is associated with tachycardia in only 26% of 

patients, and hypotension in less than 10%. Perioperative 

cardiac ischemia is often silent. Ischemic events may 

occur during a period of decreased monitoring in the 

postoperative period because of pain, fever, shivering, 

or physical activity. Invasive monitoring can provide 

additional parameters to measure blood volume, but 

introduce other risk factors. Blood pressure measurement, 

oxygen delivery, and oxygen extraction are global 

indicators, but are not representative of organ-specific 

oxygen delivery. 

Estimation of surgical blood loss is routinely recorded 

by the anesthesiologist. Intraoperative blood loss is typically 

estimated by examining the surgical field, collected 

blood in suction containers, and the presence of sponges 

saturated with blood. These estimates are notoriously 

inaccurate. Laboratory evidence of hemorrhage is used 

to supplement decision making in the operative period. 

However, intercompartmental fluid shifts during surgery 

and the dilutional effects of crystalloid therapy can make 

intraoperative hemoglobin concentrations unreliable 

representations of clinical status. 

The patient’s ability to tolerate acute anemia is altered 

by general anesthesia as well. Most anesthetics decrease 

myocardial function, resulting in decreased blood pressure, 

cardiac output, stroke volume, peripheral vascular 

resistance, and oxygen consumption. Depression of the 

central nervous system also decreases cerebral metabolic 

demands. Hypothermia also reduces metabolic rate. 

Anesthetics may affect the body’s ability to compensate 

for anemia by reducing the ability to augment cardiac 

output in response to hypovolemia. Decreased hepatic 

blood flow may inhibit the ability to metabolize lactic 

acid, thus worsening an acid-base abnormality due to 

decreased perfusion. Compensatory factors such as 

augmenting cardiac output may be inhibited by pharmacologic 

interventions, such as beta-blockade or use of 

calcium channel blockers. The complexity of these alterations 

defies simple prediction for the need for blood 

transfusion therapy. Evidence-based evaluation of bloodcomponent 

therapy and established guidelines are most 

helpful in making these difficult clinical decisions. The 

additional confounding factors of increased age and 

comorbidity make the issue increasingly complex. 

The consideration of the risks of blood transfusion 

must also be balanced in the decision to transfuse. Frequently 

cited risks include nonhemolytic transfusion 

reaction, transfusion reactions, transmission of infectious 

disease, and possible effects of immunosuppression. 

The initial recommendations concerning transfusion 

focused on calculations, stating that oxygen availability 

to tissues may be decreased when hemoglobin decreases 

below 10 g/dL. Clinical experience has repeatedly demonstrated 

that hemoglobin values less than 10 g/dL are 

well tolerated in the perioperative period. Other studies 

have demonstrated that cardiac output begins to increase 

dramatically as hemoglobin decreases below 7 g/dL. A 

recent study illustrates the effect of hemoglobin levels 

on mortality and morbidity in the perioperative period. 

A retrospective study by Carson et al. 60 examining 1958 

patients, aged 18 and older, that declined blood prod - 

ucts during the perioperative period found that overall 

mortality increased with decreasing hemoglobin. Also, 

patients with underlying cardiovascular disease defined 

as congestive heart failure, angina pectoris, or peripheral 

vascular disease, had a greater risk of death at any given 

hemoglobin concentration, compared with patients 

without cardiovascular disease (Table 20-7). 

The mortality risk greatly increased when hemoglobin 

concentration decreased to below 10 g/dL. Risk of death 

was extremely high when hemoglobin concentration 

decreased below 5–6 g/dL. 60 This information is helpful in 

demonstrating the effect of anemia, but does not address 

a decrease in risk of death as a result of receiving transfusions. 

The most important randomized study in assessing 

blood transfusion therapy was the Transfusion Require- 

Table 20-7. Adjusted odds ratio (95% confidence interval) for mortality and preoperative hemoglobin and decline in hemoglobin 

stratified by cardiovascular disease. 

Decline


ments in Critical Care (TRICC) study. 61 This was the only 

randomized trial with adequate power to evaluate clinical 

outcomes of anemia and transfusion practices. A group 

of 833 volume-resuscitated patients in the ICU were randomized 

to a liberal or restrictive transfusion threshold 

level. The restrictive group received transfusions at a 

hemoglobin concentration less than 7g/dL and was maintained 

at a hemoglobin between 7 and 9 g/dL. The liberal 

transfusion threshold group was transfused for hemoglobin 

concentrations less than 10 g/dL and maintained 

between 10–12 g/dL. The findings were not statistically 

significant; however, 30-day mortality was lower in the 

restrictive transfusion group. The restrictive transfusion 

group had a relative reduction in transfusion of 55%, 

which could result in significant cost savings. Further 

analysis identified a subgroup of patients that were 

younger than 55 years and less severely ill (as defined by 

APACHE II scores less than 20) in the restrictive transfusion 

strategy who were half as likely to die (p < 0.02) 

within the 30-day period, compared with the liberal transfusion 

strategy. 62 Another subgroup in this study consisted 

of 257 patients with ischemic heart disease. This 

group had a nonsignificant (p = 0.3) decrease in overall 

survival among those patients treated with the restrictive 

therapy regimen. Further investigation is required to 

determine groups that may benefit from a higher transfusion 

threshold, such as patients with cardiac disease, 

emphysema, more severe illness, cerebrovascular disease, 

trauma, and older patients. Patients with cardiac disease 

may be unable to tolerate compensatory responses to 

hypovolemia and anemia, such as increasing cardiac 

output and heart rate. Increasing chronotropy decreases 

coronary artery filling time and reduces blood flow to 

the endocardium at a time when metabolic demands are 

increased. As a result, myocardial ischemia may result at 

higher hemoglobin values of 20–30 g/dL. 

As yet, there are no randomized clinical trials that 

evaluated transfusion thresholds in patients with cardiovascular 

disease. Several observational studies have provided 

some insight but have come to different conclusions. 

In a group of 190 elderly patients undergoing radical 

retropubic prostatectomy, patients with a hematocrit of 

less than 28 were at a significantly higher risk of myocardial 

ischemia intraoperatively and postoperatively. 

Hematocrit levels also correlated with the duration of 

myocardial ischemic episodes. 63 Similarly, a group of 27 

high-risk patients undergoing infrainguinal arterial 

bypass procedures, who were monitored for 80 hours 

postoperatively, were determined to have a higher risk of 

morbid cardiac events when hematocrit decreased to less 

than 28%. 64 A retrospective study of more than 78,000 

Medicare patients older than 65 years admitted with 

acute myocardial infarction who received a blood transfusion 

had a decrease in short-term mortality when the 

patient’s admission hematocrit was less than 33%. Lower 

hemoglobin values correlated with more frequent in-hospital 

events, such as heart failure, shock, and death and 

with increased length of hospital stay. 65 However, a recent 

analysis in 24,112 patients enrolled in three clinical trials 

with acute coronary syndrome came to the opposite conclusion. 

66 Patients receiving blood transfusion had about 

a three- to fourfold higher risk of death and myocardial 

infarction than patients not receiving transfusion. Finally, 

a retrospective cohort study of 3783 patients with cardiovascular 

disease undergoing hip fracture repair found 

that postoperative transfusion at a hemoglobin of 8 g/dL 

or higher did not influence mortality. 67 Thus, large clin - 

ical trials are needed to provide high-quality evidence to 

guide transfusion decisions in patients with cardiovascular 

disease. 

There are few high-quality studies that establish the 

critical transfusion thresholds. The best evidence comes 

from the TRICC trial, which found a 7 g/dL threshold 

was at least as safe, and may be preferable, to a 10 g/dL 

threshold in critical care patients. Whether these results 

are applicable to geriatric patients undergoing surgery is 

unknown. Pending additional clinical trials, the best 

data suggest that a restrictive transfusion trigger (7 g/dL) 

should be used in most patients. It is unclear whether a 

higher transfusion threshold, 9–10 g/dL, should be used in 

patients with cardiovascular disease. 

The American Society of Anesthesiologists evidencebased 

guidelines for transfusion therapy from 1994 are 

still relevant today. Selected recommendations as related 

to red blood cell transfusion are summarized below 57 : 

1. Transfusion is rarely indicated at hemoglobin levels 

greater than 10 g/dL, and is almost always indicated when 

hemoglobin is less than 6 g/dL. 

2. Transfusion of a patient with a hemoglobin concentration 

between 6–10 g/dL is based on the patient’s risk 

for complications as a result of inadequate oxygenation. 

3. Use of a single hemoglobin “trigger” or other 

approaches that do not consider physiologic and surgical 

factors regarding oxygen delivery requirements is not 

recommended. 

4. Preoperative autologous blood donation, intra - 

operative blood recovery, acute normovolemic hemodilution, 

and physiologic or pharmacologic measures to 

decrease blood loss may be beneficial. However, in our 

opinion, these methods have not been established to 

work, and their application is at least very limited. These 

methodologies result in cell salvage with significant blood 

loss, and normovolemic hemodilution has not been established 

to be effective, because it results in a need to make 

patients more anemic than can be tolerated. 

5. Indications to transfuse autologous red blood cells 

may be more liberal than allogeneic red blood cells. We 

do not agree with this recommendation, because the risk 

of mislabeling may still lead to risks at transfusion.


Conclusion 

The elderly patient is a challenge to the anesthesiologist 

because of the tremendous variability of their physiologic 

conditions. This is often combined with a limited ability 

to provide accurate clinical history. The goal of this discussion 

of fluid management in the elderly is to provide 

a summary of the known data concerning fluid management 

and patients in the perioperative period. These data 

can be combined with knowledge of a patient’s comorbidities 

and used as a basis to inform clinical decision 

making for specific patients. Perhaps the most important 

and difficult concept for clinicians to grasp is that few 

generalizations will hold for all elderly patients, and 

careful observation and adaptability in treatment may 

prove most beneficial for the patient. 

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ischemic episodes are related to hematocrit level 

in patients undergoing radical prostatectomy. Transfusion 

1998;38:924–931. 

64. Nelson AH, Fleisher LA, Rosenbaum SH. Relationship 

between postoperative anemia and cardiac morbidity in 

high-risk vascular patients in the intensive care unit. Crit 

Care Med 1993;21:860–866. 

65. Wei-Chih W, Rathore S, Wang Y, Radford M, Krumholz H. 

Blood transfusions in elderly patients with acute myocardial 

infarction. N Engl J Med 2001;345(17):1230–1236. 

66. Rao SV, Jollis JG, Harrington RA, et al. Relationship of 

blood transfusion and clinical outcomes in patients with 

acute coronary syndromes. JAMA 2004;292(13):1555– 

1562. 

67. Carson JL, Duff A, Berlin JA, et al. Perioperative blood 

transfusion and postoperative mortality. JAMA 1998; 

279(3):199–205.

21 

Pain Management 

Jack M. Berger 

The United States senior population is expected to double 

over the next 30 years (www.agingstats.gov). According 

to the latest data from the National Center for Health 

Statistics, 40.3 million inpatient surgical procedures were 

performed in the United States in 1996, followed closely 

by 31.5 million outpatient surgeries. These statistics are 

from 1996 and although the ratio of outpatient to inpatient 

procedures may have changed in the past 10 years, 

the total number of surgical procedures per year has not 

diminished. And certainly, the elderly undergo a disproportionate 

number of surgical procedures compared with 

younger age groups. Therefore, acute pain secondary to 

surgery will continue to be a significant problem for 

physicians. 

In addition, estimates are that 80%–85% of individuals 

over 65 years old have at least one significant health 

problem that predisposes them to pain. Epidemiologists 

at Brown University (reporting in JAMA, June 17, 1998) 

found that between 25%–40% of older cancer patients 

studied had daily pain. Among these patients, 21% 

between the ages of 65 and 74 received no pain medication 

at all. Of those 75–84 years old, 26% received no pain 

medication, and for those older than 85, 30% were left 

untreated. 1 

In northern California, Jury Verdict No. H205732–1 of 

the California Superior Court awarded $1.5 million to the 

family of an elderly lung cancer patient in a civil suit in 

which the physician was found liable for recklessness and 

elder abuse for failure to prescribe adequate pain medication. 

This resulted in California Assembly Bill 487 that 

now requires every physician in California to obtain 12 

continuing medical education credits in pain management 

and palliative care in the next 3 years in order to 

renew their license. And so as much as providing adequate 

pain management is a moral obligation, inadequate 

pain management has become a liability. 

There are about 1.5 million frail elderly residing in 

20,000 nursing homes in the United States. Forty percent 

are over the age of 85 years. Forty-five percent to 85% 

may have pain as compared with 25%–50% of community-dwelling 

elderly. 2,3 A telephone poll conducted by 

Cooner and Amorosi from Louis Harris and Associates 

of New York City in 1997, revealed that more than half of 

older adults had taken prescription pain medications for 

longer than 6 months, and 45% had visited at least three 

physicians for their pain in the last 5 years. 4 New pain 

visits to physicians are most common in the 15- to 44-yearold 

group, whereas the lowest are in the elderly. Persistent 

pain complaints, however, are most common in the elderly, 

and pain is the most common symptom noted by the consulting 

physician. 5 Yet elderly people and young children 

are often perceived by the health care delivery system as 

being insensitive to pain. And therefore those who are 

most dependent on the health care system are most likely 

to receive the least optimal care for pain. 

Pain is a highly subjective, variable sensory and emotional 

experience, with a pathophysiology composed of 

complex neuroanatomic and neurochemical processes. 6 

Everyone has an intuitive idea of what pain is. Pain is 

always something that “hurts.” But many things hurt. A 

broken arm hurts. This is an example of acute somatic 

pain. A heart attack hurts. This is ischemic pain. A kidney 

stone and appendicitis hurt, which are examples of visceral 

pain. An amputated leg may hurt; this is phantom 

limb pain. An individual may hurt in the arm or leg on 

the side affected by a stroke. Both of these are examples 

of central neuropathic pain. The death of a loved one 

“hurts.” It is a “painful emotional experience” for which 

we use the same words of description as for physical 

injury. It is clear then that the perception of “pain” is 

always subjective and takes place in the brain. Tissue 

injury is perceived as nociception. But the site of the 

nociception does not necessarily correspond to the area 

of the body in which “the pain” is felt. Furthermore, the 

tissue injury may have actually healed while the perception 

of pain persists. 

308

21. Pain Management 309 

Three Pain Scenarios 

It is quite clear from the above introduction that pain in 

the elderly follows one of three scenarios: 

1. Acute pain results from surgery, cancer, fractures, 

medical conditions such as vascular ischemia, herpes 

zoster. 

2. Chronic pain results from various persistent medical 

and physical conditions. Specific chronic pain syndromes 

that are known to affect the geriatric population disproportionately 

include: arthritis which may affect 80% of 

patients over 65, cancer, herpes zoster and postherpetic 

neuralgia, temporal arteritis, polymyalgia rheumatica, 

atherosclerotic peripheral vascular disease, diabetic neuropathy, 

and back pain syndromes. 6 In chronic pain states, 

there is often the absence of the “normal” physiologic 

indicators of acute pain such as tachycardia, hypertension, 

and diaphoresis. Yet, there may be hyperpathia, allodynia, 

and hyperalgesia in the absence of any physical 

findings of tissue injury: 

• Allodynia is pain elicited by a nonnoxious stimulus 

(clothing, air movement, touch), mechanical (induced 

by light pressure), thermal (induced by a nonpainful 

cold or warm stimulus). 

• Hyperalgesia is exaggerated pain response to a 

mildly noxious (mechanical or thermal) stimulus. 

• Hyperpathia is delayed and explosive pain response 

to a noxious stimulus. 

3. Finally, there are those who are suffering from persistent 

pain who then experience a new acute injury or 

exacerbation of their primary condition that is superimposed 

on their primary pain state. 

Elderly patients present special problems with respect 

to treating pain in each of these three scenarios. 

Depression, Anxiety, and Pain 

Associations between pain and depression are well documented 

in elderly patients. 7,8 Studies show that elderly 

subjects who are anxious and/or depressed voice more 

localized pain complaints than their nonanxious and nondepressed 

counterparts. Furthermore, anxious and/or 

depressed individuals report more intense pain. 9 Clinical 

evidence suggests that cognitive impairment may be 

exacerbated by pain and/or its treatment, especially in the 

elderly. These patients may benefit dramatically from psychologic 

or psychiatric interventions. Common missed 

diagnoses or underdiagnosed diseases in the elderly that 

can cause pain are: endocrine disorders, neurologic disorders, 

major medical disorders including electrolyte imbalances, 

polypharmacy, dysphoria, sleep disturbances, and 

loss of appetite, etc. 6 

Assessment 

Many older adults are afraid to report pain. 10,11 There is 

often fear of losing independence because of chronic 

illness. If an older adult fears that reporting pain will lead 

to a debilitating diagnosis that may cause nursing home 

placement or further loss of physical independence, he or 

she may be less likely to report it. Or the patient may fear 

additional procedures, diagnostic tests, or medication prescriptions 

that may result from reporting pain. For acute 

postoperative pain, this is less of a problem unless the 

patient has dementia or other condition that prevents 

direct communication. 

Elderly patients may present special problems in 

obtaining an accurate pain history. Failures in memory, 

depression, and sensory impairments may hinder historytaking. 

They may tend to underreport symptoms because 

they expect pain associated with aging and their diseases, 

or because they just do not want to be a bother to anyone. 

The inability to be aware of, and to verbalize, one’s emotional 

state is called alexithymia. Patients with chronic 

pain have been found to have a significant incidence 

(33%) of alexithymia. This may be a factor in causing 

geriatric patients to express emotional distress more 

often through somatic complaints because they have 

been found to be more alexithymic. 12 

Nociception Is Not Pain 

Activity induced in the nociceptor and nociceptive pathways 

by a noxious stimulus is not pain, which is always a 

psychologic state. Although we appreciate that pain most 

often has a proximate physical cause, especially acute 

pain, activity in nociceptor systems is not equivalent to 

the experience of pain. The recognition that pain serves 

an important biologic function related to survival, raises 

the important question: To what extent do age-related 

changes in nociception affect the capacity of the pain 

experience to fulfill an “enteroceptive” function (such as 

thirst, hunger, and thermoception that constitute sensory 

indexes of the health of the body)? 13 

Age does not seem to affect success of traditional interventions 

for the treatment of pain. Assessment and intervention 

for pain in the elderly should begin with the 

assumption that all neurophysiologic processes subserving 

nociception are intact. That is to say, tissue injury 

produces the same intensity of stimulus in an elderly 

person as in a young person. There are data to suggest 

that there is impairment of Aδ fibers with aging and 

therefore of the early warning of tissue injury. 13 There are 

also data that suggest that widespread and substantial 

changes in structure, neurochemistry, and function occur 

in the dorsal horn of the spinal cord and central nervous 

system (CNS) with aging. 13

310 J.M. Berger 

Multiple studies report reductions in the descending 

inhibitory modulating systems for nociception in the 

elderly. Gibson and Ferrell 13 conclude that the reduced 

efficacy of endogenous analgesic systems might be ex - 

pected to result in a more severe pain after prolonged 

noxious stimulation. It is also possible that documented 

decline in afferent transmission pathways could be offset 

by a commensurate reduction in the endogenous inhibitory 

mechanisms of older persons, with a net result of 

little or no change in the perceptual pain experience. 13 

They further conclude that any deficit in endogenous 

analgesic response (which is stimulus intensity dependent) 

will become critical, thereby making it more difficult 

for persons of advanced age to cope with severe or 

persistent clinical pain conditions. 13 

Although there is controversy over whether the 

number and integrity of nociceptors decreases with age, 

the position that age dulls the sense of pain is untenable. 13 

It is the processing of the nociceptive information that 

may be altered in the elderly, and the elderly may be 

more sensitive to the side effects of medications that are 

used to treat pain. These observations thereby give the 

impression that the elderly are less sensitive to pain. But 

no physiologic changes in pain perception in the elderly 

have been demonstrated according to a recent five-state 

study. 1 One would not assume that a surgical incision in 

an elderly patient will “hurt” less and therefore does not 

need to be treated. Likewise, anyone who has observed 

an elderly patient with acute herpes zoster certainly can 

attest to the excruciating pain that these unfortunate 

patients report. 

Pathophysiology of Types of Pain 

Somatic Pain 

A noxious stimulus in the periphery activates nociceptors. 

This results in a release of pain-producing subs - 

tances, e.g., prostaglandins, leukotrienes, and substance 

P. Impulses travel via Aδ and C fibers to the dorsal horn 

of the spinal cord. Somatic pain is well localized and 

gnawing. There is often associated tenderness and swelling. 

Examples include fractures, bone metastasis, and 

postoperative pain. This type of pain is usually opioid 

responsive. 

Visceral Pain 

When viscera are stretched, compressed, invaded, or 

distended, pain will result. The pain is poorly localized 

and may be referred. It is described as deep, squeezing, 

cramp like, or colicky. It is frequently associated with 

sympathetic and parasympathetic symptoms: nausea, diaphoresis, 

and hypotension. Examples include bowel 

obstruction and pancreatic cancer. This type of pain is 

also usually opioid responsive. 

Neuropathic Pain 

Injury to neural tissues or dysfunctional changes of the 

nervous system from trauma, compression, tumor invasion, 

or cancer therapies result in this form of pain. The 

pain may be associated with sensory and motor deficits, 

but not always. The quality of the pain is often described 

as burning, squeezing, lancinating, or electrical. There can 

be associated sleep and eating disturbances, and significant 

patient emotional suffering. Examples include brachial 

and lumbosacral plexopathy, postherpetic neuralgia, 

neuromas, complex regional pain syndrome, diabetic neuropathy, 

and radiculopathies. Neuropathic pain is associated 

with opioid tolerance, termed “apparent opioid 

resistance.” That is, patients with neuropathic pain often 

require higher than expected doses of opioids to obtain 

pain relief and the pain relief is usually not complete. 

Neuropathic Pain and Visceral Hypersensitivity 

Injury of nerves innervating somatic structures enhances 

nociception from stimulation of viscera with convergent 

input from nearby dermatomes, suggesting that somatic 

neuropathic pain could be accompanied by an increased 

likelihood of visceral pain. 14 This raises the possibility 

that pain disorders such as fibromyalgia, chronic fatigue 

syndrome, chronic pelvic pain, and chronic interstitial 

cystitis all represent visceral hypersensitivity pain syndromes 

of neuropathic origin. 

Medication Management 

Little is known of the neurophysiologic relationships 

between pain and age-related degenerative brain diseases. 

However, Fine 15 has recently reviewed the issues of 

pharmacologic management of persistent pain in older 

patients. In general, pharmacodynamics (what the drug 

does to the patient) are unaffected in the normal aging 

process. The molecular action of morphine is the same in 

all animals, although dose requirements to produce the 

same effect may change with age. However, because centrally 

acting drugs may interact with a preexisting disease 

state, care must be taken when treating pain in patients 

with CNS disease such as parkinsonism, Alzheimer 

dementia, or stroke. 

Pharmacokinetics (what the patient does to the drug) 

are frequently affected by aging processes, and disease 

states. Pharmacokinetic changes attributable to physical 

aging may complicate medication management. (See 

Chapter 15, The Pharmacology of Opioids.) There is 

decreased liver mass and blood flow, which prolongs


opioid and acetaminophen metabolism. This is of concern, 

particularly with fixed combination drugs, such as hydrocodone 

or codeine with acetaminophen (Vicodin or 

Tylenol #3) and opioids with active metabolites (e.g., 

morphine to morphine-3-glucuronide or meperidine to 

normeperidine). 

There is decreased renal function which increases the 

risk of nonsteroidal antiinflammatory drug (NSAID) 

nephrotoxicity and accumulation of metabolites of drugs 

such as meperidine. There is decreased plasma binding, 

which increases blood levels of active drugs, opioids, and 

NSAIDs [even the cyclooxygenase (COX)-2 specifi c 

inhibitors, such as Celebrex]. 

In the elderly, there is increased CNS sensitivity to 

opioids leading to enhanced sedation, analgesia, and side 

effects including delirium. But the experience of pain 

tends to counteract the sedative effects of opioids. Therefore, 

patients who have not received adequate doses of 

opioid analgesics and who are still experiencing pain do 

not suffer respiratory depression. 16 

In acute pain situations or in a “pain crisis,” rapid 

titration of opioids in elderly patients is safe. In a study 

of 175 elderly patients versus 875 younger patients 

who were treated with intravenous (IV) morphine for 

postoperative pain in the postanesthesia care unit, there 

was no increased incidence of adverse side effects noted 

when a strict titration to pain level protocol was followed. 

It was not necessary to change the protocol according 

to age. 17 

The use of an opioid is the strategy of choice for rapid 

titration to pain relief in most clinical situations. Opioid 

side effects are usually manageable if frequent assessments 

are made. The elderly, of course, may require more 

frequent assessments and smaller incremental doses in 

order to manage side effects. The exact timing of interval 

assessments must be dictated by the needs of the individual 

case. 

The management of an acute pain crisis involves immediate 

control of the pain, maintenance of analgesia, and 

long-term management. During the initial titration to 

pain relief, there is ample opportunity to evaluate the 

patient for the causes of the pain. The best way to gain 

control is to get the syringe and titrate to effect. The dose 

depends on the history of current use or whether the 

patient is opioid naïve. The choice of drug, e.g., 1–4 mg of 

morphine, 0.2–1 mg of hydromorphone (Dilaudid), 10– 

50 mg of meperidine (Demerol), or the equianalgesic IV 

dose based on the patient’s P.O. breakthrough medication, 

is not as important. 

Opioids reach maximum plasma levels in 10–15 minutes 

after IV bolus (excluding fentanyl and its congeners), so 

bolus doses every 10–15 minutes until the patient is comfortable, 

begins to become sedated, or has decreasing 

respiratory rate is the most effective method of opioid 

analgesic loading. An alternative method involves starting 

low, then doubling the dose every 30 minutes, until 

comfort is obtained, e.g., morphine 2, 4, 8, 16 mg, etc., with 

the effect being obtained in less than 90 minutes (range 

4–215 minutes). 18 This second method may be more 

appropriate for the “younger elderly” as opposed to the 

“old elderly.” 

After loading the patient and obtaining comfort, maintenance 

dosing must be ordered. Intramuscular or IV 

bolus dosing by the nursing staff on a PRN basis is a poor 

choice. The dose required to make the patient com - 

fortable can be used as an estimate of the 3-hour dose 

requirement for maintenance, e.g., when converting to IV 

patient-controlled analgesia (PCA). 

Contraindications for IV PCA include patients 

who are unable to operate the device because of impaired 

mental status or physical limitations, and patients who 

are unwilling to use the technique, i.e., some patients do 

not want to push the button and want to be given 

their medication by the nurse. Patients with sleep apnea 

disorders pose a relative contraindication. Failure to 

achieve adequate analgesia without side effects after an 

appropriate trial is also a contraindication. If the patient 

chooses to have the nurse administer analgesia, it would 

still be advantageous to have a PCA set up, which would 

eliminate intramuscular injections that hurt and produce 

tissue injury in the elderly. Also, the medications can 

be titrated in small doses by the nurse to adequate 

analgesia. 

Postsurgical Analgesia 

Elderly patients undergo a high number of surgical interventions. 

The importance of adequate postoperative 

analgesia for reducing morbidity and mortality in the 

elderly is undisputed. 19 Epidural analgesia and IV PCA 

are both excellent postoperative techniques. Physicians 

are often reluctant to use PCA in older patients. 20,21 PCA 

was found to be effective in this population with the 

caveat that the patient is physically or mentally able to 

operate the machine. 22 Regional anesthetic techniques 

are excellent for the elderly. Although a fair amount of 

research has been published, data proving long-term 

benefit are lacking. 19 

In a study of elderly patients after abdominal surgery, 

IV PCA versus patient-controlled epidural analgesia 

(PCEA), the IV PCA group had general anesthesia with 

sufentanil, isoflurane, nitrous oxide, and atracurium for 

muscle relaxation. Postoperative loading was 5 mg of 

morphine followed by a morphine PCA of 1.5 mg, lockout 

8 minutes. The epidural group had a T7–T11 catheter 

placed, depending on surgery level, which was activated 

with 2% lidocaine with epinephrine 5 µg/mL, dosed to T4 

sensory level before induction of general anesthesia. 

A solution of 0.25% bupivacaine plus 1 µg/mL Sufenta


was infused continuously throughout the surgery 

and continued postoperatively with a solution of 

0.125% bupivacaine plus 0.5 µg/mL Sufenta at 3–5 mL/h 

with a 2- to 3-mL PCEA bolus and a lockout of 12 

minutes. 23 

The authors concluded that PCEA with local anesthetic 

and opioid provided better pain control, improved 

mental status, and better bowel function return than did 

traditional IV PCA morphine after general anesthesia. 

Orthostatic and mobility deficits were not a problem with 

the PCEA adjustments. 

Carli et al., 24 in their study of 64 patients for elective 

colon surgery randomized to an IV PCA group or epidural 

group, found that epidural analgesia enhanced functional 

exercise capacity and health-related quality of life 

indicators after colonic surgery. In their study, the PCA 

group had anesthetics consisting of 250 µg of fentanyl, 

adjusted isoflurane, nitrous oxide, oxygen, and PCA morphine 

with no basal rate but a dose of 1–2 mg every 5 

minutes. It was discontinued on day 3–4 if the verbal 

analog score was


management a priority to allow earlier discharge. 

However, if this is to be accomplished successfully, physicians 

must have knowledge of equianalgesic equivalents. 

Equivalency charts can be found in many different texts. 

An excellent revised chart can be obtained from the 

Southern California Cancer Pain Initiative (sccpi@coh. 

org), and found in a relevant article by Gammaitoni 

and associates. 28 In the author’s experience, some simple 

conversions for chronic administration include the 

following: 

• IV morphine 10 mg = 30 mg orally. 

• IV morphine 1 mg = hydromorphone 0.2 mg. 

• Oral morphine 30 mg = hydromorphone 6 mg orally. 

• Oral morphine 30 mg = oxycodone 15–20 mg orally. 

• IV morphine 60 mg/day = morphine orally 180 mg/day 

= fentanyl transdermal patch of 100 µg/h. 

• IV morphine 10 mg = hydrocodone 30 mg orally. 

An example of a common mistake is the patient 

who is obtaining excellent pain relief from an IV PCA 

of 10 mg of morphine every 3 hours. The time for discharge 

arrives, and the PCA is discontinued; the substitution 

is hydrocodone/acetaminophen (Vicodin) 5 mg/ 

500 mg tablets. The equivalency for analgesic effect for 

10 mg of morphine IV is 30 mg of hydrocodone orally. Ten 

milligrams of morphine IV every 3 hours would be eight 

doses per day of 30 mg of hydrocodone or 48 tablets of 

hydrocodone/acetaminophen per day. Of course, this 

would be a lethal dose of acetaminophen. It is unlikely 

that any patient would actually take 48 tablets per day, 

but the normal prescription of 1 to 2 tablets every 6 hours 

PRN for pain might certainly be inadequate for someone 

requiring 10 mg of morphine IV every 3 hours. 

It therefore behooves the physician managing the 

patient to convert the patient to an acceptable oral medication 

several days before discharge to ensure adequate 

pain control and lack of side effects. In converting from 

IV morphine to transdermal fentanyl, this author has 

found that 60 mg per day of IV morphine would require 

a 100 µg/h transdermal fentanyl patch, which would be 

changed every 72 hours. Because hydromorphone is 

approximately 5 times more potent than morphine, 60 mg 

per day of IV morphine would convert to 12 mg per 24 

hours of hydromorphone and again equate to a transdermal 

fentanyl patch of 100 µg/h dose. 

CYP 2D6 Enzyme and the Efficacy of 

Codeine and Codeine-Like Drugs 

Codeine, dihydrocodeine (Synalgos DC), and hydrocodone 

(Vicodin, Lortab, etc.) are not active opioids. These 

opiates must be converted to morphine by the enzyme 

Table 21-1. Medications that inhibit the enzyme CYP 2D6. 

Amiodarone (Cordarone) 

Fluoxetine (Prozac) 

Haloperidol (Haldol) 

Paroxetine (Paxil) 

Propafenone (Rythmol) 

Propoxyphene (Darvon) 

Quinidine 

Ritonavir (Norvir) 

Terbinafine (Lamisil) 

Thioridazine (Mellaril) 

Source: Data from Supernaw. 29 

CYP 2D6 to become effective. 29,30 Approximately 20% of 

the population is genetically deficient in this enzyme and 

so would report a poor analgesic response when prescribed 

these medications. Furthermore, many medications 

also inhibit the action of CYP 2D6 that are 

frequently used by elderly patients; some of these are 

shown in Table 21-1. 

Oxycodone is metabolized by CYP 2D6; therefore, 

patients who are deficient in this enzyme will have a 

greater effect from oxycodone medications. 

Opioids for Neuropathic Pain and 

Broad-Spectrum Opioids 

Many elderly patients suffer from neuropathic pain which 

is poorly responsive to opioid analgesics that act primarily 

at the µ opioid receptor (Table 21-2). 31 While affinity 

for µ, δ, and κ receptors of opiates are steric dependent, 

the affinity of “l” and “d” forms are nearly equal with 

respect to nonopiate receptor actions such as N-methyl- 

D-aspartate (NMDA) antagonist and blockage of reuptake 

of serotonin and noradrenaline. Multiple actions of 

the broad-spectrum opiates seem to be synergistic with 

respect to analgesic action, similar to using narrowspectrum 

opiates in combination with an NMDA receptor 

antagonist and a tricyclic antidepressant. As listed 

in Table 21-3, the opioids that have dual actions both 

for opioid receptors and for NMDA receptors will be 

more effective for neuropathic pain than the narrowspectrum 

opioids. The opioids in the gray-screened area 

Table 21-2. Narrow-spectrum opioids acting only at opioid 

receptors. 

Morphine 

Hydromorphone 

Codeine 

Fentanyl 

Sufentanil 

Oxycodone 

Buprenorphine


Table 21-3. Other actions of broad-spectrum opioids not at the 

opioid receptors. 

Broad-spectrum opioids acting also 

as antagonists to N-methyl-Daspartate 

receptors 

Methadone 

Ketobemidone 

Dextropropoxyphene 

Dextromethorphan 

Meperidine (pethidine) 

are common to the effects of NMDA receptor antagonism 

and inhibition of reuptake of serotonin and 

norepinephrine. 

Because dextropropoxyphene and meperidine both 

have metabolites that act in the brain of elderly patients 

and lead to confusion and even seizures, the only 

true broad-spectrum opioid analgesic available is 

methadone. 

End-of-Life Care 

Broad-spectrum opioids 

acting also as inhibitors of 

reuptake of serotonin and 

norepinephrine (similar to the 

tricyclic antidepressants) 

Methadone 

Levorphanol 

Dextromethorphan 

Dextropropoxyphene 

Tramadol 

Meperidine (pethidine) 

For 67% of patients, the last place of care was an institution, 

with 38.4% dying in a hospital and 30.5% in a nursing 

home. Only 33% died at home; 49.3% of these were on 

home hospice care; 38.2% received no formal services; 

and 12.5% had home health care nursing services without 

hospice participation. 32 

Reporting on the degree of satisfaction of bereaved 

family members with the care their loved ones received, 

hospice care at home received the highest level of overall 

satisfaction with 71% of respondents. Twenty-five percent 

of all patients with pain or dyspnea did not receive “any” 

or “enough” treatment. Inadequate pain management 

was 1.6 times more likely in a nursing home setting or 

with home health services and 1.2 times more likely in a 

hospital than with home hospice. 33 

End-of-life pain management for patients who are 

being managed at home presents problems of assessment 

and administration of medication. Patients who are still 

able to swallow can be managed with oral medications. 

Rectal suppositories, transdermal medications, and transmucosal 

medications are available. 

Kadian and Avinza are every-24-hour, single-dose 

sustained-release morphine preparations. Although their 

uptake properties differ, they both have the property 

of being packaged in a capsule that can be sprinkled 

as pellets onto applesauce or added to slurry for administration 

down an NG- or G-tube, while retaining the 

sustained-release characteristic. MS Contin is an every- 

12-hour sustained-release morphine preparation that 

cannot be broken open. Doing so destroys the integrity 

of the sustained-release capsule; the patient receives the 

entire dose as an immediate-release preparation. Oxy- 

Contin is a 12-hour sustained-release preparation of oxycodone 

that also cannot be opened or it too becomes an 

immediate-release preparation. There is currently no 

sustained-release preparation of hydromorphone or 

methadone. Fentanyl and buprenorphine are the only 

commercially available transdermal opioids. 

It is important to remember that sustained-release 

medications are encouraged for patients who have continuous 

pain. But it must be remembered that activity will 

often increase the level of pain; patients must be prescribed 

rapid-onset, short-acting medications to be used 

for such breakthrough pain. Because patients vary tremendously 

in their requirements for pain medication, 

particularly in the senior population in which the margin 

for error is smaller, it is important to titrate patients 

with immediate-release medication to determine how to 

convert to sustained-release medication. Although sustained-release 

morphine is available in capsules that are 

recommended for every-12-hour dosing and every-24- 

hour dosing, the absorption characteristics will determine 

whether a particular patient experiences adverse effects 

such as nausea or sedation, or end of dose failure. It is 

sometimes necessary to lower the dose and change to 

every-8-hour or every-12-hour dosing. 

Rarely in acute pain situations and more often in endof-life 

care, patients’ pain cannot be brought under 

control with opioid infusions alone. In such situations, 

optimum pain control with minimal side effects could be 

obtained with a combination solution of 1 mg/mL morphine 

and 1 mg/mL ketamine, with a lockout period of 8 

minutes with an IV PCA. 34 These agents can both be 

given orally as well in the same ratio, e.g., 30 mg of immediate 

release morphine sulfate with 30 mg of ketamine 

every 3–4 hours. 

Sedation of Terminally Ill 

When patients are terminally ill and traditional analgesic 

regimens are unsuccessful at providing adequate analgesia 

and relief from suffering, the following solution can 

provide benefit 35 : 

Ketamine (dissociative anesthetic, NMDA blocker) 

2 mg/mL 

Midazolam (benzodiazepine, reduces incidence of hallucinations, 

sedative effects, antianxiety) 0.1 mg/mL 

Fentanyl (potent opioid, less nausea, less pruritus, less 

constipation, enhanced effect combined with ketamine/ 

midazolam) 5 µg/mL 

IV infusion should begin at 3–5 mL/h titrating to effect. 

Doubling the concentrations will allow reduction of the 

volume infused if needed. High concentrations can be


used as subcutaneous infusion as long as the volume 

infused per hour remains less than 2 mL. 

Nonsteroidal Antiinflammatory 

Analgesics 

The antiprostaglandin effect of NSAIDs can be beneficial 

during the acute phase of soft tissue injury. This biochemical 

effect may control the inflammatory response to injury 

and provide pain relief. The duration of an NSAID’s analgesic 

effect may be different from its antiinflammatory 

effect. The antiinflammatory effect may last longer than 

the analgesic effect. 

Chronic inflammatory disease pain such as arthritis 

may warrant chronic NSAID therapy. But some authors 

have expressed concern that NSAIDs may actually interfere 

with the later stages of tissue repair and remodeling, 

where prostaglandins still help mediate debris cleanup. 

(This does not seem to be true for the COX-2 specific 

inhibitors.) Therefore, dosage, timing, and potential side 

effects of NSAIDs should be evaluated. It is not possible 

to predict patient response to a particular NSAID by 

chemical class or pharmacokinetics. 36 

Remember that COX-2 specific inhibitors do not affect 

platelet aggregation and therefore may pose a risk for 

myocardial infarction if a patient is taken off aspirin 

therapy. For the same reason, it is safe to continue COX-2 

specific inhibitors with daily low-dose aspirin. COX-2 

inhibitors also have a safer profile from the standpoint of 

gastrointestinal irritation, but care should still be taken 

in patients with borderline renal function. Baseline renal 

function tests should probably be obtained for elderly 

patients who are beginning a course of chronic coxib 

therapy or NSAID therapy. Drug holidays of 30–60 days 

every 4–6 months may also be advisable. 

Tricyclic Antidepressants and Specific 

Serotonin Reuptake Inhibitors 

Tricyclic antidepressants are often used as adjuvants in 

treating neuropathic pain because of their inhibition of 

reuptake of serotonin and norepinephrine. There is fear 

that antidepressants will cause cardiac arrhythmias. 

Tricyclic antidepressants are safe for cardiac patients, 

except for several months after a myocardial infarction 

or if a conduction defect or persistent dangerous arrhythmia 

is already present. 37 

Specific serotonin reuptake inhibitors (SSRIs) have 

safer cardiac profiles than tricyclic antidepressants. SSRIs 

are effective for depression. SSRIs do not have analgesic 

effects like the tricyclics because they are only serotonin 

reuptake inhibitors and not norepinephrine reuptake 

inhibitors. Both are necessary to modulate neuropathic 

pain. Tricyclics are more effective for pain and for 

sleep but may also cause sedation, cognitive changes, 

and dizziness. Elderly patients taking tricyclic antidepressants 

are at risk for falling, resulting in hip or other fractures. 

Again, titration and frequent reassessment are the 

key to successful treatment. In addition, many newer 

classes of antidepressants provide inhibition of reuptake 

of norepinephrine and serotonin without the associated 

sedation. 

Anticonvulsants for Neuropathic Pain 

Gabapentin (Neurontin) is probably the most effective 

agent with the fewest side effects for the treatment of 

neuropathic pain. It is absorbed in the duodenum, not 

metabolized by the liver, not protein bound, excreted 

unchanged by the kidneys, and has no ceiling dose. It is 

nontoxic to the liver and kidney. The only significant side 

effects are sedation and cognitive impairment. Starting low 

and titrating to response again is the recommendation, but 

rapid titration upward is possible as tolerated. Oxcarbazepine 

(Trileptal), lamotrigine (Lamictal), and Topamax are 

also effective substitutes. And now pregabalin (Lyrica) is 

also available and FDA approved for use in treating both 

postherpetic neuralgic and diabetic neuralgia. 

Evaluation by a psychiatrist may yield information 

about clinical depression resulting in emotional suffer - 

ing perceived as pain versus sadness, frustration, and 

isolation in response to inadequately treated pain. This 

would be valuable information in making a choice of 

treating with an SSRI versus a tricyclic or other agent 

with both serotonin and norepinephrine reuptake inhibition 

effects. 

With any of these medications, tricyclic or other antidepressants, 

anticonvulsants, etc., cognitive impairment 

caused by the medication must frequently be accepted or 

tolerated in the elderly in order to obtain pain relief. 

Pain and Insulin Resistance 

Acute, severe pain decreases insulin sensitivity. This 

would indicate that relief for acute pain is important for 

maintenance of normal glucose metabolism. Many elderly 

patients are diabetic, emphasizing the need for good 

pain relief. 38 

Regional Analgesia 

Upper extremity surgeries are amenable to brachial 

plexus anesthesia and analgesia. Brachial plexus nerve 

blocks have a prolonged duration of action in the elderly, 

approximately 2.5 times longer. This would lead to a


slower return of pain and therefore easier titration of 

postoperative medications. 39 However, elderly patients 

are frequently at risk for falls before surgery, so greater 

care must be taken in discharge criteria after a regional 

anesthetic to make sure they can maintain balance and 

that the caregiver with whom they will be discharged 

home is capable of protecting them from falls. 

Common Pain Syndromes 

Chronic lumbar pain as a result of degenerative arthritis 

is very common. Osteoarthritis is the most common cause 

of nociceptive pain in the elderly. Inflammatory pain does 

respond well to analgesics such as antiinflammatory medications 

and opioids. Cancer pain, myofascial pain syndromes, 

postherpetic neuralgia, diabetic polyneuropathy, 

radiculopathy or amyotrophy, trigeminal neuralgia, and 

central post-stroke pain (CPSP) syndrome are all common 

in the elderly. Furthermore, arthritis of the knee, hip, or 

shoulder are all common problems in the senior population, 

and surgical replacement is very advanced and 

highly successful. Diagnosis is easy and fairly certain to 

be correct. 

CPSP is a neuropathic pain syndrome characterized 

by constant or intermittent pain in a body part occurring 

after stroke. It is associated with sensory abnormalities 

in the painful body part. The incidence of CPSP is 

8% within the first year, but pain may appear up to 3 

years after the stroke. Sixty-three percent of those who 

develop pain had onset within the first month. 40 Two 

thirds of those who develop pain experience moderate to 

severe pain. This 8% incidence of pain with 5% expressing 

moderate to severe pain is similar to other neuropathic 

pain syndromes such as phantom limb pain, 41 

central pain in spinal cord injury, 42 and pain in diabetic 

neuropathy. 43 

Back Pain 

About two thirds of adults have low back pain at 

some time. Of the 65 million people in the United 

States with low back pain, approximately 151,000 undergo 

fusion of the lumbar spine each year. 44 The number of 

spinal fusion surgeries is increasing annually, in part, 

according to Deyo and associates, because of widening 

indications, including the diagnosis of back pain made by 

discography. 45,46 

Because of the high rate of unsatisfactory results 

with open spinal surgery and the more tenuous physical 

condition of elderly patients to undergo and tolerate 

open spinal surgery, less-invasive techniques for treat - 

ing discogenic pain have been developed. One such 

procedure is percutaneous diskectomy using coablation 

technology. This is a percutaneous technique to reduce 

the volume of internally disrupted disk material. 47 

Intrathecal drug delivery has also been effective for 

control of pain in unremitting low back pain and radicular 

pain. 48 

For chronic zygapophyseal joint (spinal facet joint) 

pain, radiofrequency neurotomy of the medial branch of 

the posterior spinal nerve ramus has been found to be 

effective in both the cervical and lumbar regions. 49,50 

Although low back pain is a fact of life for a substantial 

proportion of the population at all ages, the aged have a 

greater prevalence and experience greater impact on 

their quality of life than the remainder of the population. 

At the same time, they are underrepresented in research. 51 

Treatment protocols are poorly defined in the elderly. 

History and a comprehensive evaluation are necessary 

for an appropriate strategy. 52 

Thoracic and Lumbar Compression Fractures 

Epidural injections can be helpful for acute vertebral 

compression fractures, which are common in the elderly. 

Continuous epidural infusion of local anesthetic is also 

an option but requires hospitalization. Vertebroplasty 

is also an option. This involves a technique designed 

to consolidate pathologic vertebral bodies through the 

injection of orthopedic cement under fluoroscopic guidance. 

53–55 This procedure has been shown to be safe in frail 

elderly patients and can improve quality of life. 56 

Spinal Stenosis 

Neurogenic claudication is frequently a presenting 

symptom of lumbar spinal stenosis. The patient complains 

of pain in the legs with walking which is relieved with 

rest. Epidural injections can sometimes be helpful in 

early disease. In advanced disease if surgery is not an 

option, spinal infusion therapy may be helpful as an 

alternative. 57 

Herpes Zoster (AHZ, Shingles) 

The word herpes stems from the Greek herpein which 

means “to creep,” whereas zoster means “girdle.” The 

disease infects 800,000 people in the United States each 

year, and the incidence increases with advancing age. The 

etiopathogenesis of herpes begins after chicken pox, 

when the varicella virus becomes dormant in a spinal 

nerve. When reduced cell-mediated immunity occurs, 

AHZ reactivates. Reactivation leads to infection down 

the nerve to the skin with the eruption of skin lesions. 

The inflammation can also travel to reach the spinal cord 

or the trigeminal brainstem complex. 58 

The first sign of shingles is intense pain or itching, even 

before the lesions erupt on the skin. It is only along one


nerve on one side of the body. Treatment should start as 

soon as possible with antiviral medication, pain medication, 

and steroids. Steroids are safe in acute herpes zoster 

because it is an immunoglobulin G–mediated immune 

response. 58 Epidural injections usually are helpful only in 

the first 3 days after eruption. Subcutaneous infiltration 

of local anesthetic and long-acting steroid can provide 

relief and accelerate healing. Stellate ganglion sympathetic 

and superior cervical sympathetic ganglion local 

anesthetic blocks can be helpful for zoster of the face in 

the trigeminal distribution. Manabe and associates 59 

demonstrated that continuous epidural infusion of local 

anesthetic can shorten the duration of zoster-associated 

pain. 

Postherpetic Neuralgia 

Usually this disease is defined as pain that extends beyond 

the normal healing period of 6 weeks to 2 months. 

The pain takes on the characteristics of neuropathic pain 

with allodynia, and hyperalgesia. The frequency of persistent 

pain is given in Table 21-4. 60 Aggressive therapy for 

acute herpes zoster will not prevent the development of 

postherpetic neuralgia. However, it will change the quality 

of the pain from the intense unsupportable pain syndrome 

to a more diffuse, deep aching pain that can be 

supported. 61 

Treatment options for postherpetic neuralgia have 

not significantly improved over the years. Analgesics, 

even traditional opioid analgesics, offer little relief. 

Methadone can be helpful if the patient can tolerate it. 

It is a difficult medication to titrate in the elderly. Spinal 

cord stimulation can be beneficial in about 50% of cases 

of postherpetic neuralgia if the virus has not affected 

the dorsal horn of the spinal cord. Lidocaine 5% topical 

patches have been found to reduce the symptoms of 

postherpetic neuralgia about 30%–40%. Kotani et al. 62 

did report on the use of intrathecal methylprednisolone 

60 mg administered with 3 mL of 3% lidocaine once 

per week for up to 4 weeks as being 70% effective in 

reducing pain. 

Table 21-4. Persistent pain in postherpetic neuralgia as a function 

of age. 

Age group 

Percentage of patients 

with pain for 1 year 

0–19 4 4 

20–29 2 2 

30–39 15 10 

40–49 33 7 

50–59 49 18 

60–69 65 37 

>70 74 48 

Source: Reprinted with permission from de Moragas and Kierland. 60 

Case Examples 

When assessing pain problems and making clinical decisions 

for therapy in the elderly, the situation is not always 

what it seems, and care must be taken to not go down the 

wrong path. Following are two cases that illustrate this 

problem. 

Case 21-1. Lumbar Radiculopathy 

A 67-year-old male physician presented with a sudden 

onset of back and leg pain, with a foot drop. A magnetic 

resonance imaging (MRI) scan showed a protruding 

disk with nerve root impingement corresponding to 

the side of the foot drop. The patient chose not go to a 

surgeon but instead requested that this author treat him 

with epidural steroid injection therapy. He received an 

initial lumbar epidural steroid injection followed by two 

caudal steroid injections over a 3-week interval. He experienced 

rapid resolution of all symptoms, including the 

foot drop, and returned to playing golf again with no 

return of the foot drop at 3 years after epidural injections. 

The MRI image is shown in Figure 21-1A (December 10, 

2001). Figure 21-1B is a comparison MRI image (January 

1, 1995) taken when the patient volunteered to have 

a scan done for a new scanner that needed calibration. 

The disk protrusion was present in 1995 but was asymptomatic 

until 2001. It is also clear that faced with the 

MRI image of 2001 along with pain and a foot drop, 

most neurosurgeons would have considered this a surgical 

emergency (Figure 21-2). It is clear that epidural 

steroid injections cannot dissolve away a disk protrusion. 

In this case, however, the problem was an acute nerve 

root irritation in the presence of a longstanding asymptomatic 

disk protrusion that did respond to epidural 

steroid injections. 

Steroid injections are efficacious for different spine 

problems. Epidural steroid injections are being performed 

under image intensifier needle guidance both by the 

translaminar approach as well as the transforaminal 

approach to treat radiculitis and radiculopathy of the 

cervical as well as the lumbar nerve. 63–65 

Case 21-2. Excessive Treatment in 

a Missed Diagnosis 

An 85-year-old woman who was healthy, ambulatory, and 

living independently, upon getting out of bed one morning, 

experienced a sudden onset of right hip pain radiating 

down her leg. Nothing was done for a week, but she was 

not able to bear weight on that leg. After a week, she went 

to her primary doctor who immediately ordered an MRI 

scan of her lumbar spine. Based on the results of 

that scan, she was referred to a pain clinic where she


A 

B 

Figure 21-1. A: MRI from December 10, 2001. The patient was symptomatic of the disk protrusion at L4–5 (arrow). B: MRI from 

January 1, 1995. The patient was asymptomatic of the disk protrusion at L4–5 (arrow). 

Figure 21-2. Significant disk protrusion noted (arrow).


A 

Figure 21-3. A: A-P X-ray of the lower lumber spine and pelvis 

showing extensive discogenic and vertebral body degeneration 

with scoliosis to the left, osteophytes and endplate abnormalities 

on the left. B: Magnified view of the right acetabulum 

showing the small fracture (circled in black). The patient never 

complained of back pain. 

B 

underwent a series of three translaminar lumbar epidural 

steroid injections and a left-sided L3 and S1 transforaminal 

epidural steroid injection without benefit. She continued 

to be unable to walk. Surgery was recommended for 

her back, but fortunately the patient declined. After 6 

months, she was referred to this author. Upon taking the 

history and performing an examination, it was clear that 

the most likely diagnosis was a fracture of the right hip. 

The patient never complained of back pain and never 

complained of left-sided leg pain. Her pain was always 

emanating from her right hip. A plain X-ray was ordered 

by this author that revealed a fracture of the pelvis close 

to the acetabulum on the right side. It is a wonder in 

looking at the X-ray, however, that the patient never did 

suffer from back pain (Figure 21-3). 

Conclusions 

The major goal of geriatric care is often comfort and 

control of the symptoms of chronic disease. 3 The following 

guidelines are useful in approaching pain management 

in the elderly: 

1. Always ask elderly patients about pain. 

2. Accept the patient’s word about pain and its 

intensity. 

3. Never underestimate the potential effects of chronic 

pain on a patient’s overall condition and quality of 

life. 

4. Be compulsive in the assessment of pain. An accurate 

diagnosis will lead to the most effective treatment. 

5. Treat pain to facilitate diagnostic procedures. Do not 

wait for a diagnosis to relieve suffering. 

6. Use a combined approach of drug and nondrug strategies 

when possible. 

7. Mobilize patients physically and psychosocially. 

Involve patients in their therapy. 

8. Use analgesic drugs correctly. Start doses low and 

increase slowly. Achieve adequate doses and anticipate 

side effects. 

9. Anticipate and attend to anxiety and depression. 

10. Reassess responses to treatment. Alter therapy to 

maximize functional status and quality of life. 

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22 

Anesthesia Considerations for 

Geriatric Outpatients 

Kathryn E. McGoldrick 

During the past two decades, ambulatory anesthesia has 

matured and expanded. With ambulatory surgery currently 

accounting for almost 80% of all surgical procedures 

performed in the United States, it has become 

undisputedly the dominant mode of surgical practice in 

North America, as well as in many of the world’s other 

developed nations. Several factors have contributed to 

the phenomenal growth of outpatient surgery, including 

economic pressures; technologic advances that allow 

minimally invasive surgery; and new, short-acting drugs 

and anesthetic agents that have dramatically improved 

our ability to prevent and treat postoperative nausea and 

vomiting (PONV) 1 and to manage postoperative pain. 

Nonetheless, ambulatory anesthesiologists cannot afford 

the luxury of resting on our laurels. To paraphrase the 

gifted poet, Robert Frost, we still have miles to go before 

we sleep. . . . 

The elderly (≥65 years old) population is the fastest 

growing demographic segment in the United States as 

well as in many parts of the developed world. According 

to the 2000 census, there are 4.2 million Americans age 

85 years or older, an increase of 30% since 1990. Those 

75–84 years of age number 12.4 million, an increase of 

>20% since 1990. These realities have profound implications 

for clinicians, including anesthesiologists and surgeons. 

Aging, for example, increases the probability that 

an individual will require surgery. Whereas approximately 

12% of those aged 45–60 years undergo surgery annually, 

this number increases to >21% in those aged ≥65 years. 2 

Unfortunately, however, morbidity and mortality are 

increased in the geriatric population, with steep increases 

observed after age 75 years. Thus, an aging population has 

multifaceted implications for the practice of anesthesiology 

that are evident in the preoperative, intraoperative, 

and postoperative periods. 

In 2000, Dr. Lee A. Fleisher, as the recipient of the first 

Society for Ambulatory Anesthesia (SAMBA) Outcomes 

Research Award, began an investigation of the impact of 

location of care and patient factors on the rate of complications 

and readmission after outpatient surgery. 3 Not 

surprisingly, the study determined that age in excess of 

85 years, prior inpatient hospital admission within 6 

months, invasive surgery, and surgical venue were predictive 

of unanticipated admission and other adverse outcomes, 

including death. These findings are suggestive 

that not all ambulatory facilities—i.e., hospitals, freestanding 

surgicenters, or office-based operating rooms— 

are created equal in terms of their ability to successfully 

manage complicated patients having lengthy, relatively 

invasive procedures. Clearly, this important work by Dr. 

Fleisher highlights two major challenges confronting 

anesthesiologists today: the exigencies and nuances of 

gerontologic anesthesia and the safety of office-based 

surgery. 

In this context, it is important to appreciate that 15% 

of all elective surgeries performed in the United States 

in 2002 were conducted in offices. Indeed, office-based 

anesthesia is currently the fastest growing segment of 

anesthesia practice in our country. However, startling 

death rates associated with office-based anesthesia and 

surgery have been reported. The death rate for officebased 

surgery in Florida a few years ago was estimated 

at 1 : 8500, and it has been disclosed that the mortality for 

liposuction may be as high as 1:5000 procedures. 4 Vila and 

colleagues 5 reviewed all adverse incidents reported to the 

Florida Board of Medicine from April 2000 until April 

2002. Despite the implementation of corrective-action 

measures by the Board of Medicine for office-based 

surgery in 2000, the investigators found a more than 

tenfold increase in rates of adverse incidents (66 : 100,000 

versus 5.3 : 100,000) and death (9.2 : 100,000 versus 

0.78 : 100,000) when comparing offices and ambulatory 

surgery centers, respectively. There are multiple reasons 

for these alarming findings, and most of them pertain to 

the lack of regulatory control that is characteristic of 

private offices, where it is not uncommon to have clerical 

staff administer sedative-hypnotics and opioids under the 

“guidance” of the operating physician (who often may be 

322

22. Anesthesia Considerations for Geriatric Outpatients 323 

a dermatologist rather than a surgeon). Indeed, only a 

small minority of states have regulations pertaining to 

office-based surgery. Therefore, SAMBA and the American 

Society of Anesthesiologists (ASA) have joined 

together to ensure the same level of safety in offices as 

in hospitals or accredited surgicenters. To accomplish this 

goal, patients and procedures must be appropriately 

matched to venue, and anesthesia care must be delivered 

only by those with expertise in the specialty. Frail, complex 

elderly patients are inappropriate candidates for lengthy, 

relatively invasive surgical procedures performed in 

private offices. 


The preoperative evaluation of the geriatric patient characteristically 

is more complex than that of the younger 

patient because of the heterogeneity of seniors and the 

increased frequency and severity of comorbid conditions 

associated with aging. The process of aging is highly individualized. 

Different people age at varying rates and 

often in different ways. Typically, however, virtually all 

physiologic systems decline with advancing chronologic 

age. Nevertheless, chronologic age is a poor surrogate for 

capturing information about fitness or frailty. 6 Moreover, 

perioperative functional status can be difficult to quantitate 

because many elderly patients have reduced preoperative 

function related to deconditioning, age-associated 

disease, or cognitive impairment. Thus, it is challenging to 

satisfactorily evaluate the patient’s capacity to respond 

to the specific stresses associated with anesthesia and 

surgery. How, for example, does one determine cardiopulmonary 

reserve in a patient severely limited by osteoarthritis 

and dementia? Even “normal” aging results in 

alterations in cardiac, respiratory, neurologic, and renal 

physiology that are linked to reduced functional reserve 

and ability to compensate for physiologic stress. Moreover, 

the consumption of multiple medications so typical 

of the elderly can alter homeostatic mechanisms. 


In the general population, there is strong consensus that 

most routine tests are not indicated. In the subset of 

geriatric patients, our knowledge is somewhat more 

limited. Nonetheless, a recent study on routine preoperative 

testing in more than 18,000 patients undergoing 

cataract surgery is worthy of comment. Patients were 

randomly assigned to undergo or not undergo routine 

testing (electrocardiogram, complete blood cell count, 

electrolytes, blood urea nitrogen, creatinine, and 

glucose). 7 The analysis was stratified by age and disclosed 

no benefit to routine testing for any group of patients. 

Similar conclusions were drawn in a smaller study of 

elderly noncardiac surgical patients by Dzankic and colleagues. 

8 Some physicians and lay people, however, misinterpreted 

the results of the study by Schein et al., 7 

believing that patients having cataract surgery need no 

preoperative evaluation. It is vital to note that all patients 

in this trial received regular medical care and were evaluated 

by a physician preoperatively. Patients whose 

medical status indicated a need for preoperative laboratory 

tests were excluded from the study. Because “routine” 

testing for the more than 1.5 million cataract patients in 

the United States is estimated to cost $150 million annually, 

the favorable economic impact of this “targeted” 

approach is obvious. 

From these investigations and others, a few concepts 

emerge. First, routine screening in a general population 

of elderly patients does not significantly augment information 

obtained from the patient’s history. Second, the 

positive predictive value of abnormal findings on routine 

screening is limited. Third, positive results on screening 

tests have modest impact on patient care. 

The dearth of population studies of perioperative risk 

and outcomes specifically addressing the geriatric population 

can make selecting the most appropriate course of 

care challenging. Because age itself adds very modest 

incremental risk in the absence of comorbid disease, 

most risk-factor identification and risk-predictive indices 

have focused on specific diseases. 9–11 It is well known, 

for example, that normal aging produces structural 

changes in the cardiovascular system, as well as changes 

in autonomic responsiveness/control, that can compromise 

hemodynamic stability. The superimposition of such 

comorbid conditions as angina pectoris or valvular heart 

disease can further impair cardiovascular performance, 

especially in the perioperative period. 

According to the guidelines of the American College 

of Cardiology and the American Heart Association for 

preoperative cardiac evaluation, the patient’s activity 

level, expressed in metabolic units, is a primary determinant 

of the necessity for further evaluation, along with 

the results obtained from history and physical examination. 

9 These findings are then evaluated in conjunction 

with due consideration for the invasiveness of the 

planned surgical procedure. Clearly, the goal of the preoperative 

evaluation should be the identification of major 

predictors of cardiac risk such as unstable coronary syndromes 

[for example, unstable angina or myocardial 

infarction (MI) 30 days ago, compensated or prior 

congestive heart failure, diabetes mellitus, or renal 

insufficiency), the invasiveness of the surgery and the

324 K.E. McGoldrick 

functional status of the patient will have major roles in 

determining the nature and extent of preoperative testing 

or intervention. Importantly, no preoperative cardiovascular 

testing should be performed if the results will not 

change perioperative management. For those in whom 

further testing is warranted, there are several options 

including pharmacologic stress testing and dobutamine 

stress echocardiography. The use of perioperative betablockade 

in intermediate- or high-risk patients undergoing 

vascular surgery can be beneficial and may obviate 

the need for more invasive interventions. 12 However, 

there is a dearth of data pertaining to the use of perioperative 

betablockade in patients undergoing less-invasive 

outpatient surgery. 

Given the heterogeneity of the elderly population, it is 

reasonable to examine more domains than just cardiopulmonary 

capacity. A multidimensional approach seems 

indicated and should include screening for mental status, 

depression, and alcohol abuse. We have recently come to 

appreciate that subtle forms of cognitive impairment can 

predispose to worsened cognitive outcome postoperatively. 

It is mandatory to appreciate that the elderly 

patient is at much greater risk for long-term functional 

compromise after the stress of surgery than is the younger 

patient. These potential complications include, but are 

not limited to, aspiration, postoperative delirium and cognitive 

dysfunction, adverse drug interactions, malnutrition, 

pressure ulcers, urosepsis, falls, and failure to return 

to ambulation or to home. Appropriate preoperative 

optimization may well pay dividends in terms of improving 

functional status after discharge. 

Sleep Apnea 

The prevalence of sleep disorders among the general 

American population is high. Sleep apnea has received 

increasing attention during the past few decades in 

tandem with the pandemic of obesity in the United States, 

as well as the accumulation of research linking obstructive 

sleep apnea (OSA) to cognitive, behavioral, cardiovascular, 

and cerebrovascular disease. OSA is defined as 

the cessation of airflow for >10 seconds during sleep 

despite persistent respiratory effort by the abdomen and 

rib cage. OSA is usually associated with a decrease in 

arterial oxygen saturation of >4%. Although there is no 

uniform definition of hypopnea, it is characterized by 

decreased airflow for 10 seconds during sleep and is associated 

with an oxyhemoglobin desaturation of 3% from 

baseline. It should be noted for the sake of completeness 

that the three types of sleep apnea are obstructive, central, 

and mixed. Central sleep apnea, a much rarer entity than 

OSA, is also known as Ondine’s curse, an allusion to the 

mythologic man who was condemned by his rejected 

lover, a mermaid, to stay awake in order to breathe. 

Unlike OSA, respiratory efforts temporarily stop in 

central sleep apnea. Diagnosis is established during 

polysomnography. 

Conservative estimates suggest that 2% of middleaged 

women and 4% of middle-aged men are afflicted 

with this disorder. 13 Growing evidence points to a much 

higher incidence in the elderly. 14,15 Indeed, the prevalence 

of OSA is two- to threefold greater in older persons (>65 

years) compared with those in middle age. 16 Some data 

actually suggest that OSA in elders is a condition distinct 

from that of middle age. Bixler and colleagues 17 reported 

that OSA is less severe in older compared with middleaged 

persons, and suggested that central sleep apnea is 

more common than in younger counterparts. Interestingly, 

other data suggest that the associations of OSA 

with hypertension, sleepiness, and cognitive dysfunction 

are weaker in older versus middle-aged persons. 18 

Obesity is a critical independent causative/risk factor. 

The majority of people who have OSA are obese and the 

severity of the condition seems to correlate with the 

patient’s neck circumference. 13 In the minority of patients 

who are nonobese, causative risk factors are craniofacial 

and orofacial bony abnormalities, nasal obstruction, and 

hypertrophied tonsils. 19,20 

The apnea/hypopneic index (AHI) is obtained by performing 

polysomnography. The number of apneic and 

hypopneic episodes per hour is recorded, and the patient 

is assigned a corresponding number. An AHI value 

between 5 and 14 is associated with mild OSA, 15–30 

moderate, and >30 severe OSA. 21 

It is generally accepted that many patients with OSA 

have resultant daytime sleepiness associated with performance 

decrements and an increased incidence of workand 

driving-related accidents. It has also been well 

established that patients with severe apnea suffer major 

health consequences, including premature death, as a 

result of their condition. Few absolute conclusions can be 

drawn at this time about the long-term consequences of 

mild to moderate OSA. However, recently published 

findings from the Sleep Heart Health Study, 22 the Copenhagen 

City Heart Study, 23 and others 24 demonstrate a firm 

association between sleep apnea and systemic hypertension, 

even after other important patient characteristics, 

such as age, gender, race, consumption of alcohol, and use 

of tobacco products are controlled for. Additionally, 

patients with OSA have been found to have disturbances 

in inflammatory and coagulation profiles as well as altered 

vascular responsiveness. Increased sympathetic tone and 

enhanced platelet aggregation may contribute to the 

greater incidence of MI and stroke noted in these 

patients. 25,26 A preoperative assessment of comorbid conditions 

should be undertaken to detect hypertension, dysrhythmias, 

previous MI, cerebrovascular disease, and 

biventricular failure. Polycythemia, electrocardiogram 

abnormalities including right and left ventricular hypertrophy, 

and cor pulmonale may be present secondary to


Table 22-1. Conditions often associated with sleep apnea. 

• Obesity 

• Cor pulmonale 

• Systemic hypertension 

• Dysrhythmias 

• Pulmonary hypertension 

• ↑ Platelet aggregation 

• Right and/or left ventricular hypertrophy 

• Inflammatory disturbances 

• Polycythemia 

pulmonary or systemic hypertension (Table 22-1). The 

physical examination of a patient with known or suspected 

OSA should include particular attention to neck 

circumference, Mallampati class, and signs of redundant 

oropharyngeal tissue. 

In terms of pathophysiology, sleep apnea occurs when 

the negative airway pressure that develops during inspiration 

is greater than the muscular distending pressure, 

causing collapse of the airway. Obstruction can occur 

throughout the upper airway, above, below, or at the level 

of the uvula. 27,28 Because there is an inverse relationship 

between obesity and pharyngeal area, the smaller size of 

the upper airway in the obese patient causes a more negative 

pressure to develop for the same inspiratory flow. 28,29 

Kuna and Sant’Ambrogio 28 have also postulated that 

there may be a neurologic basis for the disease in that the 

neural drive to the airway dilator muscles is insufficient 

or not coordinated appropriately with the drive to the 

diaphragm. Obstruction can occur during any sleep state, 

but is often noted during rapid eye movement sleep. 

Nasal continuous positive airway pressure (CPAP) can 

ameliorate the situation by keeping the pressure in the 

upper airway positive, thus acting as a “splint” to maintain 

airway patency. 

The site(s) of obstruction can be determined preoperatively 

by such techniques as magnetic resonance imaging, 

computed tomography studies, and intraluminal pressure 

measurements during sleep. 30 Some studies suggest that 

the major site of obstruction in most patients is at the 

oropharynx, but obstruction can also occur at the nasopharynx, 

the hypopharynx, and the epiglottis. 31 

CPAP devices, at least in the recent past, were often 

not well tolerated by patients. However, many technologic 

advances have been made with positive airway pressure 

devices, making these gadgets more easily tolerated. 

Additionally, weight loss may improve OSA, and avoidance 

of alcohol and sedatives may have beneficial effects. 

Recently, atrial overdrive pacing has shown promising 

results in patients with central or OSA. 32 Interestingly, 

French investigators serendipitously observed that some 

patients who had received a pacemaker with atrial overdrive 

pacing to reduce the incidence of atrial dysrhythmias 

reported a reduction in breathing disorders after 

pacemaker implantation. These cardiologists, therefore, 

initiated a study to investigate the efficacy of atrial overdrive 

pacing in the treatment of sleep apnea symptoms 

in consecutive patients who required a pacemaker for 

conventional indications. They found that atrial pacing at 

a rate 15 beats per minute faster than the mean nocturnal 

heart rate resulted in a significant reduction in the number 

of episodes of both central and obstructive apnea. 32 Postulating 

that enhanced vagal tone may be associated with 

(central) sleep apnea, the investigators acknowledged, 

however, that the mechanism of the amelioration of OSA 

by atrial overdrive pacing is unclear. Moreover, whether 

these unexpected findings are germane to the sleep apnea 

patient with normal cardiac function is uncertain. Gottlieb 

33 has tantalizingly suggested that a central mechanism 

affecting both respiratory rhythm and pharyngeal 

motor neuron activity would offer the most plausible 

explanation for the reported equivalence in the improvement 

of central and OSA during atrial overdrive pacing. 

Do cardiac vagal afferents also inhibit respiration? 

Perhaps identification of specific neural pathways might 

also advance efforts to develop pharmacologic treatment 

for sleep apnea. 

A variety of surgical approaches to treating sleeprelated 

airway obstruction are available. They include 

classic procedures, such as tonsillectomy, that directly 

enlarge the upper airway, or tracheotomy to bypass the 

pharyngeal part of the airway, as well as more specialized 

procedures to accomplish the former objective. Examples 

include uvulopalatopharyngoplasty, lingualplasty, and 

maxillomandibular osteotomy and advancement. Many 

OSA patients can be managed effectively with one or a 

combination of therapies. 

Few definitive data exist to guide perioperative management 

of patients with OSA. Therefore, it is not surprising 

that many anesthesiologists question whether 

OSA patients are appropriate candidates for ambulatory 

surgery. The risks of caring for these challenging patients 

in the ambulatory venue are further amplified by the 

unfortunate fact that 80%–95% of people with OSA are 

undiagnosed 34 ; they have neither a presumptive clinical 

and/or a sleep study diagnosis of OSA. This is disconcerting 

because these patients may suffer perioperatively 

from life-threatening desaturation and postoperative 

airway obstruction. 

Recently, the ASA Task Force on Perioperative 

Management of Patients with Obstructive Sleep Apnea 

published practice guidelines intended to assist in the 

perioperative management of these challenging patients. 35 

The task force members commented that the literature is 

insufficient to offer guidance regarding which patients 

with OSA can be safely managed on an outpatient basis, 

as well as the appropriate time for discharge of OSA 

patients from the surgical facility. The consultants agreed, 

however, that procedures typically performed on an 

outpatient basis in non-OSA patients may also be safely


performed on an outpatient basis in patients at increased 

risk for perioperative OSA when local or regional anesthesia 

is administered. The consultants were equivocal 

concerning whether superficial procedures may be safely 

performed during general anesthesia in outpatients with 

OSA, and they believe that airway surgery should not be 

performed on an outpatient basis in patients with OSA. 

Moreover, the capabilities of the outpatient facility are 

critical, and the availability of emergency difficult airway 

equipment, respiratory care equipment, radiology and 

clinical laboratory facilities, and a transfer agreement 

with an inpatient facility should be in place if an outpatient 

facility assumes responsibility for outpatient surgery 

in OSA patients. 35 

The serious and thoughtful ongoing debate about 

whether OSA patients should undergo surgery as outpatients 

suggests there is no one-size-fits-all solution. 34 In 

deciding a management strategy, it is important to consider 

the patient’s body mass index and neck circumference, 

the severity of the OSA, the presence or absence of 

associated cardiopulmonary disease, the nature of the 

surgery, and the anticipated postoperative opioid requirement 

(Table 22-2). It seems reasonable to expect that 

OSA patients without multiple risk factors who are 

having relatively noninvasive procedures under local or 

regional anesthesia (carpal tunnel repair, breast biopsy, 

knee arthroscopy, etc.) typically associated with minimal 

postoperative pain may be candidates for ambulatory 

status. However, those individuals with multiple risk 

factors, those with severe OSA, or those OSA patients 

having airway surgery, most probably will benefit from a 

more conservative approach that includes postoperative 

admission and careful monitoring. It is imperative to 

appreciate that these patients are exquisitely sensitive to 

the respiratory depressant effects of opioids and other 

central nervous system (CNS) depressants. Additionally, 

the risk of prolonged apnea is increased for as long as 1 

week postoperatively. 

It is important not to be lulled into a false sense of 

security simply because general anesthesia is not involved. 

Certainly, the use of regional anesthesia may not necessarily 

obviate the need for securing the airway, and may 

even require emergency airway intervention if excess 

sedative-hypnotics or opioids are administered. Regardless 

of the type of anesthesia selected, sedation should be 

administered judiciously. These patients frequently have 

Table 22-2. Factors affecting perioperative management of 

obstructive sleep apnea. 

• Severity of obstructive sleep apnea (apnea/hypopnea index) 

• Body mass index and neck circumference 

• Comorbid conditions 

• Surgical invasiveness 

• Anticipated postoperative opioid requirement 

a difficult airway, and often it is more difficult to ventilate 

them via a mask than it is to intubate them, although the 

latter may also prove challenging. Moreover, it is important 

to be aware that the American Sleep Apnea Association 

36 notes that “It may be fitting to monitor sleep apnea 

patients for several hours after the last doses of anesthesia, 

longer than non-sleep apnea patients require and 

possibly through one full natural sleep period.” Notably, 

the ASA guidelines indicate that patients with OSA 

should be monitored for a median of 3 hours longer than 

their non-OSA counterparts before discharge from the 

facility. Additionally, they indicated that monitoring of 

patients with OSA should continue for a median of 7 

hours after the last episode of airway obstruction or 

hypoxemia while breathing room air in an unstimulating 

environment. 35 

When confronted with an especially challenging OSA 

patient requiring general anesthesia, a judicious approach 

may include awake fiberoptic intubation, administering 

very low-dose, short-acting narcotics, short-acting muscle 

relaxants, and a low solubility inhalational agent, and 

infiltrating the surgical site with a long-acting local anesthetic. 

Extubation should be performed only when the 

patient is without residual neuromuscular blockade and 

fully awake, using a tube changer or catheter, and CPAP 

should be available postoperatively. Elevation of the 

head of the bed to 30 degrees may facilitate pulmonary 

excursion. In the postanesthesia care unit (PACU), it is 

prudent to have a more prolonged period of observation 

and monitoring in patients with OSA, and it is, therefore, 

helpful to schedule the procedure early in the day. If no 

problems occur in the PACU, and the patient has returned 

to baseline with satisfactory analgesia, the patient is discharged 

to home. However, if episodes of desaturation or 

obtundation have occurred, or if analgesia is problematic, 

it is prudent to admit these high-risk patients to a telemetry 

ward or intensive care unit because the challenge of 

maintaining the airway will extend well into the postoperative 

period. Respiratory events after surgery in OSA 

patients may occur at any time. 

General Principles of 



Because of pulmonary changes (discussed elsewhere in 

this book) (Table 22-3), it is imperative to appreciate that 

desaturation occurs faster in older adults. Additionally, 

elderly patients are more vulnerable to desaturationrelated 

cardiac events. Therefore, proper preoxygenation 

is critical. Benumof 37 points out that maximal preoxygenation 

is achieved with 8 breaths of 100% O 2 within 60 

seconds with an oxygen flow of 10 L/min.


Table 22-3. Pulmonary changes associated with aging. 

• Reduced chest wall compliance, elastic recoil, and maximal minute 

ventilation 

• Increased work of breathing 

• Increased closing volume 

• Reduced forced expiratory volume in 1 second 

• Increased ventilation-perfusion mismatch, diffusion block, and 

anatomic shunt 

• Progressive decline in arterial oxygen tension 

• Disproportionately high incidence of postoperative respiratory 

complications 

Table 22-4. Recommendations for geriatric outpatients having 

general anesthesia. 

• Appropriate preoxygenation 

• ↓↓ Dose of anesthetic agents 

• Prevent hypotension by maintaining euvolemia and carefully 

titrating appropriate agents 

• Select shorter-acting drugs, including neuromuscular blockers 

• ? Role of bispectral index monitoring 

• Transport to postanesthesia care unit with oxygen 

• Maintain normothermia and provide adequate analgesia 

Advanced age is clearly associated with a reduction in 

median effective dose requirements for all agents that act 

within the CNS regardless of whether these drugs are 

administered via the oral, parenteral, or inhalational 

route. Indeed, the median effective dose equivalent for 

inhalation anesthetics decreases linearly with age, such 

that the “typical” 80-year-old will require only about two 

thirds of the anesthetic concentration required to produce 

comparable effects in a young adult. This reduction in 

anesthetic requirement is agent-independent and probably 

reflects fundamental neurophysiologic changes in the 

brain, such as reduced neuron density or altered concentrations 

of neurotransmitters. 

Elderly patients require less propofol (and other 

agents) for induction, and it is also important to appreciate 

that the concurrent use of midazolam, ketamine, 

and/or opioids with propofol synergistically increases the 

depth of anesthesia. Moreover, even with an appropriate 

dose reduction of propofol, hypotension is common. Less 

hypotension has been reported with appropriately titrated 

administration of mask sevoflurane for induction compared 

with a propofol infusion. 38 Interestingly, gender 

differences have been described in the pharmacokinetics 

of propofol given by continuous infusion in elderly 

patients, 39 but data in this area have been inconsistent. 

The time required for clinical recovery from neuromuscular 

blockade is markedly increased in older adults 

for nondepolarizing agents that undergo organ-based 

clearance from plasma, but is minimally different for 

atracurium, cisatracurium, or mivacurium because they 

undergo hydrolysis in plasma. The likelihood of postoperative 

pulmonary complications after long-acting muscle 

relaxants increases with advanced age, and it is not 

unusual for patients who meet rigorous extubation criteria 

in the operating room to deteriorate in the PACU. 

Therefore, it seems advisable to administer a short- or 

intermediate-acting muscle relaxant to any elderly patient 

for whom extubation is planned at the end of the surgical 

procedure (Table 22-4). 

In planning an expeditious emergence, the anesthesiologist 

should be aware that end-tidal gas monitoring 

significantly underestimates the brain concentration of 

the more soluble agents. Failure to appreciate this hysteresis 

effect leads to prolonged emergence. Moreover, 

MAC awake is more favorable if the vaporizer is turned 

down gradually rather than turned off abruptly. 40 Not 

surprisingly, it has been reported that use of shorteracting 

drugs (propofol, desflurane, sevoflurane), in conjunction 

with bispectral index (BIS) monitoring, can 

provide more rapid emergence in geriatric patients and 

facilitate PACU bypass. 41 Whether this approach will 

have a favorable effect on longer-term outcomes remains 

to be determined. Interestingly, a recent study reported 

that advancing age and deeper intraoperative anesthetic 

levels are associated with higher first-year death rates, 

and the authors recommended keeping the BIS level 

under general anesthesia close to 60 rather than in the 40 

range. 42 Additionally, because of the abnormalities in gas 

exchange characteristic of the elderly, it is recommended 

that they be transported to the PACU with 2–4 L/min of 

oxygen via nasal cannula, even after relatively minor 

ambulatory surgery. 43 


When one considers selection of anesthetic technique, it 

is important to appreciate that there are no controlled, 

randomized studies in elderly patients to show that 

regional anesthesia is superior to general anesthesia for 

ambulatory surgery. Indeed, neuraxial, plexus, or nerve 

blocks in the elderly may be associated with an increased 

risk of persistent numbness, nerve palsies, and other neurologic 

complications. Additionally, it has recently been 

demonstrated that age is a major determinant of duration 

of complete motor and sensory blockade with peripheral 

nerve block, perhaps reflecting increased sensitivity to 

conduction failure from local anesthetic agents in peripheral 

nerves in the elderly population. 44 That said, peripheral 

nerve blocks offer some appealing features, especially 

in terms of postoperative pain control. Clonidine is a 

valuable adjunct because it enhances both local anesthetic 

and narcotic efficacy, and its addition to the local 

anesthetic mixture may afford some hemodynamic advantages 

compared with epinephrine. However, one should 

select a dose of clonidine that will not produce postoperative 

sedation or hypotension. When administering central


neuraxial blockade to elderly patients, it is important to 

remember that a given dose will produce a higher level 

of block in seniors and is typically accompanied by a 

greater incidence and degree of hypotension and 

bradycardia as well as a longer duration of anesthesia. 45 

Sedation requirements are dramatically reduced under 

conditions of central neuraxial block. 46 Sensory input to 

the brain is attenuated and the BIS 50 is shifted to a higher 

index. Although recent data have supported a relaxation 

of the requirements for voiding before discharge after 

outpatient neuraxial blockade with short-acting drugs for 

low-risk surgical procedures in low-risk patients, it is 

important to appreciate that elderly patients do not meet 

these criteria. 47 Currently, it seems that elderly (≥70 years) 

patients who received neuraxial block, regardless of the 

duration of the block, should be required to demonstrate 

ability to void before discharge. 

Monitored Anesthesia Care 

Monitored anesthesia care with intravenous sedation has 

become increasingly important in the ambulatory venue 

for a variety of cogent reasons. Advances in surgical technology 

have enabled many procedures to be performed 

through an endoscope rather than a surgical incision, and 

these procedures that previously required general or 

major regional anesthesia can now be accomplished with 

local anesthesia plus sedation. Similarly, technologic 

advances in the expanding area of diagnostics have 

created an augmented demand for monitored anesthesia 

care. Additionally, demographic shifts have seen a steady 

growth in the proportion of geriatric patients with coexisting 

medical conditions that benefit from minimally 

invasive surgical and anesthetic techniques. Finally, as 

patients become more knowledgeable “consumers,” they 

frequently request anesthetic techniques that will obviate 

the side effects associated with general or neuraxial anesthesia 

and that will facilitate the most rapid return to 

their normal activities. Monitored anesthesia care nicely 

dovetails with these exigencies. 

Monitored anesthesia care is typically selected for 

patients who require supervision of vital signs and administration 

of sedative/anxiolytic drugs to supplement local 

infiltration or regional anesthesia, or to provide sedation 

during uncomfortable or unpleasant diagnostic procedures. 

In everyday clinical practice, monitored anesthesia 

care usually connotes an anesthetic state ranging from 

conscious sedation to deep sedation. However, it is 

imperative to appreciate that sedation is a continuum, 

and it is not always possible to predict how an individual 

patient will respond to a given dose of drug. 

The major objective of outpatient anesthesia is to 

provide a balance between patient comfort and patient 

safety while preventing hemodynamic or respiratory 

instability, or delay in recovery. Sedation techniques 

encompass the use of sedatives, hypnotics, analgesics, and 

subanesthetic concentrations of inhalational anesthetics 

alone or in combination to supplement local or regional 

anesthesia. These classes of drug, when combined, confer 

three important components of sedation: amnesia, anxiolysis, 

and analgesia. 

It is essential to appreciate that the technique of sedation 

is as much an art as a science, and facility is gained 

best through experience, sensitivity, and proper patient 

and surgeon selection. Monitored anesthesia care is recommended 

for patients who fear or reject general anesthesia 

or who are at increased risk because of age or 

certain coexisting medical conditions. Monitored anesthesia 

care must be used with caution, however, for 

extremely anxious, impaired, or uncooperative patients. 

Similarly, monitored anesthesia care is not a panacea for 

certain types of medical problems. For example, patients 

with severe coronary artery disease or certain morbidly 

obese patients might be managed with a greater degree 

of control under general anesthesia. Additionally, the 

surgeon must be comfortable operating on an awake 

patient and must be capable of working gently and with 

alacrity. The outpatient procedures that lend themselves 

to management with monitored anesthesia care include 

arthroscopy, biopsies, blepharoplasty and other types of 

superficial skin procedures, bronchoscopy, carpal tunnel 

repair and other types of upper extremity surgery, cataract 

extraction as well as retina and vitrectomy surgery, 

cystoscopy, dilatation and curettage, dental surgery, gastrointestinal 

endoscopy, insertion of lines and shunts, 

herniorrhaphy, rhinoplasty, and rhytidectomy. Similarly, 

many diagnostic cardiologic and radiologic procedures 

are conducted smoothly and expeditiously under monitored 

anesthesia care. 

Agents frequently used for monitored anesthesia care, 

either alone or in combination, include midazolam, propofol, 

fentanyl, and remifentanil. Interpatient variability 

is marked with midazolam, and it is important to appreciate 

that some patients may be exquisitely sensitive to its 

pharmacologic effects. Indeed, when midazolam initially 

was introduced to clinicians, reports soon began to circulate 

of deaths from unrecognized airway obstruction, 

apnea, and hypoxia predominantly in older patients with 

concomitant respiratory or cardiovascular disease. The 

package insert was appropriately revised to include warnings 

about the necessity of careful monitoring, ability to 

manage the airway, and immediate availability of emergency 

resuscitation equipment. It is imperative to appreciate 

that midazolam depresses the slope of the carbon 

dioxide response curve, and attenuates the ventilatory 

response to hypoxia. Apnea is not uncommonly encountered. 

The apparent steepness of the dose-response curve 

seen with midazolam underscores the necessity for meticulous 

titration and careful monitoring. In geriatric or 

debilitated patients, elimination is slower and the dose


should be adjusted downward. Moreover, effects are synergistic 

with narcotics. Indeed, when combined with barbiturates, 

narcotics, or propofol, the dose of midazolam 

should be reduced by at least 25% in young, healthy 

patients. This dose reduction should be much more 

marked (i.e., ≥50%) initially in elderly and frail individuals. 

Although flumazenil may have limited ability to 

reverse benzodiazepine-induced respiratory depression, 48 

it is thought to have efficacy in reversing the benzodiazepine 

component of apnea associated with administration 

of midazolam-opioid combinations. 49 Because the 

half-life of flumazenil is approximately only 1 hour, the 

potential for resedation exists and has been reported. 

Therefore, it is incumbent upon clinicians to monitor 

patients carefully for at least 2 hours after administration 

of flumazenil. 

Propofol possesses a short context-sensitive half-life 

and a high plasma clearance that produce a rapid, clearheaded 

awakening when used as the sole agent even after 

a prolonged continuous infusion. Propofol does, however, 

cause a dose-dependent reduction in arterial blood pressure 

and it should be used with caution, if at all, in hypovolemic 

patients. The respiratory effects of low-dose 

propofol are moderate. To avoid the unwanted hemodynamic 

side effects associated with relative overdosage, it 

is critical to reduce initial doses by approximately 40% 

in the elderly, even for conscious sedation. 50 Additionally, 

it is important to appreciate that recovery of psychomotor 

function after propofol sedation is prolonged in geriatric 

patients. 51 

Remifentanil, the most recently introduced opioid and 

an ultrashort-acting fentanyl analog, has a truncated 

onset, resembling that of alfentanil, and a high metabolic 

clearance. Its most relevant advantage, however, is its 

brief context-sensitive half-life (approximately 3 minutes) 

that is independent of the duration of the infusion. Remifentanil’s 

high lipid solubility and relatively high unbound 

un-ionized fraction at physiologic pH result in peak effect 

compartment concentration within 1–2 minutes after 

bolus administration. 52,53 Likewise, distribution and widespread 

esterase metabolism of remifentanil allow for 

early offset and return of spontaneous ventilation. 54 

Although remifentanil is unique among the opioids in 

terms of its metabolism and brief context-sensitive halflife, 

remifentanil shares the typical opioid-related side 

effects of bradycardia and potential to produce chest wall 

rigidity and nausea/vomiting. 

Nuances pertaining to dosing of remifentanil merit discussion. 

Elderly patients require less remifentanil because 

of altered pharmacokinetics and pharmacodynamics that 

involve a substantial reduction in central compartment 

volume and clearance, and reduction in median effective 

concentration and the equilibration between plasma and 

its effect compartment. 55 It has also been reported that 

adjusting pharmacokinetic models to lean body mass 

improve model performance. 55,56 These results suggest 

that the dosing of remifentanil should be adjusted to the 

lean body mass and that geriatric patients require as 

much as 50%–70% dosage reduction. 

Remifentanil has been used effectively by bolus injection 

for intensely stimulating procedures of brief duration, 

such as awake laryngoscopy. 57 Because of the relative 

absence of residual opioid effect, prudent use of remifentanil 

requires adjunctive analgesics to maintain satisfactory 

postoperative analgesia after painful procedures. 

This is often accomplished with a combination of nonopioid 

analgesics given well in advance of remifentanil 

discontinuation, often at or before induction or toward 

the completion of surgery. Examples of this multimodal 

approach to analgesia include preoperative oral administration 

of an appropriate nonsteroidal antiinflammatory 

drug followed by infiltration of the wound with local 

anesthetic. 

It is, perhaps, easy to be lulled into a false sense of 

security when one is involved in “only” a monitored anesthesia 

care anesthetic for a healthy patient. This misperception, 

combined with the production pressures inherent 

in contemporary clinical practice, can lead to tragic outcomes. 

Unfortunately, the literature is replete with reports 

of adverse events associated with sedation techniques. 58–60 

Some of these catastrophes reflect performance in remote 

locations with inadequate monitoring and sedation 

administered by individuals not thoroughly trained in 

monitoring, pharmacology, airway management, and 

resuscitation. 

Even in the skilled hands of an experienced anesthesiologist, 

monitored anesthesia care can be challenging. 

Patients expected to be most susceptible to the effects of 

these medications are those at the extremes of age, the 

obese, those given additive or synergistic drug combinations, 

and those with cardiopulmonary, renal, or hepatic 

disease. 

According to data from the Food and Drug Administration, 

midazolam was implicated in at least 80 deaths 

during gastrointestinal endoscopy, which occurred mainly 

in the absence of monitoring by an anesthesiologist. 58 

Respiratory events were responsible for the majority 

of the incidents, and most patients had also received 

an opioid. 

In a study by Cohen of 100,000 anesthetics, monitored 

anesthesia care morbidity was 208/10,000, higher 

than that associated with either general anesthesia or 

regional techniques. 61 In fact, during the 1990s, monitored 

anesthesia care medicolegal claims became more com - 

mon, accounting for 6% of the cases in the Closed Claims 

database. 62 Sixty-five percent of the monitored anes - 

thesia care patients involved were older, sicker (ASA 

physical status 3–5) outpatients. In contradistinction to 

most ambulatory claims that tend to involve rather minor 

types of injuries in healthier patients, 63 the monitored


anesthesia care claims reflected more severe injuries, with 

death (39%) and brain damage (15%) common. Moreover, 

payments were high (similar to that for general 

anesthesia), and the mechanism of injury was often respiratory 

(25%) or cardiovascular (14%). It is troubling that 

litigation from monitored anesthesia care–related injury 

increased during the 1990s, despite the use of pulse oximetry 

and other respiratory monitoring. The sine qua non 

of safety is that the provider must have a profound respect 

for the continuum from anxiolysis to unconsciousness. 

Adherence to uniform standards is critical. Patients re - 

ceiving monitored anesthesia care should benefit from 

the same level of preoperative, intraoperative, and postoperative 

vigilance as patients receiving general or 

regional anesthesia. Therefore, it is imperative that 

patients be monitored appropriately by qualified personnel 

who are knowledgeable about pharmacokinetics and 

pharmacodynamics, especially in the gerontologic population, 

and who are experienced in airway management 

and resuscitation. The recent development of ultrashortacting 

drugs such as remifentanil, new techniques of 

administration (e.g., patient-controlled sedation and 

target-controlled infusions), and monitoring devices such 

as the BIS may further optimize intraoperative conditions 

and expedite recovery, thereby enhancing the safety, 

efficiency, and cost-effectiveness of ambulatory surgery. 

Pain Management Pitfalls 

Many elderly individuals suffer from acute or chronic 

pain and increasingly seek treatment for their condition. 

Depression is common in the elderly and is especially 

likely to be encountered in the geriatric patient with 

chronic pain. Given the increased prevalence of pain 

management options and facilities that became available 

in the 1990s, it is not surprising that the overall percentage 

of chronic pain management claims in the Closed 

Claims increased from 2%–3% in the 1970s and 1980s to 

10% in the 1990s. The overwhelming majority (97%) of 

pain litigation in the claims database involved invasive 

procedures such as blocks, injections, ablative procedures, 

and insertion and/or removal of implantable pumps or 

stimulators. 64 Although nerve injury and pneumothorax 

were the most common adverse outcomes in pain management 

claims, devastatingly serious injuries involving 

brain damage occurred also. 

Nerve injury was the most common complication of 

invasive pain management procedures; tragically, half of 

the 63 nerve injury claims involved spinal cord injury. 

Epidural hematoma was a common mechanism of spinal 

cord injury. Therefore, the anesthesiologist should have a 

high index of suspicion concerning any unexpected motor 

or sensory findings after performance of neuraxial blockade, 

and should carefully monitor patients for an extended 

time after performance of the procedure. 

Twenty-one percent of pain management claims were 

related to pneumothorax, which was associated primarily 

with intercostal nerve blocks, trigger point injections, and 

stellate ganglion blocks. Interestingly, in nearly two thirds 

(64%) of chronic pain management claims, the injury 

became apparent only after discharge from the treatment 

facility. Because this temporal association was noted in 

some of the cases of pneumothorax, it is important to 

instruct patients about the signs and symptoms of pneumothorax 

after intercostal nerve blocks, stellate ganglion 

blocks, trigger point injections, and brachial plexus blocks. 

Additionally, it is critical to be vigilant with implantable 

device procedures in which pump programming errors, 

drug overdose, and concomitant use of other CNS depressants 

can result in death or brain damage. 


Most surgical morbidity and mortality occur in the postoperative 

period. 65 This incontrovertible fact has multifaceted 

implications for management of the geriatric 

outpatient. 

Postoperative Respiratory Insufficiency 

Postoperative hypoxemia may occur in 20%–60% of 

elderly surgical patients. 66 As highlighted previously, 

gerontologic patients have an increased alveolar-arterial 

gradient, reduced respiratory muscle strength, and 

blunted hypoxic and hypercarbic drives at baseline. Additionally, 

there is progressive loss of airway reflexes with 

age, and apnea and periodic breathing after administration 

of narcotics are more common. 67,68 Postoperative 

pain, atelectasis, and shivering further increase the likelihood 

of respiratory complications. The supine position 

during recovery increases the transpulmonary shunt, 

making hypoxemia more likely. Finally, orthopedic, upper 

abdominal, and intrathoracic procedures, which are 

common in elderly persons, have an independent effect 

in exacerbating postoperative hypoxemia and other 

respiratory complications. 69,70 Fortunately, these types of 

procedures—with the possible exception of laparoscopic 

cholecystectomy and minor orthopedic interventions— 

are not performed on patients in the ambulatory setting. 

Nonetheless, as ambulatory surgical centers become 

increasingly more inundated with patients, continued 

pressure is applied to truncate the time to discharge. 

Clearly, such tactics may not be in the best interests of 

our geriatric patients who should be observed carefully 

for signs of hypoxemia or apnea. 

The anesthesiologist must be mindful of the risk of 

postoperative aspiration in the elderly surgical patient. 

Because of alterations in pharyngeal function, diminished 

cough, and a higher incidence of gastroesophageal reflux,


elderly patients have an accentuated risk of aspiration. 71,72 

This risk is compounded by the effects of anesthesia, 

sedatives, and narcotics, as well as by such interventions 

as endotracheal intubation, nasogastric tube placement, 

and upper abdominal or neck surgery. 73–75 Most probably, 

pharyngeal manipulation alters sensation, motor function, 

and the protective reflexes that prevent aspiration. 

The duration of this effect after extubation is often presumed 

to be a function of the duration of endotracheal 

intubation or other forms of pharyngeal trespass. If so, 

this may offer some reassurance to the ambulatory anesthesiologist. 

Nonetheless, although the incidence of perioperative 

aspiration is low and is rarely associated with 

clinically important pneumonitis or pneumonia, 76 the risk 

for aspiration extends well beyond the immediate postoperative 

period. Clearly, additional research is needed 

in the areas of restoration of pharyngeal and tracheal 

reflexes, as well as the advancement of feeding after 

surgery in the elderly. 77 It seems prudent for the ambulatory 

anesthesiologist to alert the geriatric patient and 

family members to this potential hazard and to adjust 

oral intake accordingly for 24–48 hours postoperatively. 

Hypothermia 

Because of altered autonomic function, perioperative 

hypothermia is prevalent in both young and elderly surgical 

patients, but it is more frequent, pronounced, and 

prolonged in the elderly who have compromised ability 

to regain thermoregulatory control quickly. 78 Adverse 

consequences of postoperative hypothermia include 

cardiac ischemia, arrhythmias, increased blood loss, 

wound infection, decreased drug metabolism, and prolonged 

hospitalization. 79 Indeed, it has been shown that 

maintaining normothermia decreases cardiac morbidity 

by 55%. 80 

Postoperative Pain 

Postoperative pain increases the risk of adverse outcome 

in elderly patients by contributing to cardiac ischemia, 

tachycardia, hypertension, and hypoxemia. Effective 

analgesia can decrease the incidence of myocardial ischemia 

and pulmonary complications, accelerate recovery, 

promote early mobilization, shorten hospital stay, and 

reduce medical care costs. However, postoperative pain 

control often is inadequate in the elderly 81 because of 

concerns about drug overdose, adverse response, drug 

interactions, and other issues. Pain control is further complicated 

by the fact that the patient’s perception and 

expression of pain often are affected by changes in mental 

status. Current postoperative analgesic techniques include 

the use of opioids by various routes, nonsteroidal antiinflammatory 

drugs, local anesthetic techniques (neuroaxial, 

intraarticular, peripheral nerve block, etc.), and 

nonpharmacologic (transcutaneous or percutaneous 

electrical nerve stimulation, acupuncture, acupressure, 

etc.) methods. Preemptive, multimodal approaches are 

favored to minimize the risk of such opioid-related side 

effects as hypoxemia, constipation, and pruritus. A balanced 

analgesic technique combining opioids, nonopioids, 

and local anesthetic agents is recommended. 

Clearly, the elderly person is extremely vulnerable to 

drug interactions and has an enhanced probability of 

respiratory depression, urinary retention, ileus, constipation, 

and postoperative falls. The likelihood of these complications 

can be influenced by the selection of analgesics 

and, possibly, the route of administration. 82–85 Drugs such 

as clonidine, dexmedetomidine, or the nonsteroidal antiinflammatory 

agents may have a valuable role in reducing 

side effects attributable to opioids. It is imperative to 

be cognizant of the investigation by Bates and colleagues 86 

demonstrating that analgesics are the class of drugs associated 

not only with the highest number of adverse events, 

but also with the greatest number of preventable adverse 

events. Other significant offenders are sedatives and 

antibiotics. 

Postoperative Atrial Fibrillation 

In terms of cardiac function, it is well known that geriatric 

patients have decreased beta-adrenergic responsiveness, 

and they experience an increased incidence of conduction 

abnormalities, bradyarrhythmias, and hypertension. 

Fibrotic infiltration of cardiac conduction pathways and 

replacement of myocardial elastic fibers render the 

elderly individual vulnerable to conduction delay and to 

atrial and ventricular ectopy. Indeed, it is well known that 

postoperative atrial arrhythmias, and atrial fibrillation 

(AF) and flutter specifically, are seen in 6.1% of elderly 

patients undergoing noncardiothoracic surgery and in 

10%–40% of patients after cardiothoracic operations. 87–90 

Although it has been firmly established that older age 

(>60 years) is the strongest predictor of postoperative AF, 

a recent investigation found that a greater preoperative 

heart rate (≥74 beats per minute) is also independently 

associated with postoperative AF. 91 This suggests that a 

lower vagal tone before surgery may be a contributing 

trigger of this arrhythmia. Interestingly, AF occurred at a 

median of 69 hours after surgery. Because reliance on 

atrial “kick” is critically important for older adults, should 

we prophylactically treat high-risk patients to prevent 

postoperative AF? If so, should we use rate control or 

rhythm control drugs? These are unanswered questions 

and offer inviting opportunities for important research. 

However, given the types of procedures that are typically 

conducted on an ambulatory basis, geriatric outpatients 

may be at less risk for this complication than their inpatient 

counterparts.


Postoperative Cognitive Impairment 

Reports of postoperative cognitive deterioration in 

elderly patients surfaced more than a century ago, and 

anesthesia had often been implicated as a possible cause 

or contributing factor. Although improvements in surgical 

techniques and anesthetic agents and methods have 

led to improved outcomes in the elderly, a troubling 

proportion of these patients experience postoperative 

cognitive impairment. 92–95 The implications of this abrupt 

cognitive decline are devastating because affected individuals 

often become dependent and withdraw from 

society. Sadly, our knowledge about the CNS effects 

of anesthetics on the aging brain is rather primitive. 

However, the previously described age-associated changes 

imply that the aging CNS has reduced functional reserve, 

similar to the heart, lungs, and kidneys. Perhaps this putative 

reduction in brain functional reserve renders the 

elderly more likely to develop postoperative cognitive 

disturbances. 

The syndromes of postoperative cognitive impairment 

can be classified into two main categories: postoperative 

delirium and postoperative cognitive dysfunction 

(POCD). 96 Although postoperative delirium and POCD 

may have similar predisposing factors, they are not equivalent 

syndromes. Delirium is defined as an acute change 

in cognitive function that develops over a brief period of 

time, often lasting for a few days to a few weeks, and frequently 

has a fluctuating course. Onset is typically on the 

first to third postoperative day, and the patient’s confusion 

tends to wax and wane. Prospective studies have 

cited an incidence of delirium that ranges from 3% to 

>50% and is dependent on the type of surgery, the 

patient’s preoperative physical and cognitive status, and 

the age of the patient. 96 The etiology of delirium is probably 

multifactorial and may include drug intoxication or 

withdrawal, drug interaction, anticholinergic agents, metabolic 

disturbances, hypoxia, abnormal carbon dioxide 

levels, sepsis, inadequate analgesia, and organic brain 

disease. 97 Curiously, the incidence of postoperative confusion 

is similar regardless of whether spinal, epidural, or 

general anesthesia is used. 93 It has been postulated that 

postoperative delirium may be associated with failure of 

CNS cholinergic transmission. 98 It has also been suggested 

that pain, sleep deprivation, sensory deprivation 

or overload, and an unfamiliar environment may contribute 

to delirium. Recently, the use of melatonin to treat 

delirium has produced some benefit, presumably by resetting 

the circadian sleep–awake cycle of older surgical 

patients. 99 Postoperative delirium is common in the 

elderly and its incidence may be reduced by protocoldriven 

perioperative treatment. Marcantonio and colleagues, 

100 in a study of orthopedic inpatients, reported a 

reduction in postoperative delirium by one third, and of 

severe delirium by half, by adherence to multifaceted 

recommendations that included elimination or minimization 

of benzodiazepines, anticholinergics, antihistaminics, 

and meperidine. Additionally, systolic blood pressure was 

kept more than two thirds of baseline or >90 mm Hg, 

oxygen saturation was maintained at >90% (preferably 

>95%), hematocrit was maintained at >30%, early mobilization 

was encouraged, and appropriate environmental 

stimuli were provided. Because ambulatory patients 

return home to a familiar environment postoperatively 

where appropriate stimuli and support are available, one 

suspects that the incidence of delirium may be less in 

outpatients than in their hospitalized counterparts. 

POCD is defined as a “deterioration of intellectual 

function presenting as impaired memory or concentration.” 

101 The clinical features of this disorder range from 

mild forgetfulness to permanent cognitive impairment. 

We have much to learn about the pathogenesis and 

prevention of POCD. A current hypothesis is that the 

etiology is multifactorial and may include impaired preoperative 

cognitive status, as well as intraoperative events 

related to the surgery itself (e.g., microemboli), and anesthetic 

agents/depth. Additionally, physiologic and sociologic 

consequences of hospitalization and surgery may 

have a role. 

Moller and colleagues 92 in a multinational study evaluated 

cognitive function in patients aged 60 years or older 

after major abdominal and orthopedic surgery. These 

investigators found that approximately 25% of the 

patients had measurable cognitive dysfunction a week 

after their surgery and 10% had cognitive changes 3 

months postoperatively. This finding contrasted with a 

3% incidence of cognitive deterioration 3 months later in 

healthy control subjects in the same age range who did 

not undergo anesthesia and surgery. Interestingly, despite 

extensive monitoring, neither hypoxemia nor hypotension 

correlated with the occurrence of prolonged cognitive 

dysfunction. The identified risk factors for early 

POCD were increasing age and duration of anesthesia, 

low education level, a need for a second operation, postoperative 

infection, and respiratory complications. The 

only risk factor for late POCD was age. Although the 

incidence of late POCD was 14% for patients ≥70 years, 

this rate decreased to only 7% for patients between the 

ages of 60 to 70 years. 

An additional large, prospective study conducted by 

Monk and colleagues 95 evaluated the relationship of age 

to POCD. Using the same methodology as the first multinational 

study, 92 Monk and colleagues reported that 

cognitive decline occurred in 16% of patients aged 60 

years or older at 3 months after major noncardiac surgery, 

but was present in only 3%–5% of younger patients. 94 

This study also determined that rates of cognitive decline 

were higher in those ≥70 years compared with younger 

elderly patients. Interestingly, anesthetic technique does 

not seem to matter; there is no difference between


regional and general anesthesia in the incidence of 

cognitive impairment 3–6 months postoperatively even 

though short-term recovery may be better with regional 

anesthesia. 93,102 

There are few prospective studies on long-term cognitive 

outcomes after outpatient surgery, but an analysis of 

cognitive recovery after major and minimally invasive 

surgery exists. Monk classified the type of surgical procedure 

as minimally invasive (laparoscopic or superficial 

surgery), major intraabdominal surgery, or orthopedic 

surgery. 95 The incidence of POCD was significantly greater 

for patients undergoing major or orthopedic procedures 

compared with minimally invasive surgery. Because outpatient 

surgery is usually minimally invasive, these results 

suggest that outpatients may have a better cognitive 

outcome than patients who require hospitalization. The 

International Study of Postoperative Cognitive Dysfunction 

group recently conducted a longitudinal study comparing 

the incidence of POCD after inpatient versus 

outpatient surgery in patients older than 60 years. 103 At 7 

days after surgery, the incidence of POCD was significantly 

lower in the outpatient group, but this difference 

was not detected 3 months later. These results suggest 

that elderly outpatients have better cognitive outcomes 

at discharge than elderly inpatients, but we currently have 

no explanation for the difference. Possible explanations 

for the improved early outcome in outpatients include 

the healthier status of patients who qualify for outpatient 

surgery, the briefer surgical and anesthesia times, the 

minimally invasive nature of most outpatient procedures, 

or avoidance of hospitalization. 

Although we have much to learn about postoper - 

ative delirium and cognitive decline, it is clear that subclinical 

decrements in functional status may become 

evident during the perioperative period. Indeed, if a cognitive 

deficit is noted preoperatively, it may be a harbinger 

of further postoperative decline. The data on the predictive 

value of preoperative cognitive status 104 and the ability 

of that assessment to result in successful intervention (as 

may be the case with delirium) 100,105 offer compelling 

reasons to conduct a simple, brief mental status examination 

as part of the preoperative interview. 

It is important to understand that full return of cognitive 

function to preoperative levels may require several 

days, even after ambulatory surgery in young, healthy 

patients. 97,106 Indeed, Lichtor et al. 107 have suggested that 

even young adults may be sleepy for 8 hours after receiving 

intravenous sedation with midazolam and fentanyl, 

and the elderly outpatient with balance disturbances or 

age-related gait impairment may be at high risk of falling 

because of residual drowsiness. Moreover, Monk et al. 95 

have reported that POCD is detected with psychometric 

testing in 34% of young (aged 18–39 years), 35% 

of middle-aged (40–59 years), and 40% of elderly (aged 

≥60 years) patients 1 week postoperatively. Similarly, 

Johnson 108 has reported a 19.6% incidence of POCD at 1 

week postoperatively in patients aged 40–60 years. This 

rate decreased to 6.2% at 3 months. 

Nonetheless, it remains unclear which patient populations 

are most vulnerable and what the causative factors 

might be for the serious problem of POCD. As mentioned, 

there seems to be no difference in the incidence 

of POCD whether regional or general anesthesia is 

administered. 93,102,109 Hopefully, future studies will lead to 

a clearer definition of the incidence, mechanisms, and 

prevention of POCD. 

Other Postdischarge Concerns 

Although the Aldrete guidelines offer a satisfactory paradigm 

to determine when an inpatient is fit for discharge 

from the PACU to an overnight bed, or when an outpatient 

is able to bypass phase I recovery and go directly to 

a step-down unit, the Aldrete criteria are inadequate 

to assess fitness for discharge to home in an ambulatory 

patient. To that end, Chung 110 has developed a modified 

postanesthesia discharge scoring system (PADSS) that 

addresses this need. Whereas the Aldrete score focuses 

on activity (ability to move the extremities), respiration, 

blood pressure, level of consciousness, and color, the 

modified PADSS assesses such additional and germane 

parameters as ability to ambulate without dizziness, 

nausea and vomiting, pain, and surgical bleeding (Table 

22-5). 

Typically, PONV and pain are two of the most common 

reasons for unanticipated admission after planned outpatient 

surgery. 111 Apfel and colleagues 112 have shown that 

the four most relevant risk factors for predicting PONV 

are female gender, previous PONV or motion sickness, 

nonsmoking status, and postoperative opioid use. The 

Table 22-5. Modified postanesthesia discharge scoring system. 

Vital signs 

Ambulation and mental status 

Nausea and vomiting 

Pain 

Surgical bleeding 

2 = within 20% of baseline 

1 = 20%–40% of baseline 

0 = 40% of baseline 

2 = steady gait, no dizziness 

1 = walks with assistance 

0 = none/dizziness 

2 = minimal 

1 = moderate 

0 = severe 

2 = minimal 

1 = moderate 

0 = severe 

2 = minimal 

1 = moderate 

0 = severe 

Source: Reprinted from Chung, 110 with permission from Elsevier. 

Note: Total postanesthesia discharge scoring system score is 10; score 

≥9 considered fit for discharge.


Sinclair score requires a probability calculation based on 

the same first three factors as well as the age of the 

patient and the duration and type of surgery. 113 Fortunately, 

the risk of PONV is said to decrease 17% with 

each decade after age 50. 

Transient, subclinical hearing loss is not uncommon 

after spinal anesthesia. 114,115 The pathophysiology is 

thought to involve movement of perilymph from the ear 

into the subarachnoid space as cerebrospinal fluid leaks 

out. The perilymph enters the subarachnoid space via 

the cochlear aqueduct; the resultant increase in endolymphatic 

pressure in the ear is thought to contribute to 

the diminished hearing. It has been demonstrated that 

the rate of mild hearing loss after spinal anesthesia 

varies inversely with the patient’s age. A recent investigation 

disclosed that both the incidence and degree of 

hearing loss were increased in patients aged ≤30 years. 115 

Perhaps cerebrospinal fluid leakage after dural puncture 

occurs more frequently and more extensively in the 

young, and possibly this phenomenon also accounts for 

the much greater incidence of postdural puncture headache 

in the young. 

It is imperative that elderly outpatients be discharged 

from an outpatient surgery facility only if accompanied by 

an escort, and a competent individual should remain with 

the patient for at least 24 hours postoperatively. Geriatric 

patients are at higher risk for drowsiness, confusion, 

falls, urinary retention, and adverse drug interactions than 

their younger counterparts. Clinicians should provide the 

patient and his or her caregiver with clear, written postoperative 

instructions about administration of medications, 

activities to be avoided, and the phone number to 

be called should problems or questions arise. 

Summary 

Elderly patients are uniquely vulnerable and particularly 

sensitive to the stresses of hospitalization and surgery/ 

anesthesia in ways that are only partially understood. Preoperatively 

a thoughtful assessment of organ function and 

reserve is required. Efforts to identify the “best” intraoperative 

anesthetic agent or technique or approach for the 

elderly continue, but it seems that no anesthetic agent or 

technique is unequivocally superior for all conditions 

or circumstances. Therefore, clinicians should strive to 

maintain homeostasis, to avoid drug cocktails—especially 

long-acting benzodiazepines and anticholinergics—to 

administer short-acting drugs, maintain normothermia 

and euvolemia, and provide adequate postoperative analgesia. 

When possible, a case might be made for encouraging 

ambulatory surgery because of its typically brief 

duration, relatively noninvasive approach, and its ability 

to allow elderly patients to recover in their familiar, supportive 

home environment. 

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Part IV 

Anesthesia for Common Surgical 

Procedures in the Aged

23 

Sedation and Monitoring 

Sheila R. Barnett 

Sedation is often required for patients undergoing minor 

procedures. The increased availability of newer medications 

with short duration, rapid onset, and minimal side 

effects has led patients and physicians to expect comfort, 

amnesia, and good “operating” conditions for a multitude 

of minimally invasive procedures. Given the increase in 

the elderly population, it is not surprising that there has 

also been a marked increase in procedures performed in 

extremely old patients. The skillful administration of 

sedation and analgesia for interventional procedures may 

allow these very elderly patients to avoid more invasive 

surgery and the consequent associated morbidity of 

surgery and prolonged hospitalization. 1 

What Is Meant by the Term Sedation? 

Both the American Society of Anesthesiologists (ASA) 

and the Joint Commission on Accreditation of Healthcare 

Organization describe four levels of sedation, 

from minimal or anxiolysis to general anesthesia 2,3 

(Table 23-1). 

Minimal sedation or anxiolysis refers to a controlled 

state of diminished consciousness wherein the ability to 

respond to moderate verbal stimuli and the ability to 

maintain a patent airway are retained. 4,5 There is little 

impact on the cardiopulmonary status. Although this is 

popularly referred to as conscious sedation by many nonanesthesia 

specialties, the ASA task force recommends 

the use of sedation and analgesia rather than conscious 

sedation. 2 

Moderate sedation or analgesia is a drug-induced state 

during which a patient may be less responsive than with 

anxiolysis but still respond to verbal commands appropriately, 

although sometimes requiring simultaneous light 

tactile stimulation. Spontaneous respiration is maintained 

and cardiovascular parameters are unchanged. 

Deep sedation or analgesia is a drug-induced condition 

whereby the patient may be difficult to awaken but will 

respond purposefully to painful stimuli. With deep sedation, 

spontaneous respiration may not be adequate, and 

the patient may not be able to maintain a patent airway 

without assistance. Although controversial, in general, 

the ASA and many hospitals recommend the presence 

of anesthesia-trained personnel if deep sedation is 

anticipated or required to complete a procedure. 2 At 

a minimum, deep sedation requires the immediate availability 

of an individual trained in cardiopulmonary resuscitation 

and airway management. 

Sedation is a continuum of consciousness, and the 

practitioner providing sedation should be ready to 

respond appropriately to the next-higher level of sedation 

in addition to being comfortable at the current sedation 

level. This is particularly relevant when sedation is 

administered by nonanesthesiologists such as dental 

practitioners, radiologists, dermatologists, cardiologists, 

and gastroenterologists. 4,6–10 

Why Is Sedation a Particular Concern 

in Elderly Patients? 

The geriatric population is a heterogeneous group, and 

chronologic age does not always parallel physiologic age. 

Older patients present with multiple comorbidities, 

numerous medications, and less physiologic reserve. 5,11 

They can be more sensitive to the sedative and depressant 

effects of the drugs used for sedation and are at 

increased risk from additive side effects when combinations 

of medications are administered. Although brief 

episodes of hypotension or desaturation may be insignificant 

in a young patient, the same episodes in an elderly 

frail patient may result in serious consequences, such as 

cardiac ischemia and arrhythmias 12 (Table 23-2). 

341

342 S.R. Barnett 

Table 23-1. Sedation depth. 

Minimal 

Moderate 

Deep 

Patient responds appropriately to normal-volume verbal 

cues, through voice or action. The response is 

immediate. 

Patient responds purposefully to verbal or light tactile 

stimulus. The response is either verbal or physical. For 

example, opening eyes, turning head in a given 

direction, appropriate change in position. 

The patient does not respond to either verbal or tactile 

stimulus, but responds appropriately to painful stimuli. 

Comorbid Conditions 

Elderly patients carry a large burden of disease: In a 

recent study examining preoperative health status in 

elderly patients, more than 84% of 544 patients had at 

least one comorbid condition, with 30% of patients having 

three or more preoperative health conditions and 27% 

with two. 11 Disability restricting mobility is also prevalent: 

73% of people older than 80 years have at least 

one disability. These conditions have an impact on the 

delivery of sedation and may limit the options available 

for sedation. 

Cardiac conditions such as angina, hypertension, and 

congestive heart failure are all prevalent among elderly 

patients. 13–15 The high incidence of coronary artery disease 

places older patients at high risk for myocardial ischemia 

during awake procedures, especially if the procedure is 

painful and/or anxiety provoking and it proves difficult 

to relieve the pain/anxiety without resorting to unacceptable 

levels of sedation. Similarly, hemodynamic instability, 

particularly hypotension, is more likely in older 

patients because of their sensitivity to hypovolemia and 

the increased sympathetic tone that could be reduced by 

sedation. However, hypotension is not a likely result if 

stage II sedation is not exceeded. 2,16 

Age-related pulmonary changes 17 also affect the administration 

of sedation; changes in lung and chest wall compliance 

predispose the older patient to atelectasis with 

associated hypoxia that may not be amenable to treatment 

with supplemental oxygen. Hypercarbia may also 

develop and produce hypoxia (if not on supplemental 

oxygen) and may produce undesired hypertension and 

tachycardia. 

Table 23-2. Considerations for sedation in the elderly. 

1. Presence of multiple comorbidities: coronary disease, arrhythmias; 

prior cerebrovascular accidents 

2. Positioning challenges 

3. Chronic pain especially of the back and spine 

4. Prevalence of chronic hypoxia and the need for home oxygen 

5. Hearing and vision impairments that interfere with communication 

6. Dementia and cognitive dysfunction 

Renal disease may require alternations in medication 

dosing, and uremia can render patients very sensitive to 

the effects of sedation, especially the apneic side effects 

of narcotics. With the obesity epidemic in the United 

States, diabetes is becoming more prevalent and is very 

common in older patients. Glucose control can be problematic, 

and associated diabetic gastroparesis may result 

in a full stomach, even after 8 hours of fasting. 

Central nervous system aging renders older patients 

more sensitive to sedatives and analgesics, and patients 

with mild cognitive dysfunction are at particular risk for 

agitation and confusion with even small amounts of 

sedatives. 

Challenges Encountered During 

Administration of Sedation 

There are certain issues that are uniquely relevant to 

elderly patients that may impinge on the sedation plan 5,18,19 

(Table 23-3). 

Positioning 

The accelerated loss of subcutaneous and intramuscular 

fat observed with aging may result in bony prominences 

that are at risk from skin breakdown and predispose 

elderly patients to accidental injury from seemingly 

benign positions. The loss of skin elasticity and slow 

healing further contribute to complex skin wounds 

and shearing injuries. Chronic pain, especially back pain, 

may limit the ability of an elderly patient to attain or 

maintain certain positions for long periods of time. 

Vertebrobasilar insufficiency may predispose an older 

patient to unexpected cerebral ischemia with neck extension; 

this may be particularly important if manipulation 

of the airway or neck is required. Cardiopulmonary 

compromise may occur secondary to positioning. For 

instance, the prone position or Trendelenburg may be less 

well tolerated in the elderly patient with significant 

cardiac disease. 

Table 23-3. Practical considerations for the administration of 

sedation in elderly patients. 

• Allow extra time to explore the preoperative history including 

medications and comorbidities. 

• Provide written instructions in large type. 

• Provide extra copy of instructions to caretaker if applicable. 

• Allow extra time for changing clothes at the beginning and end of 

the procedure. 

• Be prepared to provide additional assistance transferring to and 

from procedure table. 

• Postoperative recovery facilities with monitoring should be 

available in the event of a slow postoperative recovery.

23. Sedation and Monitoring 343 

Communication 

Diminished visual acuity, blindness, deafness, or impaired 

hearing make it more difficult to communicate during a 

procedure. Furthermore, many common procedures such 

as colonoscopies and endoscopies take place in a darkened 

endoscopy suite, further reducing the sensory input 

to the older patient. Any written information should be 

easy to read, and extra copies should be available for 

patient’s family, especially if the patient has any cognitive 

or communication issues. 

Table 23-5. General anesthesia recommendations. 

General anesthesia is recommended in patients who are: 

• Obtunded 

• Intoxicated 

• Septic 

• Have active hematemesis 

• Have significant cognitive impairment—e.g., dementia or are 

unable to cooperate secondary to confusion or anxiety 

• At high risk from aspiration—e.g., obesity, reflux, or ascites 

• Unable to lie still secondary to pain, confusion, or other medical 

conditions 

Administering Sedation 

More than 10 million gastrointestinal procedures are 

performed in the United States and Canada annually, 20 

and the volume of procedures conducted by gastroenterologists 

in the United States has increased almost twofold 

in the past 15 years. Individual endoscopists may perform 

between 9 and 15 esophagogastroduodenoscopies and 22 

colonoscopies per week. Colonoscopy is generally an 

unpleasant procedure associated with considerable 

discomfort. It is possible to perform colonoscopies with 

no sedation, but widespread use of sedation is well known 

to many patients, and most expect the option of safe 

sedation. 21,22 Endoscopic management of biliary disease 

in the elderly may be particularly advantageous, 23 and 

skillful administration of sedation is a vital component 

for these procedures, which may be complex and at times 

uncomfortable. 24,25 

Results from a survey of sedation practices among 

1500 gastroenterologists demonstrated that 98% of 

gastroenterologists routinely used sedation of some 

type, more than 70% routinely administered oxygen, 

almost 99% monitored blood pressure and saturation, 

whereas capnography remained relatively infrequent and 

was monitored in only 3% of respondents. With respect 

to drug administration, the endoscopist was responsible 

for making decisions regarding sedation doses in 78% of 

cases unless propofol was used, in which case anesthesia 

personnel were responsible in almost 70% of the 

cases. 20 

This section particularly addresses the issues of sedation 

with respect to gastroenterology procedures. 24,25 The 

administration of sedation to an elderly patient involves 

Table 23-4. Predictors of difficult sedation. 

History of: 

Substance abuse 

Heavy alcohol use 

Chronic narcotic use 

Difficulty with previous sedation case 

Anticipated prolonged or complex procedure 

a preprocedure assessment and formulation of a plan, 

including monitoring, ensuring availability of resuscitative 

equipment, and an appropriate choice of drugs. 5,26,27 

Preprocedure Evaluation 

Before administering sedation, an assessment of the 

patient’s overall health including an estimate of the 

patient’s reserve function of major organ systems is 

needed. At a minimum, this should include a medical 

history, a comprehensive list of medications, and a brief 

physical examination including an airway assessment. 

One of the guiding principles for the successful administration 

of sedation is cooperation; preprocedure assessment 

should include an evaluation of the patient’s ability 

to cooperate at baseline. Patients who cannot cooperate 

because of dementia, sensory issues such as hearing or 

visual loss, or who are in extreme pain or disabled from 

arthritis and prior strokes and so on may not be suitable 

sedation candidates, and a deep sedation or a general 

anesthetic may be required. 2,5,24,25 

Sedation History 

A history of sedation and anesthesia is invaluable. Difficulties 

with prior procedures under sedation, substance 

and alcohol abuse, and extensive pain medication use 

have been shown to predict difficulty in sedation administration. 

In addition, technically difficult or lengthy procedures 

also predict difficulty with sedation. In these 

instances, it may be preferable to schedule elective procedures 

for deep sedation or general anesthesia 2,5,24,25 

(Tables 23-4 and 23-5). 

Consent 

The patient should understand and agree with the specific 

plan for sedation and the risks involved. When the patient 

is significantly disabled or dependent, it is important 

to involve caregivers early. Aside from consent issues 

in these patients, caregivers are likely to be needed in 

the postprocedure care of the patient. Frequently, the


surgical consent will include permission for sedation 

during the procedure, and separate consent for sedation 

is not always needed; however, specifics will depend on 

local administration and regulations within the hospital 

or facility. 

Preoperative Fasting Guidelines 

Both the ASA and the American Society for Gastrointestinal 

Endoscopy (ASGE) recommend restricting solid 

foods for 6–8 hours and allowing only clear liquids until 

2–3 hours before the procedures. In the elderly person, 

it is useful to establish who is receiving these instructions 

and who is responsible to enforce them. In the more 

frail or demented patient, adherence with fasting guidelines 

is particularly important because it can be difficult 

to predict the reaction to sedation and there may be a 

need for conversion to a deeper sedation or a general 

anesthesia. 24,25 

Monitoring 

Guidelines for monitoring have been developed by the 

ASA and ASGE. 28 At a minimum, all sedated patients 

must be monitored throughout the procedure for level of 

consciousness. Standard monitoring includes heart rate 

monitoring via pulse oximetry, noninvasive blood pressure 

at regular intervals, respiratory rate, and oxygen 

saturation, and in the elderly population, electrocardiography 

is also recommended. Postprocedure vital signs 

should also be monitored periodically during the recovery 

period until the effects of all medications have worn 

off and the patient is ready for discharge. 

The presence of a pacemaker requires the availability 

of a magnet if cautery is contemplated. Patients with a 

significant cardiac history, ongoing angina, congestive 

heart failure, or oxygen-dependent lung disease have 

almost no reserve function. These patients may not be 

suitable candidates for sedation because they may require 

additional monitoring. 

Patients may maintain normal oxygen saturation 

despite significant hypoventilation and hypercapnia, and 

monitoring of ventilation is advisable whenever deep 

sedation is contemplated, especially during long procedures. 

Capnography 28 can be used to monitor ventilation 

and to detect early increases in carbon dioxide. However, 

the role for routine capnography is not clear and probably 

unnecessary in most instances of routine (nonpropofol) 

conscious sedation. Similarly, the bispectral index 

monitor has been used to assess the level of sedation in 

patients receiving propofol for sedation; however, the 

utility has yet to be determined. 29 

It should be recognized that clinical monitoring of the 

elderly patient may be more demanding than that of the 

younger patient. During the procedure, a dedicated individual 

should be able to supervise the patient. This individual 

should not be performing the procedure but rather 

should be continuously monitoring the patient for responsiveness, 

cooperation, and vital signs. Because by definition 

a sedated patient should be responsive at all times, 

communication with the patient is one of the most valuable 

monitoring methods. 

Emergency Resuscitation 

When administering sedation, emergency resuscitative 

equipment should be available, and those providing sedation 

should ideally be trained in basic and advanced life 

support. Minimal emergency equipment should include 

dedicated oral suction, oxygen, a bag-valve-mask device, 

an oral airway, and reversal agents. 30,31 

Oxygen 

Elderly patients with limited reserve function are predisposed 

to hypoventilation and hypoxemia; this may 

be exacerbated by cardiopulmonary and other diseases. 

Studies in gastroenterology have described episodes 

of desaturation during endoscopic and colonoscopic procedures 

in both sedated and nonsedated patients 32,33 

emphasizing the vulnerability of these patients. Supplemental 

oxygen provided via nasal cannula at 4 L/min has 

been successful in abolishing or attenuating episodes of 

desaturation. As stated, monitoring of ventilation is indicated 

because oxygen may mask the development of 

hypercapnia in sedated patients, especially those receiving 

supplemental narcotics. 2,24,28 

Medications 

Intravenous administration of medications is preferable 

to oral or intramuscular administration because it provides 

a more immediate effect and allows for more precise 

dosing. In addition, the presence of an intravenous line 

can be used to administer reversal or resuscitative drugs 

if needed. The time taken for the effect of a drug to peak 

can be slower in the elderly patient, and lengthening the 

interval between incremental doses in the older patient 

is recommended. Combinations of medications can allow 

a reduction in individual doses needed to produce the 

effect. However, in the older person, there is a potential 

for exaggerated effects; this can be minimized through 

dose reduction and interval extension. Some of the drugs 

used most frequently are combinations of midazolam, 

fentanyl, and meperidine. 3,20,24,25,30 

Midazolam is the preferred benzodiazepine: it has a 

fast onset, is short acting, and has few residual effects. 

In contrast, the longer-acting benzodiazepines such as 

diazepam and lorazepam may provide equally good sedative 

effects, but may result in prolonged sedation. 22,34,35


Advanced age is associated with an increased central 

sensitivity to midazolam, 36 and the doses recommended 

are an initial bolus of 0.5–1 mg followed by incremental 

doses of 0.25–0.5 mg during the procedure. 

The narcotics remifentanil, fentanyl, and meperidine 

are popular choices for sedation and are frequently combined 

with midazolam. Fentanyl is a relatively shortacting 

opioid that has been used for many years to provide 

sedation. As with all opioids, postoperative nausea is a 

risk, and this may preclude its use in certain instances. 

The respiratory depressant effects of fentanyl may be 

exaggerated by midazolam, and doses should be reduced 

when the combination is used. In the elderly, fentanyl 

doses range from 12.5 to 50 µg, titrating to effect and 

closely monitoring for respiratory depression. The 

extreme short duration of remifentanil is particularly 

advantageous for infusions, although, as with other 

opioids, the risk of postoperative nausea may limit its 

value. 37 The combination of remifentanil and propofol 

may provide better sedation, pain relief, and toleration 

of colonoscopies compared with the administration 

of midazolam, fentanyl, and propofol. 35 However, the 

overall benefits of these and other combinations have not 

been adequately investigated at this point to make a 

single recommendation, and there are clearly multiple 

approaches to sedation that are acceptable. 37–39 

Meperidine is also popular for sedation in the younger 

generation, but in older patients it is best avoided because 

of its relatively long action, toxic metabolites, and the 

potential for central nervous system side effects. 

Dexmedetomidine is an alpha2 receptor agonist that 

has some significant advantages over the classic sedative 

choices. It is a relatively new agent currently approved 

for administration in the intensive care unit for sedation. 

A major advantage is the lack of respiratory depression 

with significant sedation and analgesia; however, it can 

cause significant hypotension. When compared with a 

propofol infusion, dexmedetomidine may cause slightly 

more hypotension and sedation, but it does have narcotic-sparing 

qualities that may be of value in frail elderly 

patients. The role of dexmedetomidine continues to be 

explored. 40,41 

Propofol 

Although in general the ASA discourages the use of propofol 

by nonanesthesia personnel, 2,30,35 propofol is clearly 

gaining popularity for sedation by nonanesthesiologists 23 

(Table 23-6). Advantages of propofol are its rapid action 

and fast clearance that make it an attractive choice for 

sedation. However, caution is required in elderly patients 

in whom administration may also result in abrupt hypotension 

and severe respiratory depression. One study 

investigated the recovery of psychomotor function in 

elderly compared with young patients after propofol 

Table 23-6. Administration of propofol for sedation: general 

recommendations. 

• Anesthesiology-trained personnel recommended for deep-sedation 

administration 

• Provision for a dedicated individual for the administration of 

sedating medication 

• Individuals administering propofol should: 

Be trained in advanced cardiac life support 

Have experience in airway management 

• Monitoring of vital signs is required 

• Emergency resuscitation equipment should be immediately 

available 

infusions. The authors compared 15 elderly patients, 

mean age 72 years, with 15 young patients, mean age 38. 

Both groups received continuous propofol infusions for 

approximately 140 minutes. Immediate recovery time to 

opening eyes was similar in each group, but the elderly 

patients had a much prolonged complete recovery of psychomotor 

function as tested using the Tieger’s dot test. 42 

Although the study numbers are small, this study emphasizes 

the potential for prolonged effects of medications 

in the elderly patient, even when the agent is regarded as 

of very short duration. 

Several protocols using propofol delivery have been 

developed by gastroenterology services with success. In 

these trials, low-dose propofol given by endoscopists provided 

a good level of low sedation and optimal operating 

environments for the procedure. It is important to note 

that in these studies individuals received specific training 

in propofol administration, and emergency equipment 

was extensive. 23,39 

In a survey conducted on gastroenterologists, propofol 

was used by about 25% of endoscopists, anesthesia providers 

were involved in 28% of endoscopies, and only 

7.7% of endoscopists reported using propofol themselves 

in their practices. In contrast, European studies suggest 

the use of propofol by endoscopists may be as high as 

34%. Interestingly, when questioned, more than 40% of 

endoscopists would choose propofol for their own procedure. 

The reasons they stated for preferring propofol was 

speed of onset and recovery, and satisfaction. 20 

Propofol for sedation is also popular among emergency 

room physicians where it is often the drug of choice for 

brief procedures such as cardioversions, fracture reductions, 

and dislocations. Overall, the role of propofol by 

nonanesthesiologists is still unresolved and varies substantially 

across the nation. 43–46 

Another new trend emerging in endoscopy studies is 

patient-controlled sedation (PCS). Lee et al. 47 randomized 

patients to receive either PCS or intravenous sedation. 

They found that in general the incidence of 

hypotension was lower in the PCS group and the patients 

recovered faster. Although this is obviously not feasible 

in the demented or cognitively fragile elderly patient,


patient autonomy may lead to less medication usage and 

high satisfaction. 

Reversal Agents 

Although reversal issues are not unique to the elderly, 

it is advisable to have naloxone, a selective opioid reversal 

agent, and flumazenil, a benzodiazepine antagonist, 

immediately available if narcotics and benzodiazepines 

are being administered. Many elderly patients take 

chronic opioid therapy for pain, 5,15 and administration of 

naloxone should be done cautiously because it may result 

in a catecholamine surge and subsequent hypertension 

and tachycardia. The initial dose to reverse narcotic respiratory 

depression is frequently less than a full dose of 

0.4 mg; in the elderly patient, an even smaller initial dose 

may be sufficient. Flumazenil will reverse the sedative 

and psychomotor effects of midazolam but not any 

narcotic respiratory depression. Usually naloxone should 

be administered first if respiratory depression is the 

primary issue after combination therapy. Sedative protocols 

using routine reversal of benzodiazepines have 

been described but these have not been popular in the 

United States. 48,49 

Scheduling and Information 

The geriatric patient may have limited mobility and other 

issues that may result in the need for extra time to change 

and transfer from a chair to a stretcher. Therefore, additional 

time in between cases and arrangements to help 

with dressing and so on should be allotted. 

All instructions should be written avoiding medical 

jargon and available in large easy-to-read print. In addition 

to preoperative instructions, written information 

should be given to patients and/or caregivers before discharge 

that clearly states what to expect postoperatively, 

whom to contact with questions, and how to arrange for 

emergency help if needed. 

Adverse Events 

Aspiration 

With advanced age, the pharyngeal reflexes are diminished, 

and elderly patients are at increased risk from 

aspiration. For this reason, fasting guidelines should be 

adhered to and the level of sedation kept to a minimum 

when possible. The age-related reduction in pharyngeal 

sensitivity compared with younger patients is an advantage 

when performing a simple upper endoscopy, and 

the elderly patient may not require any sedation. When 

sedation is required, aspiration risk is increased, and 

in the frail elderly patient aspiration can be a morbid 

event. 18,21 

Cardiopulmonary Events 

These are the most serious of all adverse events and 

include hypoxemia, hypoventilation, arrhythmias, airway 

obstruction, and hypotension. Fortunately, the incidence 

of serious complications is uncommon: results from two 

large studies looking at more than 30,000 patients 

reported complication rates of 2–5 per 1000 patients. 19,20,50 

The complications ranged from mild hypoxemia to cardiac 

ischemia. More recently, Rodriguez-Gonzzalez et al. 1 

looked retrospectively at 159 ERCPs (range 1–5 per 

patient) performed in patients over the age of 90 years 

at their institution. This included 126 very elderly patients 

with a mean age of 92 years, ranging from 90 to 101 years; 

some had more than one procedure. Forty-two percent 

of patients had significant chronic conditions—mostly 

diabetes mellitus and coronary artery disease. All 

patients underwent a procedure performed under local 

pharyngeal anesthesia, and 99% received supplemental 

intravenous sedation. The most frequently administered 

medication was midazolam, which was given in 96% of 

patients; meperidine was administered in 4%. In addition, 

hyoscine-N-butylbromide was given in 75% and glucagon 

in 25% of patients. Overall, the procedures were well 

tolerated in 92% of patients, and no patient experienced 

a direct complication from the sedation. The procedure 

was suspended for anatomic reasons in only nine or 

5.7% of cases. Four patients went to surgery subsequently 

because of inadequate endoscopic interventions and 

all four died postoperatively. Although this was an unusually 

healthy group of 90-year-olds, this study supports 

the importance of skillful sedation. It is evident from the 

data that the mortality with biliary surgery can be high 

in very elderly patients, and avoidance of a surgery may 

be beneficial. 1,23 

Elderly patients can become significantly dehydrated 

easily, especially in hot climates or if they are taking 

diuretic and antihypertensive medications. Patients that 

have had fluid restricted or received bowel preparations 

may demonstrate significant orthostatic hypotension 

when standing up for the first time after a procedure, so 

care should be taken when getting these patients up to 

ambulate. A careful plan for postoperative hydration 

should be discussed with the patient and the caretaker. 

Hypoxemia 

Hypoxia is more common in individuals receiving a combination 

of medications such as midazolam and fentanyl 

or midazolam and meperidine. Longer procedures such 

as endoscopic retrograde cholangiopancreatographies 

(ERCPs) are also more likely to be associated with 

hypoxic episodes, and supplemental oxygen is recommended. 

As discussed above, hypoventilation may be 

underappreciated, especially in long procedures in 

patients with chronic obstructive pulmonary disease,


dementia, and in patients receiving combined sedation 

with benzodiazepines and narcotics. In these instances, 

monitoring of end-tidal carbon dioxide may be merited, 

but this is not universally available or clearly stated in 

any guidelines. 5,24,25 

Summary 

In general, administration of sedation to elderly patients 

undergoing minimally invasive procedures is safe. 

Eye Surgeries in the Elderly 

Cataract extraction is a classic example of an invaluable 

surgery performed with minimal sedation. One and a half 

million cataract surgeries are performed annually in the 

United States, and the annual Medicare expenditure is in 

excess of $3.4 billion. 51,52 In general, these are very lowrisk 

outpatient surgeries, 53 but the complications related 

to the procedure can be devastating and may result in 

significant visual disability and even blindness. 54 An anesthesia 

care provider is frequently involved in the sedation 

and monitoring of these cases. 55 

Cataracts 

More than 20 million people (17.5%) over age 40 years 

have a cataract in at least one eye, and 6.1 million (5%) 

have pseudoaphakia/aphakia (prior cataract surgery) in 

the United States. By 2020, it is estimated that 30 million 

Americans will have a cataract and 9.5 million pseudophakia/aphakia. 

56,57 The majority of cataracts in the 

United States are senile or age-related cataracts and a 

major cause of blindness. The exact pathogenesis of cataracts 

is not completely understood; however, the current 

evidence suggests that a photoxidative mechanism has a 

major role. The normal crystalline lens is composed of a 

very complex structure consisting of specialized cells 

arranged in a highly ordered manner; the high content of 

the cytoplasmic protein provides the transparency critical 

to the functioning lens. During aging, the epithelial cells 

are not shed as they are in other structures, and there is 

a gradual buildup of protein and pigment, forming the 

basis of the cataract. Risk factors include aging, smoking, 

alcohol consumption, sunlight, low education, and diabetes 

mellitus. 58 

Table 23-7. Most common causes of blindness. 

1. Cataract 

2. Macular degeneration 

3. Glaucoma 

4. Diabetes mellitus 

Table 23-8. Causes of cataracts. 

1. Aging 

2. Smoking 

3. Alcohol 

4. Sunlight exposure 

5. Diabetes mellitus 

6. Steroids 

Nuclear cataracts are the type that usually occurs 

with aging and may themselves cause further eye problems 

such as glaucoma. Phacolytic glaucoma occurs when 

a mature cataract liquefies and leaks out of the capsule 

into the anterior chamber, resulting in inflammation and 

clogging of the trabecular network with subsequent 

increased intraocular pressure. Phacomorphic glaucoma 

occurs when large cataracts push forward resulting in a 

narrowing of the angle and subsequent narrow-angle 

glaucoma. 55,58 

The only known treatment for cataracts at this time 

is surgery, and fortunately, 90% of patients undergoing 

first-time cataract surgery have improved visual acuity 

and satisfaction at 4-month follow-up 59–61 (Tables 23-7 

and 23-8). 

Modern Cataract Surgery 

All cataract surgery involves removal of the cataract; 

key advances in the field have been the development of 

small foldable implantable lenses and the development 

of phacoemulsification techniques. Nowadays, patients 

can be in and out of the hospital within a few hours 

and experience immediate improvement of sight 59,60,62–65 

(Table 23-9). 

Intracapsular cataract extraction (ICCE) refers to the 

total extraction of the opacified lens and the capsule; a 

new lens is then inserted into the anterior chamber. This 

technique is less common nowadays, although it may still 

be used for selected complex cases. Extracapsular cataract 

extraction (ECCE) refers to the procedure during 

which the lens is removed but the capsule is left intact. 

This procedure is more technically challenging but advantageous 

because the capsule supplies support for the 

implantable lens. Both ICCE and ECCE procedures 

require relatively large incisions. 62–64 

Table 23-9. Complications of cataract surgery. 

1. Astigmatism 

2. Wound leak or dehiscence 

3. Prolapsed iris 

4. Flat anterior chamber 

5. Expulsive rupture of choroidal vessels 

6. Strabismus


Today, the most popular approach to cataract extraction 

in the United States is phacoemulsification. 62 Under 

an operating microscope, ultrasonically driven oscillating 

needles are inserted through a tiny incision and used to 

emulsify the lens. At the same time, a continuous irrigation/aspiration 

system is used to remove the tiny pieces 

of shattered opacified lens. Foldable implantable lenses 

are inserted through the small incision. These tiny incisions 

frequently do not require sutures for closure, allowing 

for a rapid surgery and recovery. Occasionally, mature 

cataracts are extremely hard and difficult to break 

up using standard phacoemulsification techniques; in 

these instances, the procedure may be prolonged or 

alternative techniques such as ICCE or ECCE may be 

required. 53,62,65,66 

Indications for Surgery 

Not all cataracts require immediate surgery. The key indication 

for surgery is visual impairment accompanied by 

deterioration in general function secondary to failing 

eyesight, and a promising surgical prognosis for recovery 

of vision. Generally, prognosis depends on the presence 

or absence of other ocular comorbidities, such as glaucoma 

or retinopathy. Phacomorphic glaucoma and followup 

of diabetic retinopathy through regular funduscopic 

examinations are other indications for cataract extraction. 

In older patients, even those with dementia, correction 

of vision may improve quality of life and allow for 

more independence. 67,68 

Preoperative Evaluation for Cataract Surgery 

As stated, cataract surgery is very low risk, especially as 

many surgeons are now performing these surgeries using 

phacoemulsification techniques under topical anesthesia 

with minimal sedation. Unfortunately, the preoperative 

assessment in these patients can still be problematic 

because patients have complicated histories and multiple 

illnesses. The preoperative assessment will need to identify 

patients that may need additional anesthesia, such as 

those with unstable medical conditions or conditions that 

may prohibit the patient from lying still during the procedure 

such as severe cardiopulmonary disease. 69,70 

The value of preoperative laboratory testing has been 

questioned, and a recent prospective trial evaluated more 

than 18,000 cataract patients who were randomly assigned 

to either the preoperative routine testing group or the 

no-testing group. 69 At the time of the preoperative assessment, 

the testing group received routine tests including 

blood count and chemistries. In contrast, the no-testing 

group only underwent testing if there was a change in 

their medical history or physical examination that suggested 

the need for testing at the time of the visit. After 

the procedure, there was no difference in the surgical 

complications and the postoperative or intraoperative 

events in either group, which was approximately 31.3 

events per 1000 patients. The authors suggested that 

routine laboratory testing was not indicated; however, it 

is important to recognize that all patients did receive a 

preoperative history and physical examination. In general, 

a history and physical examination before cataract 

surgery, possibly as part of a routine physical visit, are 

beneficial because these patients have complex medical 

histories. In most instances, a baseline electrocardiogram 

within 6–12 months is also recommended in the event of 

a dysrhythmia or other cardiac event during the case. 

Anticoagulation and Cataract Surgery 

Controversy surrounds the relative risks of discontinuing 

anticoagulant or antiplatelet medications for cataract 

surgery versus continuing these medications. Several 

studies have not found any increase in hemorrhagic complications 

when aspirin or warfarin are continued during 

cataract surgery. 71–75 A more recent, large cohort study 33 

in 2003 examined the impact of continuing or discontinuing 

aspirin or warfarin in patients undergoing cataract 

surgery in the United States and Canada. 74 Data on more 

than 19,000 patients undergoing cataract surgery were 

included. Twenty-four percent (4517) of patients took 

aspirin, and 4% were taking warfarin or warfarin and 

aspirin. A small percentage of patients (22.5%) discontinued 

aspirin for 2 weeks, and 28% had stopped warfarin 

4 days before surgery. The incidence of adverse events 

was extremely low in all cases. There was no difference 

in the incidence of thrombotic events in individuals who 

continued aspirin (1.49/1000 surgeries) versus those who 

discontinued aspirin (1/1000 surgeries). Similarly, there 

was no increase in ocular hemorrhage between patients 

who continued or discontinued warfarin. 

It is likely from the available evidence that anticoagulant 

and antiplatelet medication can be continued safely 

during the perioperative period. The decision to withhold 

the medication should take into account the reason the 

patient is taking the medication, the type of anesthesia 

planned (local versus regional), and whether the patient 

is monocular or not. The decision should be made in 

conjunction with the patient’s primary physician. If a 

decision to stop the anticoagulants is agreed upon, there 

should be a clear timeline for the postoperative reinstatement 

of the medications, including who is responsible for 

follow-up. 

Anesthesia for Cataract Surgery 

Recent surveys suggest that local and intracameral anesthesia 

are the preferred anesthetic techniques, although 

there are areas in this country and the world where 

regional techniques are still routinely used 65,76–78 (Table 

23-10). This section describes the different types of anesthesia 

as well as the relative merits of each approach.


Table 23-10. Common anesthetic options for cataract surgery. 

1. Retrobulbar block 

2. Peribulbar block 

3. Sub-Tenon’s block 

4. Topical anesthesia 

5. Topical anesthesia with intracameral injection 

Regional Orbital Anesthesia 

Regional anesthesia for eye surgery provides dense ocular 

anesthesia and akinesia; this may be advantageous in 

complex or prolonged cases. Retrobulbar and peribulbar 

blocks are the most common regional techniques de - 

scribed. 79 The successful regional block requires a block 

of the optic nerve and the ciliary ganglion. Blockade of 

the ciliary ganglion results in a fixed, mid-position pupil. 

The surgery may also require paralysis of the orbicularis 

oculi muscle to prevent blinking; this muscle is innervated 

by the seventh fascial nerve. 

Retrobulbar and Peribulbar Anesthesia 

The retrobulbar and peribulbar blocks are similar. The 

retrobulbar block involves the injection of local anesthetic 

agent behind the orbit within the muscular cone. 

The needle is introduced at the junction of the lateral and 

middle two thirds of the lower lid above the inferior 

orbital rim. As the needle pierces the orbital septum, it 

remains parallel to the orbit floor; after reaching the 

globe equator, the needle is redirected upward to the 

apex of the orbit. The operator may feel a pop as the 

needle traverses the bulbar fascia, entering the muscle 

cone. Between 2 to 4 mL of local anesthetic is injected 

inside the cone of muscles, close to the optic nerve. During 

the injection, an awake patient is instructed to look 

straight ahead (a primary gaze), minimizing the chance 

of an intraneural injection. The peribulbar block is very 

similar; the needle is introduced as described for the retrobulbar 

block. However, the needle is kept parallel and 

lateral to the rectus muscle, and no effort is made to enter 

the bulbar fascia. As the needle reaches the equator, the 

local anesthetic is injected, i.e., around the muscle cone, 

not inside. For the peribulbar block, a larger volume of 

anesthetic is required to allow diffusion—generally 4– 

6 mL. Additionally, it may take closer to 20 minutes to 

achieve the desired anesthesia. The peribulbar block may 

be accompanied by a second injection of 3–5 mL of local 

anesthetic injected medially in the superomedial orbit. A 

blunt-tipped needle of less than 31 mm in length is recommended 

to reduce the chance of a globe or neural 

puncture. 76–79 

Sub-Tenon’s block is a combination block. Topical 

anesthesia is applied to the conjunctiva, and one quadrant 

of the sclera is exposed to reveal Tenon’s capsule 

surrounding the sclera. A blunt catheter or needle is 

inserted into the sub-Tenon’s space, and local anesthetic 

is infused. This provides excellent anterior anesthesia, but 

topical anesthesia is required for the cornea and conjunctiva. 

There is a small risk of global puncture with this type 

of injection, but in general, complications are lower than 

those described for retrobulbar blocks. 76,79 

Monitoring and Sedation 

During the placement of the orbital block, the patient’s 

electrocardiogram, blood pressure, and oxygen saturation 

should be monitored. 80 It is important that the patient 

remains still during the injection, and this may be achieved 

by the administration of short-acting sedative medication 

accompanied by supplemental oxygen. Multiple drug 

regimens have been described, and low-dose propofol 

(30–50 mg) is probably the medication of choice, offering 

excellent conditions with few side effects and a short 

duration. 81–83 Midazolam is also frequently used, but, as a 

solo agent, may not provide a deep enough plane of sedation 

to prevent movement during the injection. Shortacting 

narcotics can be used but most prefer to avoid 

narcotics because of an increased risk of postoperative 

nausea and vomiting. 84 Combinations of a benzodiazepine, 

such as midazolam, and ketamine may result in 

improved patient cooperation, 85 but it is not clear if there 

are true advantages over low-dose propofol. The role for 

dexmedetomidine in cataract surgery has yet to be established. 

A recent double-blind study comparing the use of 

midazolam to dexmedetomidine for sedation in cataract 

surgery under peribulbar block found that patient satisfaction 

was slightly higher with dexmedetomidine. This 

advantage was offset by greater reductions in blood pressure 

and longer recovery time with delayed discharge 

compared with the midazolam group. 40 

In contrast to the requirements for block place - 

ment, minimal sedation during the case is generally 

sufficient, and short-acting anxiolysis with midazolam is 

the most popular choice. Various protocols have been 

described including patient-controlled administration 

of propofol. 86,87 However, the data so far do not show 

any particular advantage, and indeed the combination of 

midazolam and propofol often resulted in undesirable 

head movement. Furthermore, any sedation must be 

balanced against the potential downside of disorienta - 

tion and lack of cooperation in the patient during the 

procedure. 

Side Effects and Complications of 

Intraorbital Anesthesia 

Complications from intraorbital anesthesia are uncommon 

but the effects may be devastating, resulting in 

permanent visual damage or blindness (Table 23-11). 

Although the overall complication rate is less than 0.5%, 

this still has the potential to affect thousands of patients


Table 23-11. Complications of retrobulbar anesthesia. 

1. Retrobulbar hemorrhage 

2. Globe perforation 

3. Neural injection of optic nerve 

4. Vascular injection 

5. Central retinal artery or vein occlusion 

6. Brainstem anesthesia 

because of the huge number of patients undergoing 

cataract surgery. The most significant adverse events are 

described below. 

Orbital hemorrhage occurs in 0.1%–1.7% of retrobulbar 

and 0.072% of peribulbar blocks. Hemorrhage occurs 

as a result of the inadvertent puncture of the ophthalmic 

artery as it crosses the optic nerve. Immediate signs of 

hemorrhage include proptosis, subconjunctival hemorrhage, 

and increased orbital pressure. Initial treatment is 

direct intermittent pressure to the eye. If the globe relaxes 

back (retropulsion) and intraocular pressure is normal, 

cataract surgery may be continued. If increased intraocular 

pressure or proptosis persists, then a lateral canthotomy 

is performed. Retinal perfusion should be confirmed 

using the ophthalmoscope. If the intraocular pressure 

remains increased despite a patent canthotomy, then 

aqueous suppressants may be added. 

Globe perforation is most common with a retrobulbar 

block, but may also occur during a peribulbar or sub- 

Tenon’s block; the incidence varies from 0% to 0.75% of 

blocks performed. Major risk factors for perforation 

include inexperience by the operator and staphyloma of 

the eye. The visual damage after a globe perforation will 

depend on the presence or absence of a retinal detachment 

and vitreous hemorrhage 58,76 (Table 23-12). 

Optic nerve damage is very rare after a retrobulbar 

injection. 

Central Nervous System Complications 

The optic nerve sheath communicates directly with cerebrospinal 

fluid, and inadvertent injection of local anesthesia 

into the sheath may result in immediate brainstem 

anesthesia. Similarly, intraarterial injection of local anesthesia 

may cause central nervous system toxicity and seizures. 

Acute vascular injury may result from damage to 

the central retinal artery or vein; this may lead to significant 

injury. 

Topical Anesthesia for Ocular Surgery 

Topical anesthesia, mostly with lidocaine or tetracaine 

eye drops, has become very popular with surgeons 

and patients. 53,88 In a survey from 1999, the American 

Society of Cataract and Refractive Surgery found that 

topical anesthesia was used by 45% of respondents. 

Caseload was a factor contributing to choice. Surgeons 

performing five or fewer cases per month favored regional 

anesthesia, whereas surgeons performing more than 

50 cases per month preferred topical anesthesia. Eightyone 

percent of surgeons using local anesthesia used 

a combination of topical and intracameral injection, 82 

which involves a small incision and installation of local 

anesthesia into the anterior chamber. The intracameral 

injection reduces the discomfort during manipulation 

of the lens. Some patients may still require small 

amounts of midazolam or similar medications during the 

surgery. 80,89,90 

Advantages of Topical Anesthesia 

There are several advantages to topical anesthesia (Table 

23-13). The patient avoids the risk of retrobulbar hemorrhage 

and other complications, is able to see immediately, 

and the postoperative recovery is very speedy. Even 

complex cataract surgery may be performed under topical 

anesthesia. Jacobi et al. 88 found that surgical complications 

in complex surgeries were not different between 

patients receiving topical versus retrobulbar anesthesia. 

Patient satisfaction with the different techniques has 

been questioned. In the study on complex surgeries, 

Jacobi et al. found greater patient satisfaction for topical 

over retrobulbar anesthesia (p = 0.01). However, Boezaart 

et al. 78 questioned elderly patients (mean age 71 years) 

having cataract surgery and found that 70% of patients 

preferred the block over the local anesthetic. Interestingly, 

98% did not remember the insertion of the block, 

a positive benefit of sedation with the block. In general, 

patient satisfaction is high with both techniques; how - 

ever, the rapid postoperative recovery ultimately makes 

the topical approach very appealing to patients and 

physicians. 

The Role of the Anesthesiologist 

Several surveys have provided conflicting data on the 

need for an anesthesiologist during cataract surgeries. 

Table 23-12. Factors increasing risk of globe rupture. 

• Uncooperative patient 

• Long eye axial length >26 mm 

• Staphyloma 

• Long needle used for the block 

Table 23-13. Advantages of topical versus regional block. 

1. Eliminates risk of retrobulbar hemorrhage 

2. Reduces risk to the optic nerve and other structures 

3. Minimizes risk of strabismus postoperatively 

4. Very short recovery time with immediate sight


Rosenfield et al., 80 in a study of 1006 patients, found that 

in one third of cases an intervention by an anesthesia 

team was required and that the need for an intervention 

was unpredictable. The lack of predictability is perhaps 

one of the strongest arguments for anesthesia involvement. 

The International Cataract Surgery Outcomes 

Study surveyed ophthalmologists in the United States, 

Canada, Denmark, and Spain from 1993 to 1994. 90 They 

found that in the United States 78% of surgeons used 

phacoemulsification for the cataract removal. In this 

survey, they found only 14% used topical for the anesthesia, 

46% used retrobulbar, and 38% used peribulbar 

blocks. Most blocks (79%) were performed by the surgeon, 

although in 78% of cases an anesthesiologist was 

present. All patients were monitored: 97% with electrocardiogram, 

blood pressure, and oxygen saturation. The 

low rate of topical anesthesia may reflect the sampling 

era because more recent results support topical anesthesia. 

Furthermore, the international study had a high rate 

of anesthesia involvement. In an in-depth analysis of 

anesthesia management during cataract surgery, Reeves 

et al. 91 found preferences for an anesthesiologist, sedation, 

and a block for the surgery. However, these results 

were highly dependent on the selection of a relatively 

small expert panel. In contrast, the results of more recent 

surveys of ophthalmologists favor topical anesthesia. 

Thus, although not universal, anesthesiologists are still 

frequently involved in monitoring the patient during the 

cataract surgery. 

Special Situations 

There are some special circumstances in the elderly 

patient that may require alternative approaches. For 

instance, demented or uncooperative patients may require 

more sedation or even general anesthesia. Chronic pain 

patients may be unable to lie flat and be tolerant of medications. 

Occipital pain has been described during the procedure 

necessitating additional medications. In patients 

with significant cardiopulmonary disease, supplemental 

oxygen may be required during the case, and several 

instances of hypercapnia have been described. 92,93 The 

anesthesiologist should be prepared to respond to the 

variable needs of this population. 

Postoperative 

A cataract extraction is an outpatient procedure. Patients 

generally follow up with the ophthalmologist the next 

day. All patients should receive instructions from the 

ophthalmologist’s office before discharge. In patients 

receiving blocks, an eye patch is common, and vision will 

take longer to return. 94 These patients may require additional 

help at home during convalescence. 

Conclusions 

Elderly patients should be offered the opportunity to 

undergo procedures and simple surgeries under sedation 

with minimal risk. Skillful administration of sedation may 

help avoid more morbid and complex surgeries and 

improve outcomes. Sedation in the older patient is safe, 

but requires additional vigilance and patience. 

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24 

Total Hip Replacement, Joint Replacement, 

and Hip Fracture 

Idit Matot and Shaul Beyth 

Surgical treatment of hip fracture is a well-known medical 

emergency in the elderly. Similar to arthroplasty, this 

operation is performed to acutely restore function 

and decrease pain. Although the anatomic approach, 

instrumentation, and final mechanical results of hip fracture 

repair are similar to what occurs with hip arthroplasty, 

major differences between the two patient 

populations exist and create differences in perioperative 

management. 

Background 

Total Hip and Knee Arthroplasty 

Joint replacement is one of the most rewarding procedures 

in the field of orthopedic surgery in general. It is 

indicated in individuals with a painful, disabling arthritic 

joint that is no longer responsive to conservative treatment. 

For these patients, it may provide improvement in 

the quality of life. Focusing on the frequently replaced 

weight-bearing joints, i.e., hip and knee, it should be noted 

that in addition to complete primary joint replacement, a 

whole new field of reconstructive surgery has evolved 

around the implantation of prostheses that includes, but 

is not limited to, partial arthroplasty, revision procedures 

for failed implants, computer-assisted surgery, and minimally 

invasive surgery. 

Patients coming for elective joint replacement surgery 

are highly motivated and in most cases mentally prepared 

to undergo major surgery in order to regain daily functions. 

These patients undergo a thorough preoperative 

evaluation and preparation including relevant specialist 

evaluation, revision of medications, autologous blood 

donation, and preparation from a rehabilitation facility 

for the postoperative period. 

Elective total hip or knee arthroplasty (THA/TKA) is 

considered a relatively safe orthopedic procedure. Known 

complications after these procedures, not related to the 

implants used, include thromboembolism, postoperative 

anemia, infection, fractures, and death. However, despite 

the low incidence of mortality after total joint arthroplasty, 

a significant number of deaths occur given 

the extensive number of procedures being performed. 

The specific risk has been reported to be as low as 0.1% 

and as high as 3%. 1 Compared with THA, the risk of 

perioperative death after TKA is considerably lower. Preexisting 

comorbidities and the American Society of Anesthesiologists 

physical status classification are significantly 

related to the incidence of postoperative death in patients 

undergoing elective hip or knee arthroplasty. 2 Also, total 

joint arthroplasty performed for fracture or malignancy 

has a higher risk of mortality. 3,4 Other patient healthindependent 

factors that are associated with a significantly 

increased mortality include: age more than 70 

years, revision (as compared with primary) surgery, use 

of a cemented prosthesis, and simultaneous bilateral 

arthroplasty. 4 Recognition of these risk factors and implementation 

of appropriate measures may enable the 

orthopedic team to reduce perioperative mortality after 

major lower extremity surgery. 

The preoperative medical status of the patient may be 

even more important to outcome than the risks of the 

surgical procedure. Patients with preexisting cardiac or 

respiratory disease have decreased physiologic reserve 

and are at greater risk of morbidity and mortality, specifically 

cardiorespiratory collapse after an embolic load, 

hypoxemia as a result of ventilation/perfusion mismatch 

during lateral decubitus position, and myocardial ischemia 

or infarct, which may be prompted by intra- or 

postoperative blood loss, hypotension, and/or tachycardia. 

Measures to consider include optimizing medical 

therapy of patients who have a history of cardiac or pulmonary 

problems; avoiding bilateral one-stage TKA in 

patients who are ill or elderly; vigilant anesthetic monitoring, 

especially around the times of surgical interventions 

that are known to be associated with marrow and 

fat embolization; and the use of vasopressor agents during 

355

356 I. Matot and S. Beyth 

episodes of hypotension. Modifications in surgical technique 

and implant choice to reduce marrow and fat 

embolization may also be appropriate in some high-risk 

patients. The use of prophylactic antibiotics decreases 

infection rate to less than 1%. Administration of antibiotics 

30 minutes before skin incision or, during revision 

arthroplasty, after samples for bacterial culture are 

obtained, is recommended. 

Hip Fracture Surgery 

Fractures of the hip, which most frequently occur in the 

elderly, are associated with a very high mortality. With 

increasing life expectancy, these injuries are on the 

increase and will thus continue to be a substantial workload 

for trauma departments. Impaired balance and coordination, 

leading to frequent falls, paired with a high 

prevalence of osteoporosis make the elderly particularly 

prone to incur this fracture. Operative treatment of hip 

fractures is usually straightforward, but postoperative 

recovery and rehabilitation are fraught with complications. 

One-year mortality after hip fracture surgery is 

remarkably high, around 26%, with a range of 14%–36% 

reported in the literature. It is highest during the first 6 

months after injury, and after the first year it approaches 

that of unoperated patients of matching age and sex. 5 

The reported in-hospital mortality rates range from 

1.4% to 12%. 6–8 The principal causes of in-hospital death 

after hip fracture are cardiac failure and myocardial 

infarction, which occur early after the fracture, peaking at 

2 days, bronchopneumonia, which accounts for the majority 

of late deaths, and pulmonary embolism, which peaks 

in the second week after injury. The overall incidence of 

perioperative myocardial ischemia in elderly patients 

undergoing hip fracture surgery has been reported to be 

35%–42%. 9,10 Preoperative placement of an epidural 

catheter with provision of effective analgesia has recently 

been shown to reduce the preoperative incidence of 

adverse cardiac outcomes in high-risk patients with neck 

of femur fracture. 9,10 Mortality from bronchopneumonia 

and pulmonary embolism after hip fracture may be 

reduced by early surgical intervention, early mobilization, 

antibiotics, and prophylactic anticoagulation. 5,8,11 

Unlike patients scheduled for joint arthroplasty, 

patients with hip fracture are routinely admitted to the 

emergency room without prior preparation or evaluation. 

These patients should be considered as requiring urgent 

treatment. Thus, perioperative management should be 

oriented toward adequate pain control, multidisciplinary 

consultation, if needed, and optimal monitoring and riskreduction 

within a given time frame. The issue that the 

anesthesiologist must consider in the preoperative evaluation 

and clearance for urgent surgical treatment of a hip 

fracture is the timing of surgery. In most studies, patients 

wait on average 1.5–3.5 days between admission and 

surgery. 5,11–16 Results of studies of the optimal timing of 

surgery are contradictory. Whereas some studies reported 

an increased mortality if patients had surgery within 24 

hours, the majority have demonstrated a clear advantage 

of early surgical intervention. The current prevailing recommendation 

is that patients who are medically fit for 

surgery should be operated on the day of admission 16 

because delays serve to increase morbidity, mortality, 

and resource utilization. 14–16 In two recent studies, longer 

waiting time increased the risk for developing deep 

vein thrombosis and pulmonary embolism, atelectasis, 

pneumonia, 11 and decubitus ulcer formation. 16 Nevertheless, 

sufficient time should be taken to study and prepare 

patients with significant comorbidities. For these patients, 

preoperative epidural analgesia may prove to be most 

helpful. 10 

It is important to note that, although the two categories 

of hip fracture surgeries (THA and hip fracture stabilization) 

aim to improve ambulation, they differ in both 

patient characteristics (as noted above) and in the expected 

end result. For arthroplasty, the expected surgical outcome 

is functioning “better than before,” whereas the anticipated 

result of procedures for hip fractures is functioning 

“as close to before (the fracture)” as possible. 

Surgical Procedure 

Total Hip and Knee Arthroplasty 

Arthroplasty of both hip and knee joints is a procedure 

aimed to improve patients’ ambulation by means of 

replacing damaged and worn-out joint components with 

prosthetic devices. Inherently, these procedures involve 

surgical removal of articulating surfaces together with the 

subchondral bone, implantation of the substitute parts, 

and fixation of those components. 

Hip 

There are several prosthetic devices available, most of 

which share a few basic characteristics: 

1. After surgical dislocation from the acetabulum, the 

arthritic femoral head and a portion of the femoral neck 

are resected and replaced with an intramedullary stemmed 

component, anchored to its place using a premade space 

reamed through the soft spongious bone (“press-fit”) 

and/or cement surrounding the stem. 

2. If the acetabulum needs replacement, the damaged 

articulating cartilage is reamed and the prosthetic acetabular 

component is attached to its place, using the same 

techniques as above. It can then be further supported by 

screws and/or bone graft. 

3. No matter which surgical approach to the joint has 

been used (anterior, posterior, or lateral), the two artifi-

24. Total Hip Replacement, Joint Replacement, and Hip Fracture 357 

cial joint components are fit together (“reduction” of a 

“dislocated joint”) at the very last stages of the operation. 

This step is best assisted by muscle relaxation. Dislocation 

may occur shortly after surgery if the muscle tone 

that keeps the joint in place is not restored. 

Knee 

This procedure begins with a knee joint arthrotomy. The 

distal femur and the proximal tibia are shaped using measured 

templates to fit the size of the available prosthetic 

parts. These parts are later attached to the bones, covering 

the exposed surfaces. Shaping of the bony ends is 

accompanied by bleeding, especially from the trabecular 

bone. Although fitting of the prosthesis leads to hemostasis, 

the bleeding from trabecular bone is not always fully 

controlled. Blood loss from trabecular bone may therefore 

proceed after surgery and is halted because of clot 

formation and/or tamponade effect of the hematoma. 

Close monitoring of hematocrit and hemoglobin levels is 

thus essential in the postoperative period. 

The patella may be replaced either completely or 

partially, or may not be replaced at all. Also, the new 

prosthetic components may be either cemented or uncemented, 

depending on the findings and the surgeons’ 

preferences. 

Hip Fractures 

Several procedures are accepted today in the management 

of hip fractures, depending primarily on the type of fracture 

and the patient’s concurrent diseases (Figure 24-1). 

A 

B 

Extracapsular Fractures 

The vast majority of these fractures will unite after proper 

reduction and fixation. Both extra- and intramedullary 

systems are used to treat pertrochanteric and subtrochanteric 

fractures. The newest devices are introduced through 

minor skin incisions from a lateral aspect approach to 

the thigh and require not more than an hour for a skilled 

team. 

Intracapsular Fractures 

Because the retrograde blood supply to the head of the 

femur is often compromised after displaced femoral neck 

fractures, the degree of displacement dictates the nature 

of surgical procedure: 

• Minimally and nondisplaced intracapsular fractures are 

usually stabilized in their position by percutaneous introduction 

of cannulated screws into the femoral neck and 

head through the fracture line. This is a minimally invasive 

procedure that results in minor systemic effect. 

• Displaced intracapsular fractures, often termed “subcapital” 

or “femoral neck” fractures, are often treated 

Figure 24-1. (A) Intertrochanteric femoral fracture. Fracture 

line extends from greater to lesser trochanters, external to hip 

joint capsule. (B) Femoral neck fracture. Fracture line extends 

from medial to lateral cortex of the proximal femur, within the 

hip joint capsule (“sub-capital” fracture). 

by prosthetic replacement of the femoral side of the 

hip joint (hemiarthroplasty), because of the abovementioned 

risk of femoral head necrosis after compromise 

of its blood supply. From the anesthesiologist’s 

point of view, the surgical procedure itself is almost 

identical to that of complete hip joint replacement. 

Anesthetic Management 

Anesthetic Technique 

The choice of anesthetic technique is a complex medical 

decision that depends on many factors, including patient 

characteristics (e.g., comorbidity, age), type of surgery performed, 

and risks of the anesthetic techniques. Assessment


of the risks of the anesthetic technique should include 

consideration of technical factors (airway, establishment 

of regional blocks, invasive monitoring), anesthetic agent 

toxicities, incidence of critical intraoperative and postoperative 

events, and postoperative treatment of pain. 6 

Anesthesia for Hip Fracture Repair 

In recent years, regional anesthesia has been used more 

frequently in hip fracture patients. In 1981–1982, general 

anesthesia was used in 94.8% of patients, whereas in 

1993–1994, general anesthesia was used in only 49.6% of 

patients. 6 

Few studies have compared the outcome of patients 

administered general versus regional anesthesia for hip 

fracture surgery. The largest retrospective analysis that 

included 9425 hip fracture patients reported that the type 

of anesthesia did not seem to influence morbidity or 

overall mortality. 6 This finding suggests that unadjusted 

differences in outcome between general anesthesia and 

regional anesthesia are mainly a result of concomitant 

disease and not of any protective effect of one anesthetic 

technique versus another. As might be predicted from 

clinical practice, the authors found that older patients and 

those who were sicker were more likely to be receiving 

a regional anesthetic. Intraoperative hypotension and the 

use of vasopressors were more frequent in the regional 

anesthesia group than in the general anesthesia group. 

The results of this study are in agreement with two earlier 

meta-analyses 13,17 that included randomized controlled 

trials that evaluated the outcome of hip fracture surgery 

up to 1 month postoperatively. The authors were unable 

to identify any difference in long-term mortality or blood 

loss attributable to the use of either regional or general 

anesthesia. However, there was a clearly reduced incidence 

of deep vein thrombosis in the regional anesthesia 

group. Subsequent large, single-center observational 

studies 12,18 also did not identify meaningful differences in 

cardiopulmonary morbidity or mortality attributable to 

the choice of the anesthetic technique in hip surgery 

patients. A similar conclusion was reached in the 2002 

Cochrane Library review. 19,20 

In the past few years, there has been a growing interest 

in peripheral nerve blockade in orthopedic patients. Such 

techniques are used more and more often not only to 

provide anesthesia but also for postoperative analgesia 

after limb surgery. Various nerve blocks have been used 

to reduce pain after hip fracture. The 2002 Cochrane 

Library review 21 summarized the data from eight randomized 

trials involving 328 patients. Three trials related 

to placement of a nerve block (lateral cutaneous, femoral, 

triple, psoas) preoperatively and the remaining five to 

perioperative insertion. Nerve blocks resulted in lower 

reported pain levels and reduced consumption of pain 

medications (parenteral and oral) during the perioperative 

period. No clinical benefits beyond these reductions 

could be demonstrated. 

Neuraxial Anesthesia for Total Knee or 

Hip Arthroplasty 

Regional anesthesia may be of benefit to patients undergoing 

major joint surgery. A retrospective study found that 

the use of neuraxial anesthesia compared with general 

anesthesia in patients having elective total knee or hip 

replacements was associated with a lower rate of intensive 

care unit admission postoperatively. 22 In addition, intraoperative 

blood loss and transfusion requirements were 

significantly lower in patients who received neuraxial anesthesia 

or lumbar plexus block. 23–26 Neuraxial anesthesia 

and analgesia were associated with a reduction in thromboembolic 

complications. 27–29 Also, postoperative confusional 

state was reported to be less frequent in a group of 

patients who had epidural anesthesia compared with those 

patients who had surgery under general anesthesia. 30 

Others 31,32 have failed to find an advantage of general 

versus regional anesthesia in all outcome measurements 

(magnitude or pattern of postoperative cognitive dysfunction 

and incidence of major cardiovascular complications) 

except that epidural anesthesia was associated with more 

rapid achievement of postoperative in-hospital rehabilitation 

goals. The largest benefit of regional anesthesia and 

analgesia is its role in providing adequate pain control for 

rehabilitation. This topic is discussed in depth in the section 

on postoperative analgesia. 

Intraoperative Monitoring 

With advances in both anesthetic and surgical techniques, 

the need for invasive intraoperative monitoring in medically 

fit patients has diminished. Nevertheless, several 

stages in the intraoperative period can cause significant 

hemodynamic and respiratory alterations. Therefore, in 

high-risk patients or procedures (complex or revision 

surgery), the use of an arterial line for continuous hemodynamic 

and blood gas monitoring may be useful. Intraoperative 

transesophageal echocardiography may detect 

fat embolization and monitor intraoperative volume status 

and cardiac function. 33 In high-risk patients undergoing 

bilateral procedures, pulmonary artery pressure monitoring 

may also be of benefit, both as a diagnostic and a 

prognostic tool. 34 Although more invasive monitoring 

improves detection of pulmonary embolization and its 

sequelae, there is no evidence to suggest that these interventions 

improve outcome in fat emboli syndrome. 

Positioning 

The lateral decubitus positioning, which is frequently 

used for THA and displaced intracapsular fractures


Figure 24-2. Positioning of the patient on the fracture table for fracture of hip surgery (A) or in the lateral decubitus position 

for total hip arthroplasty (B) should be performed carefully because of potential morbidities. 

(Figure 24-2), requires special attention to pressure points, 

hemodynamic stability, and oxygenation. A low axillary 

roll is placed under the chest and lower shoulder to 

prevent brachial plexus stretching and axillary artery 

occlusion of the dependent side. Padding of the nonoperated 

(dependent) hip and leg is important, as well as 

padding of the nondependent leg and hand to prevent 

injury to the femoral, popliteal, and pudendal nerve, the 

brachial plexus, and the ulnar nerve. The head and neck 

should be aligned properly and supported to avoid injury 

to the cervical spine, ears, and eyes. Positioning into the 

lateral decubitus may cause brief hypotension, especially 

if the patient is hypovolemic. It may also result in hypoxemia, 

which results from increased degree of ventilation/ 

perfusion mismatch: the nondependent lung is well ventilated 

but poorly perfused and the dependent lung is 

poorly ventilated but well perfused. 35 

Cement 

Polymethylmethacrylate bone cement prepared in a liquid 

methylmethacrylate monomer is widely used to anchor 

prostheses in joint replacement surgery. Multiple adverse 

effects have been associated with the use of polymethylmethacrylate 

cement. 36,37 Hypoxemia, pulmonary hypertension, 

right ventricle failure, cardiac arrest, and sudden 

death are well-recognized complications during THA and 

to a lesser degree after TKA. Although incompletely 

understood, these complications have been in part attributed 

to formation of microemboli and activation of the 

complement system, resulting in triggering of the inflammatory 

cascade, which in turn leads to increased vascular 

endothelial permeability. 38,39 The increase of intramedullary 

pressure caused by the mechanical compression of the 

femoral canal during the insertion of the prosthetic stem 

is the most decisive pathogenic factor for the development 

of embolism. The thin-walled vessels in the medullary 

cavity are easily disrupted by focal application of compressive 

loads, allowing the intravasation of bone marrow, fat, 

and bone debris and the embolization through the venous 

system located along the linea aspera and through the 

metaphyseal vessels. Migration of bone marrow into the 

draining veins activates the coagulation system. Occlusion 

of lung capillaries by these emboli causes an increased 

arteriovenous shunt and alveolar hypoperfusion. 40–44 In 

addition, the methylmethacrylate cement causes direct 

vasodilatation leading to transient hypotension. 

The progressive decrease of serious intraoperative cardiorespiratory 

complications in the past few decades has 

been attributed to the constant improvement of anesthesiologic 

and surgical techniques. To prevent hypoxemia 

intraoperatively, 100% oxygen administration during 

cementing and prosthesis insertion in patients at risk has 

been recommended anecdotally although there are 

no prospective studies confirming the usefulness of this 

maneuver. 34 Fluid therapy to prevent hypovolemia is 

also recommended, because canine studies have shown 

that acute hemodynamic changes during prosthesis insertion 

and fat embolism may be aggravated in hypovolemic 

states. 45 Maintenance of perfusion pressure with vasoconstrictors 

to preserve right heart perfusion and function 

and to avoid fluid loading may be preferable in patients 

with preexisting heart disease with congestive symptoms. 

Modifications of surgical techniques aimed at prevention 

of embolism, e.g., by venting of the femoral shaft and 

lavage of the medullary canal (to minimize increases 

in intramedullary pressure and the amount of fatty 

bone marrow present), and increased use of total condylar 

components from long-stemmed prostheses (that 

obviate the need for extensive intramedullary manipulation) 

may be most effective at reducing the incidence of 

these complications.


Blood Management 

The likelihood of major intra- and postoperative blood 

loss and resultant transfusion of blood components is 

high in lower extremity joint replacement and hip fracture 

surgery. TKA, for example, can be associated with 

major blood loss. Lotke et al. 46 concluded in their study 

that the mean calculated total blood loss in TKA was 

approximately 1.5 L. In TKA the total blood loss is composed 

of “visible” blood loss (from the surgical field 

and wound drainage) and “hidden” blood loss (into the 

tissues). The latter can account for up to 50% of total 

blood loss. 47 Blood management should be aimed at 

addressing the total blood loss and underestimation ought 

to be avoided. 

In several series over the past decade, 48–51 32%–85% of 

the operated patients received allogeneic blood. The frequency 

of allogeneic blood transfusion varied with respect 

to the type of operative procedure (revision THA and 

bilateral TKA were associated with the highest prev - 

alence of such transfusions) and with a baseline hemoglobin 

level of 130 g/L or less. Concerns about the risks 

associated with allogeneic blood transfusion led to the 

development of a variety of blood conservation techniques 

intended to minimize the need for allogeneic 

transfusion. These include preoperative donation of 

autologous blood, acute normovolemic hemodilution, 

blood salvage, hypotensive anesthesia, improvements in 

tissue hemostasis, and pharmacologic agents such as preoperative 

use of erythropoietin and intraoperative use of 

antifibrinolytics. 52 Several studies have confirmed the use 

of these techniques to reduce allogeneic blood transfusion; 

however, their use is based on hospital resources 

and on the anesthesiologist and surgeon preferences. In 

addition to reducing the need for and exposure to allogeneic 

blood, the potential for less blood loss may translate 

into less swelling, improved range of motion, and 

earlier return to function. The anesthesiologist should be 

thoroughly acquainted with these blood conservation 

techniques and remember that all methods come with 

varying amounts of risk and cost. Also, the use of regional 

anesthesia may reduce the risk of transfusion in lower 

extremity arthroplasties. 23–26 

Postoperative Analgesia 

For lower limb orthopedic surgery, postoperative pain is 

a major problem. Peripheral nerve blocks with or without 

a catheter are the techniques of the new millennium. 53 

For acute pain management after major lower limb 

surgery, continuous femoral nerve blockade has been 

advocated as an alternative to epidural analgesia or intravenous 

opiate administered by patient-controlled analgesia 

(PCA). 54–62 Both epidural analgesia and continuous 

femoral nerve blockade are more effective than intravenous 

PCA in patients undergoing THA. Both provide 

effective postoperative pain control, reduce opiate 

requirements and associated side effects, and improve 

functional recovery. The advantage of a femoral nerve 

block in this major joint surgery seems to be the analgesic 

effect on pain during mobilization. Similar results have 

been obtained after TKA. 55–58 Moreover, as was confirmed 

by Ganapathy et al. 59 and Chelly et al., 57 compared 

with intravenous PCA, continuous femoral nerve blockade 

reduced the length of hospital stay and the frequency 

of serious complications while conveniently avoiding the 

risk of epidural hematoma associated with the use of 

anticoagulant. Thus, a continuous femoral nerve block 

should be considered after proximal lower limb surgery. 

The use of PCA boluses (for femoral nerve block), with 

or without low basal infusion rate after TKA or THR, 60,61 

significantly reduces the local anesthetic consumption 

and therefore the risk of local anesthetic toxicity and 

increases patient satisfaction. It has been argued that 

femoral nerve block does not consistently produce anesthesia 

of the obturator nerve. The addition of an obturator 

nerve block has been therefore recommended to 

improve the quality of postoperative analgesia after total 

knee replacement. 62 The need for addition of a sciatic 

nerve block to a femoral nerve block is controversial. 

Whereas Allen et al. 58 reported that it does not further 

improve analgesic efficacy, Davies et al. 63 showed that 

combined femoral and sciatic blocks offer a practical 

alternative to epidural analgesia for unilateral knee 

replacements. Others suggested posterior lumbar plexus 

block for postoperative analgesia after TNA. 64,65 

Both clonidine and opioids have been used to supplement 

the analgesic effect of local anesthetics in peripheral 

nerve blocks. The addition of opioids to local anesthetic 

solution to maintain continuous nerve blockade has been 

debated because Picard et al. 66 failed to show any positive 

effect of opioids. A detailed discussion of the different 

peripheral nerve block techniques is beyond the scope of 

this chapter. For further discussion, the reader is referred 

to Internet resources, including the New York Society for 

Regional Anesthesia Web site (http://www.nysora.com), 

the Peripheral Regional Anesthesia Web site (http://www. 

nerveblocks.net), or the RegionalBlock.com Web site 

(http://www.regionalblock.com). 

Specific Considerations 

Venous Thromboembolism, Anticoagulation, 

and Neuraxial Anesthesia 

Patients who undergo major lower extremity orthopedic 

surgery are among those considered to be at greatest risk 

for venous thromboembolism. Data suggest a deep vein 

thrombosis rate as high as 40%–84% when prophylaxis


is not administered to patients undergoing TKA, a rate 

of 45%–57% after THA, and a rate of 36%–60% in 

patients receiving hip fracture surgery. 67 Clinically 

detected pulmonary embolism occurs in 2%–10% of 

patients with deep vein thrombosis who have had knee 

or hip arthroplasty. The incidence of fatal pulmonary 

embolism is 1%–2%. Thromboembolism can occur in 

vessels in the pelvis, thigh, and calf. Most thrombi probably 

develop in the deep veins of the calf and subsequently 

extend into the thigh, but isolated thrombi in the pelvis 

or deep femoral veins can also develop. Unfortunately, 

after knee or hip arthroplasty, deep vein thrombosis is 

clinically asymptomatic in 70%–80% of patients who 

experience clinically significant pulmonary emboli. 68 

Therefore, thromboprophylaxis has become a worldwide 

standard practice for preventing complications during 

and after major lower extremity orthopedic surgery. 

Recently, the American College of Chest Physicians 

(ACCP) published its recommendation for prophylaxis 

for patients undergoing TKA, THA, and hip fracture 

surgery. 69 Either a low-molecular-weight heparin or an 

adjusted-dose warfarin is recommended for prophylaxis 

in THA and TKA (grade IA) and hip fracture surgery 

(grade IB). The ACCP also suggested that low-molecularweight 

heparin is significantly more effective than warfarin 

in preventing asymptomatic and symptomatic 

in-hospital venous thromboembolism because of the 

more rapid onset of anticoagulant activity with lowmolecular-weight 

heparin than with warfarin. Nevertheless, 

regimens for deep vein thrombosis prophylaxis are 

frequently institution- and surgeon-specific. Anesthetic 

techniques that enhance lower extremity blood flow and 

minimize the hypercoagulable state may be advantageous 

in the management of patients undergoing lower extremity 

surgery. Clearly, the incidence of intraoperative thrombosis 

formation is reduced with the use of central neuraxis 

techniques when compared with general endotracheal 

anesthesia without other active interventions. 27–29,70 Epidural 

anesthesia may prevent the development of the 

hypercoagulable state without impairing the coagulation 

process as measured by the platelet-mediated hemostasis 

time and the clotting time. Possible explanations include: 

central neuraxial blockade-induced sympathectomy, prolonged 

exposure to high systemic blood levels of local 

anesthetic, and the antiinflammatory effects of local 

anesthetics. 70 

The introduction of new anticoagulants and antiplatelet 

agents, the complexity of balancing thromboembolic 

with hemorrhagic complications, and the evolving indications 

for regional anesthesia/analgesia have raised 

concern over the issue of neuraxial anesthesia in caring 

for surgical orthopedic patients. Spinal/epidural hematoma 

is a rare but potentially catastrophic complication 

of spinal or epidural anesthesia, the incidence of which 

was estimated to be less than 1 in 150,000 epidural and 

less than 1 in 220,000 spinal anesthetics. 71 Risk factors 

include the intensity of the anticoagulant effect, epidural 

(versus spinal) technique, traumatic needle/catheter 

placement, sustained anticoagulation in an indwelling 

neuraxial catheter, catheter removal during therapeutic 

levels of anticoagulation, increased age, female gender, 

concomitant use of anticoagulant or antiplatelet medications, 

length of therapy, and twice-daily low-molecularweight 

heparin administration. 72 Decreased weight and 

concomitant hepatic or renal disease may also exaggerate 

the anticoagulant response and theoretically increase the 

risk. The onset of symptoms immediately postoperatively 

is uncommon. Immediate diagnosis of spinal hematoma 

is critical because the reported time to progress from new 

neurologic deficits to complete paralysis was approximately 

15 hours, and complete neurologic recovery was 

unlikely if more than 8 hours elapsed between the development 

of paralysis and surgical intervention. 73 Therefore, 

any new or progressive neurologic symptoms 

occurring in the presence of epidural analgesia warrant 

immediate discontinuation of the infusion (with the catheter 

left in situ) to rule out any contribution from the 

local anesthetic or volume effect. 71 Radiographic imaging, 

preferably magnetic resonance imaging, should be 

obtained as soon as possible as well as consultation with 

a neurosurgeon to determine the urgency of surgery. 

When the American Society of Regional Anesthesia 

convened for the first Consensus Conference on Neuraxial 

Anesthesia and Anticoagulation in April 1998, 

45 cases of spinal hematoma were associated with 

low-molecular-weight heparins, 40 of which involved a 

neuraxial anesthetic. Recently, recommendations for 

perioperative management of patients receiving lowmolecular-weight 

heparin thromboprophylaxis were published 

74 based on the consensus statements developed 

during the Second American Society of Regional Anesthesia 

Consensus Conference on Neuraxial Anesthesia 

and Anticoagulation. 72 Perioperative management of 

patients receiving low-molecular-weight heparins requires 

coordination and communication. Time intervals between 

neuraxial needle placement and administration of 

low-molecular-weight heparins must be maintained 74 ; 

preoperatively, 10–12 hours should elapse after the 

last thromboprophylaxis dose of low-molecular-weight 

heparin (enoxaparin 40 mg or dalteparin 5000 U/kg every 

24 hours), whereas higher doses require delays of at least 

24 hours. Postoperatively, indwelling neuraxial catheters 

should be removed at least 10–12 hours after the last dose 

of low-molecular-weight heparin, and subsequent dosing 

of the drug should take place at least 2 hours after catheter 

removal. Other anticoagulants or antiplatelet medications 

should be avoided when low-molecular-weight 

heparins are used. In contrast to nonsteroidal antiinflammatory 

drugs and aspirin, which in and of themselves 

do not seem to present significant risk to patients for


developing spinal-epidural hematomas, current practice 

is to have patients discontinue clopidogrel for a week and 

14 days for ticlopidine before performing a neuroaxial 

block. 72,74 Platelet GP IIb/IIIa inhibitors exert a profound 

effect on platelet aggregation. After administration, the 

time to normal platelet aggregation is 24–48 hours for 

abciximab and 4–8 hours for eptifibatide and tirofiban. 

Neuraxial techniques should be avoided until platelet 

function has recovered. As experience grows with the 

newer antithrombotic and/or antiplatelet agents, guidelines 

will be revised. Herbal drugs, by themselves, seem 

to represent no added significant risk for the development 

of spinal hematoma in patients having epidural or 

spinal anesthesia. 

The decision to perform neuraxial blockade on patients 

receiving thromboprophylaxis must be made on an individual 

basis, while weighing the risk of spinal hematoma 

from needle or catheter placement against the benefits 

gained. The anesthesiologists taking care of these patients 

are expected to be familiar with the updated recommendations 

for management of this patient population. 

Tourniquet-Related Complications 

The arterial tourniquet is widely used in lower extremity 

surgery to reduce blood loss and provide good operating 

conditions. The local and systemic physiologic effects and 

the anesthetic implications were recently reviewed. 75 Use 

of arterial tourniquet can be associated with complications 

ranging from the minor and self-limiting to the 

debilitating and even fatal. Localized complications result 

from either tissue compression beneath the cuff or tissue 

ischemia distal to the tourniquet. Pressure-related injuries 

to the underlying skin, nerve, muscle, and blood 

vessels are dependent on both the duration and pressure 

of tourniquet inflation. Systemic effects are related to the 

inflation or deflation of the tourniquet. Most tourniquetrelated 

complications occur as a result of equipment 

failure or improper use and are thus easily avoided with 

good clinical practice. Tourniquet failure can result in 

over-pressurization, causing tissue injury, or underpressurization, 

causing loss of hemostasis. Improper cuff 

application can result in bruising, blistering, friction burns 

to skin, and chemical burns from spirit solutions leaking 

under the tourniquet. 76 Results are conflicting from 

studies comparing postoperatively measured blood loss, 

operating time, need for blood transfusion, postoperative 

pain, analgesia requirement, and knee flexion in patients 

undergoing TKA with or without the use of tourniquet. 

Whereas some authors reported that operations without 

the use of a tourniquet cause a greater blood loss and 

need for blood transfusion, 77 others show no difference 

in operating time or total blood loss and/or blood transfusion. 

Furthermore, not using a tourniquet seems to be 

associated with significantly less postoperative pain, 

earlier knee flexion, fewer superficial wound infections, 

and fewer deep vein thromboses. 78–80 These latter studies 

question the routine use of a tourniquet during TKA. 

Local Effects 

High tourniquet pressures directly under the cuff and 

prolonged ischemia are implicated in many cases of nerve 

and muscle damage, respectively. Arterial injury and skin 

damage are uncommon complications but may occur in 

patients with peripheral vascular disease and frail skin. 

Nerve compression causes intraneural microvascular 

abnormalities and edema formation, and these subsequently 

compromise local tissue nutrition, resulting in 

axonal degeneration. 81 Intracellular creatine phosphate 

and adenosine 5′-triphosphate are depleted in muscles 

after 2 and 3.5 hours of ischemia, respectively, resulting 

in prolonged metabolic recovery of the muscle. 81,82 After 

tourniquet release, reperfusion injury of the limb ensues, 

with edema and microvascular congestion that lead to the 

“post-tourniquet syndrome,” the most common and least 

appreciated morbidity associated with tourniquet use. 83 

This syndrome is characterized by stiffness, pallor, weakness 

without paralysis, and subjective numbness of the 

extremity without objective anesthesia. Nerve injuries 

associated with the use of tourniquets range from paresthesia 

to complete paralysis, but most nerve lesions heal 

spontaneously in


the tourniquet. 88,89 These changes are often resistant to 

analgesic drugs and increased depth of anesthesia, and 

are described in detail below. 

After deflation of the tourniquet and reperfusion 

of the ischemic limb, central venous pressure and arterial 

blood pressure decrease as a result of a shift of intravascular 

volume back into the limb, aggravated by postischemic 

reactive hyperemia and the acute effects of ischemic 

metabolites released into the systemic circulation. 

In selected cases, acute blood loss complicates the 

picture. 90 

Because of the efflux of hypercapnic venous blood 

from an ischemic area into the systemic circulation and 

increase in cardiac output, deflation of the tourniquet is 

associated with a transient increase in end-tidal carbon 

dioxide tension. The increase in carbon dioxide tension is 

associated with an increase in cerebral blood volume. 

Precautions should therefore be taken in treating patients 

with increased intracranial pressures (e.g., polytrauma 

patients with head injury), and hyperventilation to normocapnia 

immediately after tourniquet deflation can 

help prevent increased cerebral blood flow velocity and 

intracranial pressure. 91–93 Modest increases in arterial 

plasma potassium and lactate concentrations, together 

with metabolic and respiratory acidosis, are observed 

for up to half an hour after tourniquet release, but are of 

minor clinical significance. 94 

Embolic phenomena (showers of fat, marrow, and 

thrombovascular emboli reaching the heart and lungs) 

after tourniquet release during TKA have been very well 

described. According to Berman et al., 95 immediately 

after tourniquet release, echogenic material is seen in the 

hearts of all patients. Although well tolerated by most, 

this phenomenon may lead to cardiac arrest or fat embolism 

syndrome (discussed in the next section) in some 

patients. 95–98 

The pharmacokinetics of anesthetic drugs may be modified 

by the use of an arterial tourniquet. Drugs administered 

before inflation of the tourniquet cuff may be 

sequestered in the isolated limb, then redistributed systemically 

after tourniquet deflation; drugs administered 

after tourniquet inflation may have altered pharmacokinetics 

because of a reduced volume of distribution. 

However, except for antibiotics, which should be administered 

before tourniquet inflation, the effect of tourniquet 

inflation or deflation on pharmacokinetics of drugs 

is of limited clinical importance. 99 

Recommendations in the literature for both safe tourniquet 

time and reperfusion intervals vary. Most authors 

suggest that tourniquet inflation should be for the shortest 

period possible, with an upper limit of 2 hours in 

healthy patients. 75 The elderly, trauma patients, and those 

with peripheral vascular disease are probably more susceptible 

to muscle injury. For surgical procedures longer 

than 2 hours, the tourniquet should be deflated every 2 

hours to allow 10 minutes of reperfusion of the muscles 

beneath and distal to the tourniquet cuff. 81 Because nerve 

damage results primarily from direct pressure beneath 

the cuff, use of the lowest pressure that causes arterial 

occlusion is recommended. Tourniquet pressures more 

than 40.0–46.7 kPa (300–350 mm Hg) should rarely be 

necessary to produce a bloodless field in normotensive 

patients with compliant vessels. However, in patients with 

atherosclerosis and the morbidly obese or hypertensive 

patients, higher pressures may be required. Common 

sense suggests that tourniquet pressure should be based 

on the patient’s systolic blood pressure, with the tourniquet 

inflated to a pressure of approximately 150 mm Hg 

above the systolic pressure. 100,101 

Fat Embolism 

Fat embolism occurs in almost all lower extremity trauma 

and intramedullary surgery, in particular, intramedullary 

nailing of long bones, hip arthroplasty, and knee arthroplasty. 

Fat emboli syndrome, however, is a severe multisystem 

manifestation of embolization that develops in 

10%–20% of these patients. 102–106 Overall mortality varies 

between 7%–20%, 107,108 and long-term morbidity is 

usually attributable to neurologic dysfunction. 109 

The diagnosis of fat emboli syndrome is clinical, usually 

one of exclusion. A high index of suspicion is required for 

early clinical diagnosis in at-risk patients. Patients may 

present with intraoperative cardiorespiratory collapse 

after femoral reaming, 107 insertion of intramedullary 

alignment guide 107 or cemented prosthesis, 108 or after 

tourniquet release. 103 Hypotension, respiratory dysfunction 

with hypoxia, tachycardia, neurologic changes that 

may present as diffuse encephalopathy and/or focal 

abnormalities, petechiae that are distributed on the upper 

body (chest, neck, and conjunctivae), lipuria, and even 

electromechanical dissociation may also be presenting 

signs. These may develop in the postoperative period. 

Laboratory tests should include arterial blood gas, 

complete blood count to identify anemia or thrombocytopenia, 

and a coagulation profile. 109 Any other treatable 

causes of neurologic dysfunction, e.g., toxic, metabolic, or 

infectious, must be excluded. 110 Urinalysis may reveal fat 

globules, but this is nonspecific. The electrocardiogram 

may be normal, reflect right heart strain, or may reveal 

ischemia. The chest radiograph is nonspecific, with diffuse 

fluffy bilateral infiltrates and opacities consistent with 

increased capillary permeability and edema. 33 

Treatment is essentially supportive, consisting of 

cardiovascular and respiratory resuscitation and stabilization. 

33 No specific drug therapy is currently recommended. 

Small prospective randomized controlled studies 

of steroid prophylaxis in patients with long bone fractures 

have indicated both a decrease in the development 

of fat emboli syndrome and a decreased incidence of


hypoxemia in steroid-treated groups compared with 

controls. 103,104 

Summary 

1. Elective THA/TKA is a relatively safe orthopedic procedure. 

Known complications include thromboembolism, 

postoperative anemia, infection, fractures, and death. Fat 

emboli syndrome is an uncommon but devastating complication 

with relatively high mortality rate and longterm 

morbidity, which is usually attributable to neurologic 

dysfunction. Preexisting comorbidities and the American 

Society of Anesthesiologists physical status classification 

are significantly related to the incidence of postoperative 

death. In contrast, fractures of the hip, which most frequently 

occur in elderly women, are associated with a 

very high mortality. Major causes are cardiac morbidity, 

bronchopneumonia, and pulmonary embolism. Patients 

who are medically fit for surgery should be operated on 

the day of admission. Perioperative management should 

be oriented toward adequate pain control and multidisciplinary 

consultation, if needed. Patients undergoing 

major lower extremity orthopedic surgery should receive 

prophylaxis with antibiotics and anticoagulants to reduce 

the risk of infection and deep vein thrombosis. The decision 

to perform neuraxial blockade on patients receiving 

thromboprophylaxis should therefore take into account 

recent recommendations for management of this patient 

population. 

2. The choice of anesthetic technique is a complex 

medical decision that depends on many factors. For hip 

fracture patients, the type of anesthesia does not seem to 

influence significantly morbidity or overall mortality. For 

THA/TKA, there is evidence to suggest that regional 

anesthesia may be of benefit because it was associated 

with a lower rate of intensive care unit admission postoperatively, 

reduced intraoperative blood loss and transfusion 

requirements, and was associated with a lower 

incidence of thromboembolic events. For all lower extremity 

operations, regional analgesia and anesthesia provide 

better pain control for the rehabilitation period. 

3. Special attention during the operation should be 

given to positioning of the patient, blood loss and transfusion 

requirements, blood pressure control, fluid management, 

careful monitoring and management during cement 

insertion and possible associated complications, and to 

tourniquet-related complications. 

4. For lower limb orthopedic surgery, postoperative 

pain is a major problem. Peripheral nerve blocks with or 

without a catheter are the techniques of choice. 

References 

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851.

25 

Transurethral Prostatectomy Syndrome and 

Other Complications of Urologic Procedures 

Daniel M. Gainsburg 

Elderly patients undergo numerous urologic procedures. 

This chapter presents some of the more common 

concerns and complications associated with these 

procedures. 

The Transurethral Prostatectomy 

Syndrome 

Transurethral prostatectomy (TURP) is considered the 

gold standard for the surgical treatment of benign prostatic 

hyperplasia (BPH). 1 During the past decade, the 

annual number of TURPs performed in the United States 

has declined from 400,000 to 100,000 because of advances 

in medical management, the introduction of minimally 

invasive thermal therapies (laser, radiofrequency, and 

microwave), 2 and the development of patient-care guidelines 

for patients with BPH. 3 

BPH is the most common nonmalignant tumor of the 

prostate, causing urinary symptoms in more than 50% of 

the aging male population. 4 TURP patients, who are often 

elderly, tend to have coexisting problems of which the 

most common are pulmonary (14.5%), gastrointestinal 

(13.2%), myocardial infarction (12.5%), arrhythmia 

(12.4%), and renal insufficiency (4.5%). 5 Therefore, these 

patients should be carefully evaluated preoperatively to 

determine the status of any coexisting diseases. 

Complications of TURP include (1) absorption of irrigating 

solution; (2) circulatory overload, hyponatremia, 

and hypoosmolality; (3) glycine and ammonia toxicity; (4) 

bladder perforation; (5) transient bacteremia and septicemia; 

(6) hypothermia; (7) bleeding and coagulopathy; 

and 8) TURP syndrome. 6 The 30-day mortality rate of 

TURP is reported to be between 0.2% and 0.8%. 5 

Common causes of death include myocardial infarction, 

pulmonary edema, and renal failure. 7 The postoperative 

morbidity rate was noted to be 18% and increased morbidity 

was found in patients with resection times exceeding 

90 minutes, gland size greater than 45 g, acute urinary 

retention, and age older than 80 years. 5 TURP syndrome 

is a general term used to describe a collection of signs 

and symptoms caused primarily by excessive absorption 

of irrigating fluid through the opened venous sinuses of 

the prostate. 

The Surgical Procedure 

TURP is performed by inserting a resectoscope through 

the urethra and resecting prostatic tissue in an orderly 

manner with an electrically powered cutting-coagulating 

metal loop. Prostatic tissue is then resected without perforating 

the prostatic capsule. If the capsule is violated, 

large amounts of irrigation solution may be absorbed into 

the circulation, and the periprostatic and retroperitoneal 

spaces. 6,8 It is this rapid absorption of irrigation solution 

into the circulation that differentiates this complication 

from that of bladder perforation. (See also the section on 

Bladder Perforation.) Prostatic capsular perforation 

occurs in about 2% of patients and presents with symptoms 

of restlessness, nausea, vomiting, and abdominal 

pain—even under spinal anesthesia. 1 If perforation is suspected, 

the operation should be terminated as quickly as 

possible and hemostasis obtained. 1 

Bleeding often occurs during TURP, but is usually controllable. 

Arterial bleeding is controlled by electrocoagulation. 

1 However, when large venous sinuses are opened, 

hemostasis becomes difficult. If this venous bleeding 

becomes uncontrollable, the procedure should be terminated 

as quickly as possible, and a Foley catheter should 

be inserted into the bladder and traction applied. 6,8 

Attempts at estimating blood loss during TURP are 

usually extremely inaccurate, because the shed blood is 

mixed with ample amounts of irrigating solution. Intraoperative 

blood loss has been estimated to range from 2 

to 4 mL/min of resection time and 20 to 50 mL/g of prostate 

tissue. 9 Bleeding requiring transfusion occurs in 2.5% 

of patients undergoing TURP. 5 

368

25. Transurethral Prostatectomy Syndrome 369 

Even though they cause no significant hemolysis, ex - 

Table 25-1. Osmolality of various irrigation solutions used for 

transparency. 2,8 ventricular ectopy are often observed. 9,20 

transurethral prostatectomy. 

cessive absorption of modern irrigation solutions can 

Solution Concentration (%) Osmolality (mOsm/kg) be associated with numerous perioperative complications, 

including circulatory overload, hyponatremia, and 

Glycine 1.2 175 

Glycine 1.5 220 hypoosmolality. Additionally, the solutes in the solutions 

Cytal 178 may cause adverse effects: glycine may cause cardiac, 

Mannitol 5 275 neurologic, and retinal effects 8,12,13 ; mannitol rapidly 

Sorbitol 3.5 165 expands intravascular volume and might lead to pulmonary 

edema in cardiac patients 6 ; sorbitol is converted to 

Glucose 2.5 139 

Urea 1 167 

Water 0 fructose and lactate, which may cause hyperglycemia and/ 

or lactic acidosis 14 ; and glucose may cause severe hyperglycemia 

in the diabetic patient. 15 

Irrigation Solutions 

The ideal irrigating solution for use during TURP would 

be isotonic, nonhemolytic, electrically inert, transparent, 

nonmetabolized, nontoxic, rapidly excreted, and inexpensive. 

Originally, distilled water was the fluid of choice 

because it was nonconductive and transparent. However, 

its absorption into the circulation caused massive hemolysis, 

dilutional hyponatremia, rare renal failure, and central 

nervous system (CNS) symptoms. 6,11 

These complications eventually led to abandonment of 

distilled water and to the use of isosmotic or nearly isosmotic 

solutions for TURP. Solutions such as normal saline 

and Ringer’s lactate are isosmotic and would be well 

tolerated if absorbed intravascularly; however, they are 

highly ionized and cause dispersion of the high-frequency 

current from the resectoscope. Recently, in a small study, 

normal saline was used as the irrigating solution in which 

a bipolar electrocautery resectoscope replaced the customary 

monopolar resectoscope. None of the patients 

developed hyponatremia or TURP syndrome. 2 

The introduction of nonconductive and also nonhemolytic 

solutions, such as glycine, Cytal (a mixture of sorbitol 

2.7% and mannitol 0.54%), sorbitol, mannitol, glucose, 

and urea, have replaced distilled water (Table 25-1). 6,8 

Glycine and Cytal are currently the two most frequently 

used solutions. 6 Although all are nonconductive solu - 

tions that allow for electrocautery resection, they are 

purposely prepared moderately hypotonic to maintain 

Signs and Symptoms 

TURP syndrome may occur anytime intraoperatively or 

postoperatively. It has been observed as early as a few 

minutes after the start of surgery 16 and as late as several 

hours after completion of surgery. 17 Recent reports noted 

that TURP syndrome occurs in 2% of patients. 5,18 

Clinical manifestations of TURP syndrome include 

neurologic, cardiovascular, and respiratory effects (Table 

25-2). The effects on the CNS include headache, dizziness, 

restlessness, agitation, confusion, seizures, and eventually 

coma. The clinical picture may be further compounded 

by the neurotoxic effects of glycine and ammonia. 6 TURP 

syndrome is usually described as being caused by hyponatremia 

and water intoxication. It is now thought that 

the classic CNS effects of TURP syndrome are not caused 

by hyponatremia, in itself, but are caused by the acute 

decrease in serum osmolality that results in the development 

of cerebral edema. 19,20 

Cardiovascular and respiratory effects occur from 

volume overload and hyponatremia. Acute hypervolemia 

will initially cause hypertension and bradycardia, which 

may progress to congestive heart failure, pulmonary 

edema, and cardiac arrest. 21 Rapidly decreasing serum 

sodium levels are associated with negative inotropic 

effects on the heart manifesting in hypotension, pulmonary 

edema, and congestive heart failure. 9,20 Electrocardiogram 

changes, such as widened QRS complexes and 

Table 25-2. Signs and symptoms of transurethral prostatectomy syndrome. 

Cardiovascular and respiratory Central nervous system Metabolic Other 

Hypertension Restlessness Hyponatremia Hypoosmolality 

Pulmonary edema Agitation Hyperglycinemia Hemolysis 

Congestive heart failure Confusion Hyperammonemia 

Hypotension 

Seizures 

Arrhythmias 

Coma 

Respiratory arrest 

Blindness 

Cardiac arrest

370 D.M. Gainsburg 

Absorption of Irrigating Solution 

Excessive absorption of irrigating solution through 

opened venous sinuses of the prostate is the primary 

cause of TURP syndrome. The amount of absorption correlates 

with (1) the height of the irrigating fluid above the 

patient which determines hydrostatic pressure, (2) amount 

of distention of the bladder by the surgeon, (3) extent of 

opened venous sinuses, and (4) the length of time of 

resection. 22 The average rate of fluid absorption is 10–30 

mL/min of resection time and as much as 8 L may be 

absorbed during a procedure. 6 A quick estimation of fluid 

volume absorbed, which compares serum sodium levels 

before and after the procedure, can be made by using the 

following equation: 

Volume absorbed 

= {(preoperative [Na + ]/postoperative [Na + ]) × ECF} − ECF 

where extracellular fluid (ECF) volume comprises 

20%–30% of body weight. 8,23 

Circulatory Overload, Hyponatremia, 

and Hypoosmolality 

The replacement of distilled water with the present generation 

of irrigating solutions has eliminated hemolysis 

as a complication of TURP. At the same time, there has 

been a decrease in the incidence of severe CNS complications 

associated with hyponatremia. 20 However, excessive 

absorption of irrigating solution still occurs and leads to 

circulatory overload. Initially, hypertension and bradycardia 

are seen with acute volume overload, which may 

progress to congestive heart failure, pulmonary edema, 

and eventually cardiac arrest. 21 

The classic CNS signs of TURP syndrome are now 

thought to be caused by acute serum hypoosmolality, 

movement of water into the cells, and consequent cerebral 

edema. 19,20 With the use of solute-based nearly isosmotic 

solutions, the incidence of severe CNS symptoms 

has been reduced because acute serum hypoosmolality 

does not occur; however, CNS symptoms can still occur 

secondary to hyponatremia. 19,20 

Sodium is an electrolyte that is essential for the ability 

of excitable cells, particularly those of the heart and brain, 

to depolarize and produce an action potential. 6,8 With 

acute decreases in serum sodium levels to 120 mEq/L, 

CNS symptoms and cardiovascular effects are observed 

(Table 25-3). 8,14 Initially, confusion and restlessness are 

noted, and with decreasing serum sodium levels, may 

progress to loss of consciousness and seizures. 24 Rapidly 

decreasing serum sodium levels are associated with hypotension, 

pulmonary edema, congestive heart failure, and 

electrocardiogram changes. At levels near 100 mEq/L, 

respiratory and cardiac arrest may occur. 24,25 Acute changes 

in serum sodium levels are more harmful than chronic 

hyponatremia. 26 Also, it is often impossible to separate 

these symptoms of cardiovascular compromise secondary 

to hyponatremia from those caused by fluid overload. 

Glycine and Ammonia Toxicity 

Glycine is a nonessential amino acid. When absorbed in 

significant amounts, glycine may cause cardiac and neurologic 

effects. 8,12,13 It is metabolized in the liver into 

ammonia and glyoxylic acid. 12 The cardiac effect of glycine 

is myocardial depression; the mechanism is unknown. 27 

Glycine has been implicated as the cause of transient 

blindness in TURP patients. It acts as an inhibitory neurotransmitter 

in the brain, spinal cord, and retina. Centrally 

acting mechanisms, such as cerebral edema, may 

cause visual impairment, but these patients have normal 

papillary light reflexes. In contrast, TURP patients with 

transient blindness have sluggish or nonreactive pupils, 

suggesting a retinal effect. Therefore, TURP blindness 

may be caused by increased glycine levels exerting an 

inhibitory effect on the retina. 28,29 

Signs of ammonia toxicity, nausea and vomiting, usually 

occur within 1 hour after surgery. With increasing 

ammonia levels, the patient lapses into a coma lasting 

about 10–12 hours, and then awakens as the ammonia 

levels decrease below 150 µmol/L. 8 A possible explanation 

for hyperammonemia in TURP patients is arginine 

deficiency. Ammonia is metabolized to urea in the liver, 

in a reaction that requires arginine. Patients who are 

Table 25-3. Signs and symptoms associated with acute hyponatremia. 

Serum Na + (mEq/L) Central nervous system changes Cardiovascular effects Electrocardiogram changes 


arginine deficient are unable to convert the excess 

ammonia created in the body when glycine solutions are 

absorbed, therefore leading to hyperammonemia. 30,31 

Bladder Perforation 

Accidental perforation of the bladder is another common 

complication of TURP with an incidence of approximately 

1% and most perforations occurring retroperitoneally. 

(See also the section on Transurethral Resection 

of Bladder Tumors.) It usually results from surgical instrumentation 

or overdistension of the bladder with irrigating 

fluid. An early sign of perforation, often unnoticed, is 

a decrease in return of irrigating solution from the 

bladder. Eventually, a significant volume of fluid will 

accumulate in the abdomen causing abdominal distention: 

patients under regional anesthesia may start to complain 

of abdominal pain and/or experience nausea and 

vomiting. Other clinical signs are hypotension followed 

by hypertension. Symptoms of intraperitoneal perforation 

are similar, develop sooner, and include severe 

shoulder pain secondary to diaphragmatic irritation. 

Diagnosis of bladder perforation is made by cystourethrography 

and treated with a suprapubic cystotomy. 8 

Transient Bacteremia and Septicemia 

The prostate harbors a variety of bacteria, which can be 

the source of perioperative bacteremia through open 

prostatic venous sinuses. The presence of an indwelling 

urinary catheter will increase the risk. Therefore, the prophylactic 

administration of antibiotics is recommended in 

TURP patients. The bacteremia is usually transient and 

symptomless, and easily treated with frequently used 

antibiotic combinations. Nevertheless, 6%–7% of these 

patients will develop septicemia. 5 Common signs are 

fever, chills, hypotension, tachycardia, and/or bradycardia. 

In severe cases, cardiovascular collapse may occur, 

with mortality rates from 25% to 75%. 32 

Hypothermia 

The use of room temperature irrigating solutions during 

TURP may cause shivering and hypothermia in many 

patients, especially in the elderly, who have a reduced 

thermoregulatory capacity. 14 Using warmed irrigating 

solutions will decrease heat loss and shivering. 33 The 

concern that warmed irrigating solutions may cause 

increased bleeding because of vasodilation has not been 

shown to be of clinical importance. 34 

Coagulopathy 

Abnormal bleeding after TURP occurs in fewer than 1% 

of cases. 9 Possible causes include dilutional thrombocytopenia 

and systemic coagulopathy. The absorption of large 

volumes of irrigating solution might result in dilution of 

platelets and coagulation factors. Systemic coagulopathy 

in TURP patients is probably caused by either primary 

fibrinolysis or disseminated intravascular coagulopathy. 

In primary fibrinolysis, a plasminogen activator, which 

converts plasminogen into plasmin, is released from the 

prostate. Plasmin then causes fibrinolysis with the resultant 

increase in bleeding. Suggested treatment for primary 

fibrinolysis is epsilon aminocaproic acid. 9 Fibrinolysis 

that is secondary to disseminated intravascular coagulopathy 

is triggered by the systemic absorption of prostate 

tissue, which is rich in thromboplastin. 35 This will, in 

turn, cause a depletion of coagulation factors and platelets. 

Treatment is supportive with fluid and blood products 

administered as needed. 14 

Anesthetic Considerations for 

Transurethral Prostatectomy 

Regional anesthesia, particularly spinal anesthesia, has 

long been considered the anesthetic technique of choice 

for TURP. 5 By allowing the patient to remain awake, this 

anesthetic technique allows early detection of mental 

status changes caused by TURP syndrome or the extravasation 

of irrigating solution. Restlessness and confusion 

are early signs of hyponatremia and/or serum hyperosmolality 

and should not be assumed to be signs of inadequate 

anesthesia. The administration of sedatives or the 

induction of general anesthesia in the presence of TURP 

syndrome can lead to severe complications and even 

death. 36 As discussed above, extravasation of irrigating 

solution secondary to either the perforation of the prostatic 

capsule or the bladder will cause the awake patient 

to complain of abdominal pain and/or experience nausea 

and vomiting. 

There is controversy concerning whether anes - 

thetic technique influences blood loss during TURP surgery. 

Some studies have reported less bleeding under 

regional anesthesia, 37–39 whereas others found no significant 

difference in blood loss between regional and 

general anesthesia. 40–43 In those studies that demonstrated 

decreased bleeding with regional anesthesia, the authors 

postulated that regional anesthesia reduces blood 

loss not only by decreasing systemic blood pressure, 

but also by decreasing central and peripheral venous 

pressures. 6,37–39 

Numerous comparative studies using neuropsychologic 

testing have been conducted to test whether the incidence 

of postoperative cognitive dysfunction would be 

less with regional anesthesia than general anesthesia. 

One small prospective study comparing spinal anesthesia 

with intravenous sedation versus general anesthesia on 

elderly TURP patients found a significant decrease in


mental status in both groups at 6 hours after surgery, but 

there were no differences in perioperative mental function 

at any time between the groups during the first 30 

days after surgery. 44 In a recent study of 438 elderly 

patients undergoing various types of surgical procedures, 

it was found that the incidence of postoperative cognitive 

dysfunction after 1 week was significantly greater after 

general than regional anesthesia, but no difference was 

found after 3 months. 45 Incidentally, this study found significantly 

greater mortality after general than regional 

anesthesia, noting that postoperative respiratory complications 

and need for prolonged intensive care occurred 

only after general anesthesia. 45 

If regional anesthesia is chosen for TURP, a T10 sensory 

level is needed to block the pain of bladder distention. 

Sensory levels above T9 are undesirable because the 

patient will not feel abdominal pain caused by perforation 

of the prostatic capsule. 6 Spinal anesthesia is often 

preferred over epidural anesthesia, because of the need 

to block sacral segments, which provide sensory innervations 

to the prostate, bladder neck, and penis. 14 Another 

advantage of regional anesthesia for TURP is improved 

postoperative pain control and decreased requirement 

for postoperative analgesics. 46 

Treatment of Transurethral 

Prostatectomy Syndrome 

Prompt treatment is essential when the signs and symptoms 

of TURP syndrome are recognized. Initially, oxygenation, 

ventilation, and cardiovascular support should 

be provided based on the patient’s symptomatology, 

while, at the same time, considering other treatable conditions 

such as diabetic coma, hypercarbia, or drug interactions. 

10 The surgeon should be asked to terminate the 

procedure as rapidly as possible. Blood samples should 

be rapidly analyzed for electrolytes, creatinine, glucose, 

and arterial blood gases. A 12-lead electrocardiogram 

recording should be obtained. 8,14 

Treatment of hyponatremia and volume overload 

is dictated by the severity of the patient’s symptoms. 

If the symptoms are mild and the serum sodium level 

is greater than 120 mEq/L, then fluid restriction and 

the administration of a loop diuretic, usually furosemide, 

are all that is necessary in returning serum sodium to 

normal levels. In severe cases, serum sodium less than 

120 mEq/L, the recommended treatment is intravenous 

administration of hypertonic saline. A 3% sodium chloride 

solution should be infused at a rate no greater than 

100 mL/h and the patient’s hyponatremia should be corrected 

at a rate no greater than 0.5 mEq/L/h. 8,47 Rapid 

correction of hyponatremia with hypertonic saline has 

been associated with cerebral edema and central pontine 

myelinolysis. 20,48 

The Future of Transurethral 

Prostatectomy Syndrome 

With advances in medical treatment and the introduction 

of new surgical techniques for the treatment of symptomatic 

BPH, TURP syndrome will become a rare complication 

of prostate surgery. In the near future, it seems 

that the new gold standard for the surgical treatment of 

BPH will be holmium laser enucleation of the prostate 

(HoLEP). 49 Advantages of HoLEP over TURP are its 

ability to be used on any size of prostate gland, decreased 

blood loss, can be performed as an ambulatory procedure, 

decreased absorption of irrigating solution, and the elimination 

of TURP syndrome. 49 Long-term complications of 

HoLEP are urethral stricture, bladder neck contracture, 

and reoperation rate higher than TURP. However, in a 

recent retrospective study of 552 patients, these complications 

were less than reported elsewhere for TURP and 

open prostatectomy. 5,18,49 Because of these advantages, 

HoLEP is becoming the preferred surgical procedure 

for BPH, especially in elderly patients with significant 

comorbidities. 

Complications of Other 

Urologic Procedures 

Transurethral Resection of Bladder Tumors 

Bladder cancer is the second most common urologic 

malignancy and these tumors occur with a male to female 

ratio of approximately 3 : 1. 14 Most patients undergo 

an endoscopic procedure of transurethral resection of 

bladder tumor (TURBT). This procedure can be performed 

with either general or regional anesthesia. If a 

regional anesthesia is chosen, then a T10 sensory level is 

required to block the pain of bladder distention. As in 

TURP, bladder perforation can occur during TURBT 

with the same signs and symptoms that have been previously 

discussed. Bladder perforation can also occur if the 

bladder tumor lies near the obturator nerve. As the obturator 

nerve courses through the pelvis, it passes near the 

lateral bladder wall, bladder neck, and prostatic urethra. 

Inadvertent bladder perforation may occur if stimulation 

of the obturator nerve by electrocautery during the procedure 

causes the thigh muscles to contract forcefully. In 

this situation, general anesthesia with muscle relaxation 

would be the preferred technique. 50,51 

Extracorporeal Shock Wave Lithotripsy 

In the United States, the annual incidence of urolithiasis 

is 16–24 cases per 10,000 persons and accounts for 7–10 

of every 1000 hospital admissions. 52 Traditionally, renal 

stones were treated with open surgical procedures that


required general anesthesia; however, in the late 1970s, a 

minimally invasive procedure, percutaneous nephrolithotomy, 

was introduced. Percutaneous nephrolithotomy 

also required general anesthesia, but had the advantage 

of shorter convalescence for patients. In 1980, a major 

noninvasive advance was made with the introduction of 

extracorporeal shock wave lithotripsy (ESWL), which 

has become the initial treatment modality for most 

patients with urinary tract stones. 53 Basically, the lithotripter 

generates repetitive high-energy shock waves that 

are focused on the stone and cause it to eventually fragment. 

The fragments are then excreted down the urinary 

tract over several weeks. 53 

First-generation lithotripters required immersion of 

the patient into a water bath and could cause physiolo - 

gic effects in patients. Immersion causes compression of 

peripheral veins, resulting in an increase in cardiac 

preload, along with an increase in central venous, right 

atrial, and pulmonary pressures. As central venous pressure 

increases, arterial pressure and cardiac output will 

typically increase. This may lead to congestive heart 

failure and decreased systemic blood pressure in patients 

who have limited cardiac reserve. 54 Immersion of a patient 

to the level of their clavicles increases the work of breathing 

and respirations often become shallow and rapid. 55 

The temperature of the water bath is of concern, especially 

in the elderly who have impaired thermoregulatory 

capacity. Cold water may induce vasoconstriction and 

shivering, whereas warm water may cause vasodilatation 

and hypotension. 54 

Cardiac arrhythmias have been observed in patients 

treated with first-generation lithotripters. It is thought 

that these arrhythmias are caused by the mechanical 

effects of the shock waves on the myocardium during the 

repolarization phase of the heart. By using electrocardiographic 

gating, the shock waves can be delivered milliseconds 

after the R wave during the refractory period of the 

heart. Newer generation lithotripters use a nonsynchronized 

mode in order to improve treatment times, but if 

induced arrhythmias are detected, a return to a gated 

mode will eliminate them. 53,56 

Because of the intense pain associated with firstgeneration 

lithotripters, general or regional anesthesia 

was required. Newer generations of lithotripters use a 

lower working voltage and have eliminated the water 

bath. Although they cause less pain, most patients still 

require intravenous sedation during treatments. Because 

the newer lithotripters use less power, the efficiency of 

stone fragmentation has decreased, causing the rate of 

re-treatment to increase. 53 

Absolute contraindications to ESWL are pregnancy, 

coagulopathy, and an active urinary tract infection. Relative 

contraindications include distal urethral stricture or 

obstruction, large stones, calcification or aneurysm of the 

renal artery or aorta, and/or renal insufficiency. 14,53 Surgical 

complications from ESWL include urinary obstruction 

from stone fragments; subcapsular, parenchymal, 

and perinephric hematomas of the kidney; transient renal 

failure; and damage to adjacent organs, such as the liver, 

pancreas, spleen, and lung. 14,53 

Laparoscopic Surgery in Urology 

Just as other surgical specialists have adapted to laparoscopic 

techniques, so have urologists. Initially, pelvic 

lymph node dissection was the most common urologic 

laparoscopic procedure performed; however, in recent 

years, the complexity of surgeries performed laparoscopically 

has become greater to include radical or donor 

nephrectomies, adrenalectomy, and radical prostatectomy. 

The advantages of this minimally invasive technique, 

although often taking longer to perform, are 

decreased postoperative pain, decreased blood loss, 

shorter hospital stays, and quicker return to normal function 

compared with open surgery. 14,57 

In addition to all the conventional complications 

and concerns associated with laparoscopic surgery, urologic 

laparoscopic procedures have their own unique set 

of problems. Because many urogenital structures are 

retroperitoneal, urologists often prefer insufflating the 

retroperitoneal space during laparoscopic surgery. 

Several studies have shown that CO 2 absorption is 

greater with retroperitoneal than intraperitoneal insufflation. 

58–60 Because the large retroperitoneal space and its 

connections with the thorax and subcutaneous tissue are 

exposed to insufflated CO 2 , subcutaneous emphysema is 

a common complication. Subcutaneous emphysema is 

observed late in the procedure, is preceded by an increase 

in end-tidal CO 2 , may extend all the way up to the head 

and neck, and is confirmed by palpation for crepitus. 57,61 

In severe cases, the upper airway may be compromised 

secondary to pharyngeal swelling caused by submucous 

CO 2 ; therefore, extubation may have to be delayed and 

ventilation adjusted in these patients. 6,57 

General anesthesia with controlled ventilation is 

preferred because insufflation of CO 2 and use of the 

steep Trendelenburg position causes increased intraabdominal 

and intrathoracic pressures. Some urologic laparoscopic 

procedures tend to be lengthy, thereby allowing 

sufficient absorption of CO 2 to cause hypercapnia and 

acidosis. 6,61 Oliguria may occur intraoperatively during 

prolonged periods of gas insufflation and then be followed 

by diuresis in the postoperative period. 6 Two possible 

mechanisms for the cause of this oliguria have been 

postulated: the first being that insufflation causes 

decreased renal cortical blood flow and renal vein obstruction 

62 ; and the second is an increase in stress hormone 

levels, such as antidiuretic hormone. 63 Because intraoperative 

oliguria during prolonged laparoscopic procedures 

may not truly reflect intravascular volume depletion,


treatment with fluid administration may lead to circulatory 

overload. 14 

Radical Prostatectomy 

Prostate cancer is the most frequently diagnosed cancer 

in men. 64 Radical prostatectomy involves the removal of 

the entire prostate gland, the ejaculatory ducts, the 

seminal vesicles, and a portion of the bladder neck. 57 The 

procedure can be performed with either a retropubic or 

perineal approach; however, in the United States, most 

urologists use the retropubic approach. 57 Prostate cancer 

is a disease of older men with an incidence estimated 

at 75% for patients over 75 years old. 65 Preoperative 

evaluation should therefore focus on other coexisting 

conditions that are prevalent in elderly patients. 57 

The perioperative mortality rate has been reported to be 

approximately 0.2%. 66 

The most common intraoperative complication is hemorrhage 

with reported blood loss ranging from less than 

500 mL to greater than 1500 mL. 57 Because of the potential 

for rapid blood loss, the use of invasive arterial pressure 

monitoring as well as adequate venous access are 

recommended. 14,57 Patients undergoing radical prostatectomy 

are often placed in a hyperextended supine position 

along with Trendelenburg, 57 which places the pubis above 

the head. 6 Significant venous air embolism from the 

prostatic fossa may occur as a result of a gravitational 

gradient between the prostatic veins and head. 67 The 

Trendelenburg position can also produce edema of the 

upper airway. 14 Early postoperative complications, which 

occur in 0.5%–2% of cases, include deep vein thrombosis, 

pulmonary embolism, hematoma, seroma, and wound 

infection, 66 whereas late surgical complications are incontinence, 

impotence, and bladder neck contracture. 68 

General or regional anesthesia with sedation may be 

used for this procedure. If regional anesthesia is chosen, 

then a sensory level of T6 is recommended. 57 Because 

many patients may not tolerate lengthy surgery in the 

Trendelenburg position, one needs to be prepared for 

conversion to general anesthesia. 57 The choice of anesthetic 

technique does not seem to influence postoperative 

morbidity 69 or quality of life. 70 

Radical Cystectomy 

The treatment of muscle-invasive bladder cancer is a 

radical cystectomy. The patient is usually male, a cigarette 

smoker, and/or had occupational chemical exposure who 

presents with painless, gross hematuria. 57 In men, 

it involves the removal of the bladder, prostate gland, 

seminal vesicles, and proximal urethra; in women, the 

bladder, uterus, fallopian tubes, ovaries, and the anterior 

vaginal wall are removed. After the bladder is removed, 

a urinary diversion is performed; an ileal conduit, bowel 

segments for continent reservoirs, or ureterostomies are 

frequently used. 57,71 

The intraoperative problems that may occur during 

radical retropubic prostatectomy may also arise in this 

procedure. However, radical cystectomy is an intraperitoneal 

procedure with increased fluid requirements. In 

addition to adequate venous access, the use of invasive 

arterial pressure monitoring and/or central venous monitoring 

to guide intravenous fluid therapy may be helpful 

because urinary output cannot be assessed. 57 Because of 

the length and extent of surgery, general or a combined 

general-epidural anesthetic technique is mandated. 14,57 

A recent study of 50 patients undergoing radical cystectomy 

comparing combined epidural-general anesthesia 

(CEGA) to general anesthesia concluded that the CEGA 

group had significantly less blood loss than the general 

anesthesia group. There were no significant differences in 

intraoperative hemodynamics or postoperative complications, 

and the CEGA group had better postoperative pain 

control. 72 

Radical Nephrectomy 

Renal cell carcinoma is the most common malignancy of 

the kidney. Because it is refractory to chemotherapy and 

radiation therapy, radical nephrectomy is the treatment 

of choice. Radical nephrectomy involves the excision of 

the kidney, surrounding fascia, the ipsilateral adrenal 

gland, and the upper ureter. 14,57 Partial nephrectomy is 

considered in those patients with small lesions or bilateral 

tumors or those at risk because of other diseases such 

as diabetes and hypertension. 73 This malignancy has a 

peak age of incidence of 60 years, and cigarette smoking 

has been identified as a risk factor. 57 Therefore, coronary 

artery disease as well as chronic obstructive pulmonary 

disease is common in these patients. 57 

Frequently used approaches for radical nephrectomy 

are the flank, subcostal, or thoracoabdominal. Potential 

complications of these approaches include significant 

pneumothorax with possible insertion of a chest tube; 

pulmonary contusion, caused by lung retraction, necessitating 

prolonged postoperative ventilation; and injuries 

to adjacent organs, in particular, splenic injury, which has 

a 10% incidence in association with a left nephrectomy. 57 

These tumors tend to be very vascular and extensive 

blood loss may occur. 57 General anesthesia with invasive 

arterial pressure monitoring and adequate intravenous 

access is recommended. 57 

In 5%–10% of patients, the tumor extends into the 

renal vein and vena cava; therefore, the extent of the 

lesion must be defined preoperatively. Several potential 

problems can occur in these patients, ranging from circulatory 

failure as a result of total occlusion by tumor of 

the vena cava, to acute pulmonary embolization of tumor 

fragments. 6 Cardiopulmonary bypass is necessary when


control of the vena cava above the tumor thrombus 

cannot be obtained. 57 If the tumor thrombus extends into 

the right atrium, then right heart catheterization is contraindicated. 

57 The use of transesophageal echocardiography 

during resection of renal cell carcinoma with vena 

cava involvement has been shown to be helpful in the 

management of these complex cases. 74,75 

Summary 

With the continuing decline in the annual number of 

TURPs being performed and the introduction of HoLEP, 

anesthesiologists will rarely, if at all, experience a patient 

with TURP syndrome. Because of its advantages over 

TURP, HoLEP will become the new gold standard for 

the surgical treatment of BPH in the elderly patient. As 

urologists become more proficient at laparoscopic techniques, 

the number of laparoscopic procedures performed 

on the elderly will increase. Because of their age and 

increased prevalence of comorbid disease, elderly patients 

are at higher risk for perioperative morbidity and mortality 

than their younger counterparts, especially during 

major surgery. Elderly patients may therefore benefit the 

most if current and future advances in urologic surgical 

techniques continue to improve outcomes. 

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26 

Thoracic Procedures 

Steven M. Neustein and James B. Eisenkraft 

From 1900 to 1990, the fraction of the population aged 

65 years and older tripled to 13%. 1 Persons aged 80 years 

and older now constitute the fastest-growing elderly 

group in the United States. 2 Between 2000 and 2020, this 

segment of the United States population is expected to 

increase by approximately 35%. 

Aging increases the susceptibility to pulmonary 

disease. 3 Lung cancer is the leading cause of cancer death 

in persons older than 70 years. 4 More than half of all lung 

cancers occur in people who are older than 65 years. 

From 1955 to 1992, worldwide mortality from lung cancer 

has increased by 180% and 580% in 65- to 82-year-old 

men and women, respectively. 5 

Most lung cancers become manifest in the geriatric 

population because they are associated with a long latency 

period after prolonged exposure to tobacco smoke or 

other predisposing factors. Surgical resection is currently 

the only available means for curing lung cancer. Those 

patients with unresectable tumors often receive chemotherapy 

and radiation treatment. Surgery is also the treatment 

of choice for localized non–small cell carcinomas, 

because often they can be excised completely. 

Lung resection for tumor is a common procedure in the 

elderly. Resection is often preceded by bronchoscopy to 

evaluate tumor involvement of the airway and to determine 

the resectability. If there is mediastinal adenopathy 

on computed tomography scan of the chest, a mediastinoscopy 

is performed to determine if this enlargement is 

the result of malignant spread of the tumor, which, if 

present, would contraindicate surgical resection. 

Although surgery is necessary to cure most lung cancers, 

the risk of operating on the elderly is increased. 6 Patients 

in this segment of the population are offered surgery less 

often than younger counterparts. 7 Elderly patients who 

are not treated survive an average 1–5 years. 8 Overall, the 

5-year survival rate for patients with lung cancer is 18.5% 

for those younger than 65 and 13.8% for those 65 years 

or older. 9 This may be attributable to a lower rate of 

surgery in elderly patients with lung cancer. 

Morbidity and Mortality of Thoracic 

Surgical Procedures in the Elderly 

Among elderly patients undergoing pneumonectomy and 

lobectomy, the associated mortality has been twice that of 

patients younger than 65 years. 10 A series of 476 patients 

were studied by Kohman et al. 11 to identify predictors of 

mortality after thoracotomy for lung cancer. Hospital 

mortality for patients undergoing pulmonary resection 

was 5.6%. The only statistically significant risk factors for 

mortality were age 60 years or older, the presence of premature 

ventricular contractions on the admission electrocardiogram 

(EKG), and the need for pneumonectomy 

(versus lobectomy). Patients younger than 60 years had a 

mortality rate of 2.4%, as compared with 7.4% in patients 

aged 60 years or older. Hospital mortality after pneumonectomy 

and lobectomy was 11.7% and 3.7%, respectively. 

More recently, a 30-day mortality rate of 22% in 

patients older than 70 years has been reported after pneumonectomy. 

12 In another report of patients more than 80 

years undergoing thoracic surgery for lung cancer, there 

was a mortality rate of only 3%. 13 In a study of 296 patients 

who were 65–89 years of age, and underwent resection 

with video-assisted thoracoscopy (VAT) for stage 1 lung 

cancer, there was a 15% incidence of morbidity, and only 

a 1% mortality rate. 14 

Gerson et al. 15 studied 177 patients who were 65 years 

of age or older and scheduled for major elective abdominal 

or noncardiac thoracic surgery. The inability to exercise, 

defined as the inability to perform supine bicycle 

pedaling for 2 minutes or to increase the heart rate to at 

least 100 beats per minute, was the best predictor of 

postoperative cardiopulmonary complications. Patients 

capable of this exercise had a perioperative cardiac or 

pulmonary complication rate of 9.3%, as compared with 

42% for those who could not perform the exercise. The 

comparative mortality rates were 0.9% and 7.2%, respectively. 

Perioperative pulmonary complications occurred 

378

26. Thoracic Procedures 379 

in 24 patients (14%). Twenty-three of these patients had 

pneumonia, and one patient had a pulmonary embolism. 

Arterial blood gases were not predictive of the incidence 

of perioperative pulmonary complications in this study, 

but this may have been caused by the paucity of patients 

with increased carbon dioxide levels. A history of congestive 

heart failure or neurologic disease has been associated 

with an increased risk of postoperative pulmonary 

dysfunction in the elderly. 16 

Perioperative chest physical therapy in the elderly, 

when combined with postoperative chest physical therapy, 

can further decrease the incidence of atelectasis. 17 In this 

study of elderly patients who underwent cardiac and 

other thoracic surgical procedures, none of the 67 patients 

with chronic obstructive pulmonary disease (COPD) who 

received both preoperative and postoperative chest physical 

therapy developed pulmonary complications, as compared 

with all 34 patients with COPD who only received 

postoperative chest physical therapy (p < 0.02). 17 In a 

more recent study, patients with COPD who had a perioperative 

chest physical therapy program that was begun 

preoperatively also had a reduction in postoperative pulmonary 

complications. 18 Elderly patients have decreased 

pulmonary function because of aging and increased duration 

of exposure to cigarette smoke, and are less likely to 

tolerate removal of lung tissue. 

In the study by Gerson et al., 15 perioperative cardiac 

complications occurred in 25 of 177 patients (14%). 

Ninety-two percent of patients who had a perioperative 

pulmonary complication, and 88% of patients who had 

a perioperative cardiac complication, were unable to 

perform 2 minutes of exercise and increase their heart 

rates to at least 100 beats per minute. A previous study 

also demonstrated this test to be a predictor of perioperative 

cardiac complications in noncardiac thoracic geriatric 

surgery. 19 

Cardiorespiratory Physiology 


A thorough preoperative assessment is essential for any 

patient scheduled to undergo thoracic surgery. It is particularly 

important for the geriatric patient, because with 

advancing age comes a decline in cardiopulmonary function. 

There is decreased elastic tissue in both peripheral 

and coronary arteries, leading to systolic hypertension, 

left ventricular hypertrophy, and decreased coronary 

reserve. There is also a decrease in the maximum achievable 

stroke volume and heart rate, and thus in maximum 

cardiac output. 

A decrease in elastic tissue occurs in the lungs with age, 

leading to an increase in lung compliance. However, the 

thorax is more rigid because of calcification so that total 

thoracic compliance may be unchanged. The decrease in 

the amount of elastic tissue leads to airway closure, and 

there is an increase in both anatomic and alveolar dead 

space. The closing capacity, closing volume, and residual 

volume increase. In addition to a decreased ventilatory 

response to hypoxia and hypercarbia, elderly patients 

may have periodic breathing during sleep, putting them 

at increased risk of apnea in the postanesthesia care 

unit. 20 The vital capacity and PaO 2 decrease with increasing 

age. 21 A frequently used formula for estimating the 

PaO 2 according to age is, PaO 2 = 100 − age (in years)/3. 

With aging, there is a decrease in both immune function, 

and ciliary function, which accounts for an increased rate 

of respiratory infections in the elderly. 22 

The patient with a preoperative forced vital capacity 

(FVC) of less than 20 mL/kg or postbronchodilator forced 

expiratory volume in 1 second (FEV 1 )/FVC of less than 

50% is at increased risk for pulmonary complications. 

Preoperative teaching of breathing exercises and planned 

bronchial therapy can decrease postoperative pulmonary 

complications. 23 

The elderly have decreased anesthetic requirements. 

There is an increase in sensitivity to anesthetic agents, 

which parallels the loss of cortical neurons and decrease 

in brain neurotransmitters that occur with aging. Premedication 

of the elderly patient for thoracic surgery 

should be light, because of the decreased pulmonary 

reserve and increased sensitivity to anesthetics. In many 

cases, premedication is best omitted. Anticholinergics to 

decrease secretions may be helpful, especially if bronchoscopy 

is planned. 


Postoperative pulmonary complications are a major 

source of morbidity and mortality after thoracic surgery. 24 

The best evaluation of pulmonary function is a careful 

history. The information to be collected includes history 

of smoking, presence of respiratory systems, and functional 

status. 

As described by Slinger and Johnston, 25 pulmonary 

function can be evaluated by assessing three aspects: 

mechanics, gas exchange, and cardiopulmonary function. 

The single most important test of respiratory mechanics 

is the FEV 1 . Patients with an FEV 1 40% are at decreased risk, whereas those 

with values

380 S.M. Neustein and J.B. Eisenkraft 

A predicted postoperative DLCO 15 mL/kg/min is associated with reduced risk, 30 

and


at rates greater than 100 breaths per minute. A highpressure 

air-oxygen supply is modulated by a solenoid 

valve, producing frequent jet pulses that result in forward 

motion of airway gas. HFPPV at rates of up to 150 breaths 

per minute has produced similar blood gas values to 

those obtained with the Sanders injector system. 35 The 

tracheobronchial wall is immobile during HFPPV, which 

may be an important advantage during laser surgery. 35 

Complications of rigid bronchoscopy include damage 

to teeth, hemorrhage, bronchial or tracheal perforation, 

airway edema, and barotrauma. These risks are greater if 

the patient moves while the rigid bronchoscopy is in 

place. Flexible fiberoptic bronchoscopy is associated with 

fewer complications. 

Flexible Fiberoptic Bronchoscopy 

An examination of the airway with the flexible fiberoptic 

bronchoscope is typically performed before a lung resection. 

Preoperatively, an antisialagogue should be administered 

to decrease secretions that would otherwise 

interfere with visualization. Although scopolamine is the 

most potent drying agent, it may cause confusion in the 

elderly and should therefore be avoided. Glycopyrrolate 

is the drying agent of choice. It has a longer duration 

of action than atropine, and does not cross the blood– 

brain barrier. 

Flexible fiberoptic bronchoscopy can be performed 

using either local or general anesthesia. Local anesthetic 

solution can be sprayed onto the base of the tongue, or 

the patient can gargle with viscous lidocaine (2%). Bilateral 

superior laryngeal nerve blocks can be performed 

either percutaneously or by using Krause forceps to hold 

local anesthetic-soaked pledgets in each piriform fossa. 

The trachea and vocal cords are anesthetized by direct 

injection of local anesthetic into the trachea through the 

cricothyroid membrane, by spraying of local anesthetic 

under direct vision, or by injection via the working 

channel of the fiberscope. 

Instead of using the blocks described above, a nebulizer 

can be used to topically anesthetize the whole airway. 

A disposable (“acorn”) nebulizer filled with lidocaine 

(4 mL of 4%) is attached to a closely fitting face mask. 

The flow of oxygen to the nebulizer creates a mist of 

lidocaine that is inhaled by the patient, who is instructed 

to hold the mist in the airway for as long as possible. The 

nasal mucosa should also be anesthetized if the fiberoptic 

bronchoscope is to be passed nasally. This can be accomplished 

with cocaine, or a mixture of lidocaine (3 mL of 

4%) and phenylephrine (1 mL of 1%). 

The technique of flexible fiberoptic bronchoscopy in 

an awake patient requires considerable cooperation 

from the patient. The elderly patient with lung disease 

may not tolerate much sedation; therefore, good topical 

anesthesia of the airway with local anesthetic is 

important. 

Fiberoptic bronchoscopy can also be performed with 

the patient under general anesthesia. The trachea is first 

intubated, and then the fiberscope is inserted through an 

adapter that will create a gas-tight seal around the instrument 

such that the patient’s lungs may be ventilated 

around the fiberscope. The passage of a fiberscope through 

an endotracheal tube during IPPV may cause a positive 

end-expiratory pressure (PEEP) effect. If PEEP is already 

being applied via the anesthesia circuit, it should be discontinued 

while the fiberscope is in place. 33 A smallerdiameter 

fiberscope should be used if the endotracheal 

tube being used is less than 8.0 mm in internal diameter. 

Problems associated with fiberoptic bronchoscopy 

include local anesthetic toxicity, bleeding, and airway 

obstruction because of passage of the fiberscope 

through a stenosed portion of the trachea, or bleeding 

into an already narrowed airway, hypoxemia, and 

bronchospasm. 32 

Mediastinoscopy 

Mediastinoscopy was initially described by Carlens 36 as a 

method for assessing spread of bronchial carcinoma. The 

procedure enables examination of the superior mediastinal 

lymph nodes lying posterior to the aortic arch. The 

lymphatic drainage of the lungs is first to the subcarinal 

and paratracheal nodes and then to the supraclavicular 

nodes and thoracic duct. Through biopsy of these nodes, 

a diagnosis can be established, and suitability for thoracotomy 

and tumor resection can be determined. Proximal 

bronchial lesions often metastasize to the mediastinum, 

whereas peripheral lesions do not. Mediastinoscopy is less 

useful in patients with left lung tumors because these 

tumors usually spread to the subaortic lymph nodes that 

are not accessible via the mediastinoscope. These subaortic 

nodes are approached by an anterior thoracotomy 

through the second or third intercostal space (Chamberlain 

operation). Malignant spread of the tumor to the 

contralateral mediastinal nodes is an absolute contraindication 

to surgical resection of the tumor, whereas metastasis 

to the ipsilateral nodes does not rule out resection. 

Traditional mediastinoscopy is performed via a transverse 

incision just above the suprasternal notch. 

Following anteriorly to the trachea, the tip of the mediastinoscope 

is passed behind the innominate (brachiocephalic) 

vessels and the aortic arch. Mediastinoscopy is 

usually not performed if the patient has had a previous 

mediastinoscopy. This is because of scarring and loss of 

usual tissue planes. 

Mediastinoscopy can be performed under local anesthesia, 

but an awake patient breathing spontaneously 

would be at increased risk for venous air embolism


because of negative intrathoracic inspiratory pressure 

and for mediastinal trauma if the patient moves. It has 

been claimed that performing mediastinoscopy under 

local anesthesia is safer in those patients with limited 

pulmonary reserve and cerebrovascular disease, both of 

which are more common in the elderly. 37 However, 

general anesthesia is usually preferred for mediastinoscopy 

and should include paralysis to prevent patient 

movement and coughing that could lead to intrathoracic 

venous congestion and possible intrathoracic trauma. 

Mediastinoscopy is performed with the patient in the 

supine position and the neck hyperextended. The elderly 

patient may not be able to tolerate this position as well 

as the younger individual, and it is advisable to test the 

patient’s range of neck motion before induction of general 

anesthesia. 

The most common complication of mediastinoscopy is 

hemorrhage, which can be sudden and massive. Blood 

should therefore be available before starting the procedure. 

Emergency thoracotomy or sternotomy may be 

required to stop the bleeding, although surgical tamponade 

via the mediastinoscope may be done as a temporizing 

measure. Needle aspiration of any structure before its 

biopsy is done so that a major vessel will not be accidentally 

biopsied. If the bleeding is venous, a large-bore 

intravenous catheter should be placed in a vein in a lower 

extremity, because fluid and medications given into an 

upper extremity vein in this situation will drain into the 

mediastinum. 38 A torn mediastinal vein may also lead to 

an air embolus, especially if the patient is breathing spontaneously. 

The reverse Trendelenburg position can 

decrease venous pressure and therefore bleeding, but this 

also increases the potential for venous air embolism. 

A pneumothorax may occur during mediastinoscopy, 

which may necessitate placement of a chest tube. The 

recurrent laryngeal nerve may be injured. The nerve 

may be damaged by the mediastinoscope or compressed 

by the tumor. Bilateral recurrent laryngeal nerve injury 

may lead to airway obstruction after tracheal extubation 

and spontaneous ventilation by the patient. An additional 

potential complication is arrhythmias that may occur 

because of stimulation of pressor receptors in the 

aortic arch. 

The mediastinoscope may compress the innominate 

(brachiocephalic) artery, leading to a decrease in blood 

flow in the common carotid and right subclavian arteries. 

This has been misdiagnosed as a cardiac arrest. 39 Transient 

left hemiparesis has also been reported after mediastinoscopy. 

40 The elderly patient is more likely to have a 

history of neurovascular insufficiency and be at risk for 

this complication. The blood pressure can be measured 

in the left arm, but the pulse in the right arm should be 

monitored continuously. The pulse is monitored most 

sensitively by an arterial catheter and pressure transducer 

system and less sensitively by a pulse oximeter. 

A damped right radial pulse pressure is an indication 

for repositioning of the mediastinoscope, relieving compression 

of the innominate artery. Other complications 

of mediastinoscopy include tracheal collapse, tension 

pneumomediastinum, hemothorax, and chylothorax. A 

chest radiograph should be obtained in the immediate 

postoperative period if a pneumothorax is suspected, 

and is taken routinely in many centers. 

Thoracotomy 

Pulmonary resection (pneumonectomy or lobectomy) is 

the most frequently performed thoracic surgical procedure. 

Whenever possible, a lobectomy rather than a pneumonectomy 

is done for a primary tumor, because this 

procedure is associated with a lower morbidity and mortality 

but offers a similar prognosis to the more extensive 

procedure. 11 

The elderly have a higher mortality rate than younger 

patients undergoing thoracotomy. 1 In one series, the 

operative mortality in elderly patients undergoing pneumonectomy 

was 22%, compared with 3.2% in younger 

patients. 41 

Cardiovascular Complications 

Arrhythmias are a common perioperative complication 

after pulmonary resection and may not be as well tolerated 

in the elderly. The older patient is more likely 

to have diastolic dysfunction and the less compliant ventricle 

is more dependent on the atrial contraction 

for proper filling. Atrial arrhythmias are more likely to 

cause hypotension in the geriatric patient. Arrhythmias 

are more common in patients older than 50 years undergoing 

pulmonary resection and are more frequently 

related to right pneumonectomy as compared with left 

pneumonectomy. 

In a retrospective study of 236 patients, a 22% incidence 

of perioperative arrhythmias has been reported in 

the perioperative period of pneumonectomies. 42 Atrial 

fibrillation, which made up 64% of all arrhythmias, was 

the most common. In 55%, the arrhythmias persisted, and 

there was a 31% in-hospital mortality rate in this group. 

Prophylactic perioperative digitalization can reduce the 

incidence of arrhythmias 43,44 but has the potential for 

toxicity and contributing to arrhythmias. A prospective, 

controlled, randomized clinical study in 140 consecutive 

patients reevaluated the role of prophylactic digoxin 

in relation to thoracic surgical procedures. 45 Patients were 

randomly allocated to receive no digoxin or digoxin 

0.5 mg twice on the night before surgery, followed by 

0.25 mg with premedication. Postoperatively, patients 

received digoxin 0.25 mg per day for 9 days. The dose of


digoxin was adjusted according to serum level, and 

patients were monitored by EKG. The overall mortality 

was 5.7%. The investigators found no significant difference 

in the incidence of arrhythmias between the two 

groups and concluded that prophylactic digitalization in 

elective thoracic operations is not justified. 

The use of perioperative metoprolol can reduce the 

incidence of atrial fibrillation after thoracotomy for lung 

resection. 46 In this prospective, randomized, double-blind 

study, the incidence of arrhythmias was 6.7% after metoprolol 

versus 40% in the control group. 

Monitoring 

Hypoxemia is likely during one-lung ventilation, and continuous 

monitoring using pulse oximetry is the standard 

of care. Patients undergoing pulmonary resection should 

have an indwelling arterial catheter for continuous blood 

pressure monitoring and arterial blood sampling. Central 

venous access allows for central delivery of drugs for 

treatment of arrhythmias, hypotension, measurement of 

pressure, and can guide the anesthesia provider in fluid 

therapy management. 

Elderly patients are more likely to have cardiovascular 

disease, and their management may be facilitated by the 

use of a pulmonary artery catheter. Patients are at greater 

risk for pulmonary edema after pneumonectomy because 

of a decreased pulmonary vasculature cross-sectional 

area (increased pulmonary vascular resistance); thus, 

a pulmonary artery catheter may be of even more value 

in these cases. If a pulmonary artery catheter is placed 

for pneumonectomy, it is imperative that its tip not be in 

the pulmonary artery of the lung to be resected at the 

time of ligation. It may be necessary to withdraw the 

catheter at the time of pulmonary artery ligation and to 

then re-advance the catheter after the ligation. 

Transesophageal echocardiography (TEE) may be 

useful during thoracic surgery. It may help to delineate 

the anatomy if a tumor is invading or compressing the 

heart. 47 It can provide real-time estimation of myocardial 

function and ventricular filling. The elderly patient is 

more likely to have a decrease in cardiac function and 

therefore is more likely to require central venous monitoring 

and/or TEE monitoring. 

Airway Management 

The placement of a double-lumen endobronchial tube 

allows collapse of the operated lung, making the surgical 

resection easier. It also facilitates suctioning and application 

of continuous positive airway pressure to the nonventilated 

lung. The most common approach to lung 

separation is the use of a left-sided double-lumen tube, 

except when the left mainstem bronchus is diseased. The 

left mainstem bronchus, being longer than the right mainstem 

bronchus, permits placement of a left-sided endobronchial 

tube with a smaller chance of upper lobe 

obstruction. In the case of a left pneumonectomy, the 

tube must be withdrawn into the trachea before ligation 

of the bronchus. 

Another alternative is placement of an endobronchial 

tube into the nonoperative side, so as to avoid disruption 

of a potentially diseased bronchus and to avoid repositioning 

in the case of a pneumonectomy. A disadvantage 

of this method is that upper lobe obstruction is likely to 

cause hypoxemia during one-lung ventilation, because 

this is the lung to be ventilated during surgery of the 

contralateral lung. 

A third method is placement of the endobronchial tube 

into the operated side. The advantage of this method is 

that upper lobe obstruction during one-lung ventilation 

is not more likely to lead to hypoxemia, because this lung 

will be collapsed during one-lung anesthesia. However, in 

the case of a right thoracotomy, the presence of the tube 

in this short bronchus may interfere with the surgeon’s 

ligation of the bronchus. 

Intubation is more likely to be difficult in the elderly 

if there is arthritis of the neck, with consequent limitation 

of mobility. Arthritis of the temporomandibular joint 

may cause limitation of mouth opening. However, if the 

patient is edentulous, which is also more likely in the 

elderly, the intubation may be easier. Thus, increased age 

may have the effect of making intubation easier or more 

difficult. Each patient must therefore be evaluated 

individually. 

In the case of a difficult intubation, it may be preferable 

to begin by placing a single-lumen tube. A tube exchanger 

can then be used to replace the single-lumen tube with 

a double-lumen tube. Alternatively, one-lung ventilation 

could be facilitated with a bronchial blocker placed 

through the single-lumen tube into the bronchus of the 

lung to be deflated. Two blockers that are now available 

are the Arndt and the Cohen tip-deflecting blocker. The 

Arndt blocker (Cook Critical Care, Bloomington, IN) has 

a lumen with a wire extending through it, ending in a 

loop. A fiberscope is passed through the loop and is used 

to guide the blocker into place. More recently, the Cohen 

tip-deflecting blocker (Cook Critical Care) has been 

introduced. This blocker has an internal wire, which 

allows the tip to be angled and directed into either bronchus. 

There is a wheel at the proximal end that, when 

turned, bends (flexes) the tip of the blocker. 

Intraoperative Anesthetic Management 

Most pulmonary resections are performed with the 

patient in the lateral decubitus position and via a posterolateral 

incision. After transection of the chest wall muscles,


the pleural space is entered either by rib resection or via 

an intercostal space. The lung should be collapsed before 

this entry to prevent injury. The lung resection is accomplished 

with ligation of the arterial and venous vessels, 

and the bronchus of the diseased lobe or lung. 

Blood loss is usually not severe enough to require 

transfusion during lobectomy or pneumonectomy, but 

blood should be available. Blood loss is likely to be 

greater during pleuropneumonectomy, pleurectomy, or 

decortication, and the patient is more likely to require 

blood transfusion. Measurement of central venous pressure 

and hematocrit, and estimation of blood loss assist 

in guiding fluid administration. A fluid warmer is important 

because heat loss may occur during thoracotomy, and 

hypothermia will delay extubation and increase the likelihood 

of arrhythmias. 

After lung resection, there is a reduction in the pulmonary 

vascular bed and an increased risk of pulmonary 

edema, especially after a pneumonectomy. 48 Fluids should 

therefore be given cautiously during and after pneumonectomy. 

Fluid overload in this situation may also cause 

right atrial distention and arrhythmias. The elderly have 

a decreased ability to tolerate these hemodynamic aberrations 

and, with a reduced cardiac function, would be 

more likely to develop pulmonary edema. Hypotension 

could lead to inadequate coronary artery perfusion, myocardial 

ischemia, and possibly infarction. 

Maintenance of general anesthesia can be accomplished 

using a potent inhaled anesthetic agent and neuromuscular 

blocking drug to prevent movement of the 

diaphragm. The elderly patient with limited cardiac 

reserve may not tolerate a potent inhaled agent and may 

require a high-dose opioid technique in which case ventilation 

must be continued postoperatively. 49 However, in 

contrast to high-dose fentanyl, an infusion of remifentanil 

can decrease the requirement for a potent inhaled agent 

and still allow the patient to awaken promptly after the 

surgery. A high Fio 2 is needed during one-lung anesthesia, 

but, after this, the addition of nitrous oxide can also facilitate 

an earlier extubation by allowing use of lesser 

amounts of potent inhaled anesthetic agent. 

After lung resection and before reinflation of remaining 

lung tissue, the endobronchial tube should be suctioned. 

The bronchial suture line is tested by applying 

20–40 cm H 2 O pressure using manual compression of the 

anesthesia circuit reservoir bag. Before closure of the 

chest, complete reexpansion of remaining lung tissue 

should be visually confirmed. Thoracostomy tubes are 

placed for drainage of air and fluid after a lobectomy. 

These tubes are not placed if a pneumonectomy has been 

performed, because there is no remaining lung tissue to 

reexpand. In this case, the use of nitrous oxide can lead 

to a tension pneumothorax once the chest is closed, 

because there is no tube to vent the space. After skin 

closure and return of the patient to the supine position, 

pressure in the postpneumonectomy thoracic cavity space 

is relieved by needle aspiration. The trachea may be 

extubated immediately after surgery, depending on the 

preoperative condition of the patient, temperature, 

hemodynamic stability, and extent of surgery and technique 

used (e.g., opioid versus potent inhaled agent). 

Early return to spontaneous ventilation is advantageous, 

because it can decrease an air leak from the lung and 

reduce stress on bronchial sutures. The double-lumen 

tube is generally replaced with a single-lumen endotracheal 

tube if the trachea is to remain intubated postoperatively. 

However, the airway may be edematous, and if 

intubation before the procedure was difficult, it may be 

prudent to change the tube over a guide or perhaps even 

not change the tube at all. The surgeon may request that 

the double-lumen tube be changed to a single-lumen tube 

after the resection in order to perform bronchoscopy. 

Postoperative Complications 

Several life-threatening complications may occur after 

thoracic surgery, and individual outcome is related to the 

underlying condition of the patient, which may be further 

impaired by aging. Outcome is also related to the extent 

of surgery. 

Cardiopulmonary complications include arrhythmias, 

which are more frequent after pneumonectomy. Factors 

predisposing to arrhythmias include sympathetic stimulation 

from pain, intraoperative cardiac manipulation, and 

a reduced vascular bed from the pulmonary resection. 50 

Arrhythmias that frequently occur after pneumonectomy 

include atrial tachycardia, atrial flutter, and atrial fibrillation. 

Multifocal atrial tachycardia is common in patients 

with obstructive pulmonary disease and right-sided heart 

strain. The elderly in particular are prone to circulatory 

compromise from these arrhythmias. 51 Right-sided heart 

failure may present in the postoperative period from a 

reduction in the pulmonary vascular bed. 

Other postoperative pulmonary complications include 

atelectasis, which may be related to intraoperative lung 

retraction and manipulation, impaired clearance of secretions, 

splinting from pain, or incomplete reexpansion 

of the remaining lung tissue after one-lung anesthesia. 

Atelectasis may lead to pneumonia, which can be fatal in 

the setting of the reduced lung tissue postthoracotomy. 50 

The elderly patient is more likely to have limited pulmonary 

reserve and be more affected by a pneumonia. The 

removal of lung tissue, especially a right-sided pneumonectomy, 

puts the patient at risk for pulmonary edema 

because of a reduced vascular bed and increased pulmonary 

arterial pressures. Fluid is therefore more likely to 

move into the lung interstitium according to the Starling 

forces. Pulmonary embolism may occur in the postoperative 

period, possibly originating from the remaining


pulmonary artery stump or tumor tissue. An elderly 

patient with limited cardiopulmonary reserve may require 

a longer period of postoperative ventilatory support than 

a younger person undergoing a similar procedure. 

Potential structural complications requiring rapid 

surgical treatment include cardiac herniation, tension 

pneumothorax, and hemorrhage. Cardiac herniation is a 

rare but catastrophic complication. It may occur after 

pneumonectomy, in which the heart herniates through a 

pericardial defect. To help avoid this complication, the 

patient should not be turned lateral, with the operative side 

dependent. 

A tension pneumothorax can occur, even if chest tubes 

are placed, if they are not functioning properly or become 

occluded. A pneumothorax created by the placement of 

a central venous catheter into the nonoperative side of 

the chest is particularly hazardous both intraoperatively 

and postoperatively, because this is the only lung to be 

ventilated during one-lung anesthesia, and takes on an 

even greater role after resection of the other lung. 

Hemorrhage may be caused by slipped sutures or 

ligatures, bleeding from raw lung surfaces, or damaged 

bronchial or intercostal arteries. Postoperative neurologic 

complications may be related to the surgery or to 

positioning. Surgical injuries can affect the phrenic nerve, 

recurrent laryngeal nerve, and spinal cord. The lateral 

decubitus position can lead to damage to the brachial 

plexus, radial nerve, ulnar nerve, sciatic nerve, and 

common peroneal nerve. 

A bronchopleural fistula may develop after pulmonary 

resection, either immediately or even years later. 52 It 

carries a mortality rate of >20%. It may result from dehiscence 

of the bronchial stump after lung resection. Treatment 

includes reduction of the air leak and prevention of 

infection. Surgical intervention may be required. Placement 

of a double-lumen endobronchial tube into the 

contralateral mainstem bronchus can allow exclusive 

contralateral ventilation and isolation of the contralateral 

lung. An alternative is the use of high-frequency jet 

ventilation, which allows ventilation with lower airway 

pressures. 32 

Postthoracotomy Pain Management 

Thoracic surgery is often followed by pain and pulmonary 

dysfunction because of the thoracic incision. There 

is a decreased functional residual capacity and vital 

capacity, which in association with pain produces atelectasis, 

hypoxia, and CO 2 retention. 53 Traditionally, opioids 

have been administered intravenously or intramuscularly 

to treat postthoracotomy pain. The disadvantage of these 

methods is that administering an amount of opioid adequate 

to relieve pain is likely to cause sedation and respiratory 

depression. The elderly patient is more likely 

to have pulmonary dysfunction and decreased central 

nervous system activity and is even more likely to have 

postoperative impairment of pulmonary function. 

Patient-controlled analgesia (PCA) is preferred over 

the intermittent administration of pain medications. A 

basal continuous delivery of medication can be programmed 

in addition to boluses. Patients have been 

reported to have less pain and sedation with PCA as 

compared with intramuscular opioids. 54,55 Patients who 

receive PCA after thoracotomy have been reported to 

require less pain medication and have a lower incidence 

of pulmonary complications. 56 PCA also allows patients 

to feel less dependent and helpless, and it is generally well 

accepted. The elderly patient is also more sensitive to the 

respiratory depressant effects of systemically administered 

opioids. It may be preferable to not use a basal 

infusion rate, but rather to use only demand dosing in 

the interest of safety. 

Ketorolac, a nonsteroidal antiinflammatory agent, does 

not cause respiratory depression and therefore may be 

a useful adjunct in the elderly. Ketorolac should not 

be used if there has been significant bleeding because 

it inhibits platelet function and can lead to further 

bleeding. 

Cryoanalgesia can be accomplished by the direct application 

of a cryoprobe intraoperatively by the surgeon to 

the intercostal nerves, which reduces but does not eliminate 

postthoracotomy pain; it is usually used together 

with other analgesic treatments. Disadvantages include 

prolonged anesthesia, possible permanent nerve trauma, 

and the loss of intercostal muscle tone. 57 

Spinal opioids administered into either the epidural or 

subarachnoid space provide excellent analgesia for 

patients after thoracotomy. Spinal opioids work by 

binding to opioid receptors in the substantia gelatinosa 

of the spinal cord. Intrathecal (subarachnoid) opioids can 

bind directly to the spinal cord, whereas those administered 

into the epidural space travel to the spinal cord 

by either passing through the dura 58 or by being absorbed 

into blood vessels that supply the spinal cord. 59 The 

analgesia provided by spinal opioids is attributable to 

the effect on the spinal cord, as opposed to a systemic 

effect. 

The subarachnoid injection of morphine can produce 

analgesia with a much smaller dose (10–15 µg/kg) than 

produced by the intravenous, intramuscular, or oral 

routes. 60,61 Patients are more comfortable postoperatively, 

and less sedated when given subarachnoid opioids. 62,63 If 

given before the surgical incision, subarachnoid opioids 

have been reported to decrease the intraoperative general 

anesthetic requirement. 64 This technique would limit the 

amount of opioids required for analgesia. The use of 

intrathecal morphine carries with it the risk of delayed 

respiratory depression. The rostral spread of intrathecal 

morphine is greater than that of other opioids that are


lipophilic and therefore bind to spinal opioid receptors 

rapidly and are reabsorbed into blood vessels. 

The placement of an epidural catheter allows for 

repeated doses and therefore provides a longer duration 

of analgesia than the “one-shot” injection of subarachnoid 

morphine. Epidural fentanyl has been administered 

as a continuous infusion to provide postoperative 

analgesia. If given through a lumbar epidural catheter, 

the fentanyl should be diluted to a volume of at least 

20 mL so that the fentanyl can reach the thoracic levels 

of the spinal cord. 65,66 Patient-controlled epidural analgesia 

may allow for improved pain treatment, compared 

with intravenous PCA. 67,68 In a large series of patients, 

epidural analgesia resulted in less intravenous morphine 

usage. 69 This would be an important consideration in 

the elderly. 

The intravenous administration of ketorolac may be 

helpful, even in the presence of an epidural, to treat 

shoulder pain that may occur from being in the lateral 

position for an extended period of time. Epidurally 

administered local anesthetic is not effective in treating 

shoulder pain of this origin. 

In a recent review of 165 studies, which included almost 

20,000 patients, the results of three methods of postoperative 

analgesia after major surgery were reported. 70 

The three different routes of treatment studied were 

intramuscular, PCA, and epidural. The highest degree 

of oxygen hemoglobin desaturation was associated 

with intramuscular analgesia (37%). The incidence of 

respiratory depression, as reflected by usage of nalox - 

one, was highest with intramuscular PCA (1.9%). 

Hypotension was most often associated with the epidural 

route (5.6%). 

The technique of interpleural analgesia was first 

described in 1986. 71 The injection of local anesthetic 

between the visceral and parietal layers of pleura may 

either block multiple intercostal nerves or the thoracic 

sympathetic chain. For patients undergoing thoracotomy, 

the catheter can be placed through an epidural needle 

under direct vision while the chest is open. This method 

of placement can avoid the risk of pneumothorax and 

aberrant placement of the catheter when performed 

percutaneously. 

The results of interpleural block for postoperative pain 

relief after thoracotomy have been mixed, ranging from 

poor 72,73 to excellent analgesia. 74–76 Chest tubes should not 

be placed on suction for approximately 15 minutes after 

the injection of local anesthetic, because this would lead 

to removal of local anesthetic and a decrease in analgesic 

effect of the block. 72 Systemic toxicity is more likely 

in the presence of pleural abnormality. 73 This technique 

may be an option when neuraxial analgesia is contraindicated. 

The elderly patient is more likely to have kyphoscoliosis, 

which may make placement of an epidural more 

difficult. 

Videothoracoscopy 

VAT is now being used for a variety of thoracic procedures, 

including pleural biopsy, lung biopsy and resection, 

closure of bronchopleural fistulas, pericardial biopsy, 

pleurodesis, and laser ablation of emphysematous 

bullae. 77–80 Even lobectomy can be performed by VAT. 

VAT uses small incisions to accommodate the video 

camera for on-screen visualization, and working instruments. 

This technique does not involve spreading of the 

ribs, and there is no need for the large incision that is 

required for open thoracotomy. There generally is less 

postoperative pain and respiratory impairment than after 

a conventional thoracotomy. Postthoracotomy pain can 

otherwise cause splinting and limit deep breathing, coughing, 

and clearing of secretions. There is a lower incidence 

of morbidity after thoracoscopy compared with thoracotomy. 

Thoracoscopy is better tolerated than thoracotomy 

by high-risk patients, which would include the elderly 

who have reduced cardiac and pulmonary function. 

Arrhythmias may still occur after VAT. 81 The use of epidural 

analgesia may help to reduce the incidence of 

arrhythmias. 81,82 Ketorolac may be a useful adjunct, especially 

if an epidural has not been placed. 

A procedure such as diagnostic VAT and pleural biopsy 

can be performed under general anesthesia, thoracic epidural 

anesthesia, or intercostal block. For procedures in 

which there is a high likelihood that thoracoscopy may 

not be adequate and a conventional thoracotomy may be 

required, unless it is expected that the patient can be 

easily tracheally intubated in the lateral position, general 

anesthesia is the best option. A double- or single-lumen 

tube with a bronchial blocker is required during general 

anesthesia to provide adequate surgical exposure. Insufflation 

of gas is usually not needed for visualization under 

these conditions. 

Videoscopic surgery, which carries a lower risk of morbidity 

and mortality, may be preferable in the elderly 

patient, who is at increased risk. 1 Patients undergoing 

either wedge resection or lobectomy for stage I lung 

cancer, which are tumors that have not spread to lymph 

nodes, have been reported to have similar 5-year survival 

rates. 83,84 Patients undergoing video-assisted lobectomies 

have been reported to have a lower incidence of complications 

than patients undergoing lobectomy with thoracotomy. 

85 Although long-term survival may be a less 

important consideration for the elderly than short-term 

results and complications, the long-term survival after 

video-assisted lobectomy seems to be similar to lobectomy 

via thoracotomy. A limited resection in the elderly 

may be preferable, because of a possible reduction in risk, 

and an increased incidence of diagnosis of stage I tumors. 1 

Age is a risk factor for mortality after thoracotomy; 

therefore, the increased usage of VAT is particularly 

advantageous in the elderly. 86


Conclusion 

The anesthesia considerations for the elderly patient 

undergoing the most frequently performed thoracic 

surgical procedures have been briefly reviewed. Optimum 

anesthesia care of the elderly patient undergoing thoracic 

surgery requires an understanding of the principles 

of anesthesia for thoracic surgery coupled with an appreciation 

of the changes associated with aging. Most 

lung cancers occur in people older than 65 years of age, 

and surgical treatment should not be withheld based on 

age alone. 1 

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27 

Cardiac Procedures 

James H. Abernathy III 

Our population, both nationally and worldwide, is getting 

increasingly older. The proportion of people aged 65 and 

older in the United States is projected to increase from 

35 million (12.4%) to 71 million (19.6%) by 2030 and 82 

million by 2050. 1 Global trends are similar: people aged 

65 and older are expected to make up 12% of the population 

by 2030 and 20% of the population by 2050. Considering 

that older patients have invasive procedures at 

almost four times the frequency of people younger than 

65, this will significantly affect our health care system. 2 

Because there are a greater number of older patients, 

surgery for cardiovascular disease is increasing. Compounding 

this, patients are increasingly presenting at an 

older age and later in their disease processes. For instance, 

in 1983, 12% of coronary artery bypass graft (CABG) 

patients were older than 65 years of age. Just 10 years 

later, half the patients undergoing CABG were older 

than 65 years of age. 3 Today, the average age of CABG 

surgery patients is 66 years of age. 4 For cardiac surgery, 

the 30-day mortality is estimated to increase by a factor 

of 1.55 per decade of age, compared with noncardiac 

surgery at 1.35 per decade of age. 5 However, despite 

the increasing age of our patients and the increased risk 

of morbidity and mortality as the patient population 

has aged, operative mortality from cardiac surgery has 

not substantially increased. The reasons for this are multifactorial 

including improved surgical techniques, dedicated 

cardiac anesthesiologists, better cardiopulmonary 

bypass (CPB) machines, improved pharmacologic interventions, 

and better anesthesia techniques and technology 

such as transesophageal echocardiography and 

epiaortic ultrasound. 

This chapter concentrates on the surgical interventions 

for elderly patients with heart disease. Surgical frequency, 

morbidity, and mortality between the aged population 

and younger patients are explored. In addition, strategies 

for preventing adverse outcomes in this unique patient 

cohort are presented. 

The Society of Thoracic Surgeons (STS) Cardiac 

Surgery Database was initiated in 1986 with the goal of 

providing risk-adjusted outcomes compared with the 

national experience. The data set contains detailed clinical 

information on more than 1.5 million registered 

patients undergoing cardiac surgical procedures from 541 

academic, private, military, and Veterans Affairs hospitals 

from 48 of the United States and Canada. It is the single 

best place to investigate risk factors and outcomes of 

cardiac operations. Most of what has been published 

regarding age and cardiac surgery revolves around multiple 

series from single institutions. 6–12 We focus mostly on 

those few studies that have utilized large databases such 

as the STS database. 

Coronary Artery Disease 

Coronary artery disease (CAD) continues to be a major 

contributor to mortality in the elderly. An even larger 

proportion of the elderly population experiences morbidity 

from their CAD. Approximately 40% of Americans 

will reach the age of 80 and, of these, 40% will have 

symptomatic heart disease. 13 Eighty-three percent of 

all cardiovascular deaths occur in patients older than 

65 years of age. 14 As the population ages, it is not surprising, 

therefore, that the median age of coronary artery 

bypass grafting has steadily increased to 66 years of 

age. Despite this increase in age at operation, there 

has been a significant decline in overall operative mortality 

and risk-adjusted mortality for CABG patients 15 


Anesthesiologists and surgeons are faced with caring 

for older and sicker patients to palliate CAD. As previously 

discussed in this book, elderly patients present with 

multiple organ system disease resulting in less physiologic 

reserve than their younger counterparts. They are more 

likely to have hypertension, diabetes mellitus, cerebral 

390

27. Cardiac Procedures 391 

2.00 

1.75 

O/E Ratio 

1.50 

1.25 

1.00 

0.75 

0.50 

All CABG Patients 

Subanalysis CABG Patients 

Medicare CABG Pts 

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 

Year of Procedure 

Figure 27-1. Observed mortality to expected mortality ratio (O/E), 1990–1999. CABG = coronary artery bypass graft. (Reprinted 

with permission from Ferguson et al. 15 Copyright © 2002. With permission of The Society of Thoracic Surgeons.) 

and peripheral vascular disease. Elderly patients presenting 

for coronary revascularization are more likely to be 

women, in New York Heart Association (NYHA) heart 

failure class IV, and have left main CAD. 16 Interestingly, 

in reviewing the STS database of more than 1 million 

patients, Ferguson et al. 15 found that, when compared 

with younger patients, fewer elderly patients are undergoing 

reoperative CABG, likely reflecting patient 

selection. 

Examining the extremes of the elderly population, 

Bridges et al. 17 investigated 575,389 nonagenarians and 

centenarians undergoing CABG. Patients older than 90 

years of age were more likely to be women, undergo 

urgent or emergent operations, have left main disease, 

unstable angina, and preoperative renal failure, and be in 

NYHA class IV. The overall operative mortality for these 

patients was 11% compared with 2.8% for those younger 

than 80 years of age. The multivariate analysis for operative 

mortality showed an increased risk for emergent or 

salvage operation [odds ratio (OR) 2.26], preoperative 

intraaortic balloon pump (IABP) (OR 2.79), perioperative 

renal failure (OR 2.08), defined as creatinine >2.0 and 

also more than twice the baseline value or a new requirement 

for dialysis, peripheral or cerebral vascular disease 

(OR 1.39), and mitral insufficiency (OR 1.50). This trend 

was evident in morbidity measures as well as with patients 

older than 90 having an increased risk of perioperative 

stroke (2.9%), renal failure (9.2%), prolonged ventilation 

(12.2%), and postoperative length of stay (median 7 

days). 17 In this population, if the patient did not have the 

preoperative risk factors of emergent operation, IABP, 

renal failure, peripheral vascular disease, or cerebral vascular 

disease, their operative mortality was only 7.2%. 

Surprisingly, this subpopulation accounted for 57% of the 

nonagenarians and centenarians undergoing CABG. 

Valvular Heart Disease 

As we age, the fibromuscular skeleton of the heart 

changes, including myxomatous degeneration and collagen 

infiltration, termed sclerosis. Aortic valve sclerosis is 

estimated to occur in 30% of elderly persons. Other agerelated 

changes include calcium deposition on the leaflets 

of the aortic valve, base of the semilunar cusps, and the 

mitral annulus. Fibrosis with valve calcification is the 

most common etiology of valvular stenosis in the elderly. 

Valvular regurgitation often occurs as a result of ischemia 

or hypertensive disease, especially at the mitral valve. 18 

The age of the patient presenting for a valve operation is 

ever increasing (Figure 27-2). 

Aortic Valve 

Aortic stenosis in patients older than 65 years of age is 

estimated to be 2% for severe stenosis, 5% for moderate 

stenosis, and 9% for mild stenosis. 18,19 Consequences of 

aortic stenosis, left ventricular hypertrophy, decreased 

left ventricular compliance, and decreased stroke volume 

are independent of etiology. The same process that causes

392 J.H. Abernathy III 

Mean Age (Years) 

72 

70 

68 

66 

64 

62 

60 

58 

AVR CAB+AVR MVR CAB+MVR 

86 87 88 89 90 91 92 93 94 95 

Year of Surgery 

Figure 27-2. Mean age by year and valve procedure. AVR = 

aortic valve replacement, CAB = coronary artery bypass, MVR 

= mitral valve replacement. (Reprinted with permission from 

Jamieson et al. 21 Copyright © 1999. With permission of The 

Society of Thoracic Surgeons.) 

sclerosis of the aortic valve seems to also affect the coronaries 

and helps to explain the association between aortic 

valve disease and CAD. 

Aortic regurgitation also occurs with increasing frequency 

in the elderly. In one study, 13% of those older 

than 80 had mild aortic regurgitation, and 16% had either 

moderate or severe regurgitation. Patients with heart 

failure and pulmonary congestion from acute aortic 

regurgitation have a 50%–80% mortality. 20 

Morbidity and mortality data for elderly patients 

undergoing aortic valve replacement (AVR) has mostly 

come from small, single institution case series. The mortality 

rates have been quoted from 5% to 10%, depending 

on comorbidities. Using the STS database, Jamieson 

et al. 21 better quantified the operative mortality risk for 

patients undergoing valve replacements with or without 

CABG. Table 27-1 delineates the increased risk of mortality 

with increasing age. The operative risk for AVR 

almost doubles with every decade over 60 years of age. 

Independent predictors of mortality have been consistently 

shown to include age, emergent procedures, 

advanced NYHA class, and renal failure. However, in the 

STS analysis by Jamieson et al., 21 age was not an independent 

risk factor. Those of statistical significance included 

salvage status (OR 7.12), perioperative renal failure (OR 

4.32), emergent case (OR 3.46), reoperation (OR 2.27), 

cardiogenic shock (OR 1.67), NYHA class IV (OR 1.56), 

prior cerebrovascular accident (OR 1.44), previous myocardial 

infarction (OR 1.36), female gender (OR 1.25), 

and diabetes mellitus (OR 1.23). 

Chiappini et al. 22 retrospectively studied 115 patients 

with a mean age of 82 years who underwent AVR alone 

or in combination with CABG. The most common presenting 

symptoms were dyspnea in 99%, congestive heart 

failure in 15%, and angina in 77%. As expected in an 

extreme elderly population presenting for heart surgery, 

20% had an ejection fraction lower than 50%, 44% had 

significant CAD, and 78% presented in NYHA class III 

Table 27-1. Operative mortality rate by age group and valve position and population size (1986–1995, The Society of Thoracic 

Surgeons database). 

Age (years) 

Procedure 

50–59 60–69 70–79 80–89 90–99 

AVR 

Mortality rate (%) 2.9 3.2 5.3 8.5 14.5 

Population 3,686 7,001 8,468 2,756 69 

AVR + CABG 


Population 1,709 6,120 10,617 3,717 64 

MVR 

Mortality rate (%) 4.1 6.1 9.8 13.4 25 

Population 2,815 4,062 3,576 621 4 

MVR + CABG 


Population 1,050 2,889 3,782 730 7 

Multiple valves 


Population 803 998 854 177 2 

Multiple + CABG 


Population 155 430 612 154 2 

Source: Adapted with permission from Jamieson et al. 21 Copyright © 1999, with permission from The Society of Thoracic Surgeons. 

AVR = aortic valve replacement, CABG = coronary artery bypass graft, MVR = mitral valve replacement.


or greater. The 30-day mortality rate was 8.5% with an 

actuarial survival rate of 86.4% at 1 year and 69% at 5 

years. There was no statistically significant difference in 

the death rate, either in hospital or out of hospital, 

between AVR or AVR-CABG groups. Logistical regression 

analysis revealed that reduced preoperative ejection 

fraction, perioperative heart failure, and type of implanted 

device were predictors of late death. Those patients who 

received a bioprosthetic valve did much better than those 

who received a mechanical or stentless valve. Having a 

patient survive an operation is not the only endpoint 

worth discussing. The elderly have to do better in life 

post-repair than before. In this patient population, 98% 

of survivors were satisfied with their choice. There was a 

statistically significant improvement in NYHA class, 2.9 

± 0.6 versus 1.6 ± 0.6, p < 0.01. 22 

Mitral Valve 

The aging process has a similar effect on the mitral valve 

as it does on the aortic valve. These same factors also 

predispose patients to worse outcomes after mitral valve 

surgery. Left ventricular diastolic function, decreased systemic 

vascular compliance, increased left ventricular mass 

index, and altered neurohormonal and autonomic influences 

have been attributed to adverse outcomes in those 

undergoing mitral valve repair. 

Mehta et al. 23 analyzed data on all patients undergoing 

mitral valve replacements, either alone or in combination 

with CABG or tricuspid valve operation between January 

1997 to December 2000 who were enrolled in the STS 

database. Of the 262,718 patients in the database, 31,688 

met the criteria. Mitral valve replacement represents the 

only cardiac operation done more frequently in those 

patients who are older than 70 years of age than in any 

other age group. The elderly patients (>60 years of age) 

were more likely to undergo an urgent operation, have a 

concomitant CABG, and need the assistance of an IABP. 

Pump times and cross-clamp times were similar across all 

age groups. 

All in-hospital adverse events increased with advancing 

age including stroke, prolonged ventilation, reoperation 

for bleeding, renal failure, atrial fibrillation, and 

mortality. Multivariate models show that the risk of operative 

mortality increases with age, even after adjusting for 

other variables (Figure 27-3). Sadly, this indicates that a 

vigorous 80 year old has increased risk of mortality independent 

of other comorbidities. Using their multiple 

regression model, Mehta et al. proposed a classification 

tree for those older than 75 years of age contemplating 

mitral valve replacement (shown in Figure 27-4). 

–2.5 

–3.0 

Log Odds 

–3.5 

–4.0 

–4.5 

20 40 60 80 100 

Patient Age (Years) 

Figure 27-3. Plot of log odds of operative mortality for mitral valve replacement versus age, after adjusting for other risk factors. 

(Reprinted with permission from Mehta et al. 23 Copyright © 2002. With permission from The Society of Thoracic Surgeons.)


Hemodynamic 

Instability? 

No 

Renal 

Failure? 

No 

NYHA 

Class IV? 

No 

Yes 

Yes 

Yes 

Concomitant 

CABG? 

No 

Yes 

N 

Mortality 

997 

31.9 

589 

25.3 

1597 

15.7 

2207 

11.4 

2535 

7.7 

Figure 27-4. Risk classification tree for elderly patients (>75 

years) undergoing mitral valve replacement. NYHA = New 

York Heart Association, CABG = coronary artery bypass graft. 

(Reprinted with permission from Mehta et al. 23 Copyright © 

2002. With permission of The Society of Thoracic Surgeons.) 

Preventing Adverse Outcomes 

Despite the existence of an increase in both morbidity 

and mortality for elderly patients undergoing cardiac 

surgery, relatively little is known about how to prevent it. 

Improvements in anesthesia techniques, medications, surgical 

techniques, and perfusion practices have improved 

cardiac surgical outcomes despite a population of advancing 

age. What little is known is covered in the following 

section. 

Cardiovascular 

Atrial fibrillation is a morbid event occurring in up to 

30% of elderly patients after cardiac surgery. Because of 

the elderly’s lower physiologic reserve, it is imperative to 

avoid beta-blocker and statin withdrawal, two offenders 

in postoperative atrial fibrillation. Additionally, their 

peripheral vascular system is more calcified and less distendable 

than younger patients. This increases their risk 

of aortic dissection and embolization with cannulation 

and initiation of CPB. Severe aortic disease or lower 

extremity vascular disease may increase the risk associated 

with IABP. Furthermore, poor coronary vasculature 

may predispose patients to incomplete revascularization 

and further ischemia after CPB. Ferguson et al. 24 demonstrated 

that the internal mammary artery was underutilized 

in elderly patients (77% for elderly versus 93% for 

younger). Those elderly patients who received an internal 

mammary artery bypass had a lower operative and postoperative 

mortality, even after controlling for other causative 

factors. 

Central Nervous System/Neurologic 

Neurologic injury remains one of the largest sources of 

morbidity and mortality after cardiac surgery. Its risk 

clearly increases with age, with quoted stroke risks ranging 

from 1% to 30% depending on age and operation. Figure 

27-5 demonstrates the increased risk of neurologic insult 

with increasing age. Roach et al. 25 studied adverse cerebral 

outcomes after CABG surgery in 2108 patients. Type 

I injuries were defined as death attributable to stroke or 

hypoxic encephalopathy, nonfatal stroke, transient ischemic 

attack, or stupor or coma at the time of discharge. 

Type II injuries were defined as new deterioration in 

intellectual function, confusion, agitation, disorientation, 

memory deficit, or seizure without evidence of focal 

injury. The predominant predictor of both type I and II 

injury was age: 6.1% of patients who were older than 70 

experienced a type I injury, and 5.8% experienced a type 

II compared with 1.9% and 1.8%, respectively, for those 

patients younger than 70 years of age. 25


PROBABILITY OF MORBID EVENT 

0.200 

0.175 

0.150 

0.125 

0.100 

0.075 

0.050 

0.025 

0.000 

NEUROLOGIC DEFICIT 

LOW CARDIAC OUTPUT STATE 

MYOCARDIAL INFARCTION 

35 45 55 65 75 85 95 

AGE (YEARS) 

Figure 27-5. Probability of incurring a morbid event during 

the perioperative cardiac surgical period and its association 

with age. Neurologic deficits increase dramatically beginning 

at age 65, whereas low cardiac output state and myocardial 

infarction remain relatively stable. (Reprinted with permission 

from Tuman KJ, McCarthy RJ, Najafi H, Ivankovich AD. 

Differential effects of advanced age on neurologic and cardiac 

risks of coronary artery operations. J Thorac Cardiovasc Surg 

1992;104(6):1510–1517. Copyright © 1992. With permission of 

the American Association for Thoracic Surgery.) 

Suggested mechanisms of cerebral injury include global 

hypoperfusion, focal occlusion of the cerebral vasculature, 

or thermal injury on rewarming. It seems that, 

despite reductions in cerebral blood flow during CPB in 

the elderly, there is a concomitant reduction in cerebral 

metabolic rate of oxygen consumption keeping the difference 

in arterial-venous oxygen content normal. 26 

Embolic phenomena have been blamed as the most likely 

culprit in central nervous system damage in the elderly. 

It is for this reason that combined carotid endarterectomy 

and CABG in the elderly remains a debated topic. 

Detecting ascending aortic atheroma either by surgical 

palpation or epiaortic ultrasound has been shown to 

reduce embolic events and improve post-bypass cerebral 

outcomes. 27,28 pH management by either alpha-stat or 

pH-stat and the association with cerebral outcomes has 

been vigorously studied. pH stat, through increased CO 2 , 

is associated with increased cerebral blood flow, but 

alpha-stat preserves cerebral autoregulation 29 (also J.P. 

Mathew et al., in press, Anesthesiology). Because most 

neurologic injuries are secondary to embolic phenomena, 

more cerebral blood flow may be detrimental. One prospective, 

randomized trial failed to show a difference 

between alpha-stat and pH-stat management in adult 

patients. 30 Based on preserving autoregulation, alpha-stat 

blood gas management would be recommended in the 

elderly. No intervention, however, has been studied in a 

population exclusive to those aged more than 65. 

Renal 

The prevalence of renal failure after cardiac operation 

varies from 2% to 15%, depending on the procedure and 

degree of preoperative renal dysfunction. 23 If it occurs, 

the mortality rate may be as high as 80%. Because the 

elderly have lower baseline glomerular filtration rate, are 

likely to have hypertension and an altered renal autoregulatory 

curve, and are more likely to have diabetes 

mellitus, they are at a higher risk of renal failure than 

their younger counterparts. The use of preoperative 

diuretics for those with depressed ejection fraction and 

radiopaque dyes often worsens preoperative renal function. 

Unfortunately, there has been no large investigation 

regarding the prevention of renal dysfunction in the 

elderly patient undergoing CPB. Mannitol as a scavenger 

of oxygen free-radicals and Lasix are often used but have 

not been specifically studied in the elderly population. 

The most important principle might be that recovery of 

renal function after bypass is directly related to the recovery 

of cardiac function. 

Cardiopulmonary Bypass Management 

CPB provides many alterations to the normal physiologic 

milieu. The optimal mean arterial pressure, perfusion 

flow, mode of perfusion (pulsatile versus nonpulsatile), 

pH and CO 2 management, temperature, and hematocrit 

have not been established for the elderly patient undergoing 

CPB. As previously mentioned, aortic cannula sites 

should be carefully chosen with the assistance of epiaortic 

ultrasound scanning to minimize embolized atheromatous 

debris. Perfusion flows range from 1.2 to 2.4 L/min/m 2 , 

with perfusion pressures varying from 30 to 80 mm Hg. 

No difference in outcomes has been demonstrated for 

flows within this range or for pulsatile versus nonpulsatile 

flows. The appropriate temperature management (normothermia 

versus hypothermia) for the elderly patient 

has not been studied. 

The optimum hematocrit while on CPB and immediately 

after for the elderly patient has not been determined. 

The absolute safe level will depend on many 

variables, including adequacy of myocardial revascularization, 

myocardial function, and, possibly, the age of the 

patient. The adequacy of tissue oxygenation and perfusion 

as determined by the mixed venous oxygen saturation 

determines transfusion in most centers. Blood-sparing 

strategies such as cell salvage techniques and retrograde 

autologous prime should routinely be used to conserve 

hematocrit and decrease the need for transfusion. The 

elderly might be a group for whom a higher hematocrit 

is beneficial; however, transfusion delivers new risks, most 

of which are related to the inflammatory response. 

Increased sternal wound infection, longer intensive care 

unit stays, and increased renal failure associated with


blood transfusion should be weighed against evidence of 

poor tissue oxygen delivery. 

With admittedly little scientific evidence to support 

their assertions, some authors empirically recommend 

the following: (1) alpha-stat blood gas management, (2) 

higher perfusion pressures throughout the perioperative 

period, (3) higher mean arterial pressures while on CPB, 

(4) higher hematocrit before termination of CPB (>24%), 

(5) mild hypothermia (32°C) during CPB, and (6) careful 

selection of the aortic cannulation site with the assistance 

of epiaortic ultrasound scanning. 31 

Conclusion 

We have demonstrated over the past several decades 

that, with continued focus on improving outcomes in 

cardiac surgery, we can be successful. Cardiac surgical 

patients are older, but their overall outcomes have 

improved. As our population ages, so too will our patients, 

and we will continue to push the envelope. Despite our 

successes, however, there are many unanswered questions. 

With continued vigilance, one day our recommendations 

will be more than empiric: they will be well-proven 

scientific assertions. 

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28 

Vascular Procedures 

Leanne Groban*and Sylvia Y. Dolinski 

Anesthesia for vascular surgery is predominantly geriatric 

anesthesia. Atherosclerosis, the underlying disease 

process in the patient with peripheral vascular disease, 

has an insidious onset but typically presents about 10 

years after the diagnosis of coronary artery disease. Given 

that persons aged 65 years and older comprise the fastestgrowing 

segment of the United States population, the 

prevalence of vascular interventions, including minimally 

invasive angioplasty, endovascular stents, and open reconstructive 

procedures, will undoubtedly increase. This 

chapter focuses on anesthetic management for the geriatric 

patient undergoing aortic and peripheral vascular 

surgery. Preoperative preparation is a key feature, because 

various comorbidities associated with advanced age, such 

as ischemic heart disease, renal insufficiency, and diabetes 

are robust predictors of cardiac complications in the vascular 

patient. 1 A brief discussion of postoperative care 

follows the discussion of surgical procedures. 


and Preparation 

*Partially funded by the Dennis Jahnigen Career Development 

Award and Paul Beeson Scholars Award (K08-AG026764-01) 

to Dr. Groban. 

Fundamental to perioperative management is an understanding 

of the specific anesthetic and overall goals for 

care of the elderly vascular patient (Table 28-1). A critical 

step to achieving these perioperative goals and obtaining 

the best possible outcome from the surgical procedure is 

a careful preoperative evaluation. Knowledge of the agerelated 

structural and functional changes that may have 

an impact on anesthesia for the geriatric patient is also 

important (Table 28-2). The aims of the preoperative 

assessment for the older vascular patient are to: (1) estimate 

risk; (2) optimize cardiovascular, respiratory, renal, 

and endocrinologic status; (3) undertake further investigation 

when necessary; (4) plan the anesthetic management; 

and (5) arrange appropriate postoperative care. 

Given that the elderly patient is at an increased risk for 

postoperative complications, because of increased comorbid 

illnesses and diminished organ functional reserve, 2 a 

detailed evaluation of both cardiac and respiratory 

systems reserve is warranted. 

Cardiac Risk Assessment 

and Intervention 

Regardless of age, cardiovascular complications (e.g., myocardial 

infarction, pulmonary edema, arrhythmias) are 

among the most serious postoperative problems in patients 

undergoing noncardiac surgery. 3 Assessment of the perioperative 

cardiac risk and its impact on long-term health 

should be accomplished during preoperative evaluations 

to ascertain potential interventions that may modify the 

cardiac risk. However, one must also take particular caution 

when applying generalizations about the elderly population 

to specific elderly persons, because the aging process 

is very heterogeneous. That is, even major vascular procedures 

are accompanied by low risk when cardiac functional 

status is good, coronary artery disease is absent, and 

the multifactorial risk index is low. 4 

The Revised Cardiac Risk Index (RCRI) is often used 

to predict the risk of major cardiac complications among 

patients undergoing major, nonemergent, noncardiac 

surgery. 1 The index was derived from 2893 patients and 

validated in 1422 patients, all aged 50 or older. The six 

independent predictors of cardiac risk identified from the 

study that are currently used include high-risk surgery 

(Table 28-3), history of ischemic heart disease, history of 

congestive heart failure, history of cerebrovascular 

disease, insulin therapy, and serum creatinine more than 

2.0 mg/dL. The presence of zero, one, two, and three or 

more predictors has been associated with cardiac complication 

rates of nearly 0.5%, 1%, 7%, and 12%, respectively. 

1,5 Thus, the higher the score based on the presence 

of risk indices, the greater the risk for cardiac morbidity. 

398

28. Vascular Procedures 399 

Table 28-1. Perioperative goals. 

For vascular surgery 

• Maintain cardiovascular stability 

• Maintain circulating blood volume 

• Decrease stress response 

• Preserve renal function 

For the geriatric surgical patient 

• Optimize medical and physical status 

• Minimize perioperative starvation and inactivity 

• Minimize the stresses of hypothermia, hypoxemia, and pain 

• Promote rapid recovery and avoid declines in functional status 

• Meticulous perioperative care to avoid complications from: 

Fluid and electrolyte perturbations 

Impaired cardiorespiratory function 

Inappropriate pharmacotherapy 

Interestingly, the RCRI does not include advanced age as 

an independent predictor of cardiovascular outcome presumably 

because ischemic heart disease, insulin-dependent 

diabetes, and renal insufficiency are already highly 

associated with age. 

The American College of Cardiology/American Heart 

Association guidelines for perioperative cardiovascular 

evaluation for noncardiac surgery 6 advocate identification 

of functional status in the assessment algorithm. This 

can be done by estimating energy demands of daily activities 

using the unit of metabolic equivalents (METs). The 

MET is a ratio comparing the energy consumption of an 

activity to energy consumption at rest. Usually, healthy 

elders can achieve 4.0 METs (e.g., showering while standing, 

toweling off, fishing, sweeping floors, playing with 

children) without dyspnea or fatigue. 7 Poor functional 

status, described as patients’ inability to perform activities 

of 5%) 

Emergent major operations, particularly in the elderly 

Aortic and other major vascular surgery (suprainguinal, abdominal, 

or thoracic) 

Peripheral vascular surgery 

Anticipated prolonged surgical procedures associated with large 

fluid shift and/or blood loss 

Intermediate (reported cardiac risk generally 75%–85% of 

their maximum age-predicted heart rate with a nonischemic 

electrocardiogram (ECG) response, are at low risk 

for postoperative cardiac events. 8 

Except in the case of emergent vascular surgery 

(when additional testing is obviated and the patient 

Table 28–2. Age-related physiologic changes and anesthetic implications. 

Structural and functional changes Physiologic consequences Clinical consequences 

Myocyte 

Impaired calcium homeostasis 

Reduced number (apoptosis) and 

increased size 

Reduced beta receptor responsiveness 

Extracellular matrix 

Increased interstitial fibrosis 

Amyloid deposition 

Conduction system 

Apoptosis of pacemaker and Hisbundle 

cells 

Valvular apparatus 

Fibrosis and calcification 

Vasculature 

Increased diameter of large arteries 

Increased medial and intimal thickness 

Decreased endothelial nitric oxide 

production 

LV = left ventricular, LVH = left ventricular hypertrophy. 

Impaired LV relaxation 

Increased myocardial stiffness 

Impaired Ca 2 + homeostasis, reduced LV relaxation, 

increased circulating catecholamines 

Increased LV stiffness 

Conduction block, atrial fibrillation, decreased 

contribution of atrial contraction to diastolic 

volume 

Aortic stenosis leads to LVH, reduced compliance, 

impaired relaxation 

Increased arterial stiffness, increased vascular 

impedance, early reflected waves, increase 

pulse wave velocity—decreasing LV 

compliance 

Greater reliance on ventricular filling and 

increases in stroke volume (rather 

than ejection fraction) to achieve 

increases in cardiac output. 

Intolerance to hypovolemia 

Intolerance to tachycardia. dysrhythmias, 

including atrial fibrillation 

Prone to large swings in blood pressure 

with clamping and unclamping

400 L. Groban and S.Y. Dolinski 

Figure 28-1. Perioperative beta-blockers: patient selection and 

preoperative risk stratification. The six independent predictors 

of complications in the Revised Cardiac Risk Index include: 

high-risk surgery, history of ischemic heart disease, congestive 

heart failure or cerebral vascular accident, preoperative insulin 

therapy, or serum creatinine >2.0 mg/dL. METS = metabolic 

equivalents. (Reprinted with permission from Auerbach and 

Goldman. 9 Copyright © 2002 American Medical Association. 

All rights reserved.) 

proceeds directly to the operating room), the decision to 

perform noninvasive testing is based on the presence of 

clinical risk factors, the patient’s functional status, and the 

type of surgery scheduled. Although little evidence exists 

showing that noninvasive imaging tests lead to therapeutic 

strategies that reduce cardiac risk, they remain a useful 

stratification tool for those elderly patients with age-related 

musculoskeletal changes that limit their functional status. 

For nonemergent vascular surgery, noninvasive testing 

(e.g., dobutamine stress echocardiography) may be indicated 

for (1) patients with stable angina, (2) patients 

scheduled for major aortic surgery who have either poor


functional status or one clinical predictor, and (3) patients 

undergoing intermediate surgery (e.g., carotid endarterectomy), 

who have poor functional status and/or two or more 

clinical predictors. Given that perioperative beta-blockade 

lowers cardiac risk, 9 it should be initiated in all patients 

undergoing major aortic surgery who carry, at minimum, 

one cardiac risk factor. If beta-blockade is contraindicated, 

alpha-adrenergic agonists can be substituted. 10 One clinical 

algorithm for preoperative risk stratification and perioperative 

beta-blockade is shown in Figure 28-1. 9 

Optimization Strategies 

Beta-Blocker Therapy 

Perioperative administration of beta-adrenergic receptor 

blockers reduces the incidence of postoperative cardiac 

complications and death in high-risk patients undergoing 

noncardiac, major vascular procedures, 9,11–15 with beneficial 

effects lasting up to 2 years. 11,14,16 Perioperative myocardial 

infarctions are not necessarily all caused by 

unstable plaque rupture and subsequent thrombosis that 

occludes coronary arteries. Many occur in the absence of 

plaque rupture and in areas not supplied by known 

severely stenosed arteries. 17 Postoperative changes in 

sympathetic activity and stress response lead to changes 

in heart rate and blood pressure predisposing to myocardial 

ischemia perhaps from imbalances in supply and 

demand of coronary perfusion. This is where beta-blocker 

therapy enters the perioperative therapeutic picture, to 

help reduce these changes in heart rate and blood pressure. 

The strongest evidence to date that beta-blockade 

decreases the incidence of postoperative myocardial 

infarction and death is from Poldermans et al. 12 These 

investigators showed that high-risk patients with positive 

dobutamine stress echocardiograms administered bisoprolol 

(7 days preoperatively to 30 days postoperatively) 

had a tenfold decrease in morbidity and mortality compared 

with untreated patients. Despite overwhelming evidence 

in support of perioperative beta-blockade, these 

agents remain underutilized 18–20 because of classic concerns 

from described contraindications of diabetes, chronic 

obstructive lung disease, and heart failure. How ever, betablockers 

are often well tolerated in these individuals, 

especially when carefully titrated. 21,22 The reluctance of 

some physicians may be attributable to the lack of published 

data regarding their beneficial effects in the geriatric 

patient. A given trial in the elderly may have insufficient 

power to promote evidenced-based therapy, because the 

elderly are often excluded from studies, and thus the 

results, in fact, may not be generalizable. However, in a 

subgroup analysis of those >80 years, the mortality after 

myocardial infarction is reduced by 30%. 18–20 

In a small prospective study of 63 elderly patients 

(>65 years) undergoing noncardiac surgery, Zaugg et al. 23 

showed no difference in in-hospital myocardial infarction 

rates between patients who received perioperative atenolol 

and those who did not receive prophylactic treatment. 

However, the perioperative use of beta-blockade in 

this study was associated with reduced analgesic requirements, 

faster recovery times from anesthesia, and 

improved hemodynamic stability, suggesting that perioperative 

beta-blockade may be not only safe, but provide 

additional beneficial effects in the elderly. Similarly, in the 

nonsurgical Metoprolol CR/XL Randomized Intervention 

Trial, 24,25 a subgroup of elderly patients ≥65 years 

(n = 1920) with chronic systolic heart failure treated with 

metoprolol exhibited risk reductions in total mortality 

(37%), sudden death (43%), death from worsening heart 

failure (36%), and hospitalizations from worsening heart 

failure (36%). These results were as favorable as the 

benefits observed in younger (75 years of age, 26 beta-blockers 

should not be withheld from any surgical, high-risk patient 

with evidence of or known risk factors for coronary artery 

disease. One must keep in mind that older patients have 

decreased beta receptor responsiveness and, thus, may 

not exhibit the expected negative chronotropic response. 

Also, because of the rapid changes in blood volume that 

occur during aortic cross-clamping and unclamping and 

the age-related reductions in baroreceptor responsiveness, 

27 the authors choose to use an esmolol infusion 

during the intraoperative period. 

Alpha Agonists 

Alpha-2 agonists provide an alternative therapy for prevention 

of cardiac morbidity and mortality in patients 

with or at risk for coronary artery disease who undergo 

vascular surgery. 10,28 In a recent study by Wallace et al., 28 

perioperative administration of oral (0.2 mg) or transdermal 

clonidine (0.2 mg/day) for 4 days reduced the incidence 

of perioperative myocardial ischemia (clonidine 

group, 14% versus placebo group, 31%) and also reduced 

the incidence of postoperative mortality in patients >60 

years of age undergoing noncardiac surgery for up to 2 

years. Mivazerol, an alpha-2 agonist administered by continuous 

infusion, significantly reduced the incidence of 

myocardial infarction in major vascular surgery patients 

who had cardiac disease. 29 However, with the potential 

for hypotension 30–32 and reductions in coronary perfusion 

pressure, the authors prefer using beta-blockers rather 

than alpha-2 agonists in the elderly in light of an increased 

prevalence of aortic stenosis with advancing age. Clearly, 

direct-comparison studies are needed to determine which 

class of sympatholytic agents provides the greatest 

cardiovascular benefit with the fewest side effects in this 

expanding surgical cohort.


Statins 

Statins may also have cardiac protective effects in major 

vascular surgery. The mechanisms through which statins 

confer their beneficial effect include antithrombotic and 

antiinflammatory effects, 33 normalization of sympathetic 

outflow, 34 improved vasodilation, 35 and attenuation of 

cardiac remodeling. 36 In two case-control studies, statins 

were associated with lower perioperative 37 and longterm 

38 mortality after major noncardiac vascular surgery. 

In two retrospective studies, preoperative use of statins 

significantly decreased cardiovascular complications 

(statin: 9.9% versus nonstatin: 16.5%) 39 and in-hospital 

mortality (statin users had a 38% reduction in the odds 

of in-hospital mortality). 40 Only the former, an observational 

study, 39 was specific to older patients (median age 

71; range 63–78). Thus, even though the latter study 40 

included 780,591 patients, it is not clear how well the 

results apply to older patients. Whether statins should be 

given to octogenarians for the prevention of cardiac 

disease and perioperative complications remains controversial. 

41,42 Interestingly, Alter et al. 43 projected that if a 

combined therapy of statins and beta-blockers in acute 

coronary syndromes would have a 25% efficacy rate, one 

would need to treat 15 elderly patients compared with 

175 in the youngest age group to show a benefit (Table 

28-4). Findings from the Prospective Study of Pravastatin 

in the Elderly at Risk primary prevention trial 44 show that 

even though statins reduce death from heart disease, nonfatal 

myocardial infarction, and fatal or nonfatal stroke 

in the elderly, they may increase risks of myositis, rhabdomyolysis, 

and cancer. 42 Thus, until more trials are conducted 

in the older high-risk patient, the decision to 

prescribe a statin for prophylaxis against perioperative 

cardiac complications awaits additional study. Also, the 

effect of abrupt discontinuation of statin therapy in the 

elderly, high-risk patient remains unclear. 45 

Preoperative Assessment 

A detailed cardiovascular history and examination with 

standard laboratory studies including a hematocrit, platelets, 

electrolytes, creatinine, and clotting profile are sufficient. 

A relatively recent 12-lead ECG is also indicated. 

Cardiovascular symptoms should be carefully determined, 

because preoperative ECG abnormalities do not 

predict postoperative cardiac complications in the 

elderly. 46 Chronic stable angina represents a low risk, 

whereas unstable angina has been associated with a high 

risk of perioperative ventricular dysfunction, ischemia, 

myocardial infarction, and arrhythmias. The high-risk 

patient should be referred to a cardiologist for additional 

testing and coronary therapies, if deemed necessary, 

before vascular surgery. Because many elderly patients 

have limited exercise capacity (because of arthritis, 

osteoporosis, and claudication) and atypical features of 

coronary artery disease, the authors recommend dobutamine 

stress echocardiography or dipyramidole-thallium 

scanning. Patients ultimately having either coronary 

stenting or angioplasty should then wait 2–4 weeks before 

their vascular procedure. Failure to wait for recovery 

after coronary intervention places these patients at high 

risk for lethal intraoperative bleeding or myocardial 

infarction. 47,48 

Patients with congestive heart failure are also at 

increased risk for postoperative cardiac complications. 

B-type natriuretic peptide (BNP) plasma level is useful 

in determining the etiology of pulmonary congestion. 49,50 

With BNP levels of ≤100 pg/mL, heart failure is highly 

unlikely. However, BNP levels are increased in healthy 

elderly 51 and should not be used in isolation from clinical 

context. BNP trends in the chronic heart failure patient 

may help determine whether medical optimization is 

required before surgery. In the elderly hypertensive 

patient with concentric left ventricular hypertrophy and 

normal systolic function, diastolic dysfunction can lead to 

congestive heart failure. These patients are exquisitely 

sensitive to factors that alter diastolic filling such as 

tachycardia, atrial fibrillation, and hypovolemia. Thus, 

identifying these patients preoperatively, with Doppler 

echocardiographic indices of diastolic performance, 52 

could help to establish the perioperative goals of fluid 

and blood pressure management. 53 

Because there is a paucity of data on patients >75 years 

of age, with normal systolic function and impaired diastolic 

function or diastolic heart failure, management of 

Table 28-4. The relation between baseline risk (1-year mortality) and number needed to treat by various relative efficacies of 

treatment. 

Age group (years) 

1-Year mortality 

Number needed to treat assuming 

a relative efficacy of 10% 

Number needed to treat 

assuming a relative efficacy of 

25% 

Number needed to treat 

assuming a relative 

efficacy of 50% 


these patients remains largely empiric and should be 

weighed on a case-by-case basis. Intraoperative and postoperative 

management emphasis should be placed on 

control of arterial hypertension (no higher than 130– 

140/80–90 mm Hg), maintenance of normal sinus rhythm 

and a low, normal heart rate (60–70 bpm), avoidance of 

ischemia, and the prevention of volume overload as well 

as an insufficient LV preload. In general, control of hypertension 

is easily done by anesthesia (to a desirable systolic 

blood pressure of 120 mm Hg). The authors also use 

a combination of low-dose infusions of nitroglycerin and 

phenylephrine titrated to maintain systolic blood pressure 

within 10% of baseline and to prevent increases in 

pulse pressure (e.g., pulse pressure > diastolic blood pressure 

≅ increased impedance) and low diastolic blood 

pressures (e.g.,


adjustments of medications. At present, there are no published 

guidelines of measures to prevent perioperative 

renal failure, although the use of acetylcysteine pre- and 

post-IV contrast has appeared in the literature. 73 Indeed, 

the use of magnetic resonance angiography as the sole 

imaging modality is an acceptable alternative for the preoperative 

evaluation of vascular architecture in high-risk 

patients, and it does not have harmful renal effects. 73 

Nonetheless, the authors strive to maintain circulating 

blood volume and cardiac output in an attempt to maintain 

renal blood flow and perfusion pressure. The two 

“renal protective” strategies often used during aortic 

surgery include low-dose dopamine (1–3 µg/kg/min) for 

its antialdosterone effect and mannitol (12.5–25 mg/70 kg), 

given before aortic cross-clamp application, for its potential 

free-radical scavenging and osmotic diuretic effects. 

Although dopamine has not been shown to have direct 

renal protective effects, it can be used to augment cardiac 

output, thus improving renal blood flow. 74 Mannitol 

increases tubular flow through its osmotic effects and by 

reducing renal tubular cellular swelling. Its renal protective 

effects were demonstrated in the renal transplant 

literature. 75 There are no large randomized controlled 

studies of its conclusive benefit in the vascular patient; 

however, one small study revealed reduced tubular injury 

by measured urinary albumin and N-acetyl glucosaminidase 

levels. 76 

Some anesthesiologists also advocate the use of loop 

diuretics in an attempt to “poison” the energy requiring 

Na + /K + -adenosine triphosphatase pump, thereby reducing 

renal metabolic O 2 demand. 58,77 However, with the 

high prevalence of diastolic dysfunction in geriatric 

patients, 78 the authors do not advise the routine use of 

loop diuretics for fear of compromising stroke volume 

and cardiac output. It has been suggested that low-dose 

fenoldopam (0.03 µg/kg/min), a selective dopaminergic-1 

receptor agonist, may have renal protective effects. 73,79,80 

At this dose, it is unlikely to contribute to the hypotension 

one often sees postoperatively in these patients. 

Cognitive Function/Delirium 

Postoperative delirium is common in elderly patients and 

is a predictor of prolonged hospital stay and functional 

decline. 81 Risk factors for postoperative delirium include 

preexisting dementia, visual impairment, alcohol use, 

duration of anesthesia, use of benzodiazepines and narcotics, 

and postoperative infection. In an effort to identify 

patients at risk, the Mini-Mental State Examination is a 

reliable screening tool that is easy to use. (See Chapter 9 

for more discussion on delirium.) In those patients considered 

to be at risk for postoperative delirium, the 

authors recommend a regional technique, if possible with 

no sedation. Although there is no evidence that regional 

anesthesia decreases the incidence of postoperative delirium, 

the authors think this is attributable to the common 

use of various sedatives (e.g., midazolam, fentanyl, propofol, 

and ketamine) during surgical procedures performed 

under regional anesthesia. 


General Anesthesia for the Vascular Patient 

After arrival in the warm operating room, standard noninvasive 

monitors are applied. Supplemental oxygen by 

nasal cannula is initiated at the time of low-dose premedication 

with either midazolam (0.5–1.0 mg) or fentanyl 

(25–50 µg). All patients should be attached to an ECG 

system capable of monitoring V5 and all limb and augmented 

leads. Normally, leads II and V5 are monitored 

simultaneously with ST segment trending. The only 

patients for whom the authors do not routinely place an 

arterial line are those presenting for a lower extremity 

bypass or amputation procedure. One has access to the 

wrists during these surgeries and often they can be 

managed without direct arterial pressure monitoring, 

unless the procedure is prolonged, the noninvasive blood 

pressure monitor cannot detect a regular pulse (e.g., 

chronic atrial fibrillation), or multiple activated clotting 

times are requested by the surgeon. Unless peripheral 

intravenous access is poor, a 16-gauge peripheral intravenous 

is started for induction. Central venous or pulmonary 

artery pressure monitoring is performed after 

induction in only those patients who are undergoing open 

aortic aneurysm/aortobifemoral bypass, because these 

surgeries predispose to large volume shifts. Central 

venous access allows assessment of right-sided filling 

pressure, the administration of vasoactive drugs, if necessary, 

and the facilitation of rapid blood transfusion. The 

elderly maintain their cardiac output by increasing stroke 

volume and preload. This preload dependency results in 

significant hypotension when hypovolemia is encountered. 

Therefore, acute blood loss during surgery is not 

well tolerated. 53 The noncompliant, older heart is exquisitely 

sensitive to volume overload. Thus, the delicate 

balance between hypotension and congestive heart failure 

warrants the use of central monitoring both intraoperatively 

and postoperatively in the geriatric patient undergoing 

major aortic surgery under general anesthesia. 

Transesophageal echocardiography is frequently used by 

one author (L.G.), because it provides real-time information 

about filling status, myocardial function, and ischemia. 

Monitoring of central and peripheral temperature 

is desirable. The aim is to maintain normothermia during 

surgical procedures using active measures including 

forced air, fluid warming devices, and warm ambient temperatures. 

The geriatric patient has less-efficient mechanisms 

of heat conservation, production, and dissipation.


Maintaining intraoperative normothermia reduces wound 

infections, cardiac events, and length of stay. 82,83 

Before preoxygenation, esmolol boluses or an esmolol 

infusion is titrated to achieve a heart rate 10%–20% 

below the patient’s baseline. The advantages of esmolol 

include its high specificity for the beta 1 receptor, and its 

short duration of action. It can be used in severe chronic 

obstructive pulmonary disease patients, because it does 

not affect forced expiratory volume in 1 second, even at 

high infusion rates. 84 Preoxygenation in the geriatric 

patient is very important because an increased closing 

volume and a delayed onset of neuromuscular blockade 

predisposes them to rapid and profound desaturation and 

hypoxemia-induced cardiac events. 85 If rushed for time, 8 

breaths at 100% oxygen over 1 minute at a 10 L/min flow 

rate is recommended. 86 

No matter if the approach to anesthesia is opioid-based 

supplemented with a volatile agent or a combined general 

and regional technique, the goals are the same (Table 

28-1). Induction is undertaken with short-acting opioids, 

any intravenous induction agent (etomidate 0.2 mg/kg; 

propofol 0.5–0.7 mg/kg; thiopental 3 mg/kg), and cisatracurium. 

General anesthesia and sedative/hypnotics have 

a direct negative effect on sympathetic output, cardiac 

contractility, vascular tone, and cardiac filling pressures 

predisposing the older patient to a greater risk of hypotension. 

After the patient either stops breathing or 

becomes obtunded, the inhalational agent is slowly added 

to maintain normotension while neuromuscular blockade 

takes effect. Long-acting neuromuscular agents such as 

pancuronium should be avoided, because even when 

reversed these agents are associated with postoperative 

pulmonary complications. 87 The authors prefer cisatracurium 

for its forgiving pharmacodynamic profile. All neuromuscular 

blockers, including cisatracurium, have an 

increased onset time by about 1 minute in the geriatric 

patient. Recovery times for pancuronium, vecuronium, 

and rocuronium are also longer, whereas recovery times 

with cisatracurium are not altered by advanced age. 88 

Heart rate responses to laryngoscopy are prevented by 

the use of the esmolol infusion (vide supra beta-blocker 

therapy). Anesthesia is maintained with any of the 

volatile agents, additional fentanyl, and a cisatracurium 

infusion at 1–3 µg/kg/min. Because minimal alveolar 

concentration (MAC) requirements are reduced in the 

elderly, bispectral index (BIS) monitoring may be useful. 

Longer-acting opioids (e.g., morphine) may be given 

toward the end of surgery to provide postoperative pain 

control if an epidural is not in place. However, one must 

keep in mind that the volume of distribution of morphine 

is smaller in the elderly, plasma and tissue drug levels are 

greater for a fixed dose, and the drug disappears more 

slowly from cerebral spinal fluid. Taken together, these 

effects can account for the more marked respiratory 

depression seen in the morphine-treated 80-year-old 

versus the morphine-treated 50-year-old. Moreover, 

plasma morphine concentration and morphine clearance 

also depend on renal function. 

Patients are extubated provided they are warm and 

have an arterial pH of >7.35. The elderly are less able to 

mount a respiratory compensation for a metabolic 

acidosis, especially in the face of pain or narcotic loads. 

They have less muscle strength, and their hypoxic drive 

to breathe is also easily blunted with residual 0.1 MAC 

inhalational agent on board. Patients with postoperative 

epidural analgesia may be more readily extubated. 

Patients not extubated at the end of surgery receive infusions 

of either low-dose propofol (15 µg/kg/min) or dexmedetomidine 

(0.2–0.7 µg/kg/h). Dexmedetomidine has 

no respiratory depressant effects and minimal blood 

pressure–lowering effects in euvolemic patients. 89,90 Heart 

rates are lower with dexmedetomidine than with placebo 

during emergence and up to 48 hours after major vascular 

surgery, suggesting a cardioprotective benefit as well. 91 

Epidural Anesthesia/Regional Techniques 

Neuraxial/regional anesthesia alone, or in combination 

with general anesthesia, has several potential benefits 

including attenuation of the stress response and the 

production of a sympathectomy (Table 28-5). These 

effects may reduce the tendency to form clots and 

enhance graft patency through improved blood flow. 92,93 

Numerous studies, however, have failed to show that 

regional anesthesia is superior to general anesthesia for 

vascular surgeries for other outcomes such as death. 94 

With the emphasis on administration of beta-blockers 

and maintenance of normothermia, morbidity and mortality 

in patients undergoing general anesthesia may be 

reduced, negating any difference one might see between 

regional and general anesthesia groups. 95 In addition, an 

inadequate or failed regional technique resulting in 

untreated tachycardia and hypertension, which leads to 

an increased need for supplementation of narcotics and 

anxiolytics, may produce hypercarbia or hypotension that 

likely will have a more adverse effect on outcome than a 

well-executed general. 

Elderly patients at risk for postoperative delirium may 

benefit from epidural pain control as opposed to systemic 

Table 28-5. Potential benefit of epidural anesthesia for vascular 

surgery. 

Reduce stress response to surgery 

Improve myocardial oxygen supply/demand balance 

Improve endocardial blood flow 

Reduce minimal alveolar concentration 

Improve graft patency 

Preserve pulmonary function 

Reduce postoperative narcotic requirements


opiates in addition to the possibility of minimal sedation 

during the surgery. 95,96 T2 epidural anesthesia reduces 

MAC and MAC awake by 50%. 97,98 The concentration of 

inhalational agent required during combined general/epidural 

technique is markedly reduced. In fact, BIS levels 

are reduced with the combination technique. 99 Intraoperative 

anticoagulation is not a contraindication for a 

neuraxial technique as long as the heparin is dosed 1 hour 

after the epidural insertion. 100 Lower extremity surgeries 

require a T-12 level. Presently, there seems to be little 

evidence in the literature that regional anesthesia provides 

a benefit in length of hospital stay, mortality, and 

cardiac morbidity over general anesthesia. 94 This may 

be because in randomized controlled trials both the 

study and control groups are closely watched, and it is 

close perioperative watching that makes a difference 

in outcome. 

However, on subgroup analysis of aortic surgery, 

Park et al. 96 found that patients who had epidurals had 

fewer postoperative complications including less cardiovascular 

and respiratory failure. A meta-analysis of randomized 

controlled trials addressing the postoperative 

effects of epidurals on pulmonary function revealed that 

there is a decreased incidence of respiratory infections 

and overall pulmonary complications, compared with 

systemic opioid administration. 98 Another recent metaanalysis 

also showed reductions in the pulmonary complications 

of pulmonary embolism, pneumonia, and 

respiratory depression. 101 

When the authors place epidurals for abdominal aortic 

surgeries at T6–8, the patients undergo test dosing with 

2% lidocaine. Before incision, morphine (2–3 mg) is 

administered epidurally. It is not until after the crossclamp 

has been removed and the patient is hemodynamically 

stable, that the epidural is redosed with 2% lidocaine, 

and a continuous 0.25% bupivacaine infusion through 

the epidural catheter is begun at a rate of 3 mL/h. As the 

blood pressure increases, the patient is given a 1- to 2-mL 

2% lidocaine bolus, and the bupivacaine infusion is 

increased by 1 mL/h. This is repeated until the patient is 

on an infusion of 4–6 mL/h at the end of the case. In the 

postanesthesia care unit, the 0.25% bupivacaine infusion 

is stopped once the postoperative infusion of 0.125% 

bupivacaine with 0.005% morphine sulfate is available, 

thereby continually controlling postoperative pain. 

In the postoperative period, if the patient is anticoagulated 

with prophylactic low-molecular-weight heparin 

(LMWH), the epidural should be removed at least 10–12 

hours after the last LMWH dose, and 2 hours before 

the next dose, 100 to reduce the risk of epidural or spinal 

hematoma associated with anticoagulation. The epidural 

is continued if the patient receives prophylactic unfractionated 

heparin for a few days postoperatively. The 

authors discourage their surgical colleagues from using 

fractionated heparin in the elderly despite creatinine 

values in the normal range. There is some evidence that 

the elderly are at increased risk of bleeding when given 

fractionated heparin. 102 

Infraaortic Vascular Procedures 

These procedures are amenable to either neuraxial techniques 

alone or combined with general anesthesia 

depending on the length of surgery and/or type of surgery. 

An ileofemoral bypass requires abdominal muscle relaxation 

better afforded by neuromuscular blockade (and 

hence, general anesthesia) than by only a neuraxial technique. 

However, patients undergoing such procedures are 

frequently already receiving anticoagulants such as intravenous 

heparin or have been recently dosed with platelet 

inhibitors such as clopidogrel, which preclude any neuraxial 

technique. Other regional techniques such as lumbar 

plexus/sciatic blocks have been associated with increased 

bleeding risks. 103 Below the knee amputations have successfully 

been performed by popliteal blocks, and distal 

foot amputations are amenable to ankle blocks. 

Aortic Surgeries 

The risk of rupture for aneurysms 6 cm, the annual rupture risk is >25%. 

The best predictor of rupture risk is an aneurysm that 

increases in size more than 1.0 cm/year. Current standard 

of care dictates that aneurysms >5.0 cm in size should be 

repaired. Advanced age is a risk factor for increased 

death and complication rates. Postoperative mortality in 

octogenarians for open aortic repair has been reported 

to be between 1.4%–9.6% (Table 28-6). Dardik et al. 104 

showed that mortality was 2.9% in those in their sixth 

decade of life compared with 7.9% in octogenarians 

(Table 28-6, Figure 28-2). Increased postoperative 

complications have also been reported with advanced 

age (Figure 28-3). Octogenarians undergoing endovascular 

abdominal aneurysm repair (EVAR), however, 

had a mortality rate of 1.9% versus 5.3% for open 

surgeries. 105 

Before aortic cross-clamp placement, heparin (100 U/ 

kg) is administered and an activated clotting time is con- 

Table 28-6. Perioperative mortality rates after elective open 

surgical repair of abdominal aortic aneurysm in octogenarians. 

Source Patients (no.) Mortality rate (%) 

Treiman (1982) 35 8.6 

Paty (1993) 116 3.0 

Akkersdijk (1994) 75 8.3 

Ohara (1995) 94 9.6 

Van Damme (1998) 52 45.7 

Kazmers (1998) 206 8.3 

Dardik (1999) 246 7.9 

Mailapur (2001) 62 1.4


Figure 28-2. Rate of in-hospital mortality after repair of intact 

abdominal aortic aneurysm compared across age groups (p < 

0.001). (Reprinted with permission from Vemuri C, Wainess 

RM, Dimick JB, et al. Effect of increasing patient age on 

complication rates following intact abdominal aortic aneurysm 

repair in the United States. J Surg Res 2004;118:26–31. 

Copyright © 2004. With permission from Elsevier.) 

firmed to be longer than 250 seconds. Depth of anesthesia 

is increased and a nitroglycerin drip is also started before 

clamp placement. Venodilatation aids in volume loading 

of the patient during aortic cross-clamping. The physiologic 

response to aortic cross-clamping is dependent on 

the preoperative myocardial function, site of clamp application, 

aortic pathology (e.g., occlusive versus aneurysmal), 

and the volume status. A diaphragmatic-level aortic 

clamp is associated with increases in central venous, pulmonary 

artery end diastolic, and pulmonary artery mean 

pressures along with increases in mean arterial pressure. 

The cardiac output also increases in patients with normal 

myocardial function because of a shift in blood volume 

proximal to the clamp. In patients with ischemic heart 

Figure 28-3. Percentage of patients with one or more complications 

after surgery for repair of intact abdominal aortic aneurysm 

according to age group (p < 0.001). (Reprinted with 

permission from Vemuri C, Wainess RM, Dimick JB, et al. Effect 

of increasing patient age on complication rates following intact 

abdominal aortic aneurysm repair in the United States. J Surg 

Res 2004;118:26–31. Copyright © 2004. With permission from 

Elsevier.)


disease, however, ventricular function can deteriorate 

secondary to increased wall tension. If afterload reducing 

agents and volume do not restore cardiac output, inotropes 

may be required. In the case of an infraceliac 

aortic cross-clamp, a shift in blood volume to a dilated 

splanchnic bed may in fact result in a decrease in venous 

return and preload, prompting the administration of 

fluids at the time of cross-clamp. 58 Distal to the clamp, 

anaerobic metabolism ensues as blood flow to the gut, 

kidney, and legs decrease. Upon removal of the crossclamp 

and reperfusion of the lower half of the body, the 

patient is subjected to a sudden decrease in afterload and 

washout of anaerobic metabolites which can lead to 

hypotension if not properly volume loaded. Cell saver 

blood and autologous blood units as well as saline are 

infused to optimize preload before unclamping. The 

nitroglycerin drip, if used, is now discontinued. The concentration 

of the inhalational agent is reduced, fractional 

inspired oxygen concentration increased, and ventilation 

increased to counteract the released acid load. Phenylephrine 

is readily available, and the surgeon releases the 

cross-clamp slowly while volume is rapidly infused to 

counteract the vasodilation and hypotension. 

Endovascular Abdominal Aortic 

Aneurysm Repair 

Since 1991, the number of endovascular graft surgeries 

has surged. Three studies looking at EVAR in the elderly 

have shown >82%–95% success rate in placement with a 


Table 28-7. Descriptive analyses of in-hospital mortality rates according either to age and significant risk factors or to ASA scoring. 

Patients 1.8 mg/dL, and congestive 

heart failure. Life expectancy after abdominal aortic 

aneurysm repair for individuals aged 70, 75, 80, and 85 

years is 10, 8, 6, and 5 years, respectively. 108 The 4-year 

survival rate was 43% compared with 17% in those octogenarians 

deemed too high a risk for surgery in the past, 

half of whom died from aneurysm rupture. 107 One study 

of ASA 4 patients showed an in-hospital mortality rate 

of 4.7% in EVAR patients compared with the open repair 

rate of 19.2% (p < 0.02). Patients older than 72 with pulmonary 

or renal risk factors had a 21.4% mortality in the 

open group compared with the EVAR group of 5.3%. In 

the same age group, those without pulmonary or renal 

risks had a 4% mortality in the open group compared 

with the EVAR of 1.6% 113 (Table 28-7). 

Two large-bore IVs and an arterial line are placed. The 

authors do not routinely place central venous catheters 

for EVAR. A phenylephrine drip is prepared. Blood is 

kept in the room in case of intraoperative aortic rupture. 

The authors prefer to place a combined spinal-epidural 

catheter as the primary anesthetic for the procedure. The 

spinal injection of 12.5 mg plain isobaric 0.5% bupivacaine 

typically provides anesthesia/analgesia for the 

duration of the procedure. During placement of the neuraxial 

catheter, the patient receives minimal amounts of 

midazolam. Intraoperatively, the patient is sedated via a 

continuous infusion of dexmedetomidine (0.2–0.7 µg/kg/ 

h) or a propofol/ketamine (190:10 mg) mixture. 

Carotid Endarterectomy 

Two landmark randomized prospective trials showed that 

endarterectomy performed in patients who are symptomatic 

and have >70% internal carotid stenosis reduces the 

risk of ipsilateral stroke from 26% to 9% over the course 

of 2 years. 114,115 During surgery, the patient is at risk for 

an intraoperative stroke, and it is thought that placing a 

shunt across the clamped artery may improve on the 

ischemia. Some surgeons routinely place a shunt in 

patients undergoing a general anesthetic, because the 

ischemia that leads to a stroke cannot be recognized until 

after the operation. Some place a shunt only in patients 

at high risk for perioperative stroke, whereas others try 

not to place a shunt at all because the majority of patients 

do tolerate cross-clamping of the carotid. Shunting has its 

inherent risks of dissection or shedding of atheroemboli. 

High-risk patients are considered those with a 100% contralateral 

carotid occlusion. 

This procedure can be performed under regional or 

general anesthetic techniques. Sensory blockade in the 

C2–C4 dermatome can be achieved with a superficial 

cervical or deep cervical plexus block with minimal or no 

sedation. Local infiltration of lidocaine by the surgeons 

is an alternative option. This allows monitoring for 

optimal cerebral blood flow perfusion during the carotid 

cross-clamping by conversing with the patient. There is 

little need for more invasive or complex cerebral monitoring 

and often less need for shunting. However, with 

high carotid bifurcations, the regional technique usually 

fails to control all the intraoperative mandibular retraction 

pain and local anesthetic supplementation by the 

surgeon is required. 

A recent Cochrane review of nonrandomized trials 

suggests that surgery performed under local anesthesia is 

associated with a reduction in the odds of death, stroke, 

myocardial infarction, and pulmonary complications 

within 30 days of the operation. In the seven randomized 

controlled trials, there were no differences in the aforementioned 

outcomes. The ongoing General Anesthetic 

versus Local Anesthetic for Carotid Surgery trial is a 

randomized controlled trial designed to determine if 

regional anesthesia leads to a reduction in postoperative 

strokes. 116 

Regional anesthesia may be associated with occasional 

intense pain and anxiety that can lead to myocardial stress. 

Not all patients are candidates for regional anesthesia, 

particularly those who are claustrophobic, very anxious, 

or experience a lot of pain from lying on a hard surface.


Two intravenous lines are placed. Both phenylephrine 

and nitroglycerin drips are attached to a T-port connector 

on one of the lines close to the intravenous catheter insertion 

site, thereby ensuring little dead space. The authors 

typically perform a superficial cervical block with 0.25% 

ropivacaine because the cardiac safety profile seems to 

be better than the other long-acting local anesthetics, 

especially if the drug is inadvertently bolused into a large 

vessel in the neck. 117 After the block is placed, an arterial 

line is inserted in the arm opposite of the surgical site if 

both arms are not tucked. Intravenous fluids are kept to 

a minimum, blood pressure is kept at or above baseline, 

and the patient is monitored by engaging the patient in 

conversation. If necessary, the surgeon can supplement 

with 1% lidocaine if pain arises from the carotid sheath. 

During removal of the plaque, it is useful to warn the 

patient that this will feel like a dull toothache. Before 

cross-clamping, a 100 mg/kg bolus of heparin is given, and 

after the cross-clamping of the carotid, the patient is 

monitored for 1–2 minutes by squeezing the patient’s 

untucked hand and listening to the patient’s speech. If 

any change in the patient’s behavior is noted, the surgeon 

is alerted, the cross-clamp removed, the blood pressure 

increased by 20% above base line, and the clamp replaced. 

If the patient again exhibits signs of decreased cerebral 

perfusion, the surgeon places a shunt. 

If a general anesthetic is required because of surgeon 

or patient preference and cooperation, then induction 

proceeds as previously described under General Anesthesia 

for the Vascular Patient. Typically, only 1–2 µg/kg 

of fentanyl (or a maximum of 150 µg) is given to maximize 

the chances for a rapid emergence. Alternatively, 

remifentanil can be used and titrated off as the patient is 

allowed to spontaneously breathe; fentanyl is then titrated 

to a respiratory rate of 8–12. The authors typically hold 

pressure over the surgical site dressing until the patient 

is extubated. The goal is a smooth emergence with minimal 

coughing. 

Intraoperatively, there are numerous techniques for 

the monitoring of cerebral ischemia, and the authors have 

typically used cerebral oximetry or spectral edge 

frequency. Other techniques include full 16-lead electroencephalography, 

jugular venous saturation, stump 

pressures, evoked potentials, and transcranial Doppler 

monitoring. 118 None is as good as an awake, cooperative, 

communicative patient. In fact, when awake patients 

were simultaneously monitored by electroencephalography, 

there was a 6.7% false-positive and a 4.5% falsenegative 

rate in detection of neurologic deficits. 119 

Carotid Stents 

Of the endovascular techniques used for treating carotid 

stenosis, stenting is the preferred technique because it 

reduces the restenosis and dissection rates compared 

with angioplasty. 120 The first randomized controlled trial 

comparing carotid stent placement with open surgery in 

high-risk patients was conducted in 2002. 121 The 30-day 

mortality, stroke, or myocardial infarction rate was 5.8% 

for the stent group and 12.6% for the carotid endarterectomy 

group (p < 0.05). At 1-year follow-up, the differences 

were still remarkable for the same endpoints: 11.9% 

in the stent group compared with 19.9% in the carotid 

endarterectomy group. 122 However, the Cochrane review 

of the five trials comparing endovascular with open 

carotid endarterectomy showed that there was no significant 

difference in the risk of perioperative stroke, myocardial 

infarction, or death. It did show a reduction in 

cranial neuropathy. 123 This technique allows very highrisk 

patients and high, surgically inaccessible cervical 

carotid lesions to be treated. However, unlike stents 

placed in a coronary vessel or aorta, carotid surgery is 

relatively safe, inexpensive, and associated with a short 

hospital stay. Atheromatous emboli are devastating, and 

neuroprotective devices such as balloon catheter or 

microfilter systems are used by surgeons. 120 Local anesthesia 

and standard noninvasive monitors are used. 

Postoperative Care 

Most elderly patients have comorbidities that warrant 

their admission to the ICU. These include cardiac, 

respiratory, and renal insufficiency. The elderly are more 

prone to delirium. Bohner et al. 124 documented the 

incidence to be 38.9% with longer ICU treatment needed. 

Early restoration to preoperative physiologic and cognitive 

functioning is most important. Longer-term postoperative 

cognitive dysfunction is also not uncommon in 

the elderly. A large study revealed that 9.9% of patients 

had some postoperative cognitive deficits compared 

with their cohort who did not have any anesthesia. 125 Of 

those >75 years of age, 14% had a persistent cognitive 

deficit. Deeper anesthesia has also been suggested to 

affect mortality in the elderly. 126 Patients 60 years and 

older who were subjected to deeper BIS values (


Finally, as pointed out in the beta-blocker therapy 

section, it is not enough to write for postoperative betablockers, 

but one must titrate to a heart rate effect. Prolonged 

increased heart rate (>95 bpm for >12 hours) is 

associated with increased myocardial infarctions and 

cardiac death. 134 

Increased heart rate, especially in the elderly, is associated 

with the development of atrial fibrillation. Both 

myocardial infarction and atrial fibrillation result in 

prolonged ICU stays. 

Conclusions 

Figure 28-5. Mortality tends to be higher if the bispectral index 

(BIS) levels are 28%, whereas it 

occurred in 77% of those whose hematocrit was


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241–242.

29 

Abdominal Procedures 


Operations on the abdominal viscera are common among 

the elderly. Few of the operations are truly elective, with 

the majority being either scheduled reasonably shortly 

after a diagnostic procedure or truly emergent procedures 

necessitated by the presence of an intraabdominal 

catastrophe. The impact of abdominal surgery on the 

elderly is significant and the potential for complications 

is high. This chapter synthesizes current thought to 

provide an approach to the elderly abdominal surgical 

patient including both emergent and elective surgeries. It 

should be stated that there are relatively few prospective 

trials regarding the perioperative management of abdominal 

surgery in the elderly. There is a good amount of 

retrospectively acquired information that provides direction 

to both current care paradigms as well as ongoing 

research. Major vascular surgery may involve an abdominal 

approach; however, vascular surgery, particularly in 

the elderly, is becoming the province of endovascular 

surgery and is not covered in this chapter. 

General Principles 

Presentation 

The presentation of abdominal symptoms in the elderly 

is frequently diminished, muted, or less specific than in 

younger patients. Significant numbers of patients over the 

age of 65 do not manifest classic symptoms of cholecystitis. 

1 Sixty percent did not have typical upper quadrant 

pain and 5% had no pain at all. Less than half were 

febrile. Approximately 30% of patients with peptic ulcer 

disease do not complain of pain and frequently the first 

sign of ulcer disease is perforation. 2 However, pain out of 

proportion to all physical findings remains the most 

common and prominent symptom of acute mesenteric 

ischemia, a frequently fatal disease in older patients. Lyon 

and Clark 3 have recently reviewed the general approach 

to the diagnosis of abdominal pain in the elderly. Anesthesiologists 

do not generally participate in the diagnosis 

of abdominal disease; however, they should be aware 

that, because symptoms are frequently nonspecific, by the 

time the patient arrives in the operating room (OR) they 

are potentially sicker than would be the case for younger 

patients. It is not uncommon for a patient to be relatively 

stable at the beginning of the operation only to become 

very unstable as the pathology evolves either in the OR 

or not long thereafter. 

Outcomes from Abdominal Surgery 

As explained in the first chapter, many patients approach 

the outcomes from their proposed surgery not in terms 

of whether their wound will heal, but on how it will affect 

their function and independence. The return to preoperative 

levels of independent activities of daily living can 

take up to 6 months after abdominal surgery. The landmark 

study by Lawrence et al. 4 indicated that function 

returns in a progressive manner with activities of daily 

living returning before the independent activities which, 

in turn, recover quicker than some measures of physical 

strength. It should be noted that the data of Lawrence et 

al. were collected before widespread use of laparoscopic 

surgical techniques. There have been a number of reports 

of a combined multimodal approach to primarily colonic 

surgery patients. 5 Included in the program is early ambulation 

and discharge home within 2 days of surgery. These 

programs have reported some success and seem to indicate 

a capacity to recover more rapidly from abdominal 

surgery than the cases reported by Lawrence. 

The risk of surgery in patients older than 90 years was 

evaluated by Denney and Denson. 6 Their report on 272 

patients undergoing 301 operations at the University of 

Southern California Medical Center found that the risk 

was more than justified in at least 70% of the nonagenarians. 

However, they did find that serious bowel obstruction 

was associated with a prohibitive perioperative 

mortality rate (63%), even though there is rarely an alter- 

416

29. Abdominal Procedures 417 

native to surgery. Reviewing their experience many years 

ago, Djokovic and Hedley-Whyte 7 reported that mortality 

in 500 patients older than 80 years was predicted by 

the American Society of Anesthesiologists (ASA) physical 

status classification. Fewer than 1% of ASA 2 patients 

died whereas 25% of ASA 4 patients died. At the time 

(1979), myocardial infarction was the leading cause of 

postoperative death. In a cohort of 2291 patients evaluated 

between 1982 and 1991, pulmonary complications 

were found to be more frequent and associated with 

longer hospital stays than cardiac complications. 8 The 

data support the idea that risk is not a function of chronologic 

age but rather of coexisting disease and physical 

status. The ASA physical score does not specifically 

include age as a factor, although many clinicians probably 

factor their assessment of the impact of age on their 

assessment of functional status. 

Both the relative risks and potential benefits associated 

with anesthesia and major abdominal surgery need to be 

individually assessed for each elderly patient. The elderly 

patient, as described in many of the preceding chapters, 

may have relatively intact function of all systems with 

limited alterations that limit the ability to respond to 

stress, or they may have function that is suboptimal and 

limiting even at rest. The heterogeneity between patients 

and even within a patient is important to keep in mind 

as any given patient is assessed. The goals of the planned 

therapy should be clear to the anesthesia and surgical 

teams. Maximization of longevity by means of a definitive 

or curative major surgical procedure may be a very 

appropriate option for elderly patients, but some patients 

may prefer a functional result short of cure. Patients may 

have alternative needs based on their perception of risk, 

concerns regarding independence and immediate responsibilities 

for spouses among myriad issues. Although 

the anesthesiologist must carefully assess all systems to 

understand the physiologic status of any given patient, 

the decision to pursue a surgical procedure has typically 

been made by the patient and their surgeon. Emergency 

surgery has repeatedly been shown to be an independent 

predictor of adverse postoperative outcomes in older surgical 

patients undergoing noncardiac surgery. 9,10 It has 

long been speculated that poorer preoperative physiology 

and preparation have a large influence on these 

results. The challenge is to prepare the patient expeditiously 

and minimize risks where intervention has the 

potential to make a difference. 

Consent and Health Proxy 

The care team should have a clear idea of how decisions 

will be made should the patient not be able to decide for 

themselves for some period of time after surgery. Regulations 

regarding health care proxies, next of kin and surrogate 

decision making, and the role of physicians in 

emergency decision making vary state by state. Particularly 

for emergent surgeries on patients with impaired 

capacity to consent, how the decision to proceed with 

surgery is made should be clear to the anesthesia team. 

Some jurisdictions allow physicians to make decisions 

regarding the need for emergency treatment, others 

do not and, surprisingly, some states do not have clear 

regulation for surrogate decision making in the absence 

of a formal health proxy. Assessment of the capacity to 

consent to a procedure is not clearly standardized. A 

reasonable expectation is that an individual consenting 

to surgery should be able to reiterate what procedure is 

being done and why. Asking a patient to reiterate the 

risks of a procedure may indicate understanding, but can 

also increase anxiety and is rarely required. Some jurisdictions 

require a separate anesthesia consent. It is best 

if there is a standard procedure to follow if there is 

a disagreement among the perioperative staff as to 

the patient’s capacity to consent. The appropriate local 

approach to “do not resuscitate” orders in place for 

patients brought to the OR should be clear to the anesthesia 

team. This area remains controversial. 11 If policy 

and time permit, the anesthesiologist should have a clear 

discussion with the patient and appropriate family 

members regarding the appropriate approach to different 

circumstances that occur in the immediate perioperative 

period. Even if the do not resuscitate order remains in 

effect, once intubated for general anesthesia it is not possible 

to remove an endotracheal tube in the absence of a 

reasonable assessment that the patient will breathe spontaneously. 

Patients and families who have indicated that 

they do want to “end up intubated on a ventilator” need 

to understand how endotracheal intubation will be 

managed in a given patient. 

Preoperative Care 

Preanesthetic Evaluation 

For emergency surgery, a comprehensive geriatric 

assessment may be difficult. Given the opportunity, the 

perioperative team should have a complete understanding 

of the physical, psychosocial, and environmental 

factors that can affect the health of the patient, with the 

goal of optimizing functional outcomes. 12 (See also 

Chapter 1.) Although the anesthesiologist might not 

be the obvious person to collect this information, there is 

no existential reason opposing it. Regardless of how 

the preparation of elderly surgical patients is organized, 

there must be mechanisms to capture this information, 

which will be important to properly design postoperative 

care plans. 

Frailty is a term used to characterize the weakest and 

most vulnerable subset of older adults. Frailty does not


Table 29-1. Changes in cardiovascular parameters in elderly patients at rest and with exercise. 

Cardiovascular parameter Aging effect at rest Aging effect with exercise 

Heart rate No change or slight decrease Less increase 

Systolic blood pressure Increased Greater increase 

Diastolic blood pressure No change Slightly greater increase 

Cardiac output No change Slightly less increase 

Ejection fraction No change Less increase 

Stroke volume No change or slight increase Greater increase 

fit neatly into a system-based assessment for preanesthetic 

evaluation and is almost never the chief complaint 

or presenting symptom for a surgical patient. The current 

clinical model for frailty focuses on muscle loss (sarcopenia) 

and diminished strength, 13 although many of those 

interested in the field tend to refer to the broader concept 

of homeostenosis or decreased ability to respond to a 

broad array of stressors. 14 The majority of work on this 

concept has been applied retrospectively to cohorts of 

medical patients and has demonstrated that frailty is 

related to increased vulnerability and poor health outcomes. 

13 Specific research into the utility of frailty as a 

means of assessment and risk stratification or as a target 

of perioperative intervention is just beginning. Although 

it seems reasonable to be concerned about the frail 

elderly, it is not currently possible to make any specific or 

general evidence-based recommendations. 

Age-related changes in cardiac function have been 

described as emanating primarily from alterations in the 

stiffness of the aorta, ultimately resulting in systolic 

hypertension, concentric left ventricular hypertrophy, 

and delayed relaxation of the left ventricle. Nonetheless, 

the resting cardiac function of an elderly patient, in the 

absence of specific cardiovascular disease, should be fairly 

normal (Table 29-1) and the ability to respond to stress 

(or exercise) is somewhat, but not seriously, limiting. If 

noticeable cardiac functional decline is present, this 

should not be attributed to old age, but rather requires a 

coherent pathophysiologic explanation. 

Diastolic function is currently conceived as an important 

aspect of aging and age-related cardiovascular 

disease. Phillip et al. 15 reported on 251 patients whose 

mean age was 72 ± 7 years to determine the prevalence 

of diastolic abnormalities. They found that only 36.5% of 

the patients had normal diastolic filling. Mild dysfunction 

was most common (48.3%), but 9.6% had mild to moderate 

abnormalities, 3.9% had pseudonormal filling properties, 

and 1.7% of patients were considered to have severe 

abnormalities suggestive of a restrictive pattern. Of 

the patients with ejection fractions >50%, 61.5% had 

diastolic filling abnormalities. 

Pulmonary function gradually declines in the elderly, 

even in those who exercise in order to maintain aerobic 

capacity. Aging is associated with structural changes such 

as decreases in lung static elastic recoil and chest wall 

compliance, and functional changes such as impaired 

respiratory muscle strength and alterations in responses 

to hypoxia. In the absence of pathology, the aging process 

does not limit a patient’s respiratory capacity, although 

the capacity to markedly increase respiration in response 

to a challenge is markedly limited. How these factors 

interact with the stress associated with surgery and anesthesia 

is of primary importance because postoperative 

respiratory complications account for approximately 

40% of the perioperative deaths in patients over 65 years 

of age. 16 In evaluating a patient, the practitioner should 

keep in mind that the breathing pattern of elderly patients 

typically involves smaller tidal volumes and an increased 

respiratory rate. This can be further exacerbated by 

intraabdominal pathology. Between the ages of 40 and 75, 

the PaO 2 (mm Hg) decreases, with significant relationship 

to changes in both Paco 2 and the body mass index (BMI). 

The following equation provides a reasonable estimate: 

PaO 2 (mm Hg) = 143.6 − (0.39 × age) − (0.56 × BMI) − 

(0.57 × Paco 2 ). After 75 years of age, arterial oxygen 

tension remains unaffected by BMI and PaO 2 , and 

remains relatively stable at around 83 mm Hg. 17 A deterioration 

of protective mechanisms of cough and swallowing 

in the elderly may lead to ineffective clearance of 

secretions and increased susceptibility to aspiration. Loss 

of protective upper-airway reflexes has been postulated 

to be related to an age-related peripheral deafferentation 

together with a decreased central nervous system reflex 

activity. 18 

Renal Assessment 

Multiple alterations in normal renal function and fluid 

and electrolyte balance are seen in the aging (Table 29-2). 

Assessment of fluid status is problematic in the older 

patient. Skin turgor is difficult to interpret because the 

loss of elasticity and thinning of the dermis makes skin 

appear dehydrated. The decrease in thirst sensation 

makes a lack of thirst not useful. Even urine output is 

suspect because of the possibility of inappropriately 

dilute urine being excreted. Estimating the patients glomerular 

filtration rate allows the practitioner to develop 

an expectation of how quickly administered fluid and 

medications may be excreted. Estimating equations 

provide some guidance but are often not accurate for


Table 29-2. Alteration in fluid balance in the elderly. 

Decrease in total body water 

Kidney 

Decrease in renal cortical 

mass 

Decline in renal blood flow 

Decrease in glomerular 

filtration rate 

Decrease in urinary 

concentrating ability 

Increase in antidiuretic 

hormone 

Increase in atrial natriuretic 

peptide 

Decrease in aldosterone 

Decrease in thirst mechanism 

Decrease in free water 

clearance 

Young body is 65% water, 80-yearold 

body 50% 

20% loss, primarily cortex by age 85 

10% decline/decade 

Down 10 mL/decade, 50% by age 80 

Less sensitivity to antidiuretic 

hormone 

Increase relative to osmolality, 

decreased in Alzheimer’s 

disease 

Fivefold over basal levels 

a given patient. Therefore, an actual measurement of 

glomerular filtration rate is preferable. 19 When medications 

that require careful control of plasma levels are 

used, drug levels should be measured. The combina - 

tion of senescence in fluid management and the current 

understanding of cardiovascular aging suggest that the 

therapeutic window for intravenous fluid is markedly 

narrowed. 

Patients presenting for emergent surgery, particularly 

those with bowel obstruction, present an important 

dilemma regarding preoperative fluid preparation. 

Patients who have been vomiting and or undergoing 

upper gastrointestinal decompression with a nasogastric 

tube may be significantly intravascularly dehydrated. 

Ideally, rehydration of these patients should begin immediately 

upon their admission to the hospital and continue 

through any diagnostic procedures that are undertaken. 

If the patient’s rehydration is not accomplished before 

surgery, the anesthesiologist is faced with the decision to 

delay operation in order to resuscitate the patient and 

hopefully ameliorate cardiovascular instability during 

induction and maintenance of anesthesia. Most studies of 

hemodynamic optimization have involved the use of a 

pulmonary artery catheter and have produced extremely 

controversial results. A meta-analysis and review in 1996 

concluded that achieving supranormal hemodynamic 

goals did not reduce mortality in critically ill patients. 20 

In subsequent years, the distinction between patients who 

had signs of organ failure at the time of resuscitation 

compared with those whose organ function was intact 

when therapy was instituted suggested that such therapy 

applied sufficiently early in the clinical course could be 

effective. In a recent review of nearly 2000 patients in 17 

randomized controlled trials designed to increase tissue 

perfusion in the perioperative period, Boyd 21 concluded 

that there was a significant reduction in mortality in the 

treatment group [odds ratios 0.45 (95% confidence interval 

0.33–0.60)]. A similar review from Kern and Shoemaker 

22 essentially agreed, indicating that patients who 

achieved an increase in oxygen delivery before the onset 

of organ dysfunction had decreased perioperative mortality. 

Essentially, all of the published trials of optimization 

of oxygen delivery for elderly patients undergoing 

either elective or emergent abdominal surgery have been 

conducted preoperatively in intensive care units, rather 

than in the OR. However, the ability to undertake preoperative 

optimization is frequently limited by facilities 

and staff. Therefore, it seems prudent to advise that 

patients who are assessed to have a high risk of organ 

failure (signs of severe dehydration and particularly those 

showing early signs of shock physiology) should undergo 

an attempt to improve oxygen delivery, initially using 

fluids but potentially including autonomic stimulation as 

well, before the induction of anesthesia. If feasible, this 

tune-up is probably best done over a number of hours in 

an intensive care environment. Preoperative optimization 

of elderly patients presenting for most elective surgeries 

is generally not necessary. Indeed, as discussed 

below, there is a strong argument to be made for the 

administration of significantly less intravenous fluid than 

is frequently prescribed. 

Bowel Preparation 

Many patients presenting for bowel surgery have undergone 

some type of preparation to clean out their bowel. 

These preparations have the potential for altering the 

fluid and electrolyte balance of the patient. Although not 

the general province of the anesthesiologist, a short overview 

of what is used and the associated side effects is 

useful. The literature for bowel preparation has been 

developed primarily by endoscopists and is the subject 

of a recent consensus statement and addendum prepared 

by a task force from the American Society of Colon 

and Rectal Surgeons, the American Society for Gastrointestinal 

Endoscopy, and the Society of American 

Gastrointestinal and Endoscopic Surgeons. 23 Tolerance 

and effectiveness of preparations for bowel surgery vary. 

Most preparations use either polyethylene glycol, an 

osmotically balanced electrolyte lavage solution or other 

osmotic laxatives such as sodium phosphate (NaP) or 

magnesium citrate. The polyethylene glycol prepara - 

tions are effective, but 4 L of fluid can be difficult to tolerate. 

NaP preparations may be safe in selected healthy 

elderly patients. Elderly patients were found to be at an 

increased risk for phosphate intoxication. Administration 

of NaP causes a significant increase in serum phosphate, 

even in patients with normal creatinine clearance. Hypokalemia 

is more prevalent in frail patients. 24 Other adverse 

effects on the elderly using oral preparations range from


confusion, dehydration with tongue dryness, and upperbody 

muscle weakness to electrolyte disturbances. 

There is considerably less agreement on the need 

for orthograde bowel preparation for colorectal surgery. 

Although this is clearly the standard of care in many 

facilities, a recent meta-analysis of 10 randomized 

trials comparing cleansing with no bowel preparation 

showed a significant increase in anastomotic dehiscences 

and a trend toward increased surgical infections 

and reoperation even though mortality was unchanged 

by orthograde bowel cleansing. 25 The anesthesiologist 

caring for colorectal surgery patients should inquire 

as to whether they underwent some type of bowel 

preparation. 

Interaction with Geriatricians 

Excellent results have been reported for programs specifically 

designed to address issues that are uniquely or 

primarily geriatric that could be easily integrated into 

perioperative care regimens. 26,27 The Hospital Elder Life 

Program (Table 29-3) is designed to prevent delirium. 

Although the results of this and other programs have 

been promising in early trials, the ability to implement 

such plans varies among institutions 28,29 and much remains 

to be learned about the general utility as well as applicability 

of these programs to the perioperative period. 30 

Much of the care offered by these geriatric-focused programs 

are not specifically reimbursable under current 

insurance programs, such that funding for these programs 

can be difficult to obtain. However, these are the types of 

programs you would want in place if your grandmother 

needed surgery. 

Table 29-3. Contents of the Hospital Elder Life Program. 

• Daily Visitor Program: cognitive orientation, communication, and 

social support 

• Therapeutic Activities Program: cognitive stimulation and 

socialization 

• Early Mobilization Program: daily exercise and walking assistance 

• Non-Pharmacologic Sleep Protocol: promotes relaxation and 

sufficient sleep 

• Hearing and Vision Protocol: hearing and vision adaptations and 

equipment 

• Oral Volume Repletion and Feeding Assistance Program: assistance 

and companionship during meals 

• Geriatric Interdisciplinary Care: nursing, medicine, rehabilitation 

therapies, pharmacy, nutrition and chaplaincy care, and support for 

patients and their families 

• Provider Education Program: geriatric education for professional 

staff 

• Links with Community Services: assist with the transition from 

hospital to home 

Data from Inouye et al., 26 and from McDowell JA, Mion LC, Lydon TJ, 

Inouye SK. A nonpharmacologic sleep protocol for hospitalized older 

patients. J Am Geriatr Soc 1998;46(6):700–705. 

Intraoperative Care 

Intravenous Access and Choice of Monitoring 

There are no studies that have specifically addressed intravenous 

access in the elderly. The following suggestions are 

based on the author’s personal experience. The skin of the 

elderly is thin with relatively diminished elasticity. A catheter 

size that will easily fit in the vein selected for cannulation 

should be chosen. A tight fit will easily disrupt the 

vein, causing a potentially large widespread hematoma. 

The skin surrounding the vein must be stretched and fixed 

with the nondominant hand to facilitate entrance of the 

intravenous catheter into the vein. This maneuver also 

straightens and fixes tortuous veins. The vein is usually not 

as “deep” as younger patients. Once in the vein, the catheter 

itself should be advanced without releasing the 

tension on the surrounding skin. This generally requires 

advancing the catheter with the index finger of the dominant 

hand. Cannulation of a vein, as well as general 

comfort for the elderly, can be facilitated by the institution 

of a forced-air warming system immediately upon entrance 

to the OR. The patient does not shiver and the veins dilate 

slightly in response to the warmth. At least two intravenous 

cannulas should be considered for major surgical 

cases. When the arms are not visually accessible to the 

anesthesiologists, great concern for vein rupture should 

always be considered when an infusion set ceases to flow 

easily. The arms should be visualized before any pressure 

is applied to the infusion system. 

Particularly fragile skin on the upper arm or an upper 

arm with excess skin relative to muscle mass may predispose 

to bruising from the blood pressure cuff. This can be 

prevented to a certain extent by a layer or two of cotton 

wadding (Webril and others) typically available from the 

OR nurses. Oscillometric blood pressure measurement 

can be difficult in the presence of substantial arrhythmias. 

A decision to place an intraarterial cannula for invasive 

blood pressure measurement and frequent blood sampling 

is based on the same considerations applied to 

younger patients. Age per se is not an indication for intraarterial 

blood pressure measurement; however, agerelated 

alterations and coexisting disease may easily 

persuade the experienced practitioner to institute such 

monitoring. Whether such monitoring is instituted before 

or after induction of anesthesia is based on experience 

and local practice, because no clear evidence exists to 

specifically recommend either practice. 

The evidence regarding measurement of central venous 

versus pulmonary artery pressure has not been specifically 

addressed regarding elderly patients. To the extent 

that central venous pressures or pulmonary artery pressures 

reflect intravascular volume, they can be useful. 

Multiple recent randomized studies of the pulmonary 

artery catheter have failed to demonstrate an advantage


over central venous pressure monitoring and have been 

associated with increased complication rates. 31,32 Transesophageal 

echocardiography has been proposed as a 

particularly effective tool for evaluating the geriatric 

heart. 15 Echocardiography is the only means currently 

available for detecting diastolic dysfunction, which is 

present in a significant number of the elderly. Echocardiography 

requires expensive equipment and extensive 

training, particularly to distinguish findings such as diastolic 

dysfunction. In the absence of direct outcome data, 

it is not possible to recommend routine echocardiographic 

monitoring of elderly abdominal surgery patients. Noninvasive 

monitoring of physiologic variables (primarily 

cardiac output), which has been successfully used in 

elderly trauma patients, should also be helpful in surgical 

cardiovascular management. 33 

Renna and Venturi 34 found that although age-related 

electroencephalogram differences exist in the normal 

population, the bispectral index (BIS, Aspect Systems) 

still correlates with the depth of sedation independently 

of age. Senile dementia may be associated with significantly 

lower BIS values. 

Urinary catheters provide important information 

during longer surgeries but their use may promote urinary 

incontinence and urinary tract infections in the elderly. 

Studies of elderly patients undergoing orthopedic surgery 

tend to favor avoidance of a catheter if the indication is 

weak, and removal of the catheter within 24 hours with 

the use of intermittent straight catheterization. These 

approaches tend to diminish urinary retention, but not 

infection rates. 35,36 A more intensive infection prevention 

program has recently demonstrated a decrease in the 

incidence of urinary tract infection from 10.4 to 3.9 

episodes per 100 patients. 37 

The physiology of thermal stability and the importance 

of maintaining normothermia in elderly patients are 

described in detail in Chapter 8. Every effort should be 

engaged to maintain normal temperatures in abdominal 

surgery patients. 

Patient positioning can be important. 38 At times, the 

patient’s ability to move extremities into certain positions 

should be explored with the patient awake in order 

to avoid damaging an extremity under anesthesia. Look 

for pressure spots, particularly around the sacrum and 

heels and provide padding. Patients with severe spine 

deformities can represent a challenge to pad appropriately; 

however, this should be done with the goal of not 

only preventing nerve damage, but also avoiding skin 

breakdown and undue stretch on contracted tendons 

and ligaments. 

Choosing an Epidural Catheter 

There is a longstanding debate regarding whether neuraxial 

techniques such as epidural analgesia reduces the 

frequency of postoperative complications. Pulmonary 

and central nervous system complications (delirium 

and postoperative cognitive dysfunction) have been the 

principal focus. Although there is no doubt that these 

techniques provide excellent analgesia and patient satisfaction, 

their benefit regarding various outcomes is much 

less clear. 39 Epidural anesthesia/analgesia is an integral 

part of the multiple modal approach to abdominal surgery 

developed by Kehlet and colleagues in Denmark. 40 

This approach to anesthesia for abdominal surgery is 

described below. Some meta-analyses have concluded 

that there is benefit to epidural analgesia; however, many 

of the studies used in these analyses are plagued with 

several problems. 

Jayr et al. 41 studied 153 patients undergoing abdominal 

cancer surgery randomized to receive either continuous 

epidural bupivacaine and morphine, or subcutaneous 

morphine infusion. This carefully designed study found 

no difference in pulmonary complications even in patients 

with preexisting pulmonary dysfunction. The authors did 

note that the epidural provided superior postoperative 

analgesia. Norris et al. 42 randomized 168 patients undergoing 

abdominal aortic aneurysm and found essentially 

the same result. 

Variations on Anesthetic Plans for the Elderly 

Most abdominal surgery is accomplished using general 

anesthesia. Lower abdominal procedures can be done 

using a primarily regional technique with the addition of 

sedation. Adjustments to regional technique for elderly 

patients are described in Chapter 19. Despite numerous 

attempts to show superiority of regional versus general 

anesthesia, substantive reviews of the subject 39,43,44 have 

failed to show a substantial difference in outcomes. Because 

many, if not most, procedures are currently undertaken 

using laparoscopic techniques, the need to create a pneumoperitoneum 

and to frequently adjust the position of the 

patient makes the use of general endotracheal anesthesia 

the preferred technique. Patients presenting for emergency 

surgery are typically administered general anesthesia, 

although there may be cases that can appropriately be 

accomplished with regional techniques. 

Laparoscopic surgery has been promoted as being 

less stressful, particularly for elderly patients. The actual 

advantage has yet to be clearly delimited; however, there 

is little reason to specifically select an open surgical 

technique if a laparoscopic technique is technically 

feasible. 45,46 

Elderly patients being prepared for general anesthesia 

require additional time to successfully achieve proper 

denitrogenation (preoxygenation). Patients with severe 

abdominal pain or distension can have limited res - 

piratory effort. Supplemental oxygen should be considered 

early in the treatment plan for such patients and


continued 4–5 days into the postoperative period. 47,48 It 

has been suggested that a full 3-minute period for preoxygenation 

be used in elderly patients to effectively prevent 

hypoxemia during the induction and intubation process. 49 

Elderly patients are prone to decreased muscular pharyngeal 

support and decreased upper airway reflexes thought 

to be secondary to age-related neural deafferentation. 50 

The general approach to patients with a propensity for 

aspiration is to use a rapid sequence induction of general 

anesthesia, which incorporates cricothyroid pressure to 

occlude the upper esophagus. Occlusion of the esophagus 

is purported to prevent passive regurgitation. There have 

been no studies that support this beneficial result from 

cricoid pressure although there are substantial numbers 

of reports indicating that it is ineffective and at times 

hampers intubation. 51,52 This procedure is so ingrained in 

United States anesthesia practice that it is hard to suggest 

that it not be used. Practitioners should at least be willing 

to release cricoid pressure should it appear to be impeding 

intubation. 

There is little to suggest a specific drug choice for 

either induction or maintenance of anesthesia based on 

aging physiology. Most comparisons of specific agents are 

based on recovery times. Regimens are usually found to 

be safe and effective without clinically significant advantages. 

53–55 It is clear that the doses of most common agents, 

with the primary exception of neuromuscular blocking 

agents, are decreased in aged patients (Table 29-4). Particular 

care should be taken with those patients whose 

hemodynamic stability is in question at the beginning of 

an anesthetic. 

A multimodal approach to perioperative care that 

seeks to reduce the stress response and organ dysfunction 

leading to earlier recovery has been extensively studied 

and promoted by Kehlet. 56 One of the principal endpoints 

of this approach, which is also referred to as fasttrack 

surgery, is to accelerate the recovery process and 

get the patient out of the hospital quickly. This approach 

to elective surgery has been used primarily in colon 

surgery. The approach begins with extensive preoperative 

counseling with the patient. The patients do not undergo 

bowel preparation (except enemas), receive no sedative 

premedication, and are not fasted but rather receive carbohydrate-loaded 

liquids until 2 hours before surgery. 

The anesthetic combines a thoracic epidural catheter plus 

short-acting inhalational anesthetic agents. Patients are 

mobilized and fed early on the first postoperative day 

(Table 29-5). Results from fast-track colonic surgery 

suggest that postoperative pulmonary, cardiovascular, 

and muscle function are improved and body composition 

preserved as well as providing the potential to achieve a 

normal oral intake of energy and protein. In a recent 

controlled study of 160 patients, hospital stay was reduced 

from 7.5 days to 3.4 days. 5 In this group, functional re - 

covery, as measured by activities of daily living, was not 

improved. Despite a higher risk for readmissions, overall 

costs and morbidity seem to be reduced. This approach 

has been shown clearly to be safe for elderly patients. For 

those who recover more rapidly, the program seems to be 

beneficial; however, one cannot expect all elderly patients 

to recover more rapidly. The utility of this approach has 

yet to be explored extensively in the United States. 

Because the program includes not only specific medical 

interventions (e.g., thoracic epidural analgesia) but also 

behavioral components that require a different approach 

by both the patient as well as doctors and nurses, it is 

necessary to reserve judgment as to whether this approach 

will effectively save resources in the United States system. 

Hopefully, this information will be available in the near 

future. 

These considerations should not discourage the use of 

these valuable techniques in the elderly, but the evidence 

does not support their use to minimize pulmonary complications. 

The use of a full range of adjunctive analgesia 

techniques, such as infiltration with local anesthetics, 

peripheral nerve blocks, nonsteroidal antiinflammatory 

agents, and others as part of a “multimodal” approach is 

appropriate. 

The one study that has evaluated atelectasis formation 

in the elderly included 45 patients between the ages of 

23 and 69. Although 87% of subjects developed some 

atelectasis, the degree of atelectasis was not associated 

with age. 57 Nonetheless, in the presence of limited reserve 

capacity, the impact of atelectasis can be severe and 

is best prevented. The application of positive endexpiratory 

pressure does not predictably reverse atelectasis 

or increase arterial oxygenation unless preceded by 

a prolonged vital capacity breath with high inflation pressures, 

referred to as a “recruitment maneuver.” 58–60 A 

peak opening inspiratory pressure of at least 40 cm H 2 O 

is needed to fully reverse anesthesia-induced collapse of 

healthy lungs. Blood pressure should be monitored during 

a recruitment maneuver because of its potential to induce 

hypotension. 

Fluid Management in the Elderly 

There is a continuing debate about the type and quantity 

of fluid that should be administered during elective major 

surgery, particularly in the elderly. There is a substantial 

collection of publications that describe the adverse effects 

of excess fluid. Persistent positive fluid balance in older 

surgical patients is associated with prolonged mechanical 

ventilation. 61 Itobi et al. 62 found that elderly patients were 

more likely to develop edema and that the presence of 

edema was associated with a delay in tolerating solid 

food, opening bowels, a prolonged hospital stay [median 

17 (range 8–59) versus 9 (range 4–27) days], and more 

postoperative complications (13 of 20 versus 4 of 18 

patients; p = 0.011). Fluid replacement for abdominal


Table 29-4. Age-related pharmacologic changes of anesthetics and drugs in anesthesia practice. 

Anesthetic/drug Pharmacodynamics Pharmacokinetics Anesthetic management 

Inhalational 

anesthetics 

Sensitivity of the brain↑ 

(cerebral metabolic 

rate)↓ 

Ventilation/perfusion mismatch 

with slow increase of 

alveolar/inspired ratio of 

inhaled gases; maximal 

cardiac output;↓ volume of 

distribution↑ 

Hypnotics 

Thiopental No changes Central volume of distribution;↓ 

intercompartmental 

clearance↑ 

Propofol No changes Central volume of distribution;↓ 


clearance↑ 

Minimal alveolar concentration down 30%; slower 

induction and emergence; delayed but more 

profound onset of anesthesia 

Induction dose reduced by 15% (20-year-old patient: 

2.5–5.0 mg/kg IV; 80-year-old patient: 2.1 mg/kg 

IV). Maintenance dose: same requirements 60 

minutes after starting a continuation infusion. 

Emergence: slightly faster 

Induction dose reduced by 20% (slower induction 

requires lower doses) (20-year-old: 2.0–3.0 mg/kg 

IV; 80-year-old: 1.7 mg/kg IV). Maintenance dose: 

same requirements 120 minutes after starting a 

continuous infusion. Emergence: slightly faster (?) 

Midazolam Sensitivity of the brain↑ Clearance↓ Sedation/induction dose reduced by 50% (20-yearold: 

0.07–0.15 mg/kg IV; 80-year-old: 0.02–0.03 mg/ 

kg IV). Maintenance dose reduced by 25%. 

Recovery: delayed (hours) 

Etomidate No changes Central clearance;↓ volume of 

distribution↑ 

Induction dose reduced by 20% (20-year-old: 0.3 mg/ 

kg IV; 80-year-old: 0.2 mg/kg IV). Emergence: 

slightly faster (?) 

Ketamine ? ? Use with caution: hallucinations, seizures, mental 

disturbance, release of catecholamines; avoid in 

combination with levodopa (tachycardia, arterial 

hypertension) 

Opioids 

Fentanyl, alfentanil, 

sufentanil 

Sensitivity of the brain↑ No changes Induction dose reduced by 50%. Maintenance doses 

reduced by 30%–50%. Emergence: may be delayed 

Remifentanil Sensitivity of the brain↑ Central volume of distribution;↓ 


clearance↓ 

Induction dose reduced by 50%. Maintenance dose 

reduced by 70%. Emergence: may be delayed 

Muscle relaxants 

Mivacurium, 

succinylcholine 

Pancuronium, 

doxacuronium, 

pipecuronium, 

vecuronium, 

rocuronium 

No changes 

No changes 

Plasma cholinesterase;↓ muscle 

blood flow;↓ cardiac output;↓ 


clearance↓ 

Muscle blood↓ flow; cardiac 

output;↓ intercompartmental 

clearance;↓ clearance; 

(volume of distribution)↓ 

Atracurium No changes No changes No changes 

Reversal agents 

Neostigmine, 

pyridostigmine 

Onset time.↑ Maintenance dose requirements.↓ 

Duration of action↑ clinically indistinguishable 

from mivacurium. Differences: no changes in initial 

dose, prolonged block with metoclopramide 

Onset time.↑ Maintenance dose requirements.↓ 

Duration of action.↑ Recommended dose reduced 

by 20% 

No changes Clearance↓ Duration of action;↑↑ because muscle relaxants have 

a markedly prolonged duration of action, larger 

doses of reversal agents are needed in elderly 

patients 

Edrophonium No changes No changes No change 

Local anesthetics Sensitivity of the nervous 

tissue (?)↑ 

Hepatic microsomal metabolism 

of amide local anesthetics 

[lidocaine (lignocaine), 

bupivacaine];↓ plasma 

protein binding;↓ cephalad 

spread↑ 

Epidural (and spinal) dose requirements.↓ Duration 

of spinal and epidural anesthesia seems clinically 

independent of age, toxicity↑ (percent free 

drug)↑ 

↑, increase; ↓, decrease. 

Source: Modified with permission from Silverstein JH, Zaugg M. Geriatrics. In: Hemmings HC, Hopkins PM, eds. Foundations of Anesthesia: 

Basic and Clinical Science. 2nd ed. London: Elsevier Mosby; 2006.


Table 29-5. Care program in patients undergoing colonic resection 

with fast-track care. 

Preoperatively 

Information of surgical procedure, expected length of stay, and 

daily milestones for recovery 

Day of surgery 

Mobilized 2 hours 

Drink 1 L 

2 protein-enriched drinks 

Solid food 

Postoperative day 1 

Mobilized >8 hours 

Drink >2 L 

4 protein-enriched drinks 

Solid food 

Remove bladder catheter 

Plan discharge 

Postoperative day 2 

Normal activity 

Remove epidural catheter 

Discharge after lunch 

Source: Reprinted with permission from Jakobsen et al. 5 

surgery is based on the idea that there is a large amount 

of insensible or unmeasurable loss through evaporation 

and that a substantial amount of fluid is transudated into 

an area often referred to as the third space. In a recent 

review, Brandstrup 63 concluded that: 

• current standard fluid therapy is not at all 

evidence-based; 

• the evaporative loss from the abdominal cavity is highly 

overestimated; 

• the nonanatomic third space loss is based on flawed 

methodology and probably does not exist; 

• the fluid volume accumulated in traumatized tissue is 

very small; and 

• volume preloading of neuroaxial blockade is not effective 

and may cause postoperative fluid overload. 

Many of the trials reviewed by Brandstrup refer 

to “restricted” intravenous fluid therapy. In a randomized 

controlled study, Brandstrup et al. 64 used two different 

fluid regimens in patients undergoing colon surgery. 

The principal difference was the absence of a preload 

and lack of replacement for third space loss (Table 29-6). 

The administered intravenous fluid volume on the day 

of operation was significantly less in the restricted group 

[median 2740 mL (range 1100–8050) versus 5388 mL 

(range 2700–11083); p < 0.0005]. The patients receiving 

less fluid had significantly lower complication rates 

[28 (33%) versus 44 (51%) in the standard group (p = 

0.013)]. In another study, patients receiving on average 

5.9 L for colon surgery had a longer duration of ileus, 

more complications after surgery, and longer hospital 

stays than patients who received about 3.6 L. 65 However, 

in the largest study (n = 253), there was no difference 

in wound healing or hospital stay between patients randomized 

who received approximately 5.7 versus 3.1 L of 

crystalloid perioperatively. 66 As compared with major 

abdominal surgery, patients undergoing ambulatory 

surgery seem to benefit from administration of >1–1.5 L 

of fluid, compared with patients who receive 500 mL, additional HAES 6% 

Blood-component therapy started at approximate 

loss >1500 mL dependent on hematocrit 

Blood-component therapy started at approximate 

loss >1500 mL dependent on hematocrit 

*Hydroxyethyl starch 6% in normal saline. 

Reprinted with permission from Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lindorff-Larsen K, Rasmussen MS, Lanng 

C, Wallin L, Iversen LH, Gramkow CS, Okholm M, Blemmer T, Svendsen PE, Rottensten HH, Thage B, Riis J, Jeppesen IS, Teilum D, Christensen 

AM, Graungaard B, Pott F. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: 

a randomized assessor-blinded multicenter trial. Ann Surg. 2003 November; 238(5): 641–648.


identical manner to younger patients with the dosage 

titrated to an effect rather than a specific dose. 

Emergence and Extubation of the Elderly 

The elderly may be particularly prone to the effects of 

inadequate reversal of muscle relaxation. 68 In elderly 

patients who are overly narcotized, hypoventilation may 

lead to respiratory acidosis that potentiates the effects of 

residual neuromuscular blockade in the recovery room, 

further increasing the rate of postoperative pulmonary 

complications. 69 There is little published guidance on 

making decisions regarding extubation of elderly patients 

after anesthesia. From clinical experience, emergence can 

sometimes be prolonged without obvious reason, and 

return of active upper airway reflexes can also be delayed. 

There are no data to suggest that standard extubation 

criteria should not be required in the elderly. 

Postoperative Care 

The postoperative care of the elderly abdominal surgery 

patient has been best described by Kehlet and colleagues. 

(See discussion of multimodal approach above and Table 

29-5.) Apart from those efforts and geriatric programs that 

incorporate specific geriatric assessments, postoperative 

care for the elderly follows the same plans used for younger 

patients. Pain management can be more demanding in the 

elderly because the therapeutic ratio of the narcotic analgesics 

seems narrowed. Nonetheless, pain control is no less 

important for the elderly. (See Chapter 21.) 

Postoperative Complications 

Elderly patients have higher levels of complications than 

younger patients. 70 The impact of illness on the elderly is 

greater, such that the number of complications associated 

with disease is considerably higher in elderly patients with 

underlying disease. There are also a number of complications 

that are both more common in the elderly and associated 

with poor outcomes. These are highlighted here so that 

they are clearly in mind as the practitioner develops a perioperative 

care plan for a patient. Delirium and postoperative 

cognitive dysfunction are mentioned but are explored 

in greater detail elsewhere in this book. (See Chapter 9.) 

Postoperative ileus is treated somewhat more in depth. 

Finally, a predilection for pneumonia represents the most 

common complication of elderly surgical patients. 

Postoperative Ileus 

Ileus is the temporary absence of propulsive bowel function. 

Two forms of postoperative ileus can be distinguished: 

(1) an uncomplicated form that occurs after 

most abdominal surgery, particularly open abdominal 

surgery, and spontaneously resolves in 2 or 3 days, and 

(2) a paralytic form that lasts more than 3 days and generally 

prolongs hospital stay. 

The list of potential etiologies for postoperative ileus 

is large. Contributory mechanisms may include alterations 

of autonomic nervous function, gastrointestinal hormones, 

inflammatory mediators, and the direct action of 

anesthetic agents. Although many factors have been 

implicated, no single mechanism or final common pathway 

has been identified. 71 

Traditional treatment for ileus has been based on nasogastric 

decompression and bowel rest. Unfortunately, 

these regimens have not been found to hasten the return 

of bowel function and seem to increase hospital stays and 

prolong recovery. 71 Interesting novel approaches to preventing 

or decreasing the duration of ileus include the use 

of nonsteroidal antiinflammatory agents, such as ketorolac. 

72 The most promising therapeutic approach on the 

horizon is alvimopan, a selective, competitive mu-opioid 

receptor antagonist with limited oral bioavailability that 

may be used to reduce length of postoperative ileus. A 

recent meta-analysis of five trials including 2195 patients 

concluded that alvimopan was effective in restoring gastrointestinal 

function and reduced time to discharge after 

major abdominal surgery, with acceptable side effects. 73 

The use of a midthoracic (T6–T8) epidural catheter with 

local anesthetic for pain relief is effective; however, lower 

thoracic and lumbar catheters are not effective in altering 

the duration of ileus. 71,74 In recent years, patients are being 

fed earlier, and the traditional marker of waiting for first 

flatus is no longer considered a reasonable endpoint. 71 

Early small feedings are most appropriate. 

Pneumonia 

Concomitant pneumonia and influenza constitute the 

leading infectious cause of death in the elderly and the 

fourth most common cause of death overall. The presence 

of concomitant illness and delays in diagnosis contribute 

to significant mortality from this disease in the elderly. 

Senescence of the immune system seems less important 

in predisposition to pneumonia than the presence of concomitant 

illness. Mortality is generally higher in older 

than in younger patients, although outcome in pneumonia 

depends primarily on the presence of underlying 

illness and the causative organism. 75 Delay in diagnosis is 

frequently secondary to the atypical presentations of 

pneumonia in the elderly. The typical symptoms of sputum 

production, fever, chills, and rigors may be absent in the 

elderly; confusion may be the only presenting symptom. 

Tachypnea is frequent; however, this vital sign is poorly 

recorded in many facilities and is not sufficiently sensitive 

in making a diagnosis. Leukocytosis is common, but by 

no means specific. Chest roentgenograms frequently


show incomplete consolidation, and the findings are difficult 

to distinguish from other diseases of the elderly, 

such as congestive heart failure, atelectasis, pulmonary 

embolism, and malignancy. Therefore, clinical diagnosis 

requires a high index of suspicion despite atypical clinical 

manifestations. In a recent review for the American 

College of Physicians, Lawrence et al. 76 concluded that 

few interventions have been shown to clearly or even 

possibly reduce postoperative pneumonia, noting that the 

quality of the evidence regarding the prevention of pneumonia 

in general was only fair. Thus, prevention of pneumonia 

in elderly patients remains a key, yet elusive goal 

in improving perioperative care. 

Conclusion 

The elderly patient presenting for abdominal surgery represents 

a challenge to the anesthesia practitioner. Patients 

may be sicker than one would presume from their clinical 

presentation. Given the likelihood of diminished reserve 

capacity in one or more organ systems, aggressive management 

to prevent organ dysfunction is in order. Fluid 

resuscitation remains a controversial issue, and determining 

appropriate endpoints for fluid administration is clinically 

challenging. In the absence of major preexisting 

disease, elderly patients should tolerate surgery and anesthesia 

and recover well if complications can be avoided. 

Certain postoperative complications, particularly central 

nervous system, gastrointestinal, and pulmonary complications, 

are most common in the elderly, are particularly 

troublesome, and their likelihood is possibly reducible by 

techniques that can be used in the perioperative period. 

Clinicians can hope to see additional data published in 

the next few years that should help to further fine-tune 

the perioperative approach to the elderly abdominal 

surgical patient. 

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54. Iannuzzi E, Iannuzzi M, Cirillo V, Viola G, Parisi R, Chiefari 

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55. Heavner JE, Kaye AD, Lin BK, King T. Recovery of elderly 

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56. Kehlet H. Fast-track colonic surgery: status and perspectives. 

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57. Gunnarsson L, Tokics L, Brismar B, Hedenstierna G. Influence 

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58. Hedenstierna G, Rothen HU. Atelectasis formation during 

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60. Lachmann B. Open up the lung and keep the lung open. 

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61. Epstein CD, Peerless JR. Weaning readiness and fluid 

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65. Nisanevich V, Felsenstein I, Almogy G, Weissman C, Einav 

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66. Kabon B, Akca O, Taguchi A, et al. Supplemental intravenous 

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69. Debaene B, Plaud B, Dilly MP, Donati F. Residual paralysis 

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70. Tiret L, Desmonts JM, Hatton F, Vourch G. Complications 

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71. Mattei P, Rombeau JL. Review of the pathophysiology and 

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Index 

A 

AA. See Anesthesiologist Assistant 

AARP. See American Association of 

Retired Persons 

ABA. See American Board of 


Abdominal operation, 11 

Abdominal procedures, 416–426 

general principles, 416–417 

consent/health proxy, 417 

outcomes from abdominal surgery, 

416–417 

presentation, 416 

intraoperative care, 420–425 

anesthetic plans for, 421–422 

emergence/extubation of elderly, 

425 

epidural catheter choice, 421 

fluid management in elderly, 

422–425 

intravenous access/monitoring 

choice, 420–421 

postoperative care, 425–426 

pneumonia, 425–426 

postoperative complications, 425 

postoperative ileus, 425 

preoperative care, 417–420 

bowel preparation, 419–420 

geriatrician’s interaction, 420 

preanesthetic evaluation, 417–418 

Abdominal surgery, 416–417 

Aberrant oncogene activation, 149 

Abnormalities, 297 

Academic Health Centers (AHCs), 

20 

Accreditation Council for Graduate 

Medical Education (ACGME), 

58 

ACE. See Angiotensin-converting 

enzyme 

Acetabulum, 356 

Acetaminophen, 209–210 

Acetylcholine receptors, 266 

ACGME. See Accreditation Council for 

Graduate Medical Education 

Acid 

barbituric, 234 

gammaaminobutryic, 32 

Acid-base abnormalities, 297 

Acidosis, 154 

Active arteriovenous shunt 

vasoconstriction, 109 

Active precapillary vasodilation, 109 

Activities of Daily Living (ADL), 8, 59, 

70, 189 

Acute onset, 124 

Acute pain, 309 

Acute pain management, 79 

Acute tubular necrosis, 298 

Adenosine 5′-diphosphate (ADP), 205 

Adequate cardiac preload, 145 

ADH. See Antidiuretic hormone 

ADL. See Activities of Daily Living 

ADP. See Adenosine 5′-diphosphate 

Adrenergic receptor activity, 142–143 

Advanced glycation end-products 

(AGEs), 31, 137 

Advance directives, 44–46 

Adverse drug reactions, 103 

Adverse events, 80 

Afferent input, 107–108 

AGE. See Advanced glycation 

end-products 

Age and gender adjusted population, 71 

Age-rationing, 50 

Age related physiologic changes, 399 

Age-related pulmonary changes, 342 

AGEs. See Advanced glycation end 

products 

Aging, 4, 68–69, 151, 211, 294–295 

cardiovascular system, 250–252 

pulmonary changes associated, 327 

central nervous system changes of, 

123–124 

cholinergic theory of, 31 

clinical studies of, 35 

concepts of, 29–32 

altered receptor systems, 31–32 

oxidative stress, 32 

programmed aging, 29–30 

stochastic aging, 30–31 

definitions, 4 

effects on gas exchange, 153–154 

exercise capacity, 154 

general physiology of, 5 

human/geriatrics, 34–35 

neurobiologic changes, 124 

pathologic, 124 

physiologic, 5 

programmed, 29–30 

proposed molecular mechanisms of, 

33 

reconciling the theories, 32–34 

respiratory system, 149–160 

social views of, 38–39 

stochastic, 30–31 

theories, 29–36 

Aging lung physiology, 149–155 

age-related changes in mechanics of 

breathing, 149–153 

aging effects on gas exchange, 

153–154 

aging/exercise capacity, 154 

airway closure concept (closing 

volume), 152–153 

breathing regulation, 154–155 

chest wall/respiratory muscles, 

149–150 

lung parenchyma, 150 

spinometry/static/dynamic tests/ 

underlying physiology, 150–152 

upper airway dysfunction, 155 

cellular mechanisms, 149 

perioperative pulmonary 

complications in elderly, 

155–160 

429

430 Index 

Aging lung physiology (cont.) 

general health status, 156–157 

strategies used to minimize 

pulmonary risk in elderly 

patients, 157–160 

Agonists 

alpha, 401 

alpha 2 -adrenergic, 200 

beta, 203 

AGS. See American Geriatric Society 

AHCs. See Academic Health Centers 

AHI. See Apnea/hypopneic index 

Airway 

closure concept, 152–153 

diameter, 153 

management, 383 

Albumin, 99 

Alfentanil, 111, 219 

Allodynia, 309 

Allogeneic transfusion requirement, 

114–115 

Alpha 1 acid glycoprotein, 99 

Alpha 1 -adrenergic antagonists, 200 

Alpha 2 -adrenergic agonists, 200 

Alpha agonists, 401 

Altered level of consciousness, 124 

Altered receptor systems, 31–32 

Alveolar concentration, 248 

Alveolar gas exchange, 153 

Alveolar surface area, 154 

Alveolar ventilation, 249 

Alveolar walls, 247 

Alzheimer’s disease, 124, 310 

AMA. See American Medical 

Association 

Ambient temperature, 116–117 

American Association of Retired 

Persons (AARP), 17 

American Board of Anesthesiology 

(ABA), 58 

American College of Cardiology, 70 

American Geriatric Society (AGS), 61 

American Medical Association (AMA), 

15 

American Society for Gastrointestinal 

Endoscopy (ASGE), 344 

American Society of Anesthesiologists 

(ASA), 5, 21, 58, 165, 259, 323 

Amiodarone, 201 

Ammonia toxicity, 370–371 

Analgesia, 146 

cumulative patient-controlled, 223 

cyo, 385 

deep sedation, 341 

neuraxial, 386 

patient-controlled, 209–224, 279 

patient-controlled epidural, 311 

postoperative, 360 

postsurgical, 311–312 

regional, 315–316 

Analgesic efficacy, 210 

Analgesics, 315 

Anesthesia. See also General anesthesia 

bronchoscopy, 381 

cataracts, 348–350 

CSA, 284 

epidural, 278–279, 404–405 

general, 404–405 

geriatric, 3–14, 60 

lumbar epidural, 286 

Medicare, 21 

monitored care, 328–330 

neuraxial, 360–362 

regional, 302–303, 327–328 

SAGA, 14 

SAMBA, 322 

spinal, 279, 303 

thermoregulatory defenses during, 

110–111 

thoracic epidural, 286 

Anesthesia care team, 23–24 

attending physician relationship, 24 

medical direction/supervision of 

concurrent procedures, 23–24 

Anesthesia considerations for geriatric 

outpatients, 322–334 

general principles of intraoperative 

management, 326–330 

general anesthesia, 326–327 

monitored anesthesia care, 328–330 

pain management pitfalls, 330 

postdischarge concerns, 333–334 

postoperative management, 330–333 

hypothermia, 331 

postoperative atrial fibrillation, 331 

postoperative cognitive impairment, 

332–333 

postoperative pain, 331 

postoperative respiratory 

insufficiency, 330–331 

preoperative evaluation, 323–326 

preoperative testing, 323–324 

sleep apnea, 324–326 

Anesthesia implications, 144–147 

Anesthesia payment methodology, 22 

Anesthesiologist Assistant (AA), 21 

Anesthesiology, 5, 102–103 

adverse drug reactions, 103 

practice impact, 102–103 

residency, 58 

Anesthetic factors, 129–130 

Anesthetic implications of chronic 

medications, 197–206 

cardiovascular drugs, 200–203 

alpha 2 -adrenergic agonists, 200 

amiodarone, 201 

angiotensin-converting enzyme 

inhibitors, 203 

beta receptor antagonists, 201–202 

calcium channel blockers, 202–203 

digoxin, 201 

disopyramide, 201 

gastrointestinal drugs, 204 

cimetidine, 204 

metoclopramide, 204 

H 1 receptor antagonists, 206 

diphenhydramine, 206 

hydroxyzine/chlor-trimeton, 206 

neuropsychiatric/pain-related 


antidementia drugs, 199–200 

Antiparkinson medications, 199 

benzodiazepines, 197–198 

carbamazepine, 198 

gabapentin, 198 

MAOIs, 198–199 

selective serotonin reuptake 


tricyclic antidepressants, 199 

nonsteroidal antiinflammatory drugs, 

205–206 

indomethacin, 205–206 

ketorolac, 205 

opioids, 206 

pentazocine, 206 

propoxyphene, 206 

oral anticoagulants, 204–206 

ticlopidine, 205 

warfarin, 204–205 

pulmonary drugs, 203–204 

beta agonists, 203 

theophylline, 203–204 

Anesthetic-induced thermoregulatory 

impairment in elderly, 111 

Anesthetic management, 182 

Anesthetics, 68 

inhalation, 246–262 

intravenous hypnotic, 229–242 

spinal, 361 

Anesthetic techniques, 158, 182 

Angina, 342 

Angiogenesis, 168 

Angiotensin-converting enzyme (ACE), 

203 

ANS. See Autonomic nervous system 

Antagonists 

alpha 1 -adrenergic, 200 

beta receptor, 201–202 

dopamine, 204 

H 1 receptor, 206 

Anticholinesterases, 272–274 

adverse effects of anticholinesterases 

in geriatric patients, 274 

edrophonium, 272–273 

neostigmine, 273–274 

pyridostigmine, 274 

Anticoagulant use, 130 

Anticoagulation, 360–362 

Antidementia drugs, 199–200 

Antidiuretic hormone (ADH), 293

Index 431 


Anxiety, 309 

Anxiolysis, 341 

Aortic valve, 391–393 

Apnea/hypopneic index (AHI), 324 

Appropriate preoperative fasting, 77 

Arrhythmias, 114, 144, 382 

Arterial sevoflurane concentration, 248 

Arthroplasty 

hip, 114, 358 

knee, 355–357 

total hip, 356–357, 359 

total knee, 358 

Arthrotomy, 357 

Artificial oxygenation, 154 

ASA. See American Society of 

Anesthesiologists 

Aspiration, 346 

Atracurium, 271 

Atropine, 274 

Attending physician relationship, 24 

Autonomic influences, 393 

Autonomic nervous system (ANS), 137 

B 

Baby boomer expectations, 17 

Back pain, 316 

Barbituric acid, 234 

Baroceptor response, 67 

Baroflex, 142 

Baroreflex, 143 

Basal metabolic rate (BMR), 97–98 

Benign prostatic hyperplasia (BPH), 

368 

Benzodiazepines, 197–198 

Beta-adrenergic blockade, 185 

Beta agonists, 203 

Beta-blockers, 186, 400 

Beta-blocker therapy, 401 

Beta receptor antagonists, 201–202 

Bilevel positive airway pressure 

(BiPAP), 159 

BiPAP. See Bilevel positive airway 

pressure 

BIS. See Bispectral index 

Bispectral index (BIS), 327, 405 

Bladder perforation, 371 

Bladder tumors, 372 

Blindness, 347 

Blood-brain barrier, 114 

Blood-component therapy, 303 

Blood flow 

cerebral, 123 

femoral, 250 

hypercapnic venous, 363 

in lower extremities, 170 

renal, 100, 102 

Blood loss, 81, 144, 384 

Blood management, 360 

Blood pressure, 203, 253 

mean arterial, 125, 283 

oscillometric, measurement, 420 

BMR. See Basal metabolic rate 

BNP. See B-type natriuretic peptide 

Body compositions, 254 

body fat changes, 98 

muscle mass, 98 

protein loss, 98 

transport proteins, 98–99 

Body fat, 253 

Body heat changes, 113 

Body heat content, 113 

Bowel preparation, 419–420 

BPH. See Benign prostatic hyperplasia 

Bradykinnin, 109 

Breathing mechanics, 149–153 

Breathing regulation, 154–155 

Broad-spectrum opioids, 313–314 

Broflex dysfunction, 283 

Bronchoconstriction, 155 

Bronchopleural fistula, 385 

B-type natriuretic peptide (BNP), 402 

Bupivacaine, 279, 284 

Busiprone, 110 

C 

CABG. See Coronary artery bypass 

graft 

Calcium channel blockers (CCBs), 198, 

202–203 

Calcium uptake, 139 

Caloric restriction, 34 

CAM. See Confusion Assessment 

Method 

Capillary blood volume, 154 

Carbamazepine, 198 

Cardiac baroflex, 142 

Cardiac muscle hypertrophy, 139 

Cardiac output, 251 

Cardiac procedures, 390 

CAD, 390–391 

preventing adverse outcomes, 394–396 

cardiopulmonary bypass 


cardiovascular, 394 

renal, 394–395 

valvular heart disease, 391–393 

aortic valve, 391–393 

mitral valve, 393 

Cardiac risk indexes, 183 

Cardiopulmonary bypass (CPB), 390 

Cardiopulmonary bypass management, 

395–396 

Cardiopulmonary complications, 384 

Cardiopulmonary events, 346 

Cardiorespiratory physiology in elderly, 

379 

Cardiovascular changes, 66–67 

Cardiovascular complications, 183–186, 

382–383 

predictors of, 184 

reducing, 184–186 

Cardiovascular disease (CVD), 137 

Cardiovascular drugs, 200–203 

alpha 2 -adrenergic agonists, 200 

amiodarone, 201 

angiotensin-converting enzyme 


beta receptor antagonists, 201–202 

calcium channel blockers, 202–203 

digoxin, 201 

disopyramide, 201 

Cardiovascular effects, 231, 240–241 

Cardiovascular parameters, 418 

Cardiovascular system, 250–252, 286 

Carotid endarterectomy, 409–410 

Carotid stents, 410 

Cataracts, 12, 347 

anesthesia, 348–350 

advantages of topical anesthesia, 

350 

central nervous system 

complications, 350 

monitoring/sedation, 349 

regional orbital anesthesia, 349 

retrobulbar/peribulbar anesthesia, 

349 

side effects/intraorbital anesthesia, 

349–350 

anesthesiologists role in, 350–351 

anticoagulation/cataract surgery, 348 

indications for, 348 

preoperative evaluation for, 348 

Catecholamine concentrations, 68 

Catheter, 81, 421 

CBF. See Cerebral blood flow 

CCBs. See Calcium channel blockers 

Cellular mechanisms, 149 

Cement, 359 

Central control, 108–109 

Central nervous system (CNS), 123, 199 

changes of aging, normal aging, 

123–124 

effects, 229–230 

Central nervous system dysfunction, 

123–132 

Central neural blockade 

epidural anesthesia, 278–279 

spinal anesthesia, 279 

Central pontine myelinolysis, 372 

Central post-stroke pain (CPSP), 316 

Central venous pressure (CVP), 300 

Cerebral blood flow (CBF), 123 

Cerebrospinal fluid (CSF), 235, 278 

Certified Registered Nurse Anesthetists 

(CRNAs), 21 

Chest wall/respiratory muscles, 149–150 

Chest X-rays (CXRs), 190 

CHF. See Congestive heart failure 

Chlor-trimeton, 206

432 Index 

Chronic medications, 197–206 

Chronic obstructive pulmonary disease 

(COPD), 156, 379 

Chronic pain, 81–83, 309 

Chronic wounds, 165–174 

in elderly resulting in significant 

morbidity/mortality, 165–168 

diabetic foot ulcers, 165–166 

ischemic wounds, 167–168 

pressure ulcers, 166 

venous ulcers, 166–167 

experimental evidence of physiologic 

impairments in elderly, 168 

angiogenesis in wound healing, 168 

decreased immune response, 168 

Cimetidine, 204 

Circulating-water mattresses, 116 

Circulatory function, alterations in, 

137–147 

adrenergic receptor activity/aging, 

142–143 

anesthesia implications, 144–147 

arrhythmias, 144 

heart/vessel structural alterations, 

137–141 

ischemic preconditioning, 144 

reflex control mechanism and aging, 

141 

renin/vasopressin activity, 143–144 

vagal activity/aging, 143 

Cisatracurium, 272 

CNS. See Central nervous system 

Coagulopathy, 114–115, 371 

Codeine-like drugs, 313–314 

Coexisting disease importance, 

181–182 

Cognitive dysfunction, 127, 182–183 

Cognitive function measurement, 7–8 

Cognitive impairment, 73 

Cold tolerance, 110 

Colloid, 284, 301 

Combined spinal-epidural (CSE), 284 

Communication skills, 58–59 

Comorbid conditions, 342 

Comorbid disease, 146 

Comorbidities, 172–173 

Comparative ethical theory, 39 

Complete sensory block (CSB), 280 

Complex regional pain syndromes, 82 

Compliance issues, 24–26 

documentation requirements, 25–26 

Medicare fraud/abuse, 25 

physicians at teaching hospitals Office 

of Inspector General, 25 

reassignment of Medicare benefits, 

24–25 

Component and Mental Component 

Scales, 7–8 

Comprehensive geriatric assessment 

(CGA), 12, 191–192 

Confusion Assessment Method (CAM), 

124 

Congestive heart failure (CHF), 185 

Conscious sedation, 341 

Context-sensitive half-time, 214 

Continuous positive airway pressure 

(CPAP), 159, 325 

Continuous spinal anesthesia (CSA), 

284 

COPD. See Chronic obstructive 

pulmonary disease 

Core competencies, 59 

Core temperatures, 117 

Coronary artery bypass graft (CABG), 

184, 390 

Coronary artery disease (CAD), 

390–391 

CPAP. See Continuous positive airway 

pressure 

CPB. See Cardiopulmonary bypass 

CPSP. See Central post-stroke pain 

Creatine 

clearance, 101 

serum, 216 

CRNAs. See Certified Registered Nurse 

Anesthetists 

Crystalloid, 302 

CSA. See Continuous spinal anesthesia 

CSB. See Complete sensory block 

CSE. See Combined spinal-epidural 

CSF. See Cerebrospinal fluid 

Cumulative patient-controlled analgesia, 

223 

Cutaneous warming, 116–117 

CVD. See Cardiovascular disease 

CVP. See Central venous pressure 

CXRs. See Chest X-rays 

Cyoanalgesia, 385 

Cystectomy, 374 

D 

Daily living, 8, 189 

activities of, 8, 59, 70, 189 

IADL, 7 

instrumental activities of, 190 

Decision making capacity, 41–42 

Decreased cardiac output, 146 

Decreased immune response, 168 

Deep sedation analgesia, 341 

Deep vein thrombosis (DVT), 167, 169 

Dehydration, 299 

Delayed wound treatment, 165 

Delirium, 81, 124–126 

anesthetic factors, 129–130 

delirium/adverse outcomes, 125–126 

after noncardiac surgery, 182–183 

patient factors, 127–128 

physiologic factors, 129 

surgery/illness factors, 128–129 

treatment/prevention, 126 

Dementia, 310 

Depression, 309 

DES. See Desflurane 

Desflurane (DES), 111, 252 

Deterioration, 38 

Determining program’s needs, 61–62 

Diabetes mellitus, 188 

Diabetic foot ulcers, 165–166 

Diagnostic related groups (DRG), 12 

Diastolic dysfunction, 139, 141, 250 

Diastolic filling pressures, 259 

Digoxin, 201 

Diphenhydramine, 206 

Disablement process, 7 

Diseases 

Alzheimer’s, 124, 310 

chronic obstructive pulmonary, 156, 

379 

comorbid, 146 

CVD, 137 

obstructive lung, 186 

venous reflux, 167 

Disopyramide, 201 

Disorganization, 38 

Disorganized thinking, 124 

Documentation requirements, 25–26 

Dopamine antagonist, 204 

Dose-response relationships, 267 

Double-lumen tube, 383 

Doxacurium, 269 

Doxazosin (Cadura), 200 

DRG. See Diagnostic related groups 

Drosophila, 30 

Drosophila melanogaster, 33 

Drug reactions, 69, 103 

Drugs 

antidementia, 199–200 

cardiovascular, 200–203 

codeine-like, 313–314 

gastroesophageal, 204 

gastrointestinal, 204 

lipid-soluble, 253 

water-soluble, 69 

Duvaldestin, 267 

DVT. See Deep vein thrombosis 

E 

ECCE. See Extracapsular cataract 

extraction 

ECG. See Electrocardiogram 

Echo-Doppler evaluation, 139 

ECT. See Electro-convulsive therapy 

Edrophonium, 272–273 

EEG. See Electroencephalogram 

Effect-site concentration, 213, 221 

Effect-site decrement, 221 

Efferent responses, 109 

Elderly population growth, 4 

Electrocardiogram (ECG), 72, 190 

Electro-convulsive therapy (ECT), 230

Index 433 

Electroencephalogram (EEG), 213 

Electrolyte disturbances, 81 

Electrolyte homeostasis, 293–294 

Embolic phenomena, 363 

Emergency resuscitation, 344 

Emphysema, 150, 247 

Endarterectomy, 409–410 

End-of-life care, 48–50, 314–315 

sedation of terminally ill, 314–315 

fetanyl, 314 

ketamine, 314 

midazolam, 314 

Endoscopic retrograde 

cholangiopancreatographies 

(ERCPs), 346 

Endovascular abdominal aneurysm 

repair (EVAR), 406 

Endovascular abdominal aortic 

aneurysm repair, 408–409 

Epidemiologic studies, 73 

Epidural absorption, 281 

Epidural anesthesia, 278–279, 404–405 

Epidural catheter choice, 421 

Epinephrine, 279 

EPP. See Equal pressure point 

Equal pressure point (EPP), 153 

ERCPs. See Endoscopic retrograde 

cholangiopancreatographies 

Erythropoietin, 360 

Esophageal Doppler monitors, 299 

ESWL. See Extracorporeal shock wave 

lithotripsy 

Ethanol, 31 

Ethical management of elderly patients, 

38–53 

advance directives, 44–46 

consent elements/decision/ 

autonomous authorization, 44 

do-not-attempt resuscitation orders 

in operating room, 46–47 

end-of-life care, 48–50 

ethical principles, 39–40 

informed consent in elderly, 40–44 

informational elements, 43–44 

personal autonomy respect, 40 

shared decision making, 41 

threshold elements, 41–43 

resource allocation/elderly, 50–51 

social views of aging, 38–39 

treatment futility, 47–48 

treatment redirection/palliative care, 

48 

Ethical principles, 39–40 

Etomidate, 240–241 

adverse effects/contraindications, 

241 

dosing in elderly, 241 

indications, 241 

metabolism/disposition, 241 

pharmacodynamics, 240 

cardiovascular effects, 240–241 

central nervous system effects, 240 

endocrine effects, 241 

respiratory effects, 241 

pharmacology, 240 

Euglycemia, 411 

EVAR. See Endovascular abdominal 

aneurysm repair 

Exercise capacity, 154, 189–190 

Extracapsular cataract extraction 

(ECCE), 347 

Extracorporeal shock wave lithotripsy 

(ESWL), 372, 373 

F 

Facilitated conduction, 112 

Faculty development, 61 

Fat embolism, 363–364 

Fels longitudinal study, 254 

Femoral blood flow, 250 

Femoral fracture, 357 

Fetanyl, 215, 217–219, 314 

Fetanyl delivery systems, 218–219 

Fistula, 385 

Flexible fiberoptic bronchoscopy, 381 

Flow limitation, 152 

Fluid balance, 419 

Fluid homeostasis, 293–294 

Fluid management, 293–306 

aging/renal function, 294–295 

clinical implications, 298–302 

in elderly, 422–425 

fluid/electrolyte homeostasis, 293–294 

perioperative transfusion in elderly, 

303–305 

potassium management, 296–297 

sodium handling, 295–296 

urinary concentration, 297–298 

acid-base abnormalities, 297 

calcium/phosphate/magnesium, 297 

nutrition, 297–298 

Fluid therapy, 359 

Fluid warming, 117 

Flumazenil, 329 

Fluoride toxicity, 255 

Folstein Mini-Mental State Exam 

(MMSE), 8 

Forced vital capacity (FVC), 379 

Frailty, 5–6 

FRC. See Functional residual capacity 

Free plasma concentrations, 282 

French paradox, 31 

Functional adaptations, 140 

Functional assessments, 70–72 

Functional recovery, 11 

Functional reserve, 67, 98 

Functional reserve concepts, 97 

Functional residual capacity (FRC), 150, 

230 

Functional status assessment, 189–190 

Functioning, 9 

Futility, 47 

FVC. See Forced vital capacity 

G 

GABA. See Gammaaminobutryic acid 

Gabapentin, 198, 315 

Gammaaminobutryic acid (GABA), 32 

GAO. See Government Accounting 

Office 

Gas exchange 

aging and, 153–154 

alveolar, 153 

Gastroesophageal reflux, 330 

Gastrointestinal drugs, 204 

cimetidine, 204 

metoclopramide, 204 

Gastrointestinal system, 286 

GDS. See Geriatric Depression Scale 

General anesthesia, 286–288, 404–405 

geriatric outpatient recommendations, 

327 

intraoperative lung expansion during, 

158 

intraoperative management, 74–76, 

326–327 

for vascular patient, 404–405 

General health status, 156–157 

Geriatric anesthesia, 3–14, 60 

aging definitions of, 4–5 

approach to patient, 8–12 

demography, 3–4 

frailty, 5–6 

general physiology of aging, 5 

growth of, 60 

organizations/resources in, 13–14 

surgical outcomes/functional deadline, 

6–7 

Geriatric anesthesiology, 58–64 

geriatric curriculum developing, 

61–63 

assessment of resources, 61 

determining program’s needs, 61–62 

faculty development, 61 

producing geriatric curriculum, 

62–63 

geriatrics as part of core 

competencies, 58–59 

geriatrics in educational program, 58 

geriatric training importance, 59–60 

growth of geriatric anesthesia, 60 

priority research questions of, 84 

research priorities, 66–84 

physiologic changes relevant to 

perioperative care, 66–84 

postoperative management, 78–83 

preoperative assessment of the 

elderly, 69–78 

teaching geriatrics, 60 

Geriatric Depression Scale (GDS), 10

434 Index 

Geriatric medical care, 3 

Geriatric patient care 

demographics/economics of, 15–27 

Medicare demographics/financing 

issues, 15–20 

Medicare policy issues for geriatric 

anesthesiologist, 20–27 

focus areas for, 12 

Geriatrics 

in educational program, 58 

as part of core competencies, 58–59 

communication, 58–59 

practice-based learning/ 

improvement, 59 

system-based practice, 59 

Gerontology, 29 

GFR. See Glomerular filtration rate 

Globe perforation, 350 

Glomerular filtration rate (GFR), 5, 101, 

255, 295 

Glucose control, 77 

Glycine, 370–371 

Glycopyrrolate, 274 

GME. See Graduate Medical Education 

Government Accounting Office (GAO), 

22 

Graduate Medical Education (GME), 

19 

Growth factor therapies, 172 

H 

H 1 receptor antagonists, 206 

Halothane, 260, 261 

Hearing loss, 12 

Heart block, 144 

Heart disease, 391–393 

Heart failure, 185 

Heart rate, 253 

Heart/vessel structural alterations, 

137–141 

Heat distribution in body, 112–114 

Hemodynamic lability, 283 

Hemodynamic response, 145 

Hemodynamic stability, 294 

Hemoglobin, 304 

Heparin blocks, 297 

Hepatic function, in elderly, 99–100 

laboratory tests, 100 

morphologic changes, 99–100 

physiologic changes, 100 

Hepatic mass, 281 

Hepatic metabolism, 198 

Herbal medications, 191 

Hernia repair, 73 

Herpes zoster, 316–317 

HI. See Hospital Insurance 

Hip arthroplasty, 114, 358 

Hip fracture, 355–364 

extracapsular fractures, 357 

intracapsular fractures, 357 

Hip fracture repair, 358 

Hip fracture surgery, 356 

Homeostenosis, 5 

Hospital elder life program, 420 

Hospital Insurance (HI), 16 

HSE. See Human Skin Equivalent 

Human Skin Equivalent (HSE), 172 

Hydromorphone, 217–218 

Hydrostatic pressure, 293 

Hydroxyzine, 206 

Hyperalgesia, 309 

Hyperammonemia, 371 

Hyperbaric bupivacaine, 284 

Hypercampic ventilatory responses, 230 

Hypercapnia, 154 

Hypercapnic venous blood flow, 363 

Hypercarbia fever, 81 

Hypernatremia, 296 

Hyperpathia, 309 

Hypertension, 103, 141, 146, 185, 202, 

342, 403 

Hyperthyroidism, 202 

Hypertrophy 

cardiac muscle, 139 

progressive ventricular, 67 

Hyperventilation, 129 

Hypokalemia, 203 

Hypomagnesaemia, 201 

Hyponatremia, 296 

Hypotension, 131, 144, 282–284, 385, 

403 

Hypothermia, 109, 114, 115, 284–285, 

331, 371 

Hypovolemia, 145 

Hypovolemic control, 145 

Hypoxemia, 152, 346–347 

Hypoxia, 67 

I 

IADL. See Instrumental activities of 

daily living 

ICCE. See Intracapsular cataract 

extraction 

ICU. See Intensive care unit 

Impaired drug metabolism, 116 

Impaired thermoregulation, 109–110 

Inattention, 124 

Increased ventricular stiffness, 140 

Individual cardiac baroflex, 142 

Indomethacin, 205–206 

Infections 

elimination, 170 

surgical wound, 115 

urinary tract, 72 

Informational elements, 43–44 

Informed consent, 41 

Infraaortic vascular procedures, 406 

Infusion duration, 214 

Inhalation agents, 249 

Inhalation anesthetics, 246–262 

pharmacodynamics of inhalation 

agents in elderly, 257–261 

aging/minimal alveolar 

concentration, 257–259 

cardiovascular actions of 

inhalational agents in elderly, 

259–261 

pharmacokinetics of, in elderly, 

246–256 

aging cardiovascular system 

influence, 250–252 

aging in pulmonary system 


body composition changes 


hepatic changes influence, 256 

renal changes influence, 255–256 

Inhibitors 

angiotensin-converting enzyme, 203 

monoamine oxidase, 198–199 

SSRIs, 199, 315 

In-hospital mortality rates, 409 

Institutional review boards (IRBs), 52 

Instrumental activities of daily living 

(IADL), 7 

Intensive care unit (ICU), 77, 287, 300, 

408 

Intercostal muscles, 149 

Interdependence, 40 

Intermediate-acting agents, 270–272 

International Study of Postoperative 

Cognitive Dysfunction 

(ISPOCD), 126 

Intertochanteric femoral fracture, 357 

Intracapsular cataract extraction 

(ICCE), 347 

Intraoperative blood loss, 144 

Intraoperative care, 420–425 

anesthetic plans for, 421–422 

emergence/extubation of elderly, 425 

epidural catheter choice, 421 

fluid management in elderly, 422–425 

intravenous access/monitoring choice, 

420–421 

Intraoperative glucose control, 77 

Intraoperative lung expansion, 158 

Intraoperative management, 74–78, 

326–330 

general anesthesia, 326–327 

monitored anesthesia care, 328–330 

pain management pitfalls, 330 

physiologic management, 76–78 

regional/general anesthesia, 74–76 

Intraoperative monitoring, 358 

Intraoperative myocardial ischemia, 

303–304 

Intraoperative research agenda items, 

77–78 

Intravenous access, 420–421 

Intravenous hypnotic agents, 230 

Intravenous hypnotic anesthetics, 

229–242 

etomidate, 240–241

Index 435 

midazolam, 237–240 

propofol, 229–234 

pharmacodynamics, 229–231 


thiopental, 234–237 

Intravenous isoprotenerol infusions, 

142 

IRBs. See Institutional review boards 

Irrigation solutions, 369 

Ischemia, 114 

Ischemic preconditioning, 144 

Ischemic wounds, 167–168 

Isoflurane, 129, 254, 255 

concentration, 258 

nitrous oxide, 129 

Isoprotenerol infusions, 142 

ISPOCD1. See International Study of 

Postoperative Cognitive 

Dysfunction 

J 

Joint arthroplasty, 356 

Joint replacement, 355–364 

K 

Ketamine, 314 

Ketorolac, 205, 385 

Kidney stone, 309 

Knee arthroplasty, 355–357 

Knee joint arthrotomy, 357 

L 

Laboratory and radiologic evaluation, 

169–170 

Laboratory tests, 100 

Laparoscopic surgery, 373–374 

Lateral decubitus position, 359 

Left ventricular ejection fraction 

(LVEF), 201 

Lidocaine, 381 

Lipid-soluble drugs, 253 

Liver function, 256 

Living will, 45 

LMWH. See Low-molecular weight 

heparin 

Local effects, 362 

Local wound care, 170–171 

Long-acting agents, 269–270 

Lower esophageal sphincter, 204 

Low-molecular weight heparin 

(LMWH), 361, 406 

Low sodium plasma levels, 101 

Lumbar compression fractures, 316 

Lumbar epidural anesthesia, 286 

Lumbar radiculopathy, 317 

Lung 

cancer, 378 

expansion, 158 

parenchyma, 150 

physiology, 149–155 

volumes, 151 

LVEF. See Left ventricular ejection 

fraction 

M 

MAC. See Minimal alveolar 

concentration 

Major autonomic thermoregulatory 

defenses, 109 

Major autonomic warm defenses, 108 

Mammals, 30 

MAOIs. See Monoamine Oxidase 

Inhibitors 

MAP. See Mean arterial pressure 

Maximal minute ventilation, 67 

Maximal neuromuscular blocking, 268 

Maximum intensity, 107 

Mean aortic pressure, 138 

Mean arterial blood pressure, 125, 283 

Mean arterial pressure (MAP), 229 

Mean cutaneous heat, 117 

Mean plasma concentrations, 282 

Mean skin temperature, 108 

Mechanical ventilation, 159–160 

Mediastinoscopy, 381–382 

Medical direction, 26 

Medical fitness, 137 

Medical Insurance Trust Fund, 17 

Medicare anesthesia, 21 

Medicare demographics/financing issues, 

15–20 

Medicare/Academic Health Center, 

19–20 

GME payments, 19–20 

pay for performance initiatives, 20 

Medicare coverage gaps, 17–19 

impact on near-poor, 18–19 

prescription drug benefit, 18 

Medicare program enacted, 15 

organization/funding, 15–16 

twenty-first century realities/Medicare 

future, 16–17 

Medicare Fee Schedule (MFS), 21 

Medicare fraud/abuse, 25 

Medicare payment methodologies for 

anesthesia services 

Medicare fee schedule for anesthesia 

services, 21–22 

Medicare’s resource based relative 

value system, 21 

proposed changes to the anesthesia 

payment methodology, 22 

sustainable growth rate formula, 

22–23 

Medicare policy issues, for geriatric 

anesthesiologist, 20–27 

anesthesia care team, 23–24 

anesthesiologist participation in 

Medicare Program, 20–21 

compliance issues, 24–26 

Medicare payment methodologies for 

anesthesia services, 21–23 

Medication management, 310–311 

Medigap, 18 

Meperidine, 217, 312, 345 

Messenger RNA (mRNA), 31 

Metabolic acidosis, 154 

Metabolic equivalents (METs), 184, 399 

Metabolic functions/electrolytes, 97–107 

aims, 97 

albumin, 99 

alpha 1 acid glycoprotein, 99 

anesthesiology practice, 102–103 

basal metabolic rate, 97–98 

functional reserve concepts, 97 

hepatic function in elderly, 99–100 

renal function, 100–103 

creatine clearence, 101 

glomerular filtration rate, 101 

renal blood flow, 100, 102 

renal mass, 100–101 

tubular function, 101–102 

Metabolism 

etomidate, 241 

hepatic, 198 

impaired drug, 116 

midazolam, 238–239 

mild hypothermia, 116 

propofol, 231 

thiopental, 236 

Methadone, 222 

Metoclopramide, 204 

Metocurine, 267 

METs. See Metabolic equivalents 

MFS. See Medicare Fee Schedule 

Midazolam, 110, 197, 237–240, 314, 

344 

adverse effects and contraindications, 

240 

effects of age on pharmacology, 240 


induction/maintenance anesthesia, 

239 

intravenous sedation, 239 

metabolism/disposition, 238–239 


cardiovascular effects, 238 

central nervous system effects, 

237–238 

respiratory effects, 238 


Mild emphysema, 247 

Mild hypothermia, 114 

complications of, 114–116 

coagulopathy/allogeneic transfusion 

requirement, 114–115 

impaired drug metabolism, 116 

myocardial ischemia/arrhythmias, 

114 

postoperative shivering, 115–116 

surgical wound infections/during 

hospitalization, 115 

Mild intraoperative hypothermia, 115

436 Index 

Minimal alveolar concentration (MAC), 

69, 230, 251, 257, 259, 405 

Minimal sedation, 341 

Mitral valve, 393 

MMSE. See Folstein Mini-Mental State 

Exam 

Moderate sedation, 341 

Modern cataract surgery, 347–350 

Modified postanesthesia discharge 

scoring system, 333 

Monitored anesthesia care, 328–330 

Monoamine Oxidase Inhibitors 

(MAOIs), 198–199 

Morbidity, 5 

Morphine, 215–217 

Morphine-6-glucuronide, 216 

Morphologic changes, 99–100 

Mortality, 5, 391 

mRNA. See Messenger RNA 

mtDNA, 34 

Multifocal atrial tachycardia, 384 

Muscles 

chest wall/respiratory, 149–150 

intercostal, 149 

MVO 2 . See Myocardial oxygen 

consumption 

Myocardial contractility, 260 

Myocardial ischemia, 114, 303–304 

Myocardial oxygen consumption 

(MVO 2 ), 235 

Mythological foundation, 51 

N 

Narrow-spectrum opioids, 313 

Nasogastric tubes, 78 

National Surgical Quality Improvement 

Program (NSQIP), 6 

National Veterans Administration 

Surgical Risk Study, 189 

NDMA. See N-methyl-d-aspartate 

nDNA. See nuclear DNA 

Necrosis, 298 

Neostigmine, 273–274 

Neo-Synephrine, 403 

Nephrectomy, 374–375 

Neuraxial analgesia, 386 

Neuraxial anesthesia, 360–362 

Neuraxial blocks, 158 

Neurologic changes, 68 

Neurologic consultation, 131 

Neuromuscular block, 268–269 

Neuromuscular blocker (NMBD), 233 

Neuropathic pain, 310, 313–315, 315 

Neuropsychiatric/pain-related 


antidementia drugs, 199–200 


benzodiazepines, 197–198 

carbamazepine, 198 

gabapentin, 198 

MAOIs, 198–199 

SSRIs, 199 

tricyclic antidepressants, 199 

Neurotransmitters, 258 

New consumerism, 43 

New York Heart Association (NYHA), 

391 

Nitric oxide, 114 

Nitrous oxide, 129, 249 

NMBD. See Neuromuscular blocker 

N-methyl-d-aspartate (NDMA), 

200 

Nociception, 309–310 

Non-cardiac surgical procedures, 

399 

Nondepolarizing neuromuscular 

blocking agents, 268, 270 

Noninvasive positive pressure 

ventilation, 159 

Nonischemic electrocardiogram, 399 

Nonshivering thermogenesis, 107 

Nonsteroidal antiinflammatory 

analgesics, 315 

Nonsteroidal antiinflammatory drugs 

(NSAIDs), 203, 205–206, 311 

indomethacin, 205–206 

ketorolac, 205 

Nonviable tissue, 171–172 

Normal thermoregulation, 107–109 

North American Symptomatic Carotid 

Endarectomy Trial, 76 

NSAIDs. See Nonsteroidal 

antiinflammatory drugs 

NSQIP. See National Surgical Quality 

Improvement Program 

nuclear DNA (nDNA), 30 

Nutrition, 297–298 

Nutritional assessment, 188–189 

NYHA. See New York Heart 

Association 

O 

Observed mortality, 391 

Obstructive lung disease, 186 

Obstructive sleep apnea (OSA), 155, 

324, 326 

Obstructive sleep apnea syndrome 

(OSAS), 187 

Office of the Inspector General (OIG), 

24–26, 25 

Offloading pressure, 172 

OIG. See Office of the Inspector 

General 

Oncogene activation, 149 

Operating room, 165 

Operations, 11 

Operative debridements, 165–174 

for chronic wounds, 165–174 

in elderly resulting in significant 

morbidity/mortality, 165–168 

experimental evidence of 

physiologic impairments in 

elderly, 168 

intraoperative risk and precautions 

for development of pressure 

ulcers, 173–174 

multidisciplinary approach for 

treating ulcers, 168–173 

operating room, 165 

Operative mortality rate, 392 

Opioids, 159, 206. See also Specific 

opioids 

addiction, 312 

drug effect, 211–215 

offset, 214–216 

onset, 211–214 

frequently used, 212 

narrow-spectrum, 313 

pharmacology, 209–224 

age/, 211 

aging/pain perception, 211 

general observations, 209–210 

opioid receptor, 210–211 

patient controlled anesthesia, 

222–224 

specific, 215–222 

relative potency of, 214 

Opioid therapy, 312–313 

anticonvulsants for neuropathic pain, 

315 

case examples, 317–319 

excessive treatment in a missed 

diagnosis, 317–319 

lumbar radiculopathy, 317 

common pain syndromes, 316–317 

back pain, 316 

herpes zoster, 316–317 

postherpetic neuralgia, 317 

spinal stenosis, 316 

thoracic/lumbar compression 

fractures, 316 

end-of-life care, 314–315 

for neuropathic pain/broad-spectrum 

opioids, 313–314 

nonsteroidal antiinflammatory 

analgesics, 315 

opioid addiction, 312 

opioid conversions, 312–313 

pain/insulin resistance, 315–316 

titration of, 312 

tricyclic antidepressants/specific 

serotonin reuptake inhibitors, 

315 

Optic nerve damage, 350 

Oral anticoagulants, 204–206 

ticlopidine, 205 

warfarin, 204–205 

Orbital hemorrhage, 350 

Organ function, 97 

Organ system functional reserve, 30

Index 437 

OSA. See Obstructive sleep apnea 

OSAS. See Obstructive sleep apnea 

syndrome 

Oscillometric blood pressure 

measurement, 420 

Osmolality, 369 

Oxidative phosphorylation, 34 

Oxidative stress, 32 

Oxygenation, 129, 154, 381 

Oxygen supply-demand ratio, 286 

Oxyhemoglobin desaturation, 154 

P 

PACU. See Postanesthesia care unit 

PADSS. See Postanesthesia discharge 

scoring system 

PAHC. See Power of Attorney for 

Healthcare 

Pain, 79–80 

acute, 309 

back, 316 

central post-stroke, 316 

chronic, 81–83, 309 

neuropathic, 310, 313–315 

opioid therapy and, 315–316 

perception, 211 


somatic, 310 

Southern California Cancer Pain 

Initiative, 313 

subjectivity of, 308 

visceral, 310 

Pain-controlled analgesia (PCA), 311 

Pain management, 173, 308–319 

acute, 79 

assessment, 309 

CYP 2D6 enzyme/efficacy of codeine/ 

codeine-like drugs, 313–314 

depression/anxiety/pain, 309 

fear of reporting, 309 

medication management, 310–311 

neuraxial blocks, 158 

nociception and, 309–310 

opioid therapy, 312–313 

pathophysiology of, 310–311 

neuropathic pain, 310 

somatic pain, 310 

visceral pain, 310 

pitfalls, 330 


postsurgical analgesia, 311–312 

postthoracotomy, 385–386 

three pain scenarios, 309 

Pairwise associations, 6 

Palliative care, 48 

Pancuronium, 270 

Parenchyma, 248 

Parkinsonism, 310 

Passive insulation, 116–117 

Pathologic aging, 124 

Pathophysiologic mechanisms, 151 

Patient-controlled analgesia (PCA), 

209–224, 279 

Patient-controlled epidural analgesia 

(PCEA), 311 

Patient-controlled sedation (PCS), 

345 

Patient Self-Determination Act (PSDA), 

44 

PCA. See Pain-controlled analgesia 

PCEA. See Patient-controlled epidural 

analgesia 

PCS. See Patient-controlled sedation 

Pedersen study, 183 

PEEP. See Positive end-expiratory 

pressure 

Pentazocine, 206 

Perioperative activity level, 138 

Perioperative beta-blockers, 400 

Perioperative care, physiologic changes 

relevant to, 66–69 

aging/pharmacokinetics/ 

pharmodynamics, 68–69 

cardiovascular changes, 66–67 

implications, 69 

neurologic changes, 68 

pulmonary changes, 67–68 

renal changes, 68 

Perioperative clonidine, 76 

Perioperative fluid therapy, 299 

Perioperative functional assessment, 

71 

Perioperative geriatrics, 3 

Perioperative goals, 399 

Perioperative heat balance, 112–114 

Perioperative hemodynamic stability, 

67 

Perioperative optimization, 73–74 

Perioperative pulmonary complications 

in elderly, 155–160 

Perioperative stroke, 130–132 

Perioperative testing, 72–73 

Perioperative thermoregulation, 

107–118 

impaired thermoregulation in elderly, 

109–110 

mild hypothermia, 114 

normal thermoregulation, 107–109 

afferent input, 107–108 

central control, 108–109 

efferent responses, 109 

thermal management, 116–117 

thermoregulation during anesthesia, 

110–111 

anesthetic-induced 

thermoregulatory impairment in 

elderly, 111 

thermoregulatory defenses during 


Peripheral nerve blockade, 280–282 


pharmacokinetics, 280–282 

system absorption, 280–281 

systemic disposition, 281–282 

Personal autonomy respect, 40 

Persuasion, 44 

Pharyngeal trespass, 78 

Phenylephrine, 408 

PHN. See Postherpetic neuralgia 

Phosphorylation, 34 

Physical therapy, 173 

Physiologic aging, 5 

Physiologic changes, 100, 399 

Physiologic factors, 129 

Physiologic management, 76–78 

Plasma concentration, 213 

Plasma metocurine, 267 

Plasma proteins, 256 

Pneumonia, 425–426 

Pneumothorax, 382 

POCD. See Postoperative cognitive 

dysfunction 

POGOe. See Portal of Geriatrics Online 

Education 

Polycythemia, 324 

Polymethylmethacrylate bone cement, 

359 

PONV. See Postoperative nausea and 

vomiting 

Portal of Geriatrics Online Education 

(POGOe), 63 

Positioning, 358–359 

Positive end-expiratory pressure 

(PEEP), 158, 381 

Postanesthesia care unit (PACU), 249, 

326 

Postanesthesia delirium, 254 

Postanesthesia discharge scoring system 

(PADSS), 333 

Postganglionic nerves, 109 

Postherpetic neuralgia (PHN), 82, 317 

Postoperative analgesia, 360 

Postoperative atrial fibrillation, 331 

Postoperative care, 425–426 

pneumonia, 425–426 

postoperative complications, 384–385, 

425 

postoperative ileus, 425 

Postoperative central nervous system 

dysfunction, 123–132 

central nervous system changes of 

aging, 123–124 

normal aging, 123–124 

pathologic aging, 124 

delirium, 124–126 

perioperative stroke, 130–132 

postoperative cognitive dysfunction, 

126–130 

Postoperative cognitive dysfunction 

(POCD), 123, 126–130, 182

438 Index 

Postoperative cognitive function, 285 

Postoperative cognitive impairment, 

332–333 

Postoperative complications, 384–385, 

425 

Postoperative ileus, 288, 425 

Postoperative management, 78–83, 302, 

330–333 

acute pain management, 79 

chronic pain, 81–83 

delirium/cognitive decline, 80–81 


pain/adverse outcomes, 79–80 

postoperative atrial fibrillation, 331 

postoperative cognitive impairment, 

332–333 

postoperative pain, 331 

postoperative respiratory insufficiency, 

78, 330–331 

Postoperative nausea and vomiting 

(PONV), 322 

Postoperative pain, 331 

Postoperative pain management, 183 

Postoperative research agenda items, 

82–83 

Postoperative respiratory assistance, 

159 

Postoperative respiratory insufficiency, 

78, 330–331 

Postoperative shivering, 115–116 

Postoperative surgical stress responses, 

285 

Postsurgical analgesia, 311–312 

Postthoracotomy pain management, 

385–386 

Potassium management, 296–297 

Power of Attorney for Healthcare 

(PAHC), 45 

Practice-based learning/improvement, 

59 

Preanesthetic evaluation, 417–418 

Preoperative assessment of the elderly, 

11, 69–78 

functional asessments, 70–72 

intraoperative management, 74–78 

perioperative optimization, 73–74 

perioperative testing, 72–73 

risk stratification, 70 

Preoperative care, 417–420 

bowel preparation, 419–420 

geriatricians interaction, 420 

preanesthetic evaluation, 417–418 

Preoperative discontinuation, 191 

Preoperative evaluation, 323–326, 

379–380 

preoperative testing, 323–324 

sleep apnea, 324–326 

Preoperative fasting guidelines, 344 

Preoperative research agenda items, 

73–74 

Preoperative risk stratification, 181–192 

cardiovascular complications, 

183–186 

coexisting disease importance, 

181–182 

cognitive dysfunction/delirium after 

noncardiac surgery, 182–183 

comprehensive geriatric assessment, 

191–192 

diabetes mellitus, 188 

exercise capacity/functional status 

assessment, 189–190 

laboratory values, 190–191 

medications, 191 

nutritional assessment, 188–189 

pulmonary complications, 186–187 

renal dysfunction, 187 

Preoperative testing, 323–324 

Preprocedure evaluation, 343 

Pressure ulcers, 166, 173–174 

Prewarming, 117 

Proactive geriatric consultation, 192 

Producing geriatric curriculum, 62–63 

computer-based materials, 63 

didactics, 62 

discussion groups, 62–63 

evaluation of curriculum, 63 

reference books, 63 

sample curriculum, 62 

stimulation, 63 

Programmed aging, 29–30 

Progressive hypoxia, 67 

Progressive neurogenic process, 266 

Progressive ventricular hypertrophy, 67 

Prolonged sedation, 258 

Proper hemostatic control, 172 

Prophylactic anticoagulation, 356 

Propofol, 111, 345 

adverse effects/contraindications, 233 

context-sensitive half-time, 233 

dosing in elderly, 231–233 

future considerations, 233–234 


infusion rate, 232 



cardiovascular effects, 231 

central nervous system effects, 

229–230 

other effects, 231 

respiratory effects, 230–231 

Propoxyphene, 206, 312 

Prostatectomy, 374 

Proteins 

body compositions, 98 

plasma, 256 

transport, 98–99 

PSDA. See Patient Self-Determination 

Act 

Pulmonary changes, 67–68, 327, 342 

Pulmonary complications, 155–160, 

186–187, 384 

Pulmonary drugs, 203–204 

beta agonists, 203 

theophylline, 203–204 

Pulmonary outcome, 287 

Pulmonary parenchyma, 248 

Pulmonary risk in elderly patients, 

157–160 

anesthesia induction, 157–158 

anesthesia muscle relaxants, 158 

caution regarding perioperative use of 

opioids, 158–159 

intraoperative lung expansion during 

general anesthesia, 158 

mechanical ventilation in elderly, 

159–160 

neuraxial blocks for pain 

management, 158 

noninvasive positive pressure 

ventilation, 159 

postoperative respiratory assistance 

to maintain lung expansion, 159 

preoperative testing, 157 

preoperative therapies, 157 

regional anesthetic techniques, 158 

surgical considerations, 157 

Pulmonary system, 286 

Pulmonary venous blood, 251 

Pupilometry, 216 

Pyridostigmine, 273, 274 

R 

Radical cystectomy, 374 

Radical nephrectomy, 374–375 

Radical prostatectomy, 374 

Radiocontrast dye, 296 

Raynaud’s syndrome, 202 

RCRI. See Revised Cardiac Risk Index 

Reactive oxygen species (ROS), 32 

Receptors 

acetylcholine, 266 

adrenergic activity, 142–143 

altered, systems, 31–32 

opioids, 210, 211 

Reduced cardiac output, 252 

Reflex control mechanism, 141 

Reflex inhibition, 286 

Regional analgesia, 315–316 

Regional anesthesia, 302–303, 327–328 

Regional anesthesia management, 

278–288 

age-related changes relevant to, 278 

beneficial aspects of regional 


cardiovascular system, 286 

gastrointestinal system, 286 

pulmonary system, 286 

central neural blockade, 278–279 

epidural anesthesia, 278–279 

spinal anesthesia, 279 

hypotension, 282–284 

hypothermia, 284–285

Index 439 

outcome/regional/general anesthesia, 

286–288 

cardiac outcome, 287 

coagulation, 287 

gastrointestinal outcome, 288 

pulmonary outcome, 287 

peripheral nerve blockade, 280–282 

postoperative cognitive function, 285 

problems, 282 

sedation, 285 

Regression line slopes, 142 

Relaxants, 266–274 

anticholinesterases, 272–274 

changes in structure of neuromuscular 

junction, 266–267 

dose-response relationships in elderly, 

267 

neuromuscular block onset, 268–269 

outcome studies, 274 

pharmacokinetics/duration of effect 

intermediate-acting agents, 270–272 

long-acting agents, 269–270 

short duration of action, 272 

Remifentanil, 220–222 

Renal blood flow, 100, 102 

Renal changes, 68 

Renal dysfunction, 187, 395 

Renal function, 294–295 

Renal impairment, 200 

Renin/vasopressin activity, 143–144 

Resource allocation, 50–51 

Respiratory depression, 198, 209 

Respiratory effects, 230–231 

Respiratory heat, 113 

Retinal effects, 369 

Revised Cardiac Risk Index (RCRI), 

398 

Risk classification tree, 394 

Risk stratification, 70 

Rocuronium, 271 

ROS. See Reactive oxygen species 

S 

SAGA. See The Society for the 

Advancement of Geriatric 


SAMBA. See Society for Ambulatory 


Scoliosis, 319 

Sedation, 285, 341–351 

administering, 343–347 

adverse events, 346 

consent, 343–344 

emergency resuscitation, 344 


monitoring, 344 

oxygen, 344 

preoperative fasting guidelines, 

344 

preprocedure evaluation, 343 

reversal agents, 346 

scheduling/information, 346 

sedation history, 343 

administration sedation, 342–343 

communication, 343 

positioning, 342 

comorbid conditions, 342 

conscious, 341 

eye surgeries in elderly, 347–351 

cataracts, 347 

modern cataract surgery, 347–350 

meaning of, 341 

minimal, 341 

moderate, 341 

as particular concern, 341 

patient-controlled, 345 

regional anesthesia management, 285 

Selective serotonin reuptake inhibitors 

(SSRIs), 199, 315 

Senescence, 30 

Senescent physiology, 12 

Senile emphysema, 150 

SEP. See Specific entropy production 

Septicemia, 371 

Sevoflurane, 256 

SGR. See Sustainable growth rate 

formula 

Shared decision making, 41 

Short duration of action, 272 

Sleep apnea, 155, 187, 324–326 

SMI. See Supplementary Medical 

Insurance 

Society for Ambulatory Anesthesia 

(SAMBA), 322 

The Society for the Advancement of 

Geriatric Anesthesia (SAGA), 14 

Society of Thoracic Surgeons (STS), 390 

Sodium conservation, 68 

Sodium handling, 295–296 

Southern California Cancer Pain 

Initiative, 313 

Specific entropy production (SEP), 30 

Specific opioids 

alfentanil, 111, 219 

fetanyl, 215, 217–219, 314 

hydromorphone, 217–218 

meperidine, 217, 312, 345 

methadone, 222 

morphine, 215–217 

remifentanil, 220–222 

sufentanil, 219–220 

Spinal anesthesia, 279, 303 

Spinal anesthetics, 361 

Spinal stenosis, 316 

SSRIs. See Selective serotonin reuptake 

inhibitors 

Static elastic recoil, 150 

Statins, 402 

Steroid-treating groups, 364 

St. John’s wort, 191 

Stochastic aging, 30–31 

Stress, 32, 285 

Stroke, 310 

Stroke management, 132 

Stroke volume (SV), 283 

STS. See Society of Thoracic Surgeons 

Subarchnoid injection, 385 

Substantial hypotension, 144 

Substituted judgment, 51 

Subtle systolic dysfunction, 141 

Sufentanil, 219–220 

Supine position, 384 

Supplemental insurance, 18 

Supplemental Security Income, 18 

Supplementary Medical Insurance 

(SMI), 16 

Surgery 

abdominal, 416–417 

hip fracture, 356 

laparoscopic, 373–374 

modern cataract, 347–350 

thoracic, 71 

Surgical dislocation, 356 

Surgical procedure, 368 

Surgical wound infections, 115 

Sustainable growth rate formula (SGR), 

22–23 

SV. See Stroke volume 

Syndromes 

common pain, 316–317 

complex regional pain, 82 

OSAS, 187 

Raynaud’s, 202 

transurethral prostatectomy, 

368–375 

visceral hypersensitivity pain, 310 

System-based practice, 59 

Systolic function, 140 

Systolic hypertension, 403 

T 

Tachycardia, 146 

TBW. See Total body water 

TEA. See Thoracic epidural anesthesia 

TEE. See Transesophageal 

echocardiography 

Telomere shortening, 31 

Thallium scanning, 73 

Theophylline, 203–204 

Theories of Aging, 4 

Therapeutic misconception, 52 

Therapy 

blood-component, 303 

electro-convulsive, 230 

fluid, 359 

growth factor, 172 

perioperative fluid, 299 

physical, 173 

wound and compression, 172 

Thermal management, 116–117 

ambient temperature/passive 

insulation/cutaneous warming, 

116–117

440 Index 

Thermal management (cont.) 

fluid warming, 117 

prewarming, 117 

Thermoception, 309 

Thermoregulatory defenses, 108 

Thiopental, 234–237 

adverse effects/contraindications, 

236–237 

dosing in elderly, 236 



pharmacodynamics, 234 

cardiovascular system, 235 

central nervous system effects, 234 

onset of central nervous system 

effects, 234–235 

respiratory system, 235–236 


Thirty-day mortality, 6 

Thoracic epidural anesthesia (TEA), 

286 

Thoracic lumbar compression fractures, 

316 

Thoracic procedures, 378–387 

airway management, 383 

bronchoscopy, 380–381 

anesthesia, 381 

ventilation/oxygenation, 381 

cardiorespiratory physiology in 

elderly, 379 

cardiovascular complications, 382–383 

flexible fiberoptic bronchoscopy, 381 

intraoperative anesthetic 


mediastinoscopy, 381–382 

monitoring, 383 

morbidity/mortality of thoracic 

surgical procedures in elderly, 

378–379 

postoperative complications, 384–385 

postthoracotomy pain management, 

385–386 

preoperative evaluation, 379–380 

thoracotomy, 382 

videothorascopy, 386 

Thoracic surgery, 71 

Threshold elements, 41–43 

decision making capacity, 41–42 

voluntariness, 42 

Thromboprophylaxis, 362 

Ticlopidine, 205 

Titration, 312 

TLC. See Total lung capacity 

Total body fat content, 252 

Total body water (TBW), 99 

Total hip arthroplasty, 356–357, 359 

Total hip replacement, 355–364 

Total knee arthroplasty, 358 

Total lung capacity (TLC), 150 

Total plasma clearance, 281 

Tourniquet-related complications, 362 

Toxic fluoride, 256 

Toxicity, 370–371 

Transesophageal echocardiography 

(TEE), 383 

Transfusion Requirements in Critical 

Care (TRICC), 305 

Transient bacteremia, 371 

Transparency, 43 

Transport proteins, 98–99 

Transpulmonary pressure, 152 

Transurethral prostatectomy (TURP), 

368 

irrigation solutions, 369 

surgical procedure, 368 

Transurethral prostatectomy syndrome, 

368–375 

absorption of irrigating solution, 370 

anesthetic considerations for, 371–372 

bladder perforation, 371 

circulatory overload/hypnonatremia/ 

hypoosmolality, 370 

coagulopathy, 371 

future of, 372 

glycine/ammonia toxicity, 370–371 


signs/symptoms of, 369 

transient bacteremia/septicemia, 371 

treatment of, 372 

Transurethral resection, 372 

Treatment futility, 47–48 

Treatment/prevention, 126 

Treatment redirection, 48 

TRICC. See Transfusion Requirements 

in Critical Care 

Tricyclic antidepressants, 199, 315 

Trimethoprim-sulfamethazine, 297 

Tubular function, 101–102 

TURP. See Transurethral prostatectomy 

U 

Ubiquitin, 114 

Ulcers 

diabetic foot, 165–166 

multidisciplinary approach for 

treating, 168–173 

summary of current usage, 169 

pressure, 166, 173–174 

venous, 166–167 

Upper airway dysfunction, 155 

Urinary concentration, 297–298 

Urinary tract infections, 72 

Urologic procedures, 368–375 

V 

Vagal activity, 143 

Valvular heart disease, 391–393 

Variable elements, 7–8 

Vascular procedures, 398–411 

cardiac risk assessment/intervention, 

398–401 

intraoperative management, 404–410 

carotid endarterectomy, 409–410 

carotid stents, 410 

endovascular abdominal aortic 

aneurysm repair, 408–409 

epidural anesthesia/regional 

techniques, 404–405 

general anesthesia for vascular 

patient, 404–405 

infraaortic vascular procedures, 

406 

postoperative care, 410–411 

optimization strategies, 401–404 

alpha agonists, 401 

beta-blocker therapy, 401 

cognitive function/delirium, 404 

preoperative assessment, 402–403 

renal, 403–404 

statins, 402 

preoperative evaluation/preparation, 

398 

Vascular resistance, 250 

Vascular stiffening, 141 

Vasoconstriction, 109, 110, 111, 143 

Vasodilation, 109 

Vasomotor tone, 284 

VC. See Vital capacity 

Vecuronium, 271 

Venous reflux disease, 167 

Venous thromboembolism, 360–362 

Venous ulcers, 166–167 

Ventilation 

alveolar, 249 

maximal minute, 67 

mechanical, 159–160 

noninvasive positive pressure, 159 

Ventilatory response, 67 

Video-assisted thoracoscopy (VAT), 378 

Virtue ethics, 39 

Visceral hypersensitivity, 310 

Visceral pain, 310 

Visual acuity, 12 

Vital capacity (VC), 150 

Volatile anesthetic agents, 256 

Volume depletion, 187 

Voluntariness, 42 

W 

Warfarin, 204–205 

Water-soluble drugs, 69 

Wound and compression therapy, 172 

Wound bed preparation, 171–172 

Wound healing, 170 

Z 

Zygapophyseal joint, 316

Geriatric Anesthesiology - The Global Regional Anesthesia Website

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