Table Of ContentPharmacology
and Physiology
for Anesthesia
FOUNDATIONS AND
CLINICAL APPLICATION
Pharmacology
and Physiology
for Anesthesia
Foundations and Clinical Application
Hugh C. Hemmings, Jr.,
MD, PhD, FRCA
Distinguished Research Professor of Anesthesiology and Vice Chair of Research
Professor of Pharmacology
Weill Cornell Medical College;
Attending Anesthesiologist
New York-Presbyterian Hospital;
Adjunct Professor
The Rockefeller University
New York, New York
Talmage D. Egan,
MD
Professor of Anesthesiology
Adjunct Professor of Pharmaceutics
Adjunct Professor of Bioengineering
Attending Anesthesiologist
Vice Chair for Research
K.C. Wong Presidential Endowed Chair
University of Utah School of Medicine
Salt Lake City, Utah
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
PHARMACOLOGY AND PHYSIOLOGY FOR ANESTHESIA: ISBN: 978-1-4377-1679-5
FOUNDATIONS AND CLINICAL APPLICATION
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Library of Congress Cataloging-in-Publication Data
Pharmacology and physiology for anesthesia : foundations and clinical application / [edited by]
Hugh C. Hemmings Jr., Talmage D. Egan.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4377-1679-5 (hardcover : alk. paper)
I. Hemmings, Hugh C. II. Egan, Talmage D.
[DNLM: 1. Anesthesia. 2. Pharmacological Processes. 3. Physiological Processes. WO 200]
617.9′6—dc23
2012037216
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PREFACE
The successful practice of the art of anesthesia, critical care, A number of features significantly enhance the use of
and pain medicine demands a sound understanding of core Pharmacology and Physiology for Anesthesia: Foundations and
scientific concepts founded in physiology and pharmacology. Clinical Application as a tool for learning, teaching, and review.
The importance of physiology and pharmacology to anesthe- These include access to the online text via the Expert Consult
siology is recognized in postgraduate anesthesia training pro- platform, including a complete, downloadable image bank.
grams and certification examinations worldwide because a Recognizing that graphics are often the most expressive
thorough understanding of these disciplines is essential for and effective way of conveying concepts, full-color illustra-
graduation, certification, and successful clinical practice. tions facilitate use of the book as a learning aid and make
Although this scientific foundation is available from a number it enjoyable to read. The text is copiously illustrated; all
of sources, the necessary level of detail is often insufficient in figures having been drawn or redrawn by the superb artists
introductory texts and perhaps too esoteric in specialized at Elsevier.
monographs targeted to academics. The goal of Pharmacology Each chapter stresses the scientific principles necessary for
and Physiology for Anesthesia: Foundations and Clinical Applica- the understanding and management of various situations
tion is to bridge this gap between introductory texts and com- encountered in anesthesia practice. Detailed explanations of
prehensive reference books by providing a detailed overview clinical techniques are avoided because this information is
of these fundamental subject areas for anesthesiologists, available in many comprehensive and subspecialty clinical
intensivists, and pain practitioners, both in training and in anesthesia texts and handbooks. This book is not intended to
practice. provide a detailed review of specialized research areas for the
Pharmacology and Physiology for Anesthesia: Foundations and scientist. Rather, the fundamental information necessary to
Clinical Application is intended to be a definitive source for understand essential concepts and principles is stressed, and
in-depth coverage of these core basic and clinical sciences in basic science concepts are related to relevant clinical anesthe-
a single text. Focusing on physiology, pharmacology, and sia applications. Chapters are self-contained with minimal
molecular-cellular biology, the text’s approach is integrated repetition and include a short list of key points for review and
and systems oriented, avoiding the artificial boundaries key references to stimulate further exploration of interesting
between the basic and clinical sciences. The book is divided topics.
into five sections: Basic Principles of Pharmacology; Nervous The expertise and hard work of the contributing authors
System; Cardiovascular and Pulmonary Systems; Gastrointes- is evident in the quality of each chapter. And as a whole, the
tinal and Endocrine Systems; and Fluid, Electrolyte, and final text reflects the know-how and skill of the professionals
Hematologic Homeostasis. at Elsevier and in particular the contributions of William
Recognizing that no single author possesses the necessary Schmitt, Joan Ryan, and Cheryl Abbott. We are confident that
breadth and depth of understanding in all the core subject Pharmacology and Physiology for Anesthesia: Foundations and
areas, each chapter is authored by an expert representing Clinical Application will help solidify your understanding of
many of the finest institutions of North America, the United core anesthesia topics and thereby improve the safety and
Kingdom, Europe, and Asia. This allows an international effectiveness of the care you render to your patients.
presentation of current anesthesia science presented by rec-
ognized experts at the cutting edge of anesthesia research and Hugh C. Hemmings, Jr.
education. Talmage D. Egan
CONTRIBUTING AUTHORS
Geoffrey W. Abbott, MSc, PhD Michael Cahalan, MD
Professor and Vice Chair Professor and Chair
Department of Pharmacology Department of Anesthesiology
School of Medicine University of Utah School of Medicine
University of California, Irvine Salt Lake City, Utah
Irvine, California
Charles D. Collard, MD
Martin S. Angst, MD Professor and Anesthesiologist-in-Chief
Professor of Anesthesia St. Luke’s Episcopal Hospital
Stanford University School of Medicine Chief, Division of Cardiovascular Anesthesia
Stanford, California Texas Heart Institute
Houston, Texas
Christian C. Apfel, MD, PhD
Adjunct Associate Professor George J. Crystal, PhD, FAHA
Departments of Anesthesia and Perioperative Care, Professor of Anesthesiology and Physiology and Biophysics
Epidemiology and Biostatistics Advocate Illinois Masonic Medical Center
Perioperative Clinical Research Core University of Illinois College of Medicine
University of California, San Francisco Chicago, Illinois
University of California San Francisco Comprehensive
Cancer Center at Mt. Zion Linda J. Demma, MD, PhD
San Francisco, California; Department of Anesthesiology
Founder and CEO Emory University School of Medicine
SageMedic, Inc. Atlanta, Georgia
Larkspur, California
Daniel A. Drennan, MD
Edward A. Bittner, MD, PhD President/CEO
Assistant Professor of Anesthesia Comprehensive Pain Specialists
Harvard Medical School; Denver, Colorado
Program Director, Critical Care Fellowship
Department of Anesthesia, Critical Care, and Pain Medicine John C. Drummond, MD, FRCPC
Massachusetts General Hospital Professor of Anesthesia
Boston, Massachusetts University of California, San Diego;
Staff Anesthesiologist
Michelle Braunfeld, MD VA San Diego Healthcare System
Clinical Professor, Liver Transplant Anesthesiology San Diego, California
David Geffen School of Medicine
University of California, Los Angeles; Thomas J. Ebert, MD, PhD
Chief, Anesthesiology Service Vice Chair for Education
Greater Los Angeles VA Medical Center Professor of Anesthesiology and Residency Program
Los Angeles, California Director
Medical College of Wisconsin
Shane Brogan, MB, BCh Milwaukee, Wisconsin
Associate Professor of Anesthesiology
Pain Management Center Talmage D. Egan, MD
University of Utah School of Medicine Professor of Anesthesiology
Salt Lake City, Utah Adjunct Professor of Pharmaceutics
Adjunct Professor of Bioengineering
Attending Anesthesiologist
Vice Chair for Research
K.C. Wong Presidential Endowed Chair
University of Utah School of Medicine
Salt Lake City, Utah
Contributing Authors
Matthias Eikermann, MD, PhD Karl F. Herold, MD, PhD
Assistant Professor Research Associate
Harvard Medical School; Department of Anesthesiology
Director of Research, Critical Care Division Weill Cornell Medical College
Department of Anesthesiology, Critical Care and Pain New York, New York
Medicine
Massachusetts General Hospital Philip M. Hopkins, MB, BS, MD, FRCA
Boston, Massachusetts; Professor of Anaesthesia
Adjunct Professor of Anesthesia and Intensive Care Director, Division of Clinical Sciences
Essen-Duisburg University Leeds Institute of Molecular Medicine
Germany University of Leeds;
Honorary Consultant Anaesthetist
Charles W. Emala, Sr., MS, MD Leeds Teaching Hospitals NHS Trust
Henrik H. Bendixen Professor of Anesthesiology Leeds Institute of Molecular Medicine
Vice Chair for Research University of Leeds
Department of Anesthesiology Leeds, United Kingdom
Columbia University
New York, New York Deborah Horner, MBChB, BSc, FRCA
Specialist Registrar
T. Miko Enomoto, MD Department of Anaesthesia
Assistant Professor of Anesthesiology St. James’s University Hospital
Department of Anesthesiology and Perioperative Medicine Leeds, United Kingdom
Oregon Health and Science University
Portland, Oregon Andrew E. Hudson, MD, PhD
Clinical Instructor
Paul Garcia, MD, PhD Department of Anesthesiology
Assistant Professor of Anesthesiology David Geffen School of Medicine
Emory University School of Medicine; University of California, Los Angeles
Staff Anesthesiologist Los Angeles, California
Atlanta VA Medical Center
Atlanta, Georgia Julie L. Huffmyer, MD
Assistant Professor of Anesthesiology
Peter Gerner, MD University of Virginia School of Medicine
Professor and Chairman Charlottesville, Virginia
Department of Anesthesiology, Perioperative Medicine,
and Intensive Care Joel O. Johnson, MD, PhD
Salzburg General Hospital Professor and Vice Chair for Clinical Affairs
Paracelsus Medical University University of Wisconsin Hospital and Clinics
Salzburg, Austria Madison, Wisconsin
Jacqueline A. Hannam, BSc(Hons) Abhinav Kant, MBBS, FRCA, FHEA
Faculty of Medical and Health Sciences Consultant Anaesthetist
Department of Anaesthesiology Department of Anaesthesia
University of Auckland Leeds General Infirmary
Auckland, New Zealand Leeds, United Kingdom
Paul M. Heerdt, MD, PhD, FAHA Mark T. Keegan, MB, MRCPI, MSc
Professor of Anesthesiology and Pharmacology Associate Professor of Anesthesiology
Weill Cornell Medical College; Division of Critical Care
Member, Memorial Sloan-Kettering Cancer Center Department of Anesthesiology
New York, New York Mayo Clinic
Rochester, Minnesota
Hugh C. Hemmings, Jr., MD, PhD, FRCA
Distinguished Research Professor of Anesthesiology and Andreas Koköfer, MD
Vice Chair for Research Resident in Anesthesia
Professor of Pharmacology Department of Anesthesiology, Perioperative Medicine,
Weill Cornell Medical College; and Intensive Care
Attending Anesthesiologist Salzburg General Hospital
New York-Presbyterian Hospital; Paracelsus Medical University
Adjunct Professor Salzburg, Austria
The Rockefeller University
New York, New York
x
Contributing Authors
Brian P. Lemkuil, MD Joseph Meltzer, MD
Assistant Clinical Professor of Anesthesia Medical Director, Cardiothoracic Intensive Care Unit
University of California, San Diego; Program Director, Anesthesiology Critical Care Medicine
Staff Anesthesiologist Fellowship Program
VA San Diego Healthcare System Associate Clinical Professor, Division of Critical Care,
San Diego, California Department of Anesthesiology
David Geffen School of Medicine
Roberto Levi, MD, DSc University of California, Los Angeles
Professor of Pharmacology Los Angeles, California
Weill Cornell Medical College
New York, New York Edward C. Nemergut, MD
Associate Professor of Anesthesiology and Neurological
Jerrold H. Levy, MD, FAHA, FCCM Surgery
Professor and Deputy Chair for Research Program Director
Emory University School of Medicine Department of Anesthesiology
Division of Cardiothoracic Anesthesiology and Critical Care University of Virginia School of Medicine
Emory Healthcare Charlottesville, Virginia
Atlanta, Georgia
Shinju Obara, MD, PhD
Cynthia A. Lien, MD Assistant Professor of Anesthesiology
Professor and Vice Chair for Academic Affairs Fukushima Medical University, School of Medicine;
Department of Anesthesiology Deputy Director, Intensive Care Department
Weill Cornell Medical College Fukushima Medical University Hospital
New York, New York Fukushima, Fukushima Prefecture, Japan
Andrew B. Lumb, MB, BS, FRCA Takahiro Ogura, MD, PhD
Consultant Anaesthetist Research Fellow
Department of Anaesthesia Department of Anesthesiology
St. James’s University Hospital National Defense Medical College
Leeds, United Kingdom Tokorozawa, Saitama, Japan;
Japan Maritime Self Defense Force Hospital
Srinand Mandyam, MD Yokosuka, Kanagawa Prefecture, Japan
Associate Physician
Oklahoma Pain and Wellness Center Einar Ottestad, MD
Tulsa, Oklahoma Clinical Assistant Professor of Anesthesia
Stanford University School of Medicine
Robert G. Martindale, MD, PhD Stanford, California
Professor of Surgery
Chief, Division of General Surgery Hahnnah Park
Director, Hospital Nutrition Service Department of Anesthesiology
Oregon Health and Science University David Geffen School of Medicine
Portland, Oregon University of California, Los Angeles
Los Angeles, California
J.A. Jeevendra Martyn, MD, FRCA, FCCM
Professor of Anesthesiology Piyush M. Patel, MD, FRCPC
Harvard Medical School; Professor of Anesthesia
Director, Clinical and Biochemical Pharmacology University of California, San Diego;
Laboratory & Anesthetist Staff Anesthesiologist
Massachusetts General Hospital; VA San Diego Medical Center
Anesthetist-in-Chief San Diego, California
Shriners Hospital for Children
Boston, Massachusetts Misha Perouansky, MD
Professor of Anesthesiology
Mary McCarthy, PhD, RN University of Wisconsin
Senior Nurse Scientist Madison, Wisconsin
Madigan Army Medical Center
Tacoma, Washington Tjorvi E. Perry, MD, MMSc
Assistant Professor of Anesthesiology
Department of Anesthesiology, Perioperative,
and Pain Medicine
Division of Cardiovascular Anesthesiology
Brigham and Women’s Hospital of Harvard Medical School
Boston, Massachusetts
xi
Contributing Authors
Alex Proekt, MD, PhD Randolph H. Steadman, MD
Assistant Professor of Anesthesiology Professor and Vice Chair
Weill Cornell Medical College Director, Anesthesia for Liver Transplant
Assistant Attending Anesthesiologist Residency Program Director
New York-Presbyterian Hospital/Weil Cornell Medical Department of Anesthesiology
Center Director, Simulation Center
New York, New York David Geffen School of Medicine
University of California, Los Angeles
Kane O. Pryor, MD Los Angeles, California
Assistant Professor of Anesthesiology
Assistant Professor of Anesthesiology in Psychiatry Kingsley P. Storer, MD, PhD
Weill Cornell Medical College; Assistant Professor of Anesthesiology
Assistant Attending Anesthesiologist Weill Cornell Medical College;
Memorial Sloan-Kettering Cancer Center Assistant Attending Anesthesiologist
New York, New York New York-Presbyterian Hospital/Weill Cornell Medical
Center
Aeyal Raz, MD, PhD New York, New York
Department of Anesthesiology
University of Wisconsin Suzuko Suzuki, MD
Madison, Wisconsin; Clinical Associate in Anesthesiology
Department of Anesthesiology Department of Anesthesiology, Perioperative,
Rabin Medical Center and Pain Medicine
Petah-Tikva, Israel; Brigham and Women’s Hospital
Affiliated with Sackler Faculty of Medicine Harvard Medical School
Tel-Aviv University Boston, Massachusetts
Tel-Aviv, Israel
Christer Svensén, MD, PhD, DESA, MSc
Peter Rodhe, PhD, MSc Associate Professor
Department of Clinical Science and Education Head, Research and Education
Section of Anaesthesiology and Intensive Care Department of Clinical Science and Education
Karolinska Institutet/Södersjukhuset Section of Anaesthesiology and Intensive Care
Stockholm, Sweden Karolinska Institutet/Södersjukhuset
Stockholm, Sweden
David Royston, FRCA
Consultant in Cardiothoracic Anaesthesia, Critical Care, Kenichi Tanaka, MD, MSc
and Pain Management Visiting Professor of Anesthesiology
Royal Brompton & Harefield NHS Foundation Trust University of Pittsburgh Medical Center
Harefield Hospital Pittsburgh, Pennsylvania
Harefield, United Kingdom
Matthew Keith Whalin, MD, PhD
John W. Sear, MA, BSc, PhD, FFARCS, FANZCA Assistant Professor of Anesthesiology
Emeritus Professor of Anaesthetics Emory University School of Medicine
University of Oxford Atlanta, Georgia
Oxford, United Kingdom
Rachel Whelan
Peter S. Sebel, MD, PhD, MBA Perioperative Clinical Research Core
Professor of Anesthesiology Department of Anesthesia and Perioperative Care
Department of Anesthesiology University of California San Francisco Comprehensive
Emory University School of Medicine Cancer Center at Mt. Zion
Atlanta, Georgia San Francisco, California
Timothy G. Short, MB, ChB, MD, FANZCA Josh Zimmerman, MD
Honorary Associate Professor Associate Professor
Department of Adult and Trauma Anaesthesia Medical Director, Preoperative Clinic
Auckland City Hospital Department of Anesthesiology
Auckland, New Zealand University of Utah School of Medicine
Salt Lake City, Utah
Roman M. Sniecinski, MD
Associate Professor of Anesthesiology
Division of Cardiothoracic Anesthesiology
Emory University School of Medicine
Atlanta, Georgia
xii
To my wife, Katherine, and daughter, Emma, whose support and understanding were essential
to the completion of this book; to my mentors Paul Greengard and John Savarese; and to my
students, all of whom have taught me so much and from whom I continue to learn
H.C. Hemmings, Jr.
To my wife, Julie, and our children: James, Adam, Ezekiel, Sarajane, and Elizabeth—I am the
luckiest; to my mentors Drs. Merritt Egan, Glen Church, K.C. Wong, Mike Cahalan,
Don Stanski, and Steve Shafer—you are the wind beneath my wings
T.D. Egan
