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Smith’s
Anesthesia for
Infants and Children
Volume1
Smith’s
Anesthesia for
Infants and Children

Tenth Edition
Peter J. Davis, MD
Professor
Department of Anesthesiology and Perioperative Medicine
Department of Pediatrics
Dr. Joseph H. Marcy Endowed Chair in Pediatric Anesthesia
University of Pittsburgh School of Medicine
Anesthesiologist-in-Chief
UPMC Children’s Hospital of Pittsburgh
Pittsburgh, Pennsylvania
Franklyn P. Cladis, MD, FAAP

Professor
Department of Anesthesiology and Perioperative Medicine
UPMC Children’s Hospital of Pittsburgh
Pittsburgh, Pennsylvania
Elsevier
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
SMITH’S ANESTHESIA FOR INFANTS AND CHILDREN, ISBN: 978-0-323-69825-2

TENTH EDITION

Copyright © 2022 by Elsevier Inc. All rights reserved.
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Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).
Chapter 30: Barry. D. Kussman retains copyright.
Notice
Practitioners and researchers must always rely on their own experience and knowledge in evaluating
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Previous editions copyrighted 2017, 2011, 2006, 1996, 1990, 1980, 1968, 1963, and 1959
Library of Congress Control Number: 2021939106
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Content Development Specialist: Kristen Helm
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Printed in the US
Last digit is the print number: 9 8 7 6 5 4 3 2 1

DEDICATION
To our patients, who have allowed us the privilege of caring for them
and providing the opportunity of learning from them, and to our mentors, who
have shaped the way we care for patients and who have profoundly impacted the
specialty of pediatric anesthesiology.
CONTRIBUTORS
Phillip S. Adams, DO, FASA Benjamin B. Bruins, MD Ira Todd Cohen, MD, MEd, FAAP
Assistant Professor Assistant Professor Professor of Anesthesiology and Pediatrics
Department of Anesthesiology and Anesthesia and Critical Care Medicine Department of Anesthesiology and Pain
Perioperative Medicine Children’s Hospital of Philadelphia Medicine
Residency Program Director Philadelphia, PA Children’s National Medical Center
UPMC Children's Hospital of Pittsburgh Thomas M. Chalifoux, MD Ashley A. Colletti, MD
Pittsburgh, PA Assistant Professor Assistant Professor
Department of Anesthesiology and Department of Anesthesiology and Pain
Devon O. Aganga, MD Perioperative Medicine Medicine
Consultant University of Pittsburgh School of Medicine University of Washington
Department of Anesthesiology and UPMC Children's Hospital of Pittsburgh Seattle Children’s Hospital
Perioperative Medicine, Mayo Clinic UPMC Magee-Women's Hospital Seattle, WA
Assistant Professor in Anesthesiology Pittsburgh, PA
College of Medicine, Mayo Clinic Erin Conner, MD
Rochester, MN Mary Chapman Assistant Professor of Anesthesiology and
Pediatric Dentist Pediatrics
Sean S. Barnes, MD, MBA UPMC Children’s Hospital of Pittsburgh Oregon Health and Science University
Assistant Professor Pittsburgh, PA Portland, OR
Anesthesiology and Critical Care Medicine
Johns Hopkins University School of Debnath Chatterjee, MD, FAAP Edward B. Cooper, MD
Medicine Associate Professor of Anesthesiology, Associate Professor
Baltimore, MD Children’s Hospital Colorado Departments of Anesthesiology and
Director of Fetal Anesthesia, Colorado Fetal Pediatrics
Bruno Bissonette, MD, FRCPC Care Center University of Cincinnati School of Medicine
Professor Emeritus of Anesthesia University of Colorado School of Medicine Cincinnati Children’s Hospital Medical
University of Toronto Aurora, CO Center
Founder and President Cincinnati, OH
Children of the World Anesthesia Rajeev Chaudhry, MD
Foundation Assistant Professor Joseph P. Cravero, MD
Rimouski, Quebec, Canada Department of Urology Anesthesiologist-in-Chief
University of Pittsburgh School of Medicine Boston Children’s Hospital
Brian Blasiole, MD, PhD UPMC Children’s Hospital of Pittsburgh Professor of Anaesthesia
Assistant Professor Pittsburgh, PA Harvard Medical School
Department of Anesthesiology and Boston, MA
Perioperative Medicine Sylvia Choi, MD, FAAP
University of Pittsburgh School of Medicine Associate Professor Jessica Cronin, MD, MBA
UPMC Children’s Hospital of Pittsburgh Department of Pediatrics Assistant Professor
Pittsburgh, PA University of Pittsburgh School of Medicine Division of Anesthesiology, Pain and
UPMC Children’s Hospital of Pittsburgh Perioperative Medicine
Adrian Bosenberg, MBChB FFA(SA) Pittsburgh, PA Children’s National Hospital
Professor Washington, DC
Department Anesthesiology and Pain Franklyn P. Cladis, MD
Management Professor Nicholas M. Dalesio, MD
University of Washington Department of Anesthesiology and Associate Professor
Pediatric Anesthesiologist Perioperative Medicine Anesthesiology and Critical Care Medicine
Seattle Children’s Hospital University of Pittsburgh School of Medicine Johns Hopkins School of Medicine
Seattle, WA UPMC Children's Hospital of Pittsburgh Baltimore, MD
Pittsburgh, PA
Claire M. Brett, MD, FAAP Jessica Davis, BA, JD, LLM
Emeritus Professor of Anesthesia and David E. Cohen, MD Troutman Pepper Hamilton Sanders, LLP
Perioperative Care and Pediatrics Associate Professor of Anesthesiology at Philadelphia, PA
Division of Pediatric Anesthesia The Children’s Hospital of Philadelphia
University of California Emeritus, Perelman School of Medicine
San Francisco, CA University of Pennsylvania
Anesthesiology and Critical Care Medicine
Children’s Hospital of Philadelphia
Philadelphia, PA
vi
CONTRIBUTORS vii
Peter J. Davis, MD Branden M. Engorn, MD Jessica A. George, MD, MEd

Professor Pediatric Anesthesiologist and Intensivist Assistant Professor
Department of Anesthesiology and Anesthesia Service Medical Group Medical Director for Pediatric Enhanced
Perioperative Medicine Rady Children’s Hospital San Diego Recovery After Surgery (ERAS) program
Dr. Joseph H. Marcy Endowed Chair in San Diego, CA Division of Pediatric Anesthesiology and
Pediatric Anesthesia Critical Care Medicine
University of Pittsburgh School of Medicine James J. Fehr, MD Johns Hopkins University School of
Anesthesiologist-in-chief Clinical Professor Medicine
UPMC Children’s Hospital of Pittsburgh Service Chief Anesthesia Baltimore, MD
Pittsburgh, PA Anesthesiology and Perioperative Pain
Stanford University School of Medicine Thierry Girard, MD
Karen A. Dean, MD Lucile Packard Children's Hospital Professor of Anesthesiology
Associate Professor of Anesthesiology, Palo Alto, CA Department of Anesthesiologie
Children’s Hospital Colorado University Hospital Basel
University of Colorado School of Medicine Jeffrey M. Feldman, MD, MSE University of Basel
Aurora, CO Attending Anesthesiologist Switzerland
Children’s Hospital of Philadelphia
Nina Deutsch, MD Professor of Clinical Anesthesiology Nancy L. Glass, MD, MBA, FAAP
Associate Professor Perelman School of Medicine Professor of Pediatrics and of Anesthesiology
Division of Anesthesiology, Pain and University of Pennsylvania Baylor College of Medicine and Texas
Perioperative Medicine Philadelphia, PA Children’s Hospital (Voluntary)
Children’s National Hospital Butterfly Team Physician, Houston Hospice
Washington, DC Marla B. Ferschl, MD Houston, TX
Professor of Anesthesia and Perioperative
James A. DiNardo, MD, FAAP Care Christine D. Greco, MD
Professor of Anaesthesia Division of Pediatric Anesthesia Section 2.01 Interim Chief, Division of Pain
Harvard Medical School University of California Medicine
Boston, MA San Francisco, CA Boston Children’s Hospital
Chief, Division of Cardiac Anesthesia Department of Anesthesiology, Critical Care
Francis X. McGowan Jr. MD Chair in Jonathan D. Finder, MD and Pain Medicine
Cardiac Anesthesia Director, Program for Technology Boston, MA
Boston Children’s Hospital Dependent Children
Boston, MA Professor, University of Tennessee Health Eliot Grigg, MD
Science Center Associate Professor
Laura A. Downey, MD Le Bonheur Children’s Hospital Department of Anesthesiology and Pain
Assistant Professor of Anesthesiology and Memphis, TN Medicine
Pediatrics University of Washington
Emory University School of Medicine Sean Flack, MBChB, DA, FCA Seattle Children’s Hospital
Children’s Healthcare of Atlanta Associate Professor, Anesthesiology and Pain Seattle, WA
Atlanta, GA Medicine
Director, Clinical Anesthesia Services Lorelei Grunwaldt, MD
John B. Eck, MD University of Washington Associate Professor of Plastic Surgery,
Associate Professor of Anesthesiology and Seattle Children’s Hospital Division of Pediatric Plastic Surgery
Pediatrics Seattle, WA Plastic Surgery
Duke University UPMC Children’s Hospital of Pittsburgh
Durham, NC Randall P. Flick, MD Pittsburgh, PA
Consultant
Peter Ehrlich, MD, MSC Department of Anesthesiology and Nina A. Guzzetta, MD, FAAP
Professor of Pediatric Surgery Perioperative Medicine, Mayo Clinic Professor of Anesthesiology and Pediatrics
Department of Surgery Assistant Professor in Anesthesiology Emory University School of Medicine
University of Michigan CS Mott Children’s College of Medicine, Mayo Clinic Children’s Healthcare of Atlanta
Hospital Rochester, MN Atlanta, GA
Ann Arbor, MI
Jeffrey L. Galinkin, MD Dawit T. Haile, MD
Demetrius Ellis, MD Anesthesiologist Consultant
Pediatrics US Anesthesia Partners Department of Anesthesiology and
University of Pittsburgh School of Medicine Greenwood Village, CO Perioperative Medicine, Mayo Clinic
UPMC Children's Hospital of Pittsburgh Assistant Professor in Anesthesiology
Pittsburgh, PA College of Medicine, Mayo Clinic
Rochester, MN
viii CONTRIBUTORS
Denise M. Hall-Burton, MD, FAAP Robert S. Holzman, MD, MA (Hon), FAAP Todd J. Kilbaugh
Assistant Professor Senior Associate in Perioperative Anesthesia Associate Professor of Anesthesiology,
Department of Anesthesiology and Boston Children’s Hospital Critical Care, and Pediatrics
Perioperative Medicine Professor of Anaesthesia Department of Anesthesiology and Critical
University of Pittsburgh School of Medicine Harvard Medical School Care Medicine
UPMC Children’s Hospital of Pittsburgh Department of Anesthesiology, Critical Perelman School of Medicine at the
Pittsburgh, PA Care and Pain Medicine University of Pennsylvania
Boston Children’s Hospital Children’s Hospital of Philadelphia
Gregory B. Hammer, MD Boston, MA Philadelphia, PA
Professor
Anesthesiology, Perioperative and Vincent C. Hsieh, MD, MS Anjali Koka, MD
Pain Medicine, and Pediatrics Associate Professor Department of Anesthesia
Stanford University School of Medicine Department of Anesthesiology and Pain Critical Care and Pain Medicine
Stanford, CA Medicine Boston Children’s Hospital
University of Washington Harvard Medical School
Jennifer L. Hamrick, MD Seattle Children’s Hospital Boston, MA
Senior Partner Seattle, WA
Anesthesia Service Medical Group Rahul Koka, MD, MPH
Pediatric Anesthesia Elizabeth A. Hunt, MPH, PhD, MD Section Chief, Pediatric General Anesthesia
Rady Children’s Hospital Drs. David S. and Marilyn M. Zamierowski Medical Director, Pediatric Operating
San Diego, CA Director Rooms
Johns Hopkins Medicine Simulation Center Assistant Professor
Justin T. Hamrick, MD Professor Anesthesia and Critical Care Medicine
Senior Partner Departments of Anesthesiology and Critical Johns Hopkins University School of
Anesthesia Service Medical Group Care Medicine, Pediatrics Medicine
Pediatric Anesthesia Health Informatics and Health Policy and Baltimore, MD
Pediatric Critical Care Medicine Management
Rady Children’s Hospital Johns Hopkins University School of Pete G. Kovatsis, MD, FAAP
San Diego, CA Medicine Senior Associate in Perioperative Anesthesia
Baltimore, MD Director of Anesthesia for Transplantation
Helen Harvey Co-Director, Anesthesia Advanced Airway
UCSD Pediatric Critical Care Fellowship James W. Ibinson, MD, PhD Management Service
Director Assistant Professor Department of Anesthesiology, Critical Care
Pediatric Critical Care Department of Anesthesiology and and Pain Medicine
University of California, San Diego, Rady Perioperative Medicine Boston Children’s Hospital
Children’s Hospital University of Pittsburgh School of Medicine Assistant Professor of Anaesthesia
San Diego, CA Chief of Anesthesiology Harvard Medical School
VA Pittsburgh Healthcare System Boston, MA
Andrew Herlich, DMD, MD, FAAP, FASA, Pittsburgh, PA
FAAOMS(H) Tatiana Kubacki, MD
Professor Emeritus Caleb Ing Assistant Professor
Department of Anesthesiology and Associate Professor Department of Anesthesiology
Perioperative Medicine Anesthesiology College of Physicians and Surgeons
University of Pittsburgh School of Medicine Columbia University Medical Center Columbia University
Clinical Professor, Department of Dental New York, NY New York, NY
Anesthesiology
University of Pittsburgh School of Dental Amanpreet Kalsi Barry D. Kussman, MBBCh, FFA (SA), FAAP
Medicine Clinical Assistant Professor Associate Professor of Anaesthesia
Pittsburgh, PA Division of Pediatric Anesthesiology Harvard Medical School
University of Michigan Boston, MA
Monica A. Hoagland, MD Ann Arbor, MI Senior Associate in Cardiac Anesthesia
Associate Professor of Anesthesiology, Boston Children’s Hospital
Children’s Hospital Colorado Evan Kharasch, MD, PhD Boston, MA
Associate Director of Obstetric and Fetal Merel H. Harmel Professor of Anesthesiology
Anesthesia, Colorado Fetal Care Center Vice-Chair for Innovation Kirk Lalwani, MD, FRCA, MCR, FASA
University of Colorado School of Medicine Department of Anesthesiology Professor of Anesthesiology and Pediatrics
Aurora, CO Duke University School of Medicine Vice Chair for Faculty Development
Durham, NC Department of Anesthesiology and
Perioperative Medicine
Oregon Health and Science University
Portland, OR
CONTRIBUTORS ix
Mary Landrigan-Ossar Ronald S. Litman, DO, ML* Lynn Martin, MD

Senior Associate in Perioperative Anesthesia Department of Anesthesiology and Critical Professor
Anesthesiology, Perioperative and Pain Medicine Care Department of Anesthesiology and Pain
Boston Children’s Hospital The Children’s Hospital of Philadelphia Medicine
Boston, MA Professor of Anesthesiology and Pediatrics University of Washington
Perelman School of Medicine at the Seattle Children’s Hospital
Robert Scott Lang, MD University of Pennsylvania Seattle, WA
Assistant Professor of Anesthesiology and Philadelphia, PA
Pediatrics, Director of Pain Management Francis X. McGowan Jr., MD, FAAP
Anesthesiology Justin L. Lockman, MD, MSEd, FAAP William J. Greeley Endowed Chair and Director,
Division of Surgical Anesthesiology, Associate Chair, Education Pediatric Anesthesiology Research
Department of Anesthesiology and Department of Anesthesiology and Critical Professor of Anesthesiology and Critical
Perioperative Medicine Care Medicine Care Medicine
A. I. duPont Hospital for Children/Sidney Children’s Hospital of Philadelphia Attending Cardiac Anesthesiologist
Kimmel Medical College at Thomas Associate Professor of Clinical Anesthesiology Children’s Hospital of Philadelphia
Jefferson University and Critical Care University of Pennsylvania Perelman School
Wilmington, DE Perelman School of Medicine of Medicine
University of Pennsylvania
Helen Victoria Lauro, MD, MPH, MSEd, Philadelphia, PA Gregory McHugh, MD
FAAP Clinical Assistant Professor
Clinical Associate Professor of Anesthesiology Joseph Losee, MD Department of Anesthesiology and
Department of Anesthesiology Ross H. Musgrave Professor of Pediatric Perioperative Medicine
State University of New York Downstate Plastic Surgery University of Pittsburgh School of Medicine
Health Sciences University Department of Plastic Surgery UPMC Children’s Hospital of Pittsburgh
Brooklyn, NY; University of Pittsburgh Medical Center Pittsburgh, PA
Site Director of Education Pittsburgh, PA
Department of Anesthesiology Carrie C. Menser, MD
State University of New York Downstate Igor Luginbuehl, MD Associate Professor of Anesthesiology
Health Sciences University Associate Professor Division of Pediatric Anesthesiology
University Hospital of Brooklyn Pediatric Anesthesiologist Monroe Carell Jr. Children’s Hospital at
Brooklyn, NY Department of Anesthesia and Pain Vanderbilt University Medical Center/
Medicine/Division of Cardiovascular Vanderbilt University School of Medicine
Elizabeth K. Laverriere, MD, MPH, FAAP Anesthesia Nashville, TN
Assistant Professor The Hospital for Sick Children
Department of Anesthesiology and Critical Toronto, Ontario, Canada Bruce E. Miller, MD
Care Medicine Associate Professor of Anesthesiology and
Children’s Hospital of Philadelphia Jennifer R. Marin, MD, MSc Pediatrics
Perelman School of Medicine at The Associate Professor of Pediatrics and Emory University School of Medicine
University of Pennsylvania Pediatric Emergency Medicine, Medical Children’s Healthcare of Atlanta
Philadelphia, PA Director Atlanta, GA
Point-of-Care Ultrasound
Susan Lei, MD UPMC Children’s Hospital of Pittsburgh Constance L. Monitto, MD
Assistant Professor and University of Pittsburgh School of Assistant Professor
Department of Anesthesiology Medicine Director, Pediatric Acute Pain Service
College of Physicians and Surgeons UPMC Children’s Hospital of Pittsburgh Division of Pediatric Anesthesiology and
Columbia University Pittsburgh, PA Critical Care Medicine
New York, NY Johns Hopkins University School of
Brian Martin, DMD, MHCDS Medicine
David Levin, MD, FRCPC, MSc, BESc (Mech) Vice President of Medical Affairs Baltimore, MD
Pediatric Anesthesiologist UPMC Children’s Hospital of Pittsburgh
Department of Anesthesia and Pain Medicine Clinical Assistant Professor Philip G. Morgan, MD
The Hospital for Sick Children (SickKids) University of Pittsburgh School of Dental Professor
Assistant Professor Medicine Anesthesiology and Pain Medicine
Department of Anesthesia Pittsburgh, PA University of Washington
The University of Toronto Seattle, WA
Toronto, Ontario Lizabeth Martin, MD
Assistant Professor Michael L. Moritz, MD
Richard Levy Department of Anesthesiology and Pain Professor
Professor Medicine Pediatrics
Anesthesiology University of Washington University of Pittsburgh Medical Center
Columbia University Medical Center Seattle Children’s Hospital UPMC Children’s Hospital of Pittsburgh
New York, NY Seattle, WA Pittsburgh, PA
x CONTRIBUTORS
Etsuro K. Motoyama, MD, FAAP Andrew Nowalk, MD, PhD Teeda Pinyavat, MD
Professor Emeritus Associate Professor and Clinical Director Assistant Professor of Anesthesiology
Anesthesiology and Pediatrics Division of Infectious Disease Department of Anesthesiology
University of Pittsburgh School of Medicine Department of Pediatrics Columbia University Medical Center
Pittsburgh, PA UPMC Children’s Hospital of Pittsburgh New York, NY
Advisory Dean
Rebecca Nause-Osthoff University of Pittsburgh School of Medicine George Demetrios Politis, MD, MPH
Clinical Assistant Professor Pediatric Residency Program Co-Director Associate Professor of Anesthesiology and
Division of Pediatric Anesthesiology Pediatric Scientist Development Program Pediatrics
University of Michigan (PedSDP) Co-Director University of Virginia Health System
Ann Arbor, MI UPMC Graduate Medical Education Charlottesville, VA
Pittsburgh, PA
Michael E. Nemergut, MD, PhD Andrew J. Powell, MD
Consultant Julie Nyquist, PhD Chief of the Division of Cardiac Imaging
Department of Anesthesiology and Director, Master of Academic Medicine Department of Cardiology
Perioperative Medicine, Mayo Clinic Program Boston Children’s Hospital
Assistant Professor in Anesthesiology Professor, Department of Medical Education Professor of Pediatrics
College of Medicine, Mayo Clinic Chair, 2021 Innovations in Medical Harvard Medical School
Rochester, MN Education Conference Boston, MA
Keck School of Medicine of the University of
Desiree Noel Wagner Neville, MD Southern California Alexander Praslick, MD
Assistant Professor of Pediatrics and Los Angeles, CA Clinical Assistant Professor
Pediatric Emergency Medicine Department of Anesthesiology and
Associate Director of Emergency Point-of- Shelley Ohliger, MD Perioperative Medicine
Care Ultrasound Assistant Professor University of Pittsburgh School of Medicine
UPMC Children’s Hospital of Pittsburgh Department of Anesthesiology UPMC Children's Hospital of Pittsburgh
and University of Pittsburgh School of Rainbow Babies and Children’s Hospital Pittsburgh, PA
Medicine Cleveland, OH
UPMC Children’s Hospital of Pittsburgh Srijaya K. Reddy, MD, MBA
Pittsburgh, PA Michale Sung-jin Ok, MD Associate Professor of Anesthesiology
Assistant Professor of Clinical Anesthesia Division of Pediatric Anesthesiology
Thanh Nguyen, MD and Pediatrics Monroe Carell Jr. Children’s Hospital at
Department of Anesthesiology University of Cincinnati College of Medicine Vanderbilt University Medical Center/
University of Colorado Anschutz Campus Cincinnati Children’s Hospital Medical Vanderbilt University School of Medicine
Children’s Hospital of Colorado Center Nashville, TN
Aurora, CO Cincinnati, OH
Paul Reynolds, MD, FAAP
Jonathan A. Niconchuk, MD Meghna D. Patel Professor
Assistant Professor of Anesthesiology Clinical Assistant Professor in Pediatric Chief of Pediatric Anesthesiology
Division of Pediatric Anesthesiology Cardiovascular ICU/Cardiology University of Michigan
Monroe Carell Jr. Children’s Hospital at Department of Pediatrics at Stanford Ann Arbor, MI
Vanderbilt University Medical Center/ University
Vanderbilt University School of Medicine Lucile Packard Children’s Hospital Karene Ricketts, MD
Nashville, TN Palo Alto, CA Associate Professor of Anesthesiology and
Pediatrics
Julie Niezgoda, MD James Peyton, MBChB MRCP FRCA Anesthesiology
Pediatric Anesthesiology Associate in Perioperative Anesthesia University of North Carolina
Cleveland Clinic Main Campus Department of Anesthesiology, Critical Care Chapel Hill, NC
Cleveland, OH and Pain Medicine
Boston Children’s Hospital Bobbie L. Riley, MD
Ken K. Nischal, MD, FAAP, FRCOphth Assistant Professor of Anaesthesia, Harvard Department of Anesthesia
Professor Medical School Critical Care and Pain Medicine
Department of Ophthalmology Boston, MA Boston Children's Hospital
University of Pittsburgh School of Medicine Harvard Medical School
Pediatric Ophthalmology Division Chief Phillip M.T. Pian, MD, PhD Boston, MA
UPMC Children’s Hospital of Pittsburgh Anesthesiologist
Pittsburgh, PA Anesthesiology Service
Veterans Affairs Eastern Colorado Health
Care System
Aurora, CO
CONTRIBUTORS xi
Mark A. Rockoff, MD Donald H. Shaffner, MD Deborah Studen-Pavlovich, DMD

Vice-Chairman Associate Professor Professor and Chair
Department of Anesthesiology, Perioperative Anesthesia and Critical Care Medicine Department of Pediatric Dentistry
and Pain Medicine Johns Hopkins University School of University of Pittsburgh School of Dental
Boston Children’s Hospital Medicine Medicine
Boston, MA Baltimore, MD Pittsburgh, PA
Thomas Romanelli, MD, FAAP Allan F. Simpao, MD, MBI Lena S. Sun, MD, FAAP, D.ABA
Assistant Professor of Anesthesiology Associate Professor of Anesthesiology and Emanuel M. Papper Professor of Pediatric
Division of Pediatric Anesthesiology Critical Care Anesthesiology
Monroe Carell Jr. Children’s Hospital at Children’s Hospital of Philadelphia Professor of Anesthesiology and Pediatrics
Vanderbilt University Medical Center/ University of Pennsylvania Perelman School Executive Vice Chairman, Department of
Vanderbilt University School of Medicine of Medicine Anesthesiology
Nashville, TN Philadelphia, PA Chief, Division of Pediatric Anesthesia
College of Physicians and Surgeons
Rachael S. Rzasa Lynn, MD Erica L. Sivak, MD Columbia University
Associate Professor Assistant Professor of Anesthesiology New York, NY
Department of Anesthesiology Department of Anesthesia and Pain Medicine
University of Colorado School of Medicine Nationwide Children’s Hospital Melissa Sutcliffe
University of Colorado Hospital Pain Columbus, OH Pediatric Neuropsychologist
Management Clinic Clinical Assistant Professor
Aurora, CO Sarah M. Smith, MD Division of Pediatric Rehabilitation
Assistant Professor Medicine
Nancy Bard Samol, MD Pediatric Cardiac Anesthesiology Children’s Hospital of Pittsburgh Inpatient
Associate Professor of Pediatric Center for Pediatric and Congenital Heart Rehabilitation Unit
Anesthesiology Disease Pittsburgh, PA
Cincinnati Children’s Hospital Medical Dell Children’s Medical Center
Center University of Texas at Austin Jonathan M. Tan, MD, MPH, MBI, FASA
Cincinnati, OH Austin, TX Assistant Professor of Anesthesiology and
Spatial Sciences
Paul J. Samuels, MD Jenna H. Sobey, MD Department of Anesthesiology Critical Care
Professor of Clinical Anesthesia and Pediatrics Assistant Professor of Anesthesiology Medicine
University of Cincinnati College of Medicine Division of Pediatric Anesthesiology Children’s Hospital Los Angeles
Cincinnati Children’s Hospital Medical Monroe Carell Jr. Children’s Hospital at Keck School of Medicine at the University of
Center Vanderbilt University Medical Center/ Southern California
Cincinnati, OH Vanderbilt University School of Medicine Spatial Sciences Institute at the University of
Nashville, TN Southern California
Jamie McElrath Schwartz, MD Los Angeles, CA
Division Chief, Pediatric Critical Care Kyle Soltys, MD
Medicine Associate Professor Jennifer M. Thomas, BSc, STD (Edu),
Co-Director, Blalock-Taussig-Thomas Thomas E. Starzl Transplant Institute MBChB, FFA
Pediatric and Congenital Heart Center University of Pittsburgh School of Medicine Emeritus Professor Paediatric Anaesthesia
Assistant Professor UPMC Children’s Hospital of Pittsburgh Red Cross War Memorial Children's Hospital
Anesthesia and Critical Care Medicine Pittsburgh, PA Department of Anaesthesia and Perioperative
Johns Hopkins University School of Medicine
Medicine Judy H. Squires, MD University of Cape Town
Baltimore, MD Associate Professor Rondebosch, Cape Town, South Africa
Chief of Ultrasound Imaging
Deborah A. Schwengel, MD Associate Program Director, Diagnostic Stevan P. Tofovic, MD, PhD, FAHA, FASN
Associate Professor Radiology Residency Associate Professor of Pharmacology and
Department of Anesthesiology and Critical Department of Radiology Chemical Biology and Medicine
Care Medicine University of Pittsburgh School of Medicine Department of Pharmacology and Chemical
Johns Hopkins University School of UPMC Children’s Hospital of Pittsburgh Biology
Medicine Pittsburgh, PA University of Pittsburgh School of Medicine
Baltimore, MD Pittsburgh, PA
Eric T. Stickles, MD
Victor L. Scott Assistant Professor of Anesthesiology and
Director Abdominal Transplant Pediatrics
Anesthesiology Alfred I. duPont Hospital for Children/
Avera Transplant Institute Sidney Kimmel Medical College at
Avera McKennan University Hospital Thomas Jefferson University
Sioux Falls, SD Wilmington, DE
xii CONTRIBUTORS
Lieu Tran, MD Keith M. Vogt, MD, PhD Eric P. Wittkugel, MD, FAAP
Assistant Professor Assisant Professor Associate Professor of Anesthesiology and
Department of Anesthesiology and Department of Anesthesiology and Pediatrics
Perioperative Medicine Perioperative Medicine Cincinnati Children’s Hospital Medical
University of Pittsburgh School of Medicine Bioengineering and Center for the Neural Center
UPMC Children’s Hospital of Pittsburgh Basis of Cognition Cincinnati, OH
Pittsburgh, PA University of Pittsburgh School of Medicine
Pittsburgh, PA Samuel Yanofsky, MD, MSEd
Premal M. Trivedi, MD Professor of Anesthesiology
Associate Professor of Anesthesiology Andrew Waberski, MD Vice Chair of Education
Department of Anesthesiology, Perioperative, Assistant Professor Department of Anesthesiology and Critical
and Pain Medicine, Division of Pediatric Division of Anesthesiology, Pain and Care Medicine
Cardiovascular Anesthesiology Perioperative Medicine Children’s Hospital Los Angeles
Texas Children’s Hospital, Baylor College of Children’s National Hospital
Medicine Washington, DC Myron Yaster, MD
Houston, TX Professor of Anesthesiology, Critical Care
Jeffrey R. Wahl, JD Medicine, and Pediatrics
Chinwe Unegbu, MD President and Co-Founder Johns Hopkins University School of Medicine
Assistant Professor MIDAS Healthcare Solutions, Inc. Retired
Division of Anesthesiology, Pain and Cleveland, OH Baltimore, MD
Perioperative Medicine
Children’s National Hospital Ari Y. Weintraub, MD Steven Zgleszewski, MD, FAAP
Washington, DC Assistant Professor of Clinical Anesthesiology Associate in Anesthesia
and Critical Care Anesthesiology, Perioperative and Pain
Samuel M. Vanderhoek Anesthesiology Medicine
Assistant Professor Perelman School of Medicine at the Boston Children’s Hospital
Department of Anesthesiology and Critical University of Pennsylvania Boston, MA
Care Medicine Children’s Hospital of Philadelphia
Johns Hopkins School of Medicine Philadelphia, PA Basil J. Zitelli, MD
Baltimore, MD Professor Emeritus
Timothy P. Welch, MD, MSPH Department of Pediatrics
Lisa Vecchione, DMD, MDS* Associate Professor of Anesthesiology and University of Pittsburgh School of Medicine
Director, Orthodontic Services Pediatrics UPMC Children’s Hospital of Pittsburgh
Cleft-Craniofacial Center Children’s Hospital and Medical Center Pittsburgh, PA
Children’s Hospital of Pittsburgh of UPMC University of Nebraska
Assistant Clinical Professor of Surgery College of Medicine Aaron L. Zuckerberg, MD
University of Pittsburgh School of Medicine Omaha, NE Children’s Diagnostic Center
Pittsburgh, PA North American Partners of Anesthesia
Emmett E. Whitaker, MD Sinai Hospital of Baltimore
Chido Vera, MD, MPH Associate Professor Baltimore, MD
Assistant Professor Departments of Anesthesiology, Neurological
Department of Radiology Sciences, & Pediatrics
VIDEO CONTRIBUTOR – SMITH
University of Vermont Larner College of
UPMC Children’s Hospital of Pittsburgh Medicine TALKS: A LECTURE-SEMINAR
Pittsburgh, PA Burlington, VT Peggy P. McNaull, MD
John Rowlingson Professor and Chair
Adriana M. Vieira, DDS, DMD, MS, PhD Robert K. Williams, MD Department of Anesthesiology
Professor and Chair University of Vermont Larner College of University of Virginia School of Medicine
Department of Pediatric Dentistry Medicine Charlottesville, VA, USA
University of Pittsburgh School of Dental Department of Anesthesiology
Medicine Burlington, VT
Pittsburgh, PA
*Deceased
P R E FA C E
Dr. Robert Smith, a distinguished pioneer in pediatric anesthesia and a great teacher and clinician, wrote the
first edition of this book in 1959, a book subsequently referred to as “the bible” of pediatric anesthesia. The
foreword to the first edition was written by the famous pediatric surgeon Robert E. Gross, the William E.
Ladd Professor of Children’s Surgery at the Harvard Medical School. Though his words in the foreword were
written over 60 years ago, at a time when the specialty of pediatric anesthesia and surgery was in its infant
stages, his words and ideas are still poignant and insightful today.
During the past decade surgery has made important strides in providing safer and improved methods for
handling various problems in infancy and childhood, indeed now making it possible to correct some condi-
tions that were previously thought to be entirely hopeless. Many factors have contributed to these dramatic
advances in pediatric surgery. Outstanding among them is the work of anesthesiologists who have focused
on the field and have provided well-standardized procedures for carrying small and critically ill patients
through operations on literally all portions and every system of the body. The surgeon realizes that the
chances for success or failure are determined in great measure by the capabilities of the person at the head
of the table who is administering the anesthetic.
In some medical circles, there seems to be an attitude that the surgical operator is managing the show; in
others, the anesthetist has an overly possessive feeling toward the patient. Neither approach is proper. It
is best for each to be cognizant of one’s own problems and also to know of the other’s difficulties; both must
work together for total care of the patient. Certainly, this is the most pleasant way to work, and surely it
is the most effective way to conduct a child through a surgical ordeal.
Since the initial printing of this textbook in 1959, the book has been markedly transformed in its content and
in its appearance. The book has gone from mainly a single- to a multi-author book and from a 400-page 70
by 100 book to a 1500-page 11.50 by 8.50 text with an online version. As learning styles have changed, so has
the format of this book. The book uses multimedia presentations to supplement, emphasize, and reinforce
concepts of pediatric anesthesia. However, even with the increases in page number, new information, and
media platforms, the basic tenets of anesthesia care and patient compassion, the legacy and tradition of the
nine previous editions have been retained.
The tenth edition has been prepared with the same considerations as the previous editions: to give anesthe-
siology care providers comprehensive coverage of physiology, pharmacology, and clinical anesthetic man-
agement of infants and children of all ages. The tenth edition has been reorganized into eight main sections.
Part I, Basic Principles and Physiology, contains updated chapters on behavioral development and respira-
tory, cardiovascular, renal, and thermal physiology.
Part II, Pharmacology, now has additional authors with specific chapters in developmental pharmacology,
intravenous anesthetic agents, inhaled anesthetic agents, opioids, local anesthetic agents, neuromuscular
blocking agents, and anesthetic adjuncts.
Part III, General Approach, addresses the basic concepts of caring for children and the principles involved in
the administration of anesthetics to children. The chapters have all been updated. Two new chapters have been
added to Part III: Normal and Difficult Airway Management and Point of Care Ultrasonography.
Part IV is a new section dedicated to Pain Management. It includes updated chapters on acute pain manage-
ment and regional anesthesia. The chapter on regional anesthesia has added some new authors with an
emphasis on ultrasound techniques. The reader will also be able to access video demonstrations of specific
regional anesthetic techniques in children. Part IV also has new chapters: Chronic Pain Management and
Palliative Pain Management.
Part V, Clinical Management of Specialized Surgical Problems, contains material written by new authors.
New authors for chapters on Anesthesia and Sedation for Out of OR Procedures, Pediatric Sedation, and
Medical Missions have been added. The chapter on Solid Organ Transplantation has been updated and also
contains new authors. The use of video has been maintained in a variety of chapters to further supplement
the clinical material. The chapter on Neonatology for Anesthesiologists has been revised into a comprehen-
sive work that updates the anesthesia provider with perinatal outcome data and serves as a primer for pedi-
atric anesthesiologists to better understand the pathophysiology of prematurity and the developmental
xiii
xiv PREFACE
physiology that occur with neonatal growth. This chapter also serves as a rich resource for the chapters on
Anesthesia for General Surgery in Neonates and Anesthesia for Fetal Surgery.
In view of the significant number of disorders that pediatric anesthesiologists are confronted with in the
everyday care of their patients, Part VI, Systemic Disorders and Associated Problems, was created to better
organize and provide information for both unusual patient diseases and to address everyday common peri-
operative anesthetic concerns. All of the chapters in this part have been updated. The chapter on Dermatol-
ogy for the Anesthesiologist has an extensive number of figures (both in the book and online) of lesions and
rashes that anesthesiologists frequently encounter. A new chapter on Infectious Diseases has been added to
this part.
Part VII, Critical Care in Pediatric Anesthesia, contains revised chapters on critical care medicine, cardiac
intensive care, and cardiopulmonary resuscitation. The Cardiopulmonary Resuscitation chapter contains
the latest (2020) recommendations from the American Heart Association.
Part VIII, Special Topics, includes updated chapters on Safety and Outcome in Pediatric Anesthesia, History
of Pediatric Anesthesia, Medicolegal and Ethical Aspects of Pediatric Anesthesia, and Statistics. A new chap-
ter on Education has been added. This chapter focuses on the role of education and provides guidance to
those who engage in teaching the specialty of pediatric anesthesiology as part of postgraduate training. The
education chapter is organized into six sections and uses “mind maps” (a graphic image of the key concepts)
to provide a quick overview of each of the chapter’s sections.
In keeping with advancements in technology, this edition is in color, and text material is further supple-
mented by a website. Videos of airway techniques, single-lung isolation, regional anesthesia, the use of
ultrasound, and anatomic dissections of congenital heart lesions are accessible with just a click of the mouse.
In addition, supplemental materials on organ transplantation, airway lesions, and pediatric syndromes
remain available.
The appendices, which can be found online at

ExpertConsult.com, include an updated list of
drugs and their dosages, normal growth curves,
normal values for pulmonary function tests in
children, and an expanded list of common and
uncommon syndromes of clinical importance for
pediatric anesthesiologists.
Finally, this edition, like the previous edition, also

includes online multiple-choice questions with an-
swers and explanations. As with any learning pro-
cess, it is important for the reader to have some
method to affirm that they understand the salient
features and to reinforce the learning process. Most
chapters have associated questions to aid the reader
in understanding the material.
In summary, considerable developments and prog-

ress in the practice of pediatric anesthesia are re-
flected in this new edition. The emphasis on the
safety and well-being of young patients during the
perianesthetic period remains unchanged—just as
Dr. Smith would have wanted.
Peter J. Davis, MD, FAAP

AC K N OW L E D G M E N T S
The project of revising a classic medical textbook presents many opportunities and challenges, and revising
this textbook during the SARS-CoV-2 (COVID-19) pandemic—when people were stressed, isolated, and
uncertain about their futures—proved to be particularly challenging. Nonetheless, the opportunity to review
and evaluate the new developments that have emerged in pediatric anesthesia since the publication of the last
edition of Smith’s Anesthesia for Infants and Children in 2017 has been rewarding. As always, we are deeply
indebted to the extraordinary work done and commitment made by Dr. Robert M. Smith in the first four
editions that made Anesthesia for Infants and Children a classic textbook in pediatric anesthesia.
Our ability to maintain this book’s standard of excellence is not just a reflection of the many gifted con-
tributors but also a result of the level of support that we have received at work and at home. We wish to thank
the staff members of the Department of Anesthesiology at UPMC Children’s Hospital of Pittsburgh for their
support and tolerance.
Our special thanks go to Joy Holden and Patty Klein, administrative assistants, of the Department of
Anesthesiology, UPMC Children’s Hospital of Pittsburgh, for their many hours of diligent work on the
book. We are also appreciative of Dr. Basil Zitelli, Professor Emeritus of Pediatrics, University of Pittsburgh
at UPMC Children’s Hospital of Pittsburgh, for his generosity in allowing us to use many of the photo-
graphs published in his own book, Atlas of Pediatric Physical Diagnosis.
Our special thanks also go to Elsevier’s Sarah Barth, Content Strategist; Kristen Helm, Content Develop-
ment Specialist; and Julie Taylor, Project Manager, for their editorial assistance.
As with the previous editions, we are deeply indebted to our family members Katie, Evan, Zara, Will,
Hunter, and Jake Davis; Julie, Andy, Elliott, Eila, and Mugsy Peet Potash; and Joseph Losee and Hudson
Cladis Losee for remaining loyal, for being understanding, and for providing moral support throughout the
lengthy and, at times, seemingly endless project. Finally, we are indebted to our patients, who grant us the
privilege to care and learn from them and who keep us humble.
Peter J. Davis, MD, FAAP

xv
CO
G NSTSEANRTYS
LO
Contributors, vi 22 Transfusion Medicine, 455

Preface, xii Michael E. Nemergut, Dawit T. Haile, Devon O. Aganga, and
Acknowledgments, xiv Randall P. Flick
PART I Basic Principles and Physiology PART IV Pain Management

1 Special Characteristics of Pediatric Anesthesia, 2 23 Acute Pain Management, 481
Peter J. Davis, Etsuro K. Motoyama, and Franklyn P. Cladis Constance L. Monitto, Jessica A. George, and Myron Yaster
2 Behavioral Development, 11 24 Regional Anesthesia, 519
Julie Niezgoda, Melissa Sutcliffe, Caleb H. Ing, and Richard J. Levy Robert Scott Lang, Denise Hall-Burton, Alexander Praslick,
3 Respiratory Physiology, 28 and Sean Flack
Etsuro K. Motoyama and Jonathan D. Finder 25 Chronic Pain Management, 578
4 Airway Physiology and Development, 78 Bobbie L. Riley, Anjali Koka, and Christine D. Greco
Robert S. Holzman 26 Pediatric Palliative Care and Hospice, 587
5 Cardiovascular Physiology, 90 Nancy L. Glass
Andrew Waberski, Chinwe Unegbu, and Nina Deutsch
6 Regulation of Fluids and Electrolytes, 119
Michael L. Moritz and Demetrius Ellis PART V C
linical Management of Specialized
7 Thermoregulation, 158 Surgical Problems
Branden Engorn, Helen Harvey, Peter J. Davis, Igor Luginbuehl,
and Bruno Bissonnette 27 Neonatology for Anesthesiologists, 596
Marla B. Ferschl and Claire M. Brett
28 Anesthesia for General Surgery in Neonates, 669
PART II Pharmacology Sean S. Barnes, Peter J. Davis, and Claire Brett
29 Anesthesia for Fetal Surgery, 709
8 Developmental Pharmacology, 179 Monica A. Hoagland, Karen A. Dean, and Debnath Chatterjee
Stevan P. Tofovic and Evan Kharasch 30 Anesthesia for Congenital Heart Disease, 732
9 Intravenous Anesthetics, 198 Barry D. Kussman, Francis X. McGowan Jr., Andrew J. Powell, and
Brian Blasiole and Peter J. Davis James A. DiNardo
10 Inhaled Anesthetics, 213 31 Anesthesia for Neurosurgery, 832
Susan Lei, Lena S. Sun and Tatiana Kubacki Jenna H. Sobey, Jonathan A. Niconchuk, Eric T. Stickles,
11 Local Anesthetics, 228 Carrie C. Menser, and Srijaya K. Reddy
Adrian T. Bösenberg 32 Anesthesia for Thoracic Surgery, 866
12 Opioids, 233 Gregory B. Hammer
Phillip M. T. Pian, Rachael S. Rzasa Lynn, Jeffrey L. Galinkin, and 33 Anesthesia for General Abdominal, Urologic Surgery, 885
Peter J. Davis Emmett E. Whitaker, Robert K. Williams, Helen Victoria Lauro, Rajeev
13 Neuromuscular Blocking Agents, 257 Chaudhry, and Peter J. Davis
John B. Eck 34 Anesthesia for Otorhinolaryngologic Surgery, 917
14 Anesthetic Adjuncts, 279 Samuel M. Vanderhoek, Nicholas M. Dalesio, and Deborah A. Schwengel
Erica L. Sivak and Denise M. Hall-Burton 35 Anesthesia for Plastic Surgery, 945
Franklyn P. Cladis, Lorelei Grunwaldt, and Joseph Losee
PART III General Approach 36 Anesthesia for Orthopedic Surgery, 969
Aaron L. Zuckerberg, Thanh Nguyen, and Myron Yaster
15 Psychological Aspects of Pediatric Anesthesia, 289 37 Anesthesia for Ophthalmic Surgery, 1001
Kirk Lalwani and Erin Conner Karene Ricketts and Ken Nischal
16 Preoperative Preparation, 302 38 Solid Organ Transplantation, 1024
Franklyn P. Cladis and Peter J. Davis Phillip S. Adams, Brian Blasiole, Peter J. Davis, Gregory McHugh,
17 Equipment, 328 Victor L. Scott, and Kyle Soltys
Allan Simpao, Jeffrey M. Feldman, and David E. Cohen 39 Anesthesia for Conjoined Twins, 1062
18 Monitoring, 358 Jennifer M. Thomas
Jonathan M. Tan and David E. Cohen 40 Anesthesia for Pediatric Trauma, 1083
19 Normal and Difficult Airway Management, 382 Rebecca Nause-Osthoff, Paul Reynolds, Aman Kalsi, Peter Ehrlich,
Pete G. Kovatsis, James Peyton, Edward B. Cooper, and Peter J. Davis Franklyn P. Cladis, and Peter J. Davis
20 Point-of-Care Ultrasonography, 405 41 Anesthesia for Burns, 1113
Desiree Noel Wagner Neville and Jennifer R. Marin Thomas Romanelli
21 Induction, Maintenance, and Recovery, 423
Shelley Ohliger, Jessica Cronin, and Nina Deutsch
xvi
CONTENTS xvii
42 Anesthesia for Dental Procedures, 1132 55 Dermatology for the Anesthesiologist, 1343
Andrew Herlich, Franklyn P. Cladis, Deborah Studen-Pavlovich, Thomas M. Chalifoux, Sylvia Choi, and Basil J. Zitelli
Adriana M. Vieira, Brian Martin, Mary Chapman, and Lisa Vecchione 56 Infectious Diseases, 1358
43 Anesthesia and Sedation for Out-of-Operating-Room Andrew Nowalk
Procedures, 1148
Lieu Tran, Judy Squires, Chido Vera, and Brian Blasiole
44 Pediatric Sedation, 1168 PART VII C
ritical Care in Pediatric
Mary Landrigan-Ossar and Joseph P. Cravero Anesthesia
45 Anesthesia for Surgical Missions, 1184
George Demetrios Politis 57 Cardiopulmonary Resuscitation, 1365
Jamie McElrath Schwartz, Rahul Koka, Justin T. Hamrick,
Jennifer L. Hamrick, Elizabeth A. Hunt, and Donald H. Shaffner
PART VI S
ystemic Disorders and Associated 58 Critical Care Medicine, 1413
Problems Elizabeth K. Laverriere, Benjamin Bruins, and Justin L. Lockman
59 Cardiac Critical Care Medicine, 1425
46 Endocrine Disorders, 1199 James Fehr, Meghna Patel, and Timothy Welch
Benjamin B. Bruins, Todd J. Kilbaugh, and Ari Y. Weintraub
47 Respiratory Disorders, 1214
Sarah M. Smith and Premal M. Trivedi
PART VIII Special Topics
48 Cardiovascular Disorders, 1238 60 Safety and Outcome in Pediatric Anesthesia, 1444
Phillip S. Adams Eliot Grigg, Lizabeth Martin, and Lynn Martin
49 Hematology and Coagulation Disorders, 1251 61 History of Pediatric Anesthesia, 1462
Nina A. Guzzetta, Laura A. Downey, and Bruce E. Miller David Levin and Mark A. Rockoff
50 Oncologic Disorders, 1282 62 Medicolegal and Ethical Aspects
Steven Zgleszewski, Franklyn P. Cladis, and Peter J. Davis of Pediatric Anesthesia, 1478
51 Genetic and Muscular Disorders, 1295 Jessica Davis and Jeffrey R. Wahl
Ashley A. Colletti, Philip G. Morgan, and Vincent C. Hsieh 63 Education, 1488
52 Malignant Hyperthermia, 1305 Samuel Yanofsky, Ira Todd Cohen, Franklyn P. Cladis, and Julie Nyquist
Teeda Pinyavat, Thierry Girard, and Ronald S. Litman 64 Statistics, 1499
53 Pediatric Obesity, 1319 James W. Ibinson and Keith M. Vogt
Paul J. Samuels and Michale Sung-jin Ok
54 Special Pediatric Disorders, 1330 Abbreviations, 1510
Eric P. Wittkugel and Nancy Bard Samol Index, 1516
*Deceased
PA R T I
Basic Principles and
Physiology
1. Special Characteristics of Pediatric 5. Cardiovascular Physiology, 90
Anesthesia, 2
6. Regulation of Fluids and Electrolytes, 119
2. Behavioral Development, 11
7. Thermoregulation, 158
3. Respiratory Physiology, 28
4. Airway Physiology and Development, 78
1
1
Special Characteristics of Pediatric Anesthesia
Peter J. Davis, Etsuro K. Motoyama, Franklyn P. Cladis
OUTLINE
Introduction, 2 Anatomic and Physiologic Differences, 7
Perioperative Monitoring, 2 Body Size, 7
Anesthetic Agents, 3 Relative Size or Proportion, 7
Airway Devices and Adjuncts, 4 Central and Autonomic Nervous Systems, 8
Intraoperative and Postoperative Analgesia in Neonates, 5 Respiratory System, 9
Point of Care Ultrasound, 5 Cardiovascular System, 9
Regional Analgesia in Infants and Children, 5 Fluid and Electrolyte Metabolism, 9
Fundamental Differences in Infants and Children, 6 Temperature Regulation, 9
Psychological Differences, 6 Summary, 10
Differences in Response to Pharmacologic Agents, 6
INTRODUCTION many anesthesiologists monitored only the heart rate in infants and
In the past few decades, new scientific knowledge of physiology and small children during anesthesia and surgery. Electrocardiographic
pharmacology in developing humans and technologic advancements and blood pressure measurements were either too difficult or too ex-
in equipment and monitoring have markedly changed the practice of travagant and were thought to provide little or no useful information.
pediatric anesthesia. In addition, further emphasis on patient safety Measurements of central venous pressure were thought to be inaccu-
(e.g., correct side-site surgery, correct patient identification, correct rate and too invasive, even in major surgical procedures. The insertion
procedure, appropriate prophylactic antibiotics) coupled with ad- of an indwelling urinary (Foley) catheter in infants was considered
vances in minimally invasive pediatric surgery have created a need invasive, and surgeons resisted its use.
for better pharmacologic approaches to infants and children and Smith also added an additional physiologic monitoring: soft, latex
improved skills in pediatric anesthetic management. blood pressure cuffs suitable for newborn and older infants, which
As a result of the advancements and emphasis on pediatric subspe- encouraged the use of blood pressure monitoring in children (Smith
cialty training and practice, the American Board of Anesthesiology has 1968). The Smith cuff (see Chapter 61: History of Pediatric Anesthesia;
now come to recognize the subspecialty of pediatric anesthesiology in Fig. 61.7) remained the standard monitoring device for infants and
its certification process, and the first subspecialty board examination children until the late 1970s, when automated blood pressure devices
was administered in 2013. began to replace them.
The introduction of pulse oximetry for routine clinical use in the early
1990s has been the single most important development in monitoring and
PERIOPERATIVE MONITORING patient safety, especially related to pediatric anesthesia, since the advent of
In the 1940s and 1950s, the techniques of pediatric anesthesia, and the the precordial stethoscope in the 1950s (Smith 1956) (see Chapter 17:
skills of those using and teaching them, evolved more as an art than Equipment; Chapter 18: Monitoring). Pulse oximetry is superior to clini-
as a science, as Dr. Robert Smith (now deceased) vividly and elo- cal observation and other means of monitoring, such as capnography,
quently recollected through his firsthand experiences in his chapter for the detection of intraoperative hypoxemia (Coté et al. 1988, 1991). In
on the history of pediatric anesthesia (see Chapter 61: History of Pe- addition, Spears and colleagues (1991) have indicated that experienced
diatric Anesthesia, updated by Mark A. Rockoff and David Neville pediatric anesthesiologists may not have an “educated hand” or a “feel”
Levine). The anesthetic agents and methods available were limited, as adequate to detect changes in pulmonary compliance in infants. Pulse
was the scientific knowledge of developmental differences in organ oximetry has revealed that postoperative hypoxemia occurs commonly
system function and anesthetic effect in infants and children. Moni- among otherwise healthy infants and children undergoing simple surgical
toring pediatric patients was limited to inspection of chest movement procedures, presumably as a result of significant reductions in functional
and occasional palpation of the pulse until the late 1940s, when Smith residual capacity (FRC) and resultant airway closure and atelectasis
introduced the first physiologic monitoring to pediatric anesthesia by (Motoyama and Glazener 1986). Consequently, the use of supplemental
using the precordial stethoscope for continuous auscultation of heart- oxygen in the postanesthesia care unit (PACU) has become a part of
beat and breath sounds (Smith 1953, 1968). Until the mid-1960s, routine postanesthetic care (see Chapter 3: Respiratory Physiology).
2
CHAPTER 1 Special Characteristics of Pediatric Anesthesia 3
Although pulse oximetry greatly improved patient monitoring,

there were some limitations, namely, motion artifact and inaccuracy in
ANESTHETIC AGENTS
low-flow states and in children with levels of low oxygen saturation More than a decade after the release of isoflurane for clinical use, two
(e.g., cyanotic congenital heart disease). Advances have been made in volatile anesthetics, desflurane and sevoflurane, became available in
the new generation of pulse oximetry, most notably through the use of the 1990s in most industrialized countries. Although these two agents
Masimo Signal Extraction Technology (SET). This device minimizes are dissimilar in many ways, they share common physiochemical and
the effect of motion artifact, improves accuracy, and has been shown pharmacologic characteristics: very low blood gas partition coeffi-
to have advantages over the existing system in low-flow states, mild cients (0.4 and 0.6, respectively), which are close to those of nitrous
hypothermia, and moving patients (Malviya et al. 2000; Hay et al. oxide and are only fractions of those of halothane and isoflurane; rapid
2002; Irita et al. 2003). induction of and emergence from surgical anesthesia; and hemody-
Trending of hemoglobin (Hgb) can also be performed with oxim- namic stability (See Chapter 10: Inhaled Anesthetic Agents; Chapter 21:
etry. Noninvasive pulse cooximetry (SpHb) has been used in both Induction, Maintenance, and Recovery). In animal models, the use of
children and neonates to measure SpHb. Pulse cooximetry uses pulse inhaled anesthetic agents has been shown to attenuate the adverse ef-
oximeter technology that involves sensors with light emitting diodes fects of ischemia in the brain, heart, and kidneys, whereas other studies
of many wavelengths. Patino and colleagues (2014) demonstrated in have raised concerns regarding the anesthetic agents causing neurotox-
children undergoing major surgical procedures with anticipated sub- icity in infants and children. (See Chapter 2: Behavioral Development.)
stantial blood loss that SpHb followed the trend in invasively measured Although these newer, less soluble inhaled agents allow for faster
Hgb with respect to bias and precision and that the trend accuracy was emergence from anesthesia, emergence excitation or delirium associ-
better than the absolute accuracy. In both term and preterm neonates ated with their use has become a major concern to pediatric anesthe-
who weighed less than 3000 g at birth, Nicholas and colleagues (2015) siologists (Davis et al. 1994; Sarner et al. 1995; Lerman et al. 1996;
noted a good agreement between the noninvasive SpHb and the inva- Welborn et al. 1996; Cravero et al. 2000; Kuratani and Oi 2008).
sive Hgb. In a study of adults and children, Park and colleagues (2018) Adjuncts, such as opioids, analgesics, serotonin antagonists, and
noted that the difference between lab-measured Hgb and SpHb was a1-adrenergic agonists, have been found to decrease the incidence of
less in children than in adults. emergence agitation (Aono et al. 1999; Davis et al. 1999a; Galinkin
Monitoring of cerebral function and blood flow, as well as infrared et al. 2000; Cohen et al. 2001; Ko et al. 2001; Kulka et al. 2001; Voepel-
brain oximetry, has advanced the anesthetic care and perioperative Lewis et al. 2003; Lankinen et al. 2006; Aouad et al. 2007; Tazeroualti
management of infants and children with congenital heart disease and et al. 2007; Bryan et al. 2009; Erdil et al. 2009; Kim et al. 2009; Hauber
traumatic brain injuries. Depth of anesthesia can be difficult to assess et al. 2015).
in children, and anesthetic overdose was a major cause of anesthesia- Propofol has increasingly been used in pediatric anesthesia as an
associated cardiac arrest and mortality. Depth-of-anesthesia monitors induction agent, for intravenous sedation, or as the primary agent of a
(bisectral index monitor [BIS], Patient State Index, Narcotrend) have total intravenous anesthetic technique (Martin et al. 1992). Propofol
been used in children and have been associated with the administra- has the advantage of aiding rapid emergence and causes less nausea
tion of less anesthetic agent and faster recovery from anesthesia. How- and vomiting during the postoperative period, particularly in children
ever, because these monitors use electroencephalography and a sophis- with a high risk for vomiting. When administered as a single dose
ticated algorithm to predict consciousness, the reliability of these (1 mg/kg) at the end of surgery, propofol has also been shown to de-
monitors in children younger than 1 year of age is limited. crease the incidence of sevoflurane-associated emergence agitation
More recently, interest has developed in the use of noninvasive (Aouad et al. 2007).
monitors to assess fluid responsiveness. Static variables (central venous Dexmedetomidine is an a1-adrenergic agonist approved for use as
pressure, pulmonary artery wedge pressure, and left ventricle area) are a sedation agent for adult ICU patients (Mason and Lerman 2011). In
not reliable predictors of fluid responsiveness. Dynamic indicators that pediatrics, off-label use of dexmedetomidine is common and has been
are based on cardiopulmonary interactions in mechanically ventilated used in the settings of procedural sedation and ICU sedation. It also
patients, such as aortic peak velocity, systolic blood pressure variation has been administered as an adjunct to general anesthesia in order to
(SPV), pulse pressure variation (PPV), and pleth variability index decrease both opioid and inhalational anesthetic requirements. It has
(PVI), have been shown to be predictive in adults. In children, the re- been used to treat supraventricular tachycardia and junctional ectopic
sults of studies involving dynamic variables have been mixed, but it tachycardia in pediatric cardiac patients and has been used successfully
appears that aortic peak velocity is a reliable indicator of fluid respon- for both prophylaxis and treatment of emergence agitation in postop-
siveness (Marik et al. 2009; Feldman et al. 2012; Byon et al. 2013; erative surgical patients (Erdil et al. 2009; Jooste et al. 2010; Gupta
Gan et al. 2013; Pinsky 2014; Nicholas et al. 2015). et al. 2013; Sun et al. 2014). In order to attenuate the biphasic hemo-
In addition to advances in monitors for individual patients, hospi- dynamic response of dexmedetomidine, the package insert recom-
tal, patient, and outside agency initiatives have focused on more global mends infusing the drug over 10 minutes. However, studies involving
issues. Issues of patient safety, side-site markings, time-outs, and rapid bolus administration (less than 3 seconds) of dexmedetomidine
proper patient identification, together with appropriate administra- in both healthy children and children who had received a heart trans-
tion of prophylactic antibiotics, have now become major priorities for plant demonstrated minimal clinical significance (Jooste et al. 2010;
healthcare systems. World Health Organization (WHO) checklists are Dawes et al. 2014; Hauber et al. 2015).
positive initiatives that have ensured that the correct procedure is per- Remifentanil, a µ-receptor agonist, is metabolized by nonspecific
formed on the correct patient and have fostered better communication plasma and tissue esterases. The organ-independent elimination of
among healthcare workers. In anesthesia, patient safety continues to be remifentanil, coupled with its clearance rate (highest in neonates and
a mantra for the specialty. Improved monitoring, better use of anes- infants compared with older children), makes its kinetic profile differ-
thetic agents, and the development of improved airway devices, cou- ent from that of any other opioid (Davis et al. 1999b; Ross et al. 2001).
pled with advancements in minimally invasive surgery, continue to In addition, its ability to provide hemodynamic stability, coupled with
advance the frontiers of pediatric anesthesia as a specialty medicine its kinetic profile of rapid elimination and nonaccumulation, makes
and improve patient outcomes and patient safety. it an attractive anesthetic option for infants and children. Numerous
4 PART 1 Basic Principles and Physiology
clinical studies have described its use for pediatric anesthesia (Wee Equipment; Chapter 19: Normal and Difficult Airway Management).
et al. 1999; Chiaretti et al. 2000; Davis et al. 2000, 2001; German et al. The importance of these advanced airway devices cannot be over-
2000; Dönmez et al. 2001; Galinkin et al. 2001; Keidan et al. 2001b; stated, as evidenced by their use in the algorithms for the difficult
Chambers et al. 2002; Friesen et al. 2003). When combined, intrave- pediatric airway (Park et al. 2017; Garcia-Marcinkiewicz et al. 2019;
nous hypnotic agents (remifentanil and propofol) have been shown to Fiadjoe and Nishisaki 2020).
be as effective and of similar duration as propofol and succinylcholine The variety of pediatric endotracheal tubes (ETTs) has focused on
for tracheal intubation. improved materials and designs. ETTs are sized according to the inter-
The development of more predictable, shorter-acting anesthetic nal diameter; however, the outer diameter (the parameter most likely
agents (see Part II: Pharmacology) has increased the opportunities for involved with airway complications) varies according to the manufac-
pediatric anesthesiologists to provide safe and stable anesthesia with turer (Table 1.1). Tube tips are both flat and beveled, and a Murphy eye
less dependence on the use of neuromuscular blocking agents. may or may not be present. The position of the cuff varies with the
Remimazolam is a new benzodiazepine that is metabolized by tissue manufacturer. The use of cuffed endotracheal tubes in pediatrics con-
carboxylesterases to an inactive metabolite. In adult volunteers it tinues to be controversial. In a multicenter, randomized prospective
is rapidly metabolized with fast onset and recovery times and has study of 2246 children from birth to 5 years of age undergoing general
moderate hemodynamic effect (Masui 2020; Schüttler et al. 2020). anesthesia, Weiss and colleagues (2009) noted that cuffed ETTs com-
pared with uncuffed ETTs did not increase the risk for postextubation
stridor (4.4% vs. 4.7%) but did reduce the need for ETT exchanges
AIRWAY DEVICES AND ADJUNCTS (2.1% vs. 30.8%), thereby reducing the possibility of additional trauma
Significant changes in pediatric airway management that have patient from multiple intubation attempts.
safety implications have emerged over the past few years. The laryngeal There has been a recent gradual but steady trend toward the routine
mask airway (LMA), in addition to other supraglottic airway devices and exclusive use of cuffed ETTs in pediatric anesthesia, including in
(e.g., the King LT-D, the Cobra pharyngeal airway), has become an infants (Dullenkopf et al. 2005; Weiss et al. 2009; Litman and Maxwell
integral part of pediatric airway management. Although the LMA is 2013; Tobias 2015). Murat (2001) was the first to propose the use of
not a substitute for the endotracheal tube, it can be safely used for cuffed ETTs exclusively for children of all ages with the record of no
routine anesthesia in both spontaneously ventilated patients and pa- complications without using uncuffed ETTs for a 3-year span in a
tients requiring pressure-controlled support (Keidan et al. 2001a). The major children’s hospital in Paris. The change in practice of not using
LMA can also be used in the patient with a difficult airway to aid in uncuffed ETT is due to the recognition that the shape of the glottic
ventilation and to act as a conduit to endotracheal intubation both opening at the cricoid ring, the narrowest fixed diameter in the upper
with and without a fiber optic bronchoscope. airways, is more elliptic in shape than circular, with a larger anteropos-
In addition to supraglottic devices, advances in technology for vi- terior (AP) diameter and a narrower transverse diameter (Dalal et al.
sualizing the airway have improved patient safety. Since the larynx 2009; Litman and Maxwell 2013). These findings mean that the most
could be visualized, at least 50 devices intended for laryngoscopy have appropriately sized uncuffed ETT (,20 cm H2O leak pressure) would
been invented. The newer airway visualization devices have combined compress the lateral wall mucosa of the cricoid, causing ischemia
better visualizations, video capabilities, and high resolution. even when there are enough anteroposterior spaces left for air leaks
The development and refinement of airway visualization equip- (Motoyama 2009). A recently developed thin-walled (with smaller
ment such as the McGrath, C-MAC, and Glidescope have added more outer diameter), cuffed endotracheal tube specifically designed for
options to the management of the pediatric airway and literally give pediatric anesthesia (Microcuff by Kimberly-Clark) has two major
the laryngoscopist the ability to see around corners (see Chapter 17: modifications: the cuff is made of ultrathin polyurethane, allowing a
TABLE 1.1 Measured Outer Diameters of Pediatric Cuffed Tracheal Tubes According
to the Internal Diameter of Tracheal Tubes Supplied by Different Manufacturers
ID Tracheal Tube Brand 2.5 3 3.5 4 4.5 5 5.5
OD (mm) Sheridan Tracheal Tube Cuffed Murphy NA 4.2 4.9 5.5 6.2 6.8 7.5
Sheridan Tracheal Tube Cuffed Magill NA 4.3 NA 5.5 NA 6.9 NA
Mallinckrodt TT High-Contour Murphy NA 4.4 4.9 5.7 6.3 7 7.6
Mallinckrodt TT High-Contour Murphy P-Series NA 4.3 5 5.7 6.4 6.7 7.7
Mallinckrodt TT Lo-Contour Magill NA 4.5 4.9 5.7 6.2 6.9 7.5
Mallinckrodt TT Lo-Contour Murphy NA 4.4 5 5.6 6.2 7 7.5
Mallinckrodt TT Hi-Lo Murphy NA NA NA NA NA 6.9 7.5
Mallinckrodt TT Safety Flex NA 5.2 5.5 6.2 6.7 7.2 7.9
Portex TT-Profile Soft Seal Cuff, Murphy NA NA NA NA NA 7 7.6
Rüsch Ruschelit Super Safety Clear Magill 4 5.1 5.3 5.9 6.2 6.7 7.2
Rüsch Ruschelit Super Safety Clear Murphy NA NA NA NA NA 6.7 7.3
Halyard Microcuff (formerly Kimberly-Clark Healthcare) NA 4.3 5.0 5.6 6.3 6.7 7.3
ID, Inner diameter; OD, outer diameter.

Modified from Weiss, M., Dullenkopf, A., Gysini, C., et al. (2004). Shortcomings of cuffed pediatric tracheal tubes. British Journal of Anaesthesia,
92, 78–88.
more effective tracheal seal at a much lower pressure than the pressure therapeutic applications in pediatric patients of all ages. In addition
known to cause tracheal mucosal necrosis, and the short cuff is located to its widely accepted role in regional anesthesia and vascular access,
more distally near the tip of the endotracheal tube shaft, allowing more ultrasonography can facilitate diagnostic procedures including airway
reliable placement of the cuff below the nondistensible cricoid ring management, pulmonary pathology like pneumothorax, fluid man-
and reducing the chance of endobronchial intubation (Dullenkopf agement, and nasogastric tube positioning. (See Chapter 20: Point of
et al. 2005; Litman and Maxwell 2013). Whether the new, more costly Care Ultrasonography.)
endotracheal tube actually reduces the incidence of intubation-related
airway injury is being investigated. REGIONAL ANALGESIA IN INFANTS
A main concern with cuffed endotracheal tubes relates to excessive
AND CHILDREN
pressure in the cuff. The exact pressure a cuff needs to exert against the
wall of the tracheal mucosae to induce ischemia is not known; recom- Although conduction analgesia has been used in infants and children
mendations range from 20 to 30 cm H2O. In an observational trial of since the beginning of the 20th century, the controversy about whether
200 pediatric patients, Tobias and colleagues (2012) noted that when anesthetic agents can be neurotoxic has caused a resurgence of interest
cuff pressures were measured, 23.5% of the patients had pressures in regional anesthesia (Abajian et al. 1984; Williams et al. 2006).
greater than 30. Various devices have been prepared to monitor intra- As newer local anesthetic agents with less systemic toxicity become
cuff pressure (Krishna et al. 2014; Ramesh et al. 2014; Kako et al. available, their role in the anesthetic/analgesic management of chil-
2015; Tobias 2015). Although the role of cuffed ETTs in neonates and dren is increasing. Studies of levobupivacaine and ropivacaine have
infants who require prolonged ventilation has yet to be determined demonstrated safety and efficacy in children that are greater than that
(Sathyamoorthy et al. 2015), it is clear that in neonates undergoing of bupivacaine, the standard regional anesthetic used in the 1990s
minimally invasive surgery, cuffed endotracheal tubes allow for more (Ivani et al. 1998, 2002, 2003; Hansen et al. 2000, 2001; Lönnqvist et al.
effective ventilation and more reliable end-tidal gas monitoring while 2000; McCann et al. 2001; Karmakar et al. 2002). A single dose of local
likely maintaining safety (de Wit et al. 2018; Thomas et al. 2018). anesthetics through the caudal and epidural spaces is most often used
for a variety of surgical procedures as part of general anesthesia and for
INTRAOPERATIVE AND POSTOPERATIVE postoperative analgesia. Insertion of an epidural catheter for continu-
ous or repeated bolus injections of local anesthetics (often with opi-
ANALGESIA IN NEONATES oids and other adjunct drugs) for postoperative analgesia has become
It has long been thought that newborn infants do not feel pain the way a common practice in pediatric anesthesia. The addition of adjunct
older children and adults do and therefore do not require anesthetic or medications, such as midazolam, neostigmine, tramadol, ketamine,
analgesic agents (Lippmann et al. 1976). Thus in the past, neonates and clonidine, to prolong the neuroaxial blockade from local anes-
undergoing surgery were often not afforded the benefits of anesthesia. thetic agents has become more popular, even though the safety of these
Later studies, however, indicated that pain experienced by neonates agents on the neuroaxis has not been determined (Ansermino et al.
can affect behavioral development (Dixon et al. 1984; Taddio et al. 2003; de Beer and Thomas 2003; Walker and Yaksh 2012) (see also
1995; Taddio and Katz 2005). Rats exposed to chronic pain without the Part IV: Pain Management).
benefit of anesthesia or analgesia showed varying degrees of neuro- In addition to neuroaxial blockade, specific nerve blocks that are
apoptosis (Anand et al. 2007). However, to add further controversy performed with or without ultrasound guidance have become an
to the issue of adequate anesthesia for infants, concerns have been integral part of pediatric anesthesia (see Chapter 24: Regional Anes-
raised regarding the neurotoxic effects of both intravenous and inha- thesia) (Boretsky et al. 2013; Hall-Burton and Boretsky 2014; Long
lational anesthetic agents (GABAergic and NMDA antagonists) (see et al. 2014; Visoiu et al. 2014; Suresh et al. 2015). The use of ultra-
Chapter 2: Behavioral Development). sound has allowed for the administration of smaller volumes of local
Although postoperative cognitive dysfunction (POCD) is an adult anesthetic and for more accurate placement of the local anesthetic
phenomenon, animal studies by multiple investigators have raised (Willschke et al. 2006; Gurnaney et al. 2007; Ganesh and Gurnaney
concerns about anesthetic agents being toxic to the developing brains 2009). The use of catheters in peripheral nerve blocks has also
of infants and small children (Jevtovic-Todorovic et al. 2003; Mellon changed the perioperative management for a number of pediatric
et al. 2007; Jevtovic and Olney 2008; Wang and Slikker 2008; Rappa- surgical patients. Continuous peripheral nerve catheters with infu-
port et al. 2015). Early work by Uemura and colleagues (1985) noted sions are being used by pediatric patients at home after they have been
that synaptic density was decreased in rats exposed to halothane in discharged from the hospital (Ganesh et al. 2007; Gurnaney et al.
utero. Further work with rodents, by multiple investigators, has shown 2014; Visoiu et al. 2014). The use of these at-home catheters has
evidence of apoptosis in multiple areas of the central nervous system allowed for shorter hospital stays.
during the rapid synaptogenesis period. This window of vulnerability As pediatric regional anesthesia becomes more prevalent, the abil-
appears to be a function of time, dose, and duration of anesthetic ex- ity to collect data, audit practice patterns, and report on complications
posure. In addition to the histochemical changes of apoptosis, the ex- in infants and children undergoing regional anesthesia becomes es-
posed animals also demonstrated learning and behavioral deficits later sential to improving care for children. In this context, the Pediatric
in life. The potential neurotoxic risk of anesthetic agents is less clear in Regional Anesthesia Network (PRAN) was formed (Polaner et al. 2012;
human pediatric patients. Studies performed on this population have Long et al. 2014; Taenzer et al. 2014; Suresh et al. 2015). Walker and
helped to clarify this risk, and it appears that a single short anesthetic colleagues (2018) reported on over 100,000 blocks in children from the
in early infancy has no adverse effects on IQ at 2 and 5 years of age. See PRAN registry and noted that there was no added risk of placing a
Chapter 2 (Behavioral Development) for a more in-depth discussion. block in the anesthetized child. The risk of transient neurologic deficit
was 2.4:10,000 patients and severe local anesthetic systemic toxicity
was 0.76:10,000 patients.
POINT OF CARE ULTRASOUND In addition to advances in anesthetic pharmacology and equip-
Ultrasound has advanced the care of many medical specialties, in- ment, advances in the area of pediatric minimally invasive surgery (MIS)
cluding pediatric anesthesiology. This technology has diagnostic and have improved patient morbidity, shortened the length of hospital
stays, and improved surgical outcomes (Fujimoto et al. 1999). Al- TABLE 1.2 Aspects of Developmental
though MIS imposes physiologic challenges in the neonate and small
Assessment and Common Developmental
infant, numerous neonatal surgical procedures can nevertheless be
successfully approached with such methods, even in infants with single-
Milestones
ventricle physiology (Georgeson 2003; Ponsky and Rothenberg 2008). Follows dangling object from midline through 1 month
The success of MIS has allowed for the evolution of robotic techniques, a range of 90 degrees
stealth surgery (scarless surgery), and Natural Orifice Transluminal Follows dangling object from midline through 3 months
Endoscopic Surgery (NOTES) (Dutta and Albanese 2008; Dutta et al. a range of 180 degrees
2008; Isaza et al. 2008). Consistent conjugate gaze (binocular vision) 4 months
Alerts or quiets to sound 0–2 months
FUNDAMENTAL DIFFERENCES IN INFANTS
Head up 45 degrees 2 months
AND CHILDREN Head up 90 degrees 3–4 months
Regardless of all the advances in equipment, monitoring, and patient Weight on forearms 3–5 months
safety initiatives, pediatric anesthesia still requires a special under- Weight on hands with arms extended 5–6 months
standing of anatomic, psychological, and physiologic development.
Complete head lag, back uniformly rounded Newborn
The reason for undertaking a special study of pediatric anesthesia is
that children, especially infants younger than a few months of age, Slight head lag 3 months
differ markedly from adolescents and adults. Many of the important Rolls front to back 4–5 months
differences, however, are not the most obvious. Although the most Rolls back to front 5–6 months
apparent difference is size, it is the physiologic differences related to Sits with no support 7 months
general metabolism and immature function of the various organ Hands predominantly closed 1 month
systems (including the heart, lungs, kidneys, liver, blood, muscles,
Hands predominantly open 3 months
and central nervous system) that are of major importance to the
anesthesiologist. Foot play 5 months
Transfers objects from hand to hand 6 months
Psychological Differences Index finger approach to small objects 10 months
For a child’s normal psychological development, continuous support and finger-thumb opposition
of a nurturing family is indispensable at all stages of development; Plays pat-a-cake 9–10 months
serious social and emotional deprivation (including separation from
Pulls to stand 9 months
parents during hospitalization), especially during the first 2 years of
Walks with one hand held 12 months
development, may cause temporary or even lasting damage to psycho-
social development (Forman et al. 1987). A young child who is hospi- Runs well 2 years
talized for surgery is forced to cope with separation from parents, to Social smile 1–2 months
adapt to a new environment and strange people, and to experience Smiles at image in mirror 5 months
the pain and discomfort associated with anesthesia and surgery Separation anxiety/stranger awareness 6–12 months
(see Chapter 2: Behavioral Development; Chapter 15: Psychological
Interactive games: peek-a-boo and pat-a-cake 9–12 months
Aspects of Pediatric Anesthesia).
The most intense fear in an infant or a young child is created Waves “bye-bye” 10 months
by separation from the parents, and it is often conceived as loss of Cooing 2–4 months
love or abandonment. The sequence of reactions observed is often Babbles with labial consonants (“ba,” “ma,” “ga”) 5–8 months
as follows: angry protest with panicky anxiety, depression, and de- Imitates sounds made by others 9–12 months
spair, and eventually apathy and detachment (Bowlby 1973). Older
First words (approximately four to six, including 9–12 months
children may be more concerned with painful procedures and the
“mama,” “dada”)
loss of self-control that is implicit with general anesthesia (Forman
Understands one-step command (with gesture) 15 months
et al. 1987). Repeated hospitalizations for anesthesia and surgery
may be associated with psychosocial disturbances in later childhood Ages are averages based primarily on data from Arnold Gesell.
(Dombro 1970). In children who are old enough to experience Modified from Illingworth, R. S. (1987). The development of the infant
fear and apprehension during anesthesia and surgery, the emotional and young child: normal and abnormal. New York: Churchill Livingstone.
factor may be of greater concern than the physical condition; in fact,
it may represent the greatest problem of the perioperative course
(see Chapter 15: Psychological Aspects of Pediatric Anesthesia) Differences in Response to Pharmacologic Agents
(Smith 1980). The extent of the differences among infants, children, and adults in
All of these responses can and should be reduced or abolished response to the administration of drugs is not just a size conversion.
through preventive measures to ease the child’s adaptation to the hos- During the first several months after birth, rapid development and
pitalization, anesthesia, and surgery. The anesthesiologist’s role in this growth of organ systems take place, altering the factors involved in
process, as well as having a basic understanding of neurobehavioral uptake, distribution, metabolism, and elimination of anesthetics and
development, is important (Table 1.2). Anesthesiologists must also related drugs. Interindividual variability of a response to a given drug
be open to new ideas regarding the role of family-centered care, spe- may be determined by a variety of genetic factors. Genetic influences
cifically in regard to pediatric patients with psychiatric diagnoses or in biotransformation, metabolism, transport, and receptor site all
special needs who may benefit from the presence of service animals. affect an individual’s response to a drug. These changes appear to
Ambardekar and colleagues (2013) reported on the use of a service be responsible for developmental differences in drug response and
animal to help with the induction of anesthesia. can be further modified by age-related and environmental factors.
The pharmacology of anesthetics and adjuvant drugs and their differ-

ent effects in neonates, infants, and children are discussed in detail in 30
65
Part II (Pharmacology). 60
55 25
0.8
Anatomic and Physiologic Differences 50
Body Size 95 0.7 45
3 90 20
As stated, the most striking difference between children and adults is 34 40
85 0.6
size, but the degree of difference and the variation even within the 32 35
80
pediatric age group are hard to appreciate. The contrast between an 30 15
75 0.5
infant weighing 1 kg and an overgrown and obese adolescent weighing 30
28 70
more than 100 kg who appear in succession in the same operating
26
Surface area in square meters

65 25
room is overwhelming. It makes considerable difference whether body 0.4
weight, height, or body surface area (BSA) is used as the basis for size 2 60 10
comparison. As pointed out by Harris (1957), a normal newborn in- 20
22 55
fant who weighs 3 kg is 1/3 the size of an adult in length, but 1/9 the
Height in centimeters
0.3
20
Weight in kilograms
adult BSA and 1/20 the adult weight (Fig. 1.1). Of these body measure- 50
Weight in pounds
15
Height in feet
ments, BSA is probably the most important, because it closely parallels
18 45
variations in basal metabolic rate measured in kilocalories per hour
per square meter. For this reason, BSA is believed to be a better crite- 5
16 40
rion than age or weight in judging basal fluid and nutritional require- 0.2
10
ments. For clinical use, however, BSA proves somewhat difficult to
14 35
determine, although a nomogram such as that of Talbot and associates
(1952) facilitates the procedure considerably (Fig. 1.2). For the anes-
thesiologist who carries a pocket calculator, the following formulas may 1 30
be useful to calculate BSA:
10
Formula of DuBois and DuBois (1916 ) 9 5
25 0.1
BSA (m2 ) 0.007184 Height 0.725 Weight 0.425 8
Formula of Gehan and George (1970 )

20
BSA (m 2
) = 0.0235 Height 0.42246
Weight 0.51456
.
Fig. 1.2 Body Surface Area Nomogram for Infants and Young Children.

(From Talbot, N. B., Sobel, E. H., McArthur, J. W., & Crawford, J. D. (1952).

Functional endocrinology from birth through adolescence. Cambridge, MA:

Harvard University Press.)
At full-term birth, BSA averages 0.2 m2, whereas in the adult it aver-
ages 1.75 m2. Table 1.3 shows the relation of age, height, and weight to
BSA. A simpler, crude estimate of BSA for children of average height
and weight is given in Table 1.4. The formula is also reasonably accu-
rate in children of normal physique weighing 21 to 40 kg (Vaughan
and Litt 1987):
BSA (m2 ) ( 0.02 kg) 0.40.
The caloric need in relation to BSA of a full-term infant is about

30 kcal/m2 per hour. It increases to about 50 kcal/m2 per hour by
2 years of age and then decreases gradually to the adult level of 35 to
40 kcal/m2 per hour.
Relative Size or Proportion

Weight Surface Length
1/21 area 1/3.3
Less obvious than the difference in overall size is the difference in rela-
1/9 tive size of body structure in infants and children. This is particularly
Fig. 1.1 Proportions of Newborn to Adult With Respect to Weight,

true with the head, which is large at birth (35 cm in circumference)—
Surface Area, and Length. (Data from Crawford, J. D., Terry, M. E., &

in fact, larger than chest circumference. Head circumference increases
Rourke, G. M. (1950). Simplification of drug dosage calculation by by 10 cm during the first year and an additional 2 to 3 cm during the
application of the surface area principle. Pediatrics, 5, 785.) second year, when it reaches three-fourths of the adult size (Box 1.1).
TABLE 1.3 Relation of Age, Height,

and Weight to Body Surface Area (BSA)*
Age (years) Height (cm) Weight (kg) BSA (m2)
Premature 40 1 0.1
Newborn 50 3 0.2
1 75 10 0.47
2 87 12 0.57
3 96 14 0.63
5 109 18 0.74
10 138 32 1.10
13 157 46 1.42
16 (Female) 163 50 1.59
16 (Male) 173 62 1.74
*Based on standard growth chart and the formula of DuBois and
DuBois (1916): BSA (m2) 5 0.007184 3 Height0.725 3 Weight0.425.
Fig. 1.3 A Normal Infant Has a Large Head, Narrow Shoulders and

Chest, and a Large Abdomen.

TABLE 1.4 Approximation of Body Surface
Area (BSA) Based on Weight
Weight (kg) Approximate BSA (m2) muscles. Furthermore, the rib cage is cartilaginous, and the thorax is
1–5 0.05 3 kg 1 0.05
too compliant to resist inward recoil of the lungs. In the awake state,
the chest wall is maintained relatively rigid with sustained inspiratory
6–10 0.04 3 kg 1 0.10
muscle tension, which maintains the end-expiratory lung volume
11–20 0.03 3 kg 1 0.20 (i.e., FRC). Under general anesthesia, however, the muscle tension is
21–40 0.02 3 kg 1 0.40 abolished and FRC collapses, resulting in airway closure, atelectasis,
and venous admixture unless continuous positive airway pressure
Modified from Vaughan, V. C., III, & Litt, I. F. (1987). Assessment of
growth and development. In R. E. Behrman & V. C. Vaughn III (Eds.),
(CPAP) or positive end-expiratory pressure (PEEP) is maintained. (See
Nelson’s textbook of pediatrics (13th ed.). Philadelphia: Saunders. Chapter 3: Respiratory Physiology.)
Central and Autonomic Nervous Systems

The brain of a neonate is relatively large, weighing about 1/10 of the
BOX 1.1 Typical Patterns of Physical Growth body weight compared with about 1/50 of the body weight in an adult.
Weight The brain grows rapidly; its weight doubles by 6 months of age and
Birth weight is regained by the 10th to 14th day. triples by 1 year of age. By the third week of gestation, the neural plate
Average weight gain per day: 0 to 6 months 5 20 g; 6 to 12 months 5 15 g. appears, and by 5 weeks’ gestation, the three main subdivisions of the
Birth weight doubles at 4 months, triples at 12 months, and quadruples at forebrain, midbrain, and hindbrain are evident. By the eighth week of
24 months. gestation, neurons migrate to form the cortical layers, and migration is
During the second year, average weight gain per month: 0.25 kg. complete by the sixth month. Cell differentiation continues as neu-
After 2 years of age, average annual weight gain until adolescence: 2.3 kg. rons, astrocytes, oligodendrocytes, and glial cells form. Axons and
synaptic connections continually form and remodel. Fig. 1.4 plots
Length/Height gestational brain growth as a percentage of brain weight at term
By the end of the first year, birth length increases by 50%. (Kinney 2006). At birth, about one-fourth of the neuronal cells are
Birth length doubles by 4 years of age and triples by 13 years of age. present. The development of cells in the cortex and brain stem is nearly
Average height gain during the second year: 12 cm. complete by 1 year of age. Myelinization and elaboration of dendritic
After 2 years of age, average annual growth until adolescence: 5 cm. processes continue well into the third year. Incomplete myelinization
is associated with primitive reflexes, such as the Moro and grasp re-
Head Circumference
flexes in the neonate; these are valuable in the assessment of neural
Average head growth per week: 0 to 2 months 5 0.5 cm; 2 to 6 months 5
development. (See Chapter 27: Neonatology for Anesthesiologists.)
0.25 cm.
At birth, the spinal cord extends to the third lumbar vertebra. By
Average total head growth: 0 to 3 months 5 5 cm; 3 to 6 months 5 4 cm;
the time the infant is 1 year of age, the cord has assumed its permanent
6 to 9 months 5  2 cm; 9 to 12 months 5 1 cm.
position, ending at the first lumbar vertebra (Gray 1973).
In contrast to the central nervous system, the autonomic nervous
system is relatively well developed in the newborn. The parasympa-
At full-term birth, the infant (Fig. 1.3) has a short neck and a chin thetic components of the cardiovascular system are fully functional at
that often meets the chest at the level of the second rib; these infants birth. The sympathetic components, however, are not fully developed
are prone to upper airway obstruction during sleep. In infants with until 4 to 6 months of age (Friedman 1973). Baroreflexes to maintain
tracheostomy, the orifice is often buried under the chin unless the head blood pressure and heart rate, which involve medullary vasomotor
is extended with a roll under the neck. The chest is relatively small in centers (pressor and depressor areas), are functional at birth in awake
relation to the abdomen, which is protuberant with weak abdominal newborn infants (Moss et al. 1968; Gootman 1983). In anesthetized
Cardiovascular System
HUMAN BRAIN GROWTH During the first minutes after birth, the newborn infant must change
100 his or her circulatory pattern dramatically from fetal to adult types of
90 circulation to survive in the extrauterine environment. Even for several
months after initial adaptation, the pulmonary vascular bed remains
80
% Full-term brain weight
exceptionally reactive to hypoxia and acidosis. The heart remains ex-

70 tremely sensitive to volatile anesthetics during early infancy, whereas
60 the central nervous system is relatively insensitive to these anesthetics.
50 Complicating factors involving the cardiovascular system are the
40 age-related changes and large variability in vital signs that occur with
age. This is especially pronounced in newly born term and premature
30
infants. As a result, defining hypotension in these infants becomes
20 challenging. Cardiovascular physiology in infants and children is dis-
10 cussed in Chapter 5 (Cardiovascular Physiology) and Chapter 27
0 (Neonatology for the Anesthesiologist).
18 20 22 24 26 28 30 32 34 36 38 40
Fluid and Electrolyte Metabolism
Gestational age (wks)
Like the lungs, the kidneys are not fully mature at birth, although the
Fig. 1.4 Normal Brain Growth From 20 to 40 Weeks’ Gestation.

formation of nephrons is complete by 36 weeks’ gestation. Maturation
Brain weight is expressed as a percentage of term brain weight. (From
continues for about 6 months after full-term birth. The glomerular fil-
Kinney, H. C. (2006). The near-term (late preterm) human brain and risk tration rate (GFR) is lower in the neonate because of the high renal
for periventricular leukomalacia: A review. Seminars in Perinatology, 30, vascular resistance associated with the relatively small surface area for
81–88. Data from Guihard-Costa, A. M., & Larroche, J. C. (1990). Dif- filtration. Despite a low GFR and limited tubular function, the full-term
ferential growth between the fetal brain and its infratentorial part. Early newborn can conserve sodium. Premature infants, however, experience
Human Development, 23(1), 27–40.) prolonged glomerulotubular imbalance, resulting in sodium wastage
and hyponatremia (Spitzer 1982). On the other hand, both full-term and
premature infants are limited in their ability to handle excessive sodium
newborn animals, however, both pressor and depressor reflexes are loads. Even after water deprivation, concentrating ability is limited at
diminished (Wear et al. 1982; Gallagher et al. 1987). birth, especially in premature infants. After several days, neonates can
The laryngeal reflex is activated by the stimulation of receptors produce diluted urine; however, diluting capacity does not mature fully
on the face, nose, and upper airways of the newborn. Reflex apnea, until after 3 to 5 weeks of life (Spitzer 1978). After water deprivation in
bradycardia, or laryngospasm may occur. Various mechanical and the term infant, the urine concentrating ability is only about 50% to 60%
chemical stimuli, including water, foreign bodies, and noxious gases, that of an adult. The premature infant is prone to hyponatremia when
can trigger this response. This protective response is so potent that it sodium supplementation is inadequate or with overhydration. Further-
can cause death in the newborn (see Chapter 3: Respiratory Physiology; more, dehydration is detrimental to the neonate regardless of gesta-
Chapter 5: Cardiovascular Physiology). tional age. The physiology of fluid and electrolyte balance is detailed in
Chapter 6 (Regulation of Fluids and Electrolytes).
Respiratory System
At full-term birth, the lungs are still in the stage of active development. Temperature Regulation
The formation of adult-type alveoli begins at 36 weeks postconception Temperature regulation is of particular interest and importance in
but represents only a fraction of the terminal air sacs with thick septa pediatric anesthesia. There is a better understanding of the physiology
at full-term birth. It takes more than several years for functional and of temperature regulation and the effect of anesthesia on the control
morphologic development to be completed, with a 10-fold increase in mechanisms. General anesthesia is associated with mild to moderate
the number of terminal air sacs to 400 to 500 million by 18 months of hypothermia, resulting from environmental exposure, anesthesia-
age, along with the development of rich capillary networks surround- induced central thermoregulatory inhibition, redistribution of body
ing the alveoli. Similarly, control of breathing during the first several heat, and up to 30% reduction in metabolic heat production (Bissonette
weeks of extrauterine life differs notably from control in older children 1991). Small infants have a disproportionately large BSA, and heat loss
and adults. Of particular importance is the fact that hypoxemia de- is exaggerated during anesthesia, particularly during the induction of
presses, rather than stimulates, respiration. Anatomic differences in the anesthesia, unless the heat loss is actively prevented. General anesthesia
airway occur with growth and development. Recently, the age-old decreases but does not completely abolish thermoregulatory threshold
concept of the child having a funnel-shaped larynx with the cricoid as temperature to hypothermia. Mild hypothermia can sometimes be
the narrowest portion of the airway has been challenged (Holzki et al. beneficial intraoperatively, and profound hypothermia is effectively
2018). Findings by Litman and colleagues (2003) using MRI and used during open heart surgery in infants to reduce oxygen consump-
video-bronchoscopic images by Dalal and colleagues (2009) both re- tion. Postoperative hypothermia, however, is detrimental because of
vealed that the shape of the infant larynx was more cylindrical (as for marked increases in oxygen consumption, oxygen debt (dysoxia), and
adults) than funnel shaped and did not change much with growth. resultant metabolic acidosis (Bissonette 1991). In the surgical neonate,
They also suggested for infants and children that the glottis, not the hypothermia in the perioperative period occurs frequently and has
cricoid, may be the narrowest portion in the paralyzed or cadaveric been associated with adverse events (Morehouse et al. 2014; Engorn
position (which can be gently widened with an ETT); the cricoid re- et al. 2017). The use of forced-air warming devices has become an
mains the solid narrowest segment of the upper airway system. The important component in the prevention of intraoperative hypother-
development of the respiratory system and its anatomy and physiology mia. Though concerns about its use and association with surgical
are detailed in Chapter 3 (Respiratory Physiology). site infection have been raised, clinical evidence for this is lacking.
Regulation of body temperature is discussed in detail in Chapter 7 use of preoperative sedation via the transmucosal route, the wide use of
(Thermoregulation). topical analgesia with a eutectic mixture of local anesthetic cream be-
fore intravenous catheterization, expanded use of regional anesthesia
with improved accuracy and safety by means of ultrasound devices, and
SUMMARY more general acceptance of parental presence during anesthetic induc-
Pediatric anesthesia as a subspecialty has evolved because the needs of tion and in the recovery room. Furthermore, a more diverse anesthetic
infants and young children are fundamentally different from those of approach has evolved through the combined use of regional analgesia,
adults. The pediatric anesthesiologist should be aware of the child’s together with the advent of newer and less soluble volatile anesthetics,
cardiovascular, respiratory, renal, neuromuscular, and central nervous intravenous anesthetics, sedatives, and shorter-acting synthetic opioids
system responses to various drugs, as well as to physical and chemical and muscle relaxants. Finally, the scope of pediatric anesthesia has sig-
stimuli, such as changes in blood oxygen and carbon dioxide tensions, nificantly expanded with the recent development of organized pain
pH, and body temperature. Their responses are different both qualita- services in most pediatric institutions. As a result, pediatric anesthesi-
tively and quantitatively from those of adults and among different ologists have assumed the leading role as pain management specialists,
pediatric age groups. More importantly, the pediatric anesthesiologist thus further extending anesthesia services and influence beyond the
should always consider the child’s emotional needs and create an envi- boundary of the operating room.
ronment that minimizes or abolishes fear and distress.
There have been many advances in the practice of anesthesia to
improve the comfort of young patients over the last decade. These ad-
REFERENCES
vances include a relaxation of preoperative fluid restriction, more fo- Complete references used in this text can be found online at Expert
cused attention to the child’s psychological needs with more extensive Consult.com.
2
Behavioral Development
Julie Niezgoda, Melissa Sutcliffe, Caleb H. Ing, Richard J. Levy
OUTLINE
Introduction, 11 Executive Functioning, 22
Prenatal Growth, 12 Sensorimotor, 22
Postnatal Growth, 12 Anesthetic Neurotoxicity, 22
Developmental Assessment, 12 Brief Evidence From Preclinical Models, 23
Motor Development, 13 Proposed Mechanisms of Neurotoxicity, 23
Primitive Reflexes, 13 Neurocognitive Effects in Rodents and Nonhuman Primates, 23
Gross Motor Skills, 14 Problems With Translating to Humans, 23
Fine Motor Development, 14 Observational Studies in Children, 23
Language Development, 14 Academic Achievement, 24
Cognitive Development, 18 Learning Disability, 24
Clinical Relevance of Growth and Development in Pediatric Clinical Diagnoses of Developmental and Psychiatric
Anesthesia, 19 Disorders, 25
Neuropsychological Testing as a Tool for Assessing the Neuropsychological Testing and Behavioral Surveys, 25
Neurodevelopmental Effects of Anesthesia, 20 Vulnerable Age Periods, 26
Neuropsychological Domains, 22 Potentially Toxic Exposure Doses, 26
Intelligence, 22 The Problem With Observational Studies, 26
Speech and Language, 22 Clinical Trials, 26
Visual-Spatial Skills, 22 Summary and Recommendations, 26
Attention and Processing Speed, 22 Acknowledgments, 27
Learning and Memory, 22
(Gesell and Amatruda 1951). For example, immobility caused by a

INTRODUCTION neuromuscular disorder prevents an infant from exploration of the
Assessment of growth and development of infants and children typi- environment, thus impeding cognitive development. A deficit in one
cally falls under the domain of the pediatrician or pediatric subspecial- domain might interfere with the ability to assess progress in another
ist. Delays or deviations from normal often dictate the need to conduct area. For example, a child with cerebral palsy who is capable of concep-
extensive diagnostic evaluations and management strategies. Familiar- tualizing matching geometric shapes but does not have the gross or
ity with developmental stages may also benefit the pediatric anesthesi- fine motor skills necessary to perform the function could erroneously
ologist, allowing the practitioner to recognize the different coping be labeled as having cognitive developmental delay.
mechanisms children use to respond to the anxiety and stresses It is possible for the anesthesiologist to obtain a gestalt of a child’s
throughout the perioperative period. Growth issues, especially failure growth and development level while recording a preoperative history
to thrive, may indicate a serious underlying medical condition that and during the physical examination. However, the anesthesiologist
could affect the management and anesthetic plan for children. needs to realize that these assessments are usually done by pediatri-
A variety of processes are encompassed in growth and develop- cians over time and are best performed when the child is physically
ment: the formation of tissue; an increase in physical size; the progres- well, familiar with the examiner, and under minimal stress. Therefore
sive increases in strength and ability to control large and small muscles a child who is developing normally could be assessed as delayed during
(gross motor and fine motor development); and the advancement of a preoperative assessment.
complexities of thought, problem solving, learning, and verbal skills The goal of this chapter is to review the developmental and behav-
(cognitive and language development). There is a systematic approach ioral issues faced in routine pediatric practice to help the anesthesiolo-
for tracking neurologic development and physical growth in infants, gist tailor an anesthetic plan that is geared to the appropriate age of the
because attainment of milestones is orderly and predictable. However, child with the goal of decreasing postoperative complications such as
a wide range exists for normal achievement. The mastering of a par- behavioral disturbances, emotional reactions, or escalation in medical
ticular skill often builds on the achievement of an earlier skill. Delays care that might result from the stress of the perioperative process. A
in one developmental domain may impair development in another great deal of concern has arisen over the past two decades regarding
11
the safety of administering general anesthesia during early childhood. Of the three parameters, weight is the most sensitive measurement
These issues are more complex than the potential behavioral or emo- of well-being and is the first to show deviance as an indication of an
tional changes that may result in the postoperative period because of underlying problem. Causes of weight loss and failure to thrive include
perioperative stress impacting specific developmental stages of the congestive heart failure, metabolic or endocrine disorders, malignancy,
pediatric patient. They relate to the mounting evidence of animal data infections, and malabsorption problems. Inadequate increases in
showing that early exposure to anesthetics can induce apoptotic neu- height over time can occur secondary to significant weight loss, and
rodegeneration and subsequent maladaptive behaviors in immature decreased head circumference is the last parameter to change, signify-
animals (Rappaport et al. 2015). The relevance of animal data to anes- ing severe malnutrition. Pathologies such as hydrocephalus or in-
thetic practice is unknown. The final section of this chapter evaluates creased intracranial pressure may appear on growth charts as head
some of the current published retrospective and ongoing prospective circumference measurements that are rapidly increasing and crossing
human studies with regard to this topic. To better understand this is- percentiles. Small head size can be associated with craniosynostosis or
sue, there is a need for well-designed clinical studies to generate data a syndromic feature. Notable changes in head circumference measure-
regarding the neurodevelopmental risks of pediatric anesthesia. The ments in children should alert the anesthesiologist to the potential of
importance of using neuropsychological testing in future pediatric underlying neurologic problems.
clinical research as a tool for assessing the neurodegeneration/neuro- Because significant weight fluctuation is a potential red flag for
developmental effects of anesthesia on the central nervous system serious underlying medical conditions, anesthesiologists should be
(CNS) during this critical period is reviewed. familiar with the normal weight gain expected for children. It is not
unusual for a newborn’s weight to decrease by 10% in the first week of
life because of the excretion of excess extravascular fluid or possibly
PRENATAL GROWTH poor oral intake. Infants should regain or exceed birth weight by
The most dramatic events in growth and development occur before 2 weeks of age and continue to gain approximately 30 g/day, with a
birth. These changes are overwhelmingly somatic, with the transforma- gradual decrease to 12 g/day by the end of the first year. Healthy,
tion of a single cell into an infant. The first 8 weeks of gestation are full-term infants typically double their birth weight at 6 months and
known as the embryonic period and encompass the time when the ru- triple it by 1 year of age. Many complex formulas are available to esti-
diments of all of the major organs are developed. This period denotes a mate the average weight for normal infants and children. A relatively
time in which the fetus is highly sensitive to teratogens such as alcohol, simple calculation to recall is the “rule of tens”; that is, the weight of
tobacco, mercury, thalidomide, and antiepileptic drugs. The average a child increases by about 10 pounds per year until approximately 12
embryo weighs 9 g and has a crown-to-rump length of 5 cm. The fetal to 13 years of age for females and 16 to 17 years of age for males.
stage (more than 9 weeks’ gestation) consists of increases in cell number Therefore one could expect weight gain of 20 pounds by age 2 years,
and size and structural remodeling of organ systems (Moore 1972). 30 pounds by 3 years, 40 pounds by 4 years, and so on. The weight in
During the third trimester, weight triples and length doubles as pounds can be converted to kilograms by dividing it by 2.2. Expected
body stores of protein, calcium, and fat increase. Low birth weight can length in centimeters is estimated by the following formula:
result from prematurity, intrauterine growth retardation (small for
gestational age, SGA), or both. Large-for-gestational-age (LGA) infants ( Age in years 6 ) 77.
are those whose weight is above the 90th percentile at any gestational
age. Deviations from the normal relationship of infant weight gain
DEVELOPMENTAL ASSESSMENT
with increasing gestational age can be multifactorial. Potential causes
include maternal diseases (e.g., diabetes, pregnancy-induced hyperten- Developmental assessment serves different purposes, depending on
sion, and seizure disorders), prenatal exposure to toxins (e.g., alcohol, the age of the child. In the neonatal period, behavioral assessment can
drugs, and tobacco), fetal toxoplasmosis-rubella-cytomegalovirus- detect a wide range of neurologic impairments. During infancy, assess-
herpes simplex-syphilis (TORCHES) infections, genetic abnormalities ment serves to reassure parents and to identify sensory, motor, cogni-
(e.g., trisomies 13, 18, and 21), fetal congenital malformations (e.g., tive, and emotional problems early, when they are most amenable to
cardiopulmonary or renal malformations), and maternal malnutrition treatment. Middle childhood and adolescence assessments often help
or placental insufficiency (Kinney and Kumar 1988). with addressing academic and social problems.
Milestones are useful indicators of mental and physical develop-
ment and possible deviations from normal. It should be emphasized
POSTNATAL GROWTH that milestones represent the average age for children to attain skills
Postnatal growth is measured by changes in weight, length, and head and that there can be variable rates of mastery that fall into the normal
circumference plotted chronologically on growth charts. This is an es- range. An acceptable developmental screening test must be highly sen-
sential component of pediatric health surveillance, because almost any sitive (detect nearly all children with problems); specific (not identify
problem involving physiologic, interpersonal, or social domains can too many children without problems); have content validity, test-re-
adversely affect growth. test, and interrater reliability; and be relatively quick and inexpensive
Growth milestones are the most predictable, taking into context to administer. The most widely used developmental screening test is
each child’s specific genetic and ethnic influences (Johnson and Blasco the Denver Developmental Screening Test (DDST), which provides a
1997). It is essential to plot the child’s growth on gender- and age- pass/fail rating in four domains of developmental milestones: gross
appropriate percentile charts. Charts are now available for certain motor, fine motor, language, and personal-social. The original DDST
ethnic groups and genetic syndromes such as trisomy 21 and Turner was criticized for underidentification of children with developmental
syndrome. Deviation from growth over time across percentiles is of disabilities, particularly in the area of language. The reissued DDST-II
greater significance for a child than a single weight measurement. For is a better assessment for language delays, which is important because
example, an infant at the 5th percentile of weight for age may be of the strong link between language and overall cognitive develop-
growing normally, failing to grow, or recovering from growth failure, ment. Table 2.1 lists the prevalence of some common developmental
depending on the trajectory of the growth curve. disabilities (Levy and Hyman 1993).
CHAPTER 2 Behavioral Development 13
TABLE 2.1 Prevalence of Developmental birth because of the high flexor tone of the newborn infant. When the
neonate’s head is turned to one side, there is increased extensor tone of
Disabilities
the upper extremity on the same side and increased flexor tone on the
Condition Prevalence per 1000 contralateral side. The ATNR is a precursor to hand-eye coordination,
Cerebral palsy 2–3 preparing the infant for gazing along the upper arm and voluntary
Visual impairment 0.3–0.6 reaching. The disappearance of this reflex at 4 to 6 months allows
the infant mobility to roll over and begin to examine and manipulate
Hearing impairment 0.8–2
objects in the midline with both hands.
Mental retardation 25
The palmar grasp reflex is present at birth and persists until 4 to
Learning disability 75 6 months of age. When an object is placed in the infant’s hand, the
Attention deficit hyperactivity disorder 150 fingers close and tightly grasp the object. The grip is strong but unpre-
Behavioral disorders 60–130 dictable. The waning of the early grasp reflex allows infants to hold
Autism 9–10 objects in both hands and ultimately to voluntarily let them go.
The Moro reflex is probably the most well-known primitive reflex
and is present at birth. It is likely to occur as a startle to a loud noise or
sudden changes in head position. The legs and head extend while the
MOTOR DEVELOPMENT arms jerk up and out, followed by adduction of the arms and tightly
clenched fists. Bilateral absence of the reflex may mean damage to the
Primitive Reflexes infant’s CNS. Unilateral absence could indicate birth trauma, such as a
The earliest motor neuromaturational markers are primitive reflexes fractured clavicle or brachial plexus injury.
that develop during uterine life and generally disappear between the Postural reflexes support control of balance, posture, and move-
third and sixth months after birth. Newborn movements are largely ment in a gravity-based environment. The protective equilibrium re-
uncontrolled, with the exception of eye gaze, head turning, and suck- sponse can be elicited in a sitting infant by abruptly pushing the infant
ing. Development of the infant’s CNS involves strengthening of the laterally. The infant will extend the arm on the contralateral side and
higher cortical center, which gradually takes over function of the primi- flex the trunk toward the side of the force to regain the center of grav-
tive reflexes. Postural reflexes replace primitive reflexes between 3 and ity (Fig. 2.1). The parachute response develops around 9 months and
6 months of age as a result of this development (Schott and Rossor is a response to a free-fall motion, where the infant extends the ex-
2003). These reactions allow children to maintain a stable posture even tremities in an outward motion to distribute weight over a broader
if they are rapidly moved or jolted (Box 2.1). area. Postural reactions are markedly slow in appearance in the infant
The asymmetric tonic neck reflex (ATNR) or “fencing posture” is who has CNS damage. Children who fail to gain postural control con-
an example of a primitive reflex that is not immediately present at tinue to display traces of primitive reflexes. They also have difficulty
with control of movement affecting coordination, fine and gross mo-
tor development, and other associated aspects of learning, including
BOX 2.1 Definitions of Primitive Reflexes reading and writing. Table 2.2 lists the average times of appearance and
disappearance of the more common primitive reflexes.
Automatic stepping reflex: Although the infant cannot support his or her
weight when a flat surface is presented to the sole of the foot, he or she
makes a stepping motion by bringing one foot in front of the other.
Crossed extension reflex: When an extremity is acutely stimulated to with-
draw, the flexor muscles in the withdrawing limb contract completely,
whereas the extensor muscles relax. The opposite occurs (full extension,
with relaxation of contracting muscles) in the opposite limb.
Galant reflex: An infant whose back is stroked on one side moves or swings
in that direction.
Moro reflex: When the infant is startled with a loud noise or when the head
is lowered suddenly, the head and legs extend and the arms raise up and
out. Then the arms are brought in and the fingers close to make fists.
Palmar reflex: When an object is placed into the infant’s hand or when the
palm of the infant’s hand is stroked with an object, the hand closes around
the object.
Asymmetric tonic neck reflex (“fencing”): When the infant’s head is
rotated to one side, the arm on that side straightens and the opposite arm
flexes.
Landau reflex: When the infant is held in a horizontal position, he or she
raises the head and bring the legs up into a horizontal position. If the head
is forced down (flexed), the legs also lower into a vertical position.
Derotational righting reflex: When the infant turns the head one direction,
the body leans in the same direction to maintain balance.
Protective equilibrium reflex: When a lateral force is applied to the infant, he
or she responds by leaning into the force and extending the contralateral arm.
Parachute reflex: When the infant is facing down and lowered suddenly, the
arms extend out in a protective maneuver. Fig. 2.1 The Protective Equilibrium Response is Demonstrated in an

Infant Being Pushed Laterally. Note the extended contralateral arm.

that is necessary for interactive play with other children. Fig. 2.3 shows
TABLE 2.2 Primitive Reflexes
the red flags to watch for in the abnormal physical development of the
Present by Gone by infant.
Reflex (Months) (Months)
Automatic stepping Birth 2 Fine Motor Development
Crossed extension Birth 2 At birth, the neonate’s fingers and thumbs are typically tightly fisted.
Galant Birth 2
Normal development moves from the primitive grasp reflex, where the
infant reflexively grabs an object but is unable to release it, to a volun-
Moro Birth 3–6
tary grasp and release of the object. By 2 to 3 months of age, the hands
Palmar Birth 4–6 are no longer tightly fisted, and the infant begins to bring them toward
Asymmetric tonic neck 1 4–6 the mouth, sucking on the digits for self-comfort. Objects can be held
(“fencing”) in either hand by age 3 months and transferred back and forth by
Landau 3 12–24 6 months. In early development, the upper extremities assist with bal-
Derotational head righting 4 Persists ance and mobility. As the sitting position is mastered with improved
balance, the hands become more available for manipulation and explo-
Protective equilibrium 4–6 Persists
ration. The evolution of the pincer grasp is the highlight of fine motor
Parachute 8–9 Persists development during the first year. The infant advances from “raking”
small objects into the palm to the finer pincer grasp, allowing opposi-
tion of the thumb and the index finger, whereby small items are picked
up with precision. Children younger than 18 months of age generally
Gross Motor Skills use both hands equally well, and true “handedness” is not established
One principle in neuromaturational development during infancy is until 36 months (Levine et al. 1999). Advancements in fine motor skills
that it proceeds from cephalad to caudad and proximal to distal. Thus continue throughout the preschool years, when the child develops bet-
arm movement comes before leg movement (Feldman 2007). The up- ter eye-hand coordination with which to stack objects or reproduce
per extremity attains increasing accuracy in reaching, grasping, trans- drawings (e.g., crosses, circles, and triangles). Fig. 2.4 lists and demon-
ferring, and manipulating objects. Gross motor development in the strates the chronologic order of fine motor development.
prone position begins with the infant tightly flexing the upper and
lower extremities and evolves to hip extension while lifting the head
LANGUAGE DEVELOPMENT
and shoulders from a table surface around 4 to 6 months of age. When
pulled to a sitting position, the newborn has significant head lag, Delays in language development are more common than delays in any
whereas the 6-month-old baby, because of development of muscle other developmental domain (Glascoe 2000). Language includes re-
tone in the neck, raises the head in anticipation of being pulled up. ceptive and expressive skills. Receptive skills are the ability to under-
Rolling movements start from front to back at approximately stand the language, and expressive skills include the ability to make
4 months of age as the muscles of the lower extremities strengthen. An thoughts, ideas, and desires known to others. Because receptive lan-
infant begins to roll from back to front at about 5 months. The abilities guage precedes expressive language, infants respond to several simple
to sit unsupported (about 6 months old) and to pivot while sitting statements such as “no,” “bye-bye,” and “give me” before they are ca-
(around 9 to 10 months of age) provide increasing opportunities to pable of speaking intelligible words. In addition to speech, expression
manipulate several objects at a time (Needleman 1996). Once thoraco- of language can take the forms of gestures, signing, typing, and “body
lumbar control is achieved and the sitting position mastered, the child language.” Thus speech and language are not synonymous. The
focuses motor development on ambulation and more complex skills. hearing-impaired child or child with cerebral palsy may have normal
Locomotion begins with commando-style crawling, advances to creep- receptive language skills and intellect to understand dialogue but needs
ing on hands and knees, and eventually reaches pulling to stand other forms of expressive language to vocalize responses. Conversely,
around 9 months of age, with further advancement to cruising around children may talk but fail to communicate; for example, a child with
furniture or toys. Standing alone and walking independently occur autism may vocalize by using “parrot talk” or echolalia that has no
around the first birthday. Advanced motor achievements correlate meaningful content and does not represent language.
with increasing myelinization and cerebellum growth. Walking several Language development can be divided into the three stages of pre-
steps alone has one of the widest ranges for mastery of all of the speech, naming, and word combination. Prespeech is characterized by
gross motor milestones and occurs between 9 and 17 months of age. cooing or babbling until around 8 to 10 months of age, when babbling
Milestones of gross motor development are presented in Figs. 2.2 and becomes more complex with multiple syllables. Eventually random
2.3. The accomplishment of locomotion not only expands the infant’s vocalization (“da-da”) is interpreted and reinforced by the parents as a
exploratory range and offers new opportunities for cognitive and real word and the child begins to repeat it. The naming period (ages
motor growth, but it also increases the potential for physical dangers 10 to 18 months) is when the infant realizes that people have names
(Vaughan 1992). and objects have labels. Once the infant’s vocalizations are reinforced
Most children walk with a mature gait, run steadily, and balance on as people or things, the infant begins to use them appropriately.
one foot for 1 second by 3½ years of age. The sequence for additional At around 12 months of age, some infants understand as many as
gross motor development is as follows: running, jumping on two feet, 100 words and can respond to simple commands that are accompanied
balancing on one foot, hopping, and skipping. Finally, more complex by gestures. Early into the second year, a command without a gesture
activities such as throwing, catching, and kicking balls; riding bicycles; is understood. Expressive language is slower, and an 18-month-old
and climbing on playground equipment are mastered. Development child has a limited vocabulary of around 25 words. After the realization
beyond walking incorporates improved balance and coordination and that words can stand for things, the child’s vocabulary expands at a
progressive narrowing of additional physical support. Complex motor rapid pace. Preschool language development begins with word combi-
skills also incorporate advanced cognitive and emotional development nation at 18 to 24 months and is the foundation for later success in
1–2 Months 11–12 Months

• Prone, lies tightly flexed, • Walks well along furniture
pelvis high in both directions
• Starts to lift head off • Stands by self for
surface 2–3 inches 3–5 seconds with feet wide
• Head lag when pulled to sit • Rises from floor to stand
• Kicks legs in random large with support
movements • 9–16 months: walks
independently (avg.:
3–4 Months 11–12 months)
• Begins to center head on
back and belly
• Props on forearms on belly 18 Months
• Rolls from back to side • Begins to walk up and down
• Kicks R and L leg separately stairs holding rail or hand
• Begins to run or walk more
quickly
5–6 Months • Begins to use riding toys by
• Brings feet to hands while pushing off with feet
on back • Pushes and pulls large toys
• Begins to roll from tummy around the room
to back • While standing, throws a
• Begins to sit, arms 6–8 inch play ball
propping forward
• Pull to sit, holds head in
line with body
• Takes full weight on legs
when held in standing 24 Months
position • Squats well to play with toys
• Runs well without falling
• Walks up stairs by self with
7–8 Months one hand on rail and using
• Plays on belly with toys, two feet on each step
arms straight • Kicks ball forward 3 feet
• Rolls in both directions • Jumps with both feet forward
• Begins to push up on and down
hands and knees rocking
• May use commando-type 3 Years
crawl to pull self forward • When running, able to make
• Can use both hands to play sharp turn
• Jumps down from a
14–24 inch-high surface
9–10 Months • Pedals tricycle a short
• Creeps well on hands and distance
knees • Imitates one foot standing
• Steady in a variety of sitting 2–4 seconds
positions • Catches ball with hands and
• Able to move between sit, arms extended
kneel, and stand
• Stands and plays at
surfaces 4 Years
• Cruises around furniture • Stands on one foot
5 seconds
• Hops on one foot forward
1–3 times
• Throws tennis ball
underhand 8–10 feet
• Pedals and steers tricycle for
longer distances
5 Years
• Gallops 10 feet smoothly and
even
• Hops on either foot 8–10
times
• Throws a ball to a target
overhand and underhand
Fig. 2.2 Gross Motor Skills Development Chart.

3 months
A B
6 months
C D E
9 months
F G H
18 months
12 months
I J
K
Fig. 2.3 Abnormal Developmental Findings. A, Difficulty lifting head and stiff legs with little or no movement.

B, Pushing back with head, keeping hands fisted, and lacking arm movement. C, Rounded back, inability to
lift head up, and poor head control. D, Difficulty bringing arms forward to reach out, arching back, and stiffen-
ing legs. E, Arms held back and stiff legs. F, Using one hand predominantly; rounded back and poor use of
arms when sitting. G, Difficulty crawling and using only one side of the body to move. H, Unable to straighten
back and cannot bear weight on legs. I, Difficulty getting to standing position because of stiff legs and pointed
toes; only using arms to pull up to standing. J, Sitting with weight to one side and strongly flexed or stiffly
extended arms; using hand to maintain seated position. K, Inability to take steps independently, poor stand-
ing balance, many falls, and walking on toes. (Redrawn from What every parent should know [pamphlet],

2006, Pathways Awareness Foundation.)
school. Vocabulary increases from 50 to 100 words to more than 2000 Language is a critical barometer of both cognitive and emotional
words during this time. Sentence structure advances from two- and development (Coplan 1995). Mental retardation may first surface as a
three-word phrases to sentences incorporating all of the major gram- concern with delayed speech and language development around
matic rules. A simple correlate is that a child should increase the num- 2 years of age; however, the average age of diagnosis is 3 to 4 years. All
ber of words in a sentence with advancing age—for example, two- children whose language development is delayed should undergo au-
word sentences by 2 years of age, three-word sentences by age 3 years, diologic testing. If a child’s expressive skills are advanced compared
and so on (Table 2.3). with his or her receptive skills (e.g., child speaks five-word sentences
1–2 Months 11–12 Months

• Holds hands fisted with • Uses more refined pincer grasp
thumbs in palms and with (grasping with pads of the thumb
random opening and closing and index finger)
of hands • Manipulates blocks
• Brings hands to mouth • Opens baby book
• Swipes with full arm • Puts objects in and takes out of
movement container
• Follows faces with eyes to • Uses smooth release for large
center objects
18 Months
3–4 Months • Turns pages of thick book
• Brings hands together • Accurately inserts two shapes into
• Moves thumb out of palm shape sorter
• Brings object to mouth • Holds crayon with fisted position
• Reaches toward center for • Picks up small objects using neat
a toy pincer grasp to place in container
• In supported sitting, • Uses two hands together at
visually follows objects center of body
• Uses each hand for a different
function
24 Months
5–6 Months • Stacks six cubes
• Reaches across center of • Inserts three shapes in shape
body sorter
• Brings hands together to • Imitates vertical stroke
play • Holds crayon with thumb and
• Reaches with one hand at a fingers pointing toward paper,
time to grasp toy palm down
• Holds and shakes rattle
3 Years
• Imitates horizontal and vertical
strokes
• Copies a circle
• Builds 10-cube tower
7–8 Months • Matches simple shapes
• Bangs object on table • Colors within large pictures and
surface shapes
• Grasps small objects • Holds a crayon with fingers
using a raking motion straight, thumb pointed toward
• May begin grasp with paper
thumb opposed to the • Snips with scissors
index and middle fingers
• Transfers objects from 4 Years
hand to hand • Uses scissors to cut paper in
two pieces
• Cuts on a 5-inch line
• Copies cross
9–10 Months • Traces lines
• Uses pincer grasp • Holds crayon using a three-finger
(grasping with pads of grasp (thumb, index, and middle
thumb and index finger) finger)
• Holds sippy cup • Demonstrates hand preference
• Uses control to let go of
objects 5 Years
• Takes objects out of • Cuts simple shapes with accuracy
container (circle, square)
• Claps hands • Copies square
• Bangs toys/objects • Uses mature grasp on pencils
together • Prints name
• Imitates six-cube block design
• Folds paper in half
Fig. 2.4 Fine Motor Skills Development Chart.

TABLE 2.3 Cognitive and Language Communication Skills Development

Average Age
of Attainment
(Months) Cognitive Language Communication
2 Stares briefly at area when object is removed Smiles in response to face or voice
4 Stares at own hand Monosyllabic babble
8 Object permanence—uncovers toy after seeing it covered Inhibits to “no”
Follows one-step command with gesture (wave to “come here”)
10 Separation anxiety from familiar people Follows one-step command without gesture (“give it to me”)
12 Egocentric play (pretends to drink from cup) Speaks first real word
18 Cause-and-effect relationships no longer need to be demonstrated Speaks 20–50 words
to understand (pushes car to move, winds toy on own)
Distraction techniques may no longer succeed
24 Mental activity is independent of sensory processing or motor Speaks in two-word sentences
manipulation (sees a child in a book with a mask on face and
can later reenact event)
36 Capable of symbolic thinking Speaks in three-word sentences
48 Immature logic is replaced Speaks in four-word sentences
Conventional logic and wisdom Follows three-step commands
but does not understand simple commands), a pervasive development and doubt and corresponds to Freud’s anal stage. A sense of either
disorder could be the cause. identity or role confusion corresponds to the crisis experienced in
Freud’s genital stage (puberty) (Table 2.4).
Piaget’s name is synonymous with the study of cognitive develop-
COGNITIVE DEVELOPMENT ment. A central tenet of his theory is that cognition is qualitatively
The concept of a developmental line implies that a child passes different at different stages of development (Hobson 1985). During
through successive stages. The psychoanalytic theories of Sigmund the sensorimotor stage, children learn basic things about their rela-
Freud and Erik Erikson and the cognitive theory of Jean Piaget de- tionship with their environment. Thoughts about the nature of ob-
scribe stages in the development of cognition and emotion that are jects and their relationships are acted out and tied immediately to
as qualitatively different as the milestones attained in gross motor sensations and manipulation. With the arrival of language, the nature
development. of thinking changes dramatically, and symbols increasingly take the
At the core of Freudian theory is the idea of biologically deter- place of things and actions. Stages of preoperational thinking, con-
mined drives. The core drive is sexual, broadly defined to include crete operations, and formal operations correspond to the different
sensations that include excitation or tension and satisfaction or release ages of preschool, school age, and adolescence, respectively. At all
(Freud 1952). There are discrete stages: oral, anal, oedipal, latent, and stages, children are not passive recipients of knowledge but actively
genital. During these stages the focus of the sexual drive shifts with seek out experiences (assimilation) and use them to build on how
maturation and is at first influenced primarily by the parents and sub- things work.
sequently by an enlarging circle of social contacts. Defense mecha- Cognitive development and neuromaturational development are
nisms in early childhood can develop pathologically to disguise the closely related, and it is sometimes difficult to distinguish between the
presence of conflict. The emotional health of the child and adult de- two in the infant and child. Early in the neonatal period, cognitive
pends on the resolution of the conflicts that arise throughout these development begins when the infant responds to visual and auditory
stages. stimuli by interacting with surroundings to gain information. Activi-
Erikson’s (1963) chief contribution was to recast Freud’s stages in ties such as mouthing, shaking, and banging objects provide informa-
terms of the emerging personality. For example, basic trust, the first of tion to the infant beyond the visual features. Infant exploration begins
Erickson’s psychosocial stages, develops as infants learn that their ur- with the body, with activities such as staring intently at a hand and
gent needs are met regularly. The consistent availability of a trusted touching other body parts. These explorations represent an early dis-
adult creates the conditions for secure attachment. The next stage es- covery of “cause and effect,” as the infant learns that voluntary move-
tablishes the child’s internal sense of either autonomy versus shame ments generate predictable tactile and visual sensations (e.g., kicking
TABLE 2.4 Classic Stage Theories of the Development of Emotion and Cognition
3–6 Years 6–12 Years 12–20 Years
Theory 0–1 Years (Infancy) 2–3 Years (Toddler) (Preschool) (School Age) (Adolescents)
Freud: psychosexual Oral Anal Oedipal phallic Latency Puberty and genital
Erikson: psychosocial Basic trust Autonomy vs. shame and doubt Initiative vs. guilt Industry vs. inferiority Identity vs. role confusion
Piaget: cognitive Sensorimotor (stages I–IV) Sensorimotor (stages V and VI) Preoperational Concrete operational Formal operational
Egocentric thought
understand detailed explanations, so procedures should be told in

BOX 2.2 Abnormal Cognitive Signs
simple, nonthreatening language. Comprehension of conversation is
1 month: Failure to be alert to environmental stimuli. May indicate sensory more advanced than verbal expression. The receptive and expressive
impairment. language discordance often results in frustration on the child’s behalf,
5 months: Failure to reach for objects. May indicate motor, visual, and/or putting toddlers at increased risk for stormy inductions and postop-
cognitive deficit. erative emotional and behavioral reactions. Toddlers also fear pain and
6 months: Absent babbling. May indicate hearing deficit. bodily harm. Whenever possible, a parent or trusted caregiver should
7 months: Absent stranger anxiety. May be due to multiple care providers be present for potentially painful or threatening procedures. Children
(e.g., neonatal intensive care unit). at this age are comforted by a familiar toy or treasured object and
11 months: Inability to localize sound. May indicate unilateral hearing loss. respond to magical thinking or stories.
The preschooler’s view of the world is egocentric or self-centered.
Modified from Seid, M., et al. (1997). Perioperative psychosocial inter-
ventions for autistic children undergoing ENT surgery. International The child is unable to understand or conceptualize another individu-
Journal of Pediatric Otorhinolaryngology, 40, 107. al’s point of view, does not comprehend why people do not understand
him or her, and has no appreciation for others’ feelings. These children
have concerns with bodily integrity and demonstrate the need for reas-
the side of the crib moves a mobile). Signs of abnormal cognitive surances. Anxiety can be allayed by giving the child a sense of mastery
development are outlined in Box 2.2. and participation, such as allowing him or her to “hold” the mask for
A communication system develops between the infant and primary induction. Their preoperational thinking is very literal, and it is im-
caregiver. Accordingly, the infant begins to display anxiety at the end of portant to use caution when using similes or metaphors; for example,
this developmental period if the person most familiar to the child is if a provider states that the child will be given a “stick” (intravenous
not available. The ability to maintain an image of a person develops line or shot), the child may wait to be handed a tree branch. At this
before that of an object, and therefore the infant may display separa- stage, any explanation appears to be more important than the actual
tion anxiety when a loved one leaves the room. Object permanence, a content of the explanation. Children who were given explanations,
major milestone, develops around 9 months when the infant under- whether accurate or not, were found to have fewer postoperative be-
stands that objects continue to exist even if they are covered up and not havioral changes than those who were not given explanations (Bothe
seen. With locomotion the child explores greater areas and develops a and Galdston 1972). Although the preschooler’s vocabulary is improv-
substantial sense of social self as well as an early appreciation of the ing, cognitively the child may have difficulty remembering a sequence
behavior standards expected by adults. Interactive play and pretend of events or establishing causality, leading to misconceptions about
play begin at 30 months, and playing in pairs occurs around 24 to procedures.
36 months. School-age children, during the “concrete operations” stage, are
Childhood cognitive development and the effect it has on the more independent. Their activities become goal oriented, and their
child’s perception of the hospitalization and surgery are important for language skills develop rapidly. They have a sense of conscience and
the pediatric anesthesiologist to understand how to help the child deal can appreciate the feelings of others. Children are able to draw on
with the stresses during this time. One out of four children will be previous experience and knowledge to formulate predictions about
hospitalized by age 5 years. Although extreme emotional reactions are related issues. They have an increased need for explanation and par-
rare, at least 60% of children demonstrate signs of stress-related anxi- ticipation. Rather than giving children choices in the operating room
ety during the perioperative period. Children between the ages of (e.g., intravenous injection vs. mask for going to sleep), details about
1 and 3 years, previously hospitalized children, and children who have the procedure and options available for the child should be discussed
undergone turbulent anesthetic inductions are at increased risk for preoperatively in a nonthreatening environment (McGraw 1994).
exhibiting adverse postoperative behavioral reactions. Stress and anxi- Adolescents are caught in a difficult period between childhood and
ety can be manifested by behavioral problems such as nightmares, adulthood. Physically, they are maturing and may feel self-conscious
phobias, agitation, avoidance of caregivers, emotional distress, and re- about their bodies. Psychologically, they are striving to know who they
gressive behaviors (e.g., temper tantrums, bed-wetting, and loss of are. Adolescents have developed the ability to recognize and exhibit
previously acquired developmental milestones). Allowing adequate mature defense mechanisms (e.g., the adolescent whose appendicitis
preoperative evaluation and psychological preparation for both the “at least gets me out of my math test”). They are more likely to cooper-
parent and child based on specific needs relative to the child’s develop- ate with a physician perceived to be attentive and nonjudgmental.
mental stage is a method the anesthesiologist can invoke to reduce the Concerns regarding coping, pain, losing control, waking up prema-
emotional trauma of anesthesia. turely, not waking up, and dying are very real for teenagers. Clear ex-
Erikson (1963) describes the infants’ motivations as dependent on planations and assurances should be provided regarding these issues.
the satisfaction of basic human needs (e.g., food, shelter, and love). The need for independence and privacy is important and should be
According to Freud, the child directs all of his or her energies to the respected.
mother and fears her loss because her absence may jeopardize the
child’s satisfaction, creating tension and anxiety. This dependence is CLINICAL RELEVANCE OF GROWTH AND
the essence of separation anxiety. Before this stage, infants are able to
DEVELOPMENT IN PEDIATRIC ANESTHESIA
accept surrogates and respond favorably to anyone holding them.
Once stranger anxiety develops, active participation of the parents An overview of basic growth and development can be obtained in a
during the hospitalization should be encouraged to maintain a preoperative consultation by reviewing the history and observing for
sense of security for the child and promote bonding (Thompson and gross and fine motor milestones during the physical examination. A
Standford 1981). 1-month-old infant displaying well-developed extensor tone when
Toddlers have developed ambulation skills that allow exploration, suspended in a ventral position might be interpreted by the parent
but they are well bonded to their parents and much less willing to be as having advanced motor development, when, in reality, issues of
separated, especially when they are stressed. They are too young to an upper motor neuron lesion should be considered. Other signs of
spasticity are early rolling, pulling to a direct stand at 4 months of age, dysmorphic features can be found by examining the head, hands,
and walking on the toes. Persistent closing of fists beyond 3 months of and skin.
age could be the earliest indication of neuromotor dysfunction. An
afebrile 2-month-old baby with tachypnea, rales, audible murmur, and
failure to gain weight should raise concerns about a significant cardiac NEUROPSYCHOLOGICAL TESTING AS A TOOL FOR
lesion and the need for a cardiac consultation. A 7-month-old infant ASSESSING THE NEURODEVELOPMENTAL EFFECTS
with poor head control who is unable to sit without support or to lift
his or her chest off the table in the prone position may indicate hypo-
OF ANESTHESIA
tonia and a possible neuromuscular disorder. Spontaneous postures, The earliest studies attempting to elucidate any risks of anesthesia ex-
such as “frog legging” when prone or scissoring, may provide visual posure on young children were limited in outcomes. These studies
physical clues of hypotonia or spasticity, respectively. At 9 months of tended to focus on achievement/presence of a learning disability or IQ
age, the child should stand erect on a parent’s lap or cruise around of- scores. However, such outcome measures may not be the most sensitive
fice furniture, and the 12-month-old child will want to get down and to subtle insult/injury in the brain (Lezak et al. 2012).
walk. Weakness in the 3- or 4-year-old child may be best discovered by Assessment of neurocognitive functioning requires a solid under-
observing the quality of stationary posture and transition movements. standing of both psychometrics and developmental needs related to
The Gowers sign (arising from sitting on the floor to standing using assessment (Lezak et al. 2012; Baron 2018; Sattler 2018; Anderson et al.
the hands to “walk up” the legs) is a classic example of pelvic girdle and 2019). These nuanced challenges are typically best understood by a
quadriceps muscular weakness. Fine motor evaluation can be easily pediatric neuropsychologist with expertise and training in these do-
evaluated by handing the infant a tongue depressor or toy. The new- mains (Lezak et al. 2012). The rapidly changing abilities in a child from
born infant should grasp it reflexively; by 4 months of age, the infant birth to age 18 preclude the use of a single measure or measures across
should reach and retain the object, and by the age of 6 months, the all time points. For example, measures of executive functioning look
child can transfer an object from hand to hand. The development of different for an 8-year-old, whose frontal lobes are not yet fully devel-
fine pincer grasp by 12 months of age allows the child to pick up small oped, and a 14-year-old, who would be expected to engage more easily
objects with precision and increases the risk for foreign body aspira- in problem-solving activities and thinking ahead (Baron 2018). Thus
tion. The observation of a child who constantly uses one hand while an expert with understanding of the challenges of pediatric cognitive
neglecting the other should prompt the clinician to examine the con- assessment can best determine an appropriate outcome battery.
tralateral upper extremity for weakness associated with hemiparesis. In identifying appropriate outcome measures, it is important to
Abnormal head size, significant weight gain or loss, and short stat- assess all possible neuropsychological domains that may be applicable.
ure may be indicative of genetic concerns. The presence of three or The next section describes each primary neurocognitive domain and
more dysmorphic features should raise concerns of a syndrome with includes a table of assessments (Table 2.5) useful for assessing each
possible difficult airway or cardiac issues. Almost 75% of superficial domain. It should be noted that this table is not comprehensive,
TABLE 2.5 Age-Appropriate Instruments Across Cognitive Domains

Task/Age Range (Time) Description
Intellectual Ability
Bayley Scales of Infant and Toddler Development, The BSID-4 measures cognitive, language, motor, social-emotional, and adaptive behavior skills. Specific
4th ed. (BSID-4)/16 days–42 mos (Bayley 2019) cognitive skills assessed include visual preference, attention, memory, sensorimotor, exploration and
manipulation, and concept formation.
Wechsler Preschool and Primary Scale of The WPPSI-IV is designed with a five-factor structure similar to its counterpart for older children, the WISC-V. It
Intelligence, 4th ed. (WPPSI-IV)/2:6–7:7 yrs measures verbal comprehension, visual spatial skills, fluid reasoning, visual working memory, and processing
(Wechsler 2012) speed. It has a full and abbreviated version, with separate forms for younger and older children.
Wechsler Intelligence Scale for Children, 5th ed. The WISC-V is similar to its counterpart for younger children, the WPPSI-IV. It has a five-factor structure
(WISC-V)/6:0–16:11 yrs (Wechsler 2014) assessing verbal comprehension, visual spatial skills, fluid reasoning, visual and auditory working memory, and
processing speed. A full-scale IQ score can be procured by administering 7 of the 10 core subtests.
Wechsler Abbreviated Scale of Intelligence The WASI-II is an abbreviated measure of intelligence. It comprises four subtests (although a full-scale IQ
(WASI-II)/6:0–90:11 yrs (Wechsler 2011) score can also be estimated by administering only two of them). The estimated IQ is based on
measures of perceptual reasoning and verbal comprehension.
Speech and Language

Clinical Evaluation of Language Fundamentals The CELF-P-2 can be administered as a whole or in pieces. It measures many aspects of expressive and
Preschool, 2nd ed. (CELF-P-2)/3:0–6:11 yrs receptive language skills, including word and sentence structure, phonologic awareness, and direction
(Wing et al. 2004) following.
Clinical Evaluation of Language Fundamentals, The CELF-5 assess oral and written language and aspects of nonverbal communication.
5th ed. (CELF-5)/5:0–21:11 yrs (Wiig et al. 2014)
Peabody Picture Vocabulary Test, 5th ed. The PPVT-5 is a measure of single-word receptive vocabulary. A child can point to indicate their response.
(PPVT-5)/2:6–90 yrs (Dunn 2019)
Expressive Vocabulary Test, 3rd ed. The EVT-3 is a measure of single-word expressive language and is conormed with the PPVT-5. Children
(EVT-3)/2:6–90 yrs (Williams 2019) provide an oral response to visual stimulus to assess word-finding ability.
TABLE 2.5 Age-Appropriate Instruments Across Cognitive Domains—cont’d

Task/Age Range (Time) Description
Visual Spatial
Beery-Buktenica Developmental Test of Visual The VMI-6 requires a child to copy increasingly complex geometric figures. Supplemental tests of visual perception
Motor Integration, 6th ed. (VMI-6)/2 yrs1 and motor coordination help parse out the relative contributions of any deficits in these related areas.
(Beery et al. 2010)
Judgment of Line Orientation Test (JOLO)/ The JOLO assesses perception of lines and angles. This skill is thought to underlie more complex visual
7–74 yrs (Benton et al. 1983) analysis.
Attention and Processing Speed

Conners Kiddie Continuous Performance Test, The K-CPT-2 is a continuous performance test that measures attention challenges in young children. The measure,
2nd ed. (K-CPT-2)/4–7 yrs (Conners 2015) administered on a computer, provides indices of inattentiveness, impulsivity, sustained attention, and vigilance.
Conners Continuous Performance Test, 3rd ed. The CPT-3, similar to the K-CPT-2, is a continuous performance measure that yields scores regarding a child’s
(CPT-3)/81 yrs (Conners 2014) inattentiveness, impulsivity, sustained attention, and vigilance. The measure, administered on
a computer, provides an array of scores that also target response time.
Weschler Working Memory Tests Both the WPPSI-IV and the WISC-V contain multiple measures that require short-term and/or working
(Wechsler 2012, 2014) memory. On the WPPSI-IV, these measures require visual attention. The WISC-V includes both auditory
and visual measures of attention.
NEPSY, 2nd ed. (NEPSY-II)/3–16 yrs (Korkman The NEPSY-II is a broadband neuropsychological measure. However, it has many subtests geared toward
et al. 2007) assessing short-term attention, working memory, and aspects of executive functioning.
Test of Everyday Attention for Children, 2nd ed. The TEA-Ch-2 is a comprehensive and engaging measure that assesses selective, divided, sustained, and
(TEA-Ch-2)/6–16 yrs (Manly et al. 2016) alternating attention using both motor- and non-motor-based tasks. The test uses a variety of visually
engaging stimuli, administered both via computer and paper and pencil, to target these skills. Separate
forms are available for children aged 5–7 and 8–16.
Symbol Digit Modalities Test (SDMT)/81 yrs The SDMT can be administered in an oral or written format, individually or in a group setting. The measure
(Smith 1982) assesses information processing speed via matching symbols with its predetermined numerical pair.
Learning and Memory

California Verbal Learning Test for Children The CVLT-C is a classic list learning test that assesses a child’s ability to learn a list of words over five
(CVLT-C)/5–16 yrs (Delis et al. 1994) learning trials and then recall those words after a short- and long-delay. Indices are available for
learning and recall as well as ancillary measures such as semantic clustering.
Child and Adolescent Memory Profile (ChAMP)/ The ChAMP is a measure of both verbal and visual memory. It includes assessment of both immediate and
5–21 yrs (Sherman and Brooks 2015) delayed recall. It is easy to administer and is visually engaging.
Children’s Memory Scale (CMS)/5–16 yrs The CMS is a somewhat older battery that includes a wide variety of memory measures. It includes subtests that
(Cohen 1997) assess for both visual and verbal memory, working memory, and immediate and delayed memory.
Executive Functioning
Delis-Kaplan Executive Function System The D-KEFS is a collection of executive functioning measures designed to assess cognitive flexibility, response
(D-KEFS)/81 yrs (Delis et al. 2001) inhibition, problem solving, and planning. Many of the measures are based on more “classic” tests, such as
the original Trail Making Test and Stroop test, but break down these measures so that subcomponents, such
as attention, visual scanning, and processing speed, can be parsed out from the more complex function.
NEPSY, 2nd ed. (NEPSY-II)/3–16 yrs The NEPSY-II is a broadband neuropsychological measure designed to assess many aspects of cognition. It has
(Korkman et al. 2007) a variety of subtests that specifically target attention and executive functioning, designed to be applicable to
children as young as 3. For example, the Statue subtest is able to assess motor persistence and inhibition by
asking a child to maintain a specific position with eyes closed while ignoring sound distracters.
Trail Making Test (TMT)/71 yrs (Reitan 1971) The TMT was originally part of the Halstead Reitan battery. This test assesses visual scanning, attention,
cognitive flexibility, and fine motor skills. There is a separate version for children ages 7–14.
Behavior Rating Inventory of Executive The BRIEF-2 includes parent, teacher, and self-report versions of a questionnaire designed to assess execu-
Functioning, 2nd ed. (BRIEF-2)/5–18 yrs tive functioning including emotional, behavioral, and cognitive regulation. Older versions of the original
(Gioia et al. 2015) BRIEF are available for assessing preschool-aged children and transition-aged adolescents.
Emotion/Behavior
Child Behavior Checklist (CBCL)/1.5–18 yrs The CBCL is one of the most commonly used measures to assess for both internalizing (anxiety, depression)
(Achenbach and Rescorla 2001) and externalizing (ADHD, oppositionality) challenges in children and adolescents. The measure includes
parallel forms for parents, teachers, and the children themselves with items pertaining to a wide variety
of behavioral challenges, including those specifically meant to represent symptoms from specific diagnoses
included in the Diagnostic and Statistical Manual (DSM).
Behavior Assessment System for Children, The BASC-3, similar to the CBCL, is a measure that assess both internalizing and externalizing symptoms
3rd ed. (BASC-3)/2–25 yrs (Reynolds 2015) in children and adolescents. The measure can be completed by parents, teachers, or the child, and includes
a variety of internal validity measures in addition to behavioral scales.
because many more tests are available. However, these are some of the children (Anderson et al. 2019). Additionally, the relevance of execu-
most commonly used measures. tive functioning measures to real-world abilities has been called into
question (Burgess et al. 2006). However, the use of laboratory mea-
Neuropsychological Domains sures in combination with questionnaires designed to tap daily func-
Intelligence tioning has been suggested for a more ecologically valid assessment
Intelligence is a general overall ability indicator. It is not necessarily (Gioia and Isquith 2004).
sensitive to subtle CNS damage in itself. Indeed, seminal studies have
demonstrated that IQ may not be affected by subtle acquired brain Sensorimotor
injury. However, an intelligence score provides a gross global starting Sensorimotor tests refer to assessment of both motor skills and aspects
point from which the neuropsychologist can interpret patterns (Lezak of sensation that apply to brain function (Lezak et al. 2012; Baron
et al. 2012). 2018). Motor measures may speak to speed, motor overflow, motor
coordination, and balance skills (Baron 2018). Sensory measures may
Speech and Language pertain to tactile discrimination and smell. Documentation of motor
Speech is the motor aspect of communication, whereas language refers skills may involve lateralization and localization of brain dysfunction
to meaningful communication itself (Lezak et al. 2012; Baron 2018). (Lezak et al. 2012). Similarly, smell identification tests are useful in
Language can be broken down into multiple subcomponents. It con- identifying brain injury (Bakker et al. 2016) but are less likely useful
tains the basic aspects of receptive and expressive communication and for targeting more subtle brain damage. Most neuropsychological
more nuanced, higher-level skills such as grammar, syntax, and word examinations include some measure of psychomotor functioning. (See
finding (Baron 2018). Table 2.5.)
Visual-Spatial Skills
ANESTHETIC NEUROTOXICITY
Visual-spatial skills include visual-perceptual, visual-spatial, and visual-
constructional skills. These domains represent a child’s ability to per- Data regarding the potential neurotoxicologic effects of anesthetic
ceive the world around them, relationships in space between objects, agents on the immature brain have generated great interest and con-
and the ability to integrate what the hand does with what the eyes see cern and led to a U.S. Food and Drug Administration (FDA) warning
(Baron 2018). These tests usually involve a variety of visual stimuli and against prolonged anesthetic exposure in young children. The phe-
graphomotor measures completed by the child. nomenon of anesthesia-induced neurotoxicity was first identified in
rodent models nearly two decades ago. Since then, convincing evidence
Attention and Processing Speed that anesthetics interfere with neurodevelopment has emerged in vari-
Attention is a base skill necessary for engaging in other cognitive ous preclinical animal models. Translating such findings to humans,
functions (Baron 2018). Although attention may seem a simple term however, has been challenging given that a child’s need for anesthesia
at first glance, it is quite complex when broken down (Scott 2011). and surgery is inevitably linked to various medical comorbidities.
Baron (2018) reviewed the evidence for defining attention based on Each year, approximately 1.2 million children in the United States
its subcomponents. It is a complex domain including selective atten- under 5 years of age undergo ambulatory surgery, and another 144,000
tion, divided attention, shifting attention, and executive attentional children of the same age undergo inpatient surgery (Rabbitts 2010;
control. These subdomains relate to a child’s ability to focus on cer- Tzong et al. 2012). Concern for the potential neurotoxicity of anes-
tain information, ignore other stimuli, focus for longer periods of thetic agents in the developing brain first emerged when immature
time, focus on two targets simultaneously, and so forth (Baron 2018). rodents, exposed to a cocktail of commonly used anesthetic agents,
Processing speed is a more straightforward concept related to how fast developed neuronal apoptosis in the brain and subsequently demon-
a child can think. Because measures of processing speed typically tap strated functional behavioral deficits in adulthood (Jevtovic-Todorovic
another skill at the same time (e.g., language, fine motor skills), how- et al. 2003). Since then, the concept of anesthetic neurotoxicity has been
ever, obtaining a “pure” measure of processing speed is challenging explored in hundreds of preclinical animal studies, and the association
(Anderson et al. 2019). between anesthetic exposure during neurodevelopment and subse-
quent histologic and cognitive and behavioral abnormalities has been
Learning and Memory confirmed in a variety of animal models, from worms to nonhuman
Learning and memory encompass a child’s ability to encode, consoli- primates (Loepke and Soriano 2008; Vutskits and Xie 2016). Other
date, and recall information (Anderson et al. 2019). Typically, neuro- potential mechanisms of toxicity, beyond apoptosis, have also been
psychological tests evaluate these skills for both verbal and visual explored and identified. Although there is convincing evidence that
information. Memory measures are designed to ascertain challenges in anesthetic exposure is detrimental to neurodevelopment in animals,
any aspect of the memory system, thought to be primarily housed in translating these findings to humans has been challenging. The chal-
the medial temporal lobe (Anderson et al. 2019). There are also some lenges stem from differences in brain development between species,
measures, geared toward older adolescents, that assess functional, daily marked dissimilarities between dosage and duration of exposure in the
memory. preclinical setting versus the clinical context, an incomplete under-
standing of the window of vulnerability in children, and a poorly
Executive Functioning defined phenotype of injury in humans.
Executive functioning is an umbrella term that covers higher-order In the face of these challenges, a number of clinical studies have
thinking skills such as problem-solving, planning, and organizing explored the association between anesthetic exposure in children and
(Baron 2018). These skills are also involved in emotion and behavior subsequent neurodevelopmental deficit. The vast majority of these
regulation (Anderson et al. 2019), and the primary brain areas thought studies have been observational in nature and, as such, have been un-
to be responsible for such skills are the frontal lobes (Baron 2018). able to establish a causal relationship. Despite these obstacles, in 2016
Executive functions are considered more complex skills that emerge the FDA released a warning against “repeated or lengthy (.3 hours)
with age (Baron 2018), and thus limited measures exist for younger use of anesthetic and sedation drugs during surgeries or procedures in
children younger than 3 years or in pregnant women during their third anesthetic agents, durations of exposure, and outcome measures
trimester” (FDA Drug Safety Communication 2016). (Istaphanous and Loepke 2009). Virtually all of the commonly used
anesthetic agents have been shown to elicit such neurotoxicologic re-
Brief Evidence From Preclinical Models sponses in animal studies (Istaphanous and Loepke 2009).
The deleterious effect of anesthetics on the developing brain was The majority of rodent exposure paradigms have focused on post-
assessed in seminal studies of MK801, a ketamine-like, N-methyl- natal day 7. This is because synaptogenesis peaks on day of life 7 in
d-aspartate (NMDA) receptor antagonist, and ethanol, a known rodents, and this time point has been shown to be the period of great-
NMDA antagonist and g-aminobutyric acid (GABA)-mimetic agent est vulnerability (Rice and Barone 2000; Yon et al. 2005; Sanno et al.
(Ikonomidou et al. 1999, 2000; Jevtovic-Todorovic et al. 2003). These 2010). However, critics have raised concern regarding the clinical rel-
early studies, which demonstrated widespread apoptotic cell death in evance of this age, given that the 7-day-old mouse or rat translates
the immature rodent brain after exposure, raised concern for the neu- roughly to a prenatal time point during human gestation or one that
rodevelopmental consequences of perinatal drug use and provided a approximates that of a full-term infant (Istaphanous and Loepke
potential explanation for the decreased brain size and behavioral ab- 2009). Furthermore, the period of vulnerability in rodents has been
normalities seen with fetal alcohol syndrome (Ikonomidou et al. 1999, defined largely on the basis of induced apoptosis and neurodegenera-
2000). Subsequently, it was found that exposure to anesthetics with tion in the immature brain (Rice and Barone 2000; Yon et al. 2005;
NMDA antagonist and/or GABAA agonist properties also triggered Sanno et al. 2010). Thus it has been challenging to meaningfully trans-
widespread apoptotic cell death at a critical time point during rodent late the findings in rodents to infants and children.
neurodevelopment (Jevtovic-Todorovic et al. 2003). Although the A major advance within the field over the last several years has been
mechanisms of neurotoxicity are unknown, it has been proposed that the emergence of studies using nonhuman primates. Employing such
the process may be mediated by the oxidative stress–associated mito- a robust model carries significance because neurodevelopment at birth
chondrial apoptosis pathway (Olney et al. 2004; Yon et al. 2005; Zhang is similar between nonhuman primates and human infants (Vutskits
et al. 2010; Bai et al. 2013; Boscolo et al. 2013). and Davidson 2017). Furthermore, a clinical anesthetic can be well
modeled in the infant monkey, and physiologic parameters can be as-
Proposed Mechanisms of Neurotoxicity sessed and homeostasis can be maintained (Vutskits and Davidson
Anesthetic agents cause oxidative stress within the cell by inducing 2017). In nonhuman primate work, infant rhesus macaques were ex-
reactive oxygen species (ROS) formation within mitochondria (Zhang posed to sevoflurane for 4 hours on days of life 6 to 10 followed by
et al. 2010; Bai 2013). ROS produced during exposure to anesthetics subsequent exposures on days of life 14 and 28. The monkeys demon-
permit cytochrome c mobilization from the inner mitochondrial strated increased anxiety compared with controls that underwent
membrane (Kapetanaki et al. 2009). Simultaneously, the outer mito- maternal separation (Raper et al. 2015). In other work, infant rhesus
chondrial membrane becomes permeable following GABAA receptor macaques were exposed to isoflurane for 5 hours on days of life 6, 9,
stimulation and NMDA receptor antagonism (Olney et al. 2004). The and 12 and demonstrated motor reflex deficits at 1 month of age and
combination of these factors permits cytochrome c release into the increased anxiety at 12 months of age (Coleman et al. 2017). Impor-
cytosol and initiates a cascade of cellular events that ultimately leads to tantly, there were no significant effects of a single isoflurane exposure
apoptotic neuronal cell death (Olney et al. 2004). (Coleman et al. 2017). These investigations are important because they
Although much of the neurotoxicity work has focused on oxidative suggest that multiple exposures to a volatile anesthetic, at a critical
stress and apoptosis, it is now understood that other mechanisms may time during development, may impact long-term neurodevelopment.
be involved. These include abnormalities of NMDA and/or GABA re-
ceptor expression, activity, and signaling; alterations in brain trophic Problems With Translating to Humans
and growth factor production and signaling; neuroinflammation; and Attempts to translate findings from preclinical investigations of
dysregulation of other growth and survival pathways (Olney et al. anesthesia-induced neurotoxicity in the developing animal brain to
2004; Vutskits et al. 2006; Johnson et al. 2008; Bai et al. 2013; Erasso humans have been limited, for several reasons (Mintz et al. 2012).
et al. 2013; Hofacer et al. 2013; Olsen and Brambrink 2013; Ma et al. First, the anesthetic dosage and durations of exposure in animal stud-
2016). Furthermore, other downstream developmental processes such ies often exceed clinically relevant concentrations and length of time.
as synaptogenesis, neurogenesis, and dendritic branching may become Second, the differences in timing and rates of brain maturation across
disrupted (Olney et al. 2004; Vutskits et al. 2006; Johnson et al. 2008; species make comparisons to human development difficult. Third,
Bai et al. 2013; Erasso et al. 2013; Hofacer et al. 2013; Olsen and assessment of neurodevelopmental outcome in most animal species
Brambrink 2013; Ma et al. 2016). Recent evidence also suggests delete- fails to provide meaningful information regarding the complexities of
rious effects of anesthetics on developing neuronal circuits, synapse higher-order cognitive function in children (van Loo and Martens
density and neurotransmission, and the number of mitochondria in 2007; Istaphanous et al. 2010; Mintz et al. 2012; Workman et al. 2013).
the synaptic terminal (Vutskits and Davidson 2017). Finally, in vivo histologic assessment of the brain in children follow-
ing anesthetic exposure is not possible. Thus investigators have not
Neurocognitive Effects in Rodents and Nonhuman been able to prove that anesthesia-induced neuronal apoptosis or
Primates other histopathology actually occurs in humans (Mintz et al. 2012).
In 2003, the first preclinical study evaluating long-term neurocognitive
outcome in rodents following newborn anesthetic exposure was pub- Observational Studies in Children
lished (Jevtovic-Todorovic et al. 2003). In this work, 7-day-old rats Due to the significant costs and challenges of performing prospective
were exposed to a combination of midazolam, nitrous oxide, and iso- studies of anesthetic neurotoxicity, the vast majority of studies have
flurane for 6 hours. The rats demonstrated impairments in synaptic been observational in nature, comparing children exposed to surgery
function within the hippocampus and displayed persistent cognitive and anesthesia with those not exposed at all. The challenge with inter-
defects as juveniles and young adults several weeks following exposure preting this type of study, however, is that the impact of anesthesia
(Jevtovic-Todorovic et al. 2003). Since then, numerous studies have exposure cannot be isolated from the operative procedure or the surgi-
corroborated these findings in both mice and rats using different cal experience. Since children who need surgery typically undergo a
procedure to address some underlying medical condition, adequately cohort compared with unexposed children (O’Leary et al. 2016). How-
controlling for such confounding variables can be difficult. Further- ever, a follow-up study identified 2346 sibling pairs from Ontario who
more, most of the observational studies were performed using preex- were discordant for anesthesia exposure before 5 years of age and
isting data sets. Whereas observational studies using preexisting data found no statistically significant increased risk of EDI deficit (O’Leary
can increase efficiency in generating results, interpretations are limited et al. 2019).
by the availability of data. A number of studies originating in the United States have also used
Interpretation of the many observational studies of anesthetic neu- academic achievement as an outcome measure. One investigation from
rotoxicity has been challenged by the amount of heterogeneity in the Iowa studied 113 children who were exposed to anesthesia for circum-
methodology used. Differences in the patient populations evaluated, cision, pyloromyotomy, or inguinal hernia repair before the age of 1
types of procedures performed, age at exposure, anesthetic dosage and (Block et al. 2012). In this study, anesthetic-exposed children were
durations, age at evaluation, outcome measures assessed, and chosen found to have academic achievement scores that were lower than ex-
comparison groups make analysis of the data as a whole and compari- pected based on the population norms (Block et al. 2012). However,
sons between studies difficult. Despite these limitations, however, the results were no longer significant after excluding children with
some interpretation is possible. A reasonable approach to reviewing underlying CNS problems (Block et al. 2012). In a study from the
this literature is to categorize the investigations based on the outcome Mayo Clinic, 350 children from Minnesota exposed to anesthesia for
measure used. surgery before 2 years of age were evaluated using academic achieve-
ment testing and assessment for learning disability (Flick et al. 2011).
Academic Achievement Outcomes in children with a single anesthetic exposure did not differ
Given the fact that educational databases are readily available in mul- from unexposed children; however, children with multiple exposures
tiple countries around the world, a large number of studies have uti- demonstrated a higher risk of developing a learning disability (Flick
lized academic achievement and teacher evaluations as a primary et al. 2011).
outcome measure of neurodevelopment in a variety of different pa- In a study from Singapore, 100 children who were exposed to anes-
tient populations. In a study of 110 monozygotic twins from the Neth- thesia for minor surgery were compared with an unexposed group
erlands, children exposed to anesthesia for surgery before 3 years of (Bong et al. 2013). In this study, no differences in the Primary School
age were compared with their unexposed twin siblings. In this twin Leaving Examination academic assessment were found between co-
study, no differences in standardized tests and teacher ratings at horts at 12 years of age; however, a higher risk of learning disability
12 years of age were found based on anesthesia exposure (Bartels et al. was detected in the exposed group (Bong et al. 2013). In an Australian
2009). This study is interesting because it is the only work to compare study focusing on a birth cohort from Perth, 781 children were as-
monozygotic twins who were discordant for anesthesia exposure. In sessed using a wide range of outcomes such as academic achievement,
another investigation, children in Denmark were evaluated using a ICD-9 coded clinical diagnoses, and directly assessed neuropsycho-
national database. In this study, 2689 Danish children exposed to an- logical tests (Ing et al. 2014a). Although anesthetic exposed children
esthesia for inguinal hernia repair before 1 year of age were compared were found to have an increased risk of deficits in neuropsychological
with a random sampling of 5% of the population, and no differences testing and an increased risk of an ICD-9 coded clinical diagnosis, no
were found in nationwide standardized test scores obtained at 15 to differences in academic achievement were found (Ing et al. 2014a).
16 years of age (Hansen et al. 2011). The same Danish database was used In summary, the vast majority of studies of anesthetic neurotoxic-
to evaluate another group of children who underwent pyloromyotomy ity in children that have used academic achievement or teacher evalu-
at #3 months of age and also found no difference in standardized test ations as outcome measures have shown either a marginal effect or no
scores between cohorts (Hansen et al. 2013). A study from Sweden that effect at all. In a few studies, other outcomes were evaluated in addition
evaluated 33,514 children who experienced a single anesthetic exposure to academic achievement scores. In those studies, no differences in
before the age of 4, without being admitted to the hospital, found that academic achievement were identified, but differences between co-
anesthetic-exposed children had lower test scores compared with unex- horts were found with regard to learning disability, neuropsychological
posed children (Glatz et al. 2017). However, the difference was quite testing, and the presence of ICD-9 coded clinical diagnoses. Although
small relative to other factors such as sex and maternal education level the latter group of studies raises questions about the presence of subtle
(Glatz et al. 2017). However, a subset of anesthesia-exposed boys from differences in specific neurodevelopmental domains between groups
this study were found to have scored lower on a military enlistment IQ of children, these investigations are reassuring given that school per-
test compared with unexposed boys (Glatz et al. 2017). formance appears to be generally unaffected by anesthetic exposure,
Other research that originated in Canada, evaluating children who particularly a single exposure.
underwent surgery and anesthesia exposure prior to 4 years of age,
utilized the Early Development Instrument (EDI), a questionnaire Learning Disability
completed by each child’s kindergarten teacher (Graham et al. 2016). Learning disability is defined using academic achievement scores and
In a study from Manitoba, 4470 exposed children were evaluated and IQ testing and has been used as an outcome measure in a number of
found to have lower scores than unexposed children (Graham et al. clinical studies assessing for anesthetic neurotoxicity (Beers et al.
2016). Interestingly, this study found that children who were exposed 2014). In a study from Rochester, Minnesota, children with single and
between the ages of 2 and 4 years had worse scores than children who multiple exposures to anesthesia were evaluated (Wilder et al. 2009).
were exposed between birth and 2 years of age. One reason for this Those exposed to anesthesia for surgery before 4 years of age were
difference is that the older exposed cohort received general anesthesia found to have an increased risk of learning disability following 2 or
for dental procedures (Graham et al. 2016). It is well known that chil- more exposures; however, no such risk was detected following a single
dren who require anesthesia for such procedures often have preexisting exposure (Wilder et al. 2009) (Fig. 2.5). One limitation of this work is
neurobehavioral problems. Another study from Ontario used the same that the children included in the study were born between 1976 and
EDI outcome assessment in 28,366 children who underwent surgery 1982 (Wilder et al. 2009), and a vast majority of the children were
before the age of 5 (O’Leary et al. 2016). This work found a statistically exposed to halothane, an anesthetic agent no longer commonly
significant increase in deficit (as measured by EDI) in the exposed used today. A follow-up study, evaluating a cohort of children born in
healthcare database of children from Taiwan (Tsai et al. 2018). These

50 investigations evaluated the same cohort of patients but reported dis-
Exposures (no.) crepant results. One study found no increased risk of ADHD following
Multiple
single or multiple exposure to anesthesia, whereas the other found an
40
1 association with an increased risk following multiple, but not single,
Learning disability
None exposures (Tsai et al. 2018). Importantly, the latter study employed a
diagnosis (%)
30 broader definition of ADHD with longer follow-up times (Tsai et al.

2018). Thus exposure to surgery and anesthesia at a young age has
been associated in some studies with an increased risk of subsequent
20
clinical diagnoses for psychiatric and developmental disorders.
10 Neuropsychological Testing and Behavioral Surveys

A number of observational studies have been performed using direct
neuropsychological testing. The outcomes in these studies were mea-
0
sured by trained neuropsychologists via assessments administered to
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
children in controlled settings. Because behavior is difficult to evaluate
Age (years)
in a test, some studies have also included behavioral surveys completed
by caregivers. In a study from Perth, 321 children exposed to anesthesia
Fig. 2.5 The Effects of the Number of Anesthetics Administered

before 3 years of age were found to have an increase in deficits in recep-

Before Age 4 on the Incidence of Learning Disabilities. (From Wilder,
tive and expressive language as well as abstract reasoning at age 10 (Ing

R. T., Flick, R. P., Sprung, J., Katusic, S. K., Barbaresi, W. J., Mickelson, C.,
et al. (2009). Early exposure to anesthesia and learning disabilities in a
et al. 2012). However, in this work, not all cognitive domains were af-
population-based birth cohort. Anesthesiology, 110, 796–804.) fected and there were no differences in behavior and motor function
(Ing et al. 2017b). A limitation of this study was that these children
were born between 1989 and 1992, and the vast majority received
Minnesota between 1996 to 2000, was performed to address this limi- halothane, an antiquated inhalational anesthetic (Ing et al. 2017b).
tation using a similar experimental methodologic approach (Hu et al. Of the studies that incorporated neuropsychological testing, two
2017). In this study, 72% of children received sevoflurane, and a simi- large-scale ambidirectional studies have been performed. An ambidi-
lar association between anesthetic exposure and learning disability was rectional study is one that retrospectively identifies children who re-
identified (Hu et al. 2017). Similarly, in a work from Singapore, chil- ceived surgery and anesthesia in the past and then brings them into a
dren who underwent anesthesia exposure for minor procedures were testing facility for prospective testing. The benefit of this type of study
found to have an increased risk of learning disability compared with compared with a traditional prospective study is that subjects are old
unexposed children (Bong et al. 2013). Although this finding was con- enough for neuropsychological testing at the time of study enrollment,
sistent with the results from Minnesota, the definition of learning thus reducing the amount of time needed to perform the study. The
disability differed between the studies. Overall, however, learning dis- first study published using this approach was the multicenter Pediatric
ability has been found to be associated, to some degree, with exposure Anesthesia Neurodevelopment Assessment (PANDA) study, which
to anesthesia and surgery, particularly following multiple exposures. A evaluated 105 healthy children exposed to anesthesia for hernia repair
major caveat, though, is that the term “learning disability” has not been before age 3 (Sun et al. 2016). In order to control for sociodemo-
consistently defined between studies. graphic and parental variables, exposed children were compared with
their unexposed siblings (Sun et al. 2016). Children were evaluated
Clinical Diagnoses of Developmental and Psychiatric between 8 and 15 years of age and a range of outcomes were measured
Disorders by neuropsychologists and reported by caregivers (Sun et al. 2016). No
Clinical diagnoses of developmental and psychiatric disorders are differences were found in the primary outcome of IQ or in the major-
typically made by medical providers and recorded either in healthcare ity of secondary outcomes (Sun et al. 2016). Differences were identified
administrative databases or research databases. In a study using the in Child Behavior Checklist (CBCL) surveys, however, in which parents
New York State Medicaid healthcare administrative data set, a cohort reported more behavioral problems in anesthetic-exposed children
of 383 children exposed to anesthesia for inguinal hernia repair before (Sun et al. 2016).
the age of 3 years was identified and compared with children without A second investigation that utilized an ambidirectional approach
surgery (DiMaggio et al. 2009). Children in this cohort who were ex- was the Mayo Anesthesia Safety in Kids (MASK) study, which enrolled
posed to anesthetic and surgery had an increased risk of an ICD-9 380 children exposed to a single anesthetic, 206 children exposed to
coded diagnosis for developmental delay or behavioral disorder multiple anesthetics, and 411 children without any anesthetic exposure
(DiMaggio et al. 2009). A larger study of a cohort of children enrolled (Warner et al. 2018). No differences were found in the primary out-
in Medicaid in Texas and New York evaluated 38,493 children who come of IQ or a range of other secondary outcomes (Warner et al.
underwent a single common pediatric surgical procedure (Ing et al. 2018). However, differences in processing speed and fine motor ability
2017a). In this investigation, a single exposure was associated specifi- were detected in children with multiple exposures (Warner et al. 2018).
cally with an increased risk of a mental disorder diagnosis and an In addition, parents reported differences in executive function as mea-
attention deficit hyperactivity disorder diagnosis (ADHD) (Ing et al. sured by the Behavior Rating Inventory of Executive Function (BRIEF)
2017a). In a study of 350 Minnesota children exposed to anesthesia and behavior as measured by the CBCL in children with single and
before 2 years of age, those with multiple exposures had an increased multiple exposures (Warner et al. 2018). In a follow-up cluster analysis
risk of ADHD, whereas no such risk was found following a single ex- of the children in the MASK cohort, only 23.3% of multiply exposed
posure (Sprung et al. 2012). Importantly, these findings were con- children grouped into a cluster of patients with overall lower perfor-
firmed in subsequent work assessing a more modern cohort of chil- mance in most neuropsychological tests (Zaccariello et al. 2019).
dren (Hu et al. 2017). Two studies have been published using a national This implies that children who received multiple anesthetics are not
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blessé !… Comme m’adressant à moi-même, je me contentai de
murmurer : — Est-ce donc pour nous heurter si douloureusement
que nous nous sommes rencontrés ? Le temps s’écoule d’une façon
irréparable et voilà que nous l’employons à nous faire du mal !…
Charles, nous séparerons-nous ainsi ?
Il parut touché. Néanmoins, il se tenait sur la défensive car il
répondit : — Cela dépend de toi. Promets-moi de ne plus faire
aucune allusion au sujet qui nous divise et pendant le peu d’instants
qui nous restent à passer ensemble, je me charge de te prouver que
je t’aime toujours autant.
— Ton âme m’est trop chère pour que j’accepte cette condition,
dis-je en sanglotant, j’aurais beau te promettre mon silence sur ce
point, je sais que je manquerais à mon engagement. Songe, je t’en
conjure, que si je t’obéissais, ce serait, devant Dieu, comme si je
plantais un poteau indicateur, à ton intention, sur la route qui va en
enfer.
— Alors, reprit Charles en se dirigeant vers la la sortie, nous
n’avons plus rien à nous dire… Adieu !
Sur le seuil, il s’arrêta. J’espérais un revirement providentiel.
Mais, avec une inflexion de voix d’une étrange douceur, il dit
simplement : — Prie pour moi, mon ami…!
— Ah ! tu n’avais pas besoin de me le demander !
Et je m’élançai vers lui. Mais déjà, il était de l’autre côté de la
porte et je l’entendis descendre précipitamment l’escalier.
Une heure plus tard, le cœur brisé, l’esprit en désarroi, je quittai
Lyon.
Les jours suivants, ma pensée revenait sans cesse à Charles.

Récapitulant les péripéties de notre brève entrevue, je
m’empoisonnais du sentiment amer de mon impuissance à le
sauver. A quelle profondeur sa passion le possédait ! J’ai beaucoup
confessé ; j’ai donc eu souvent affaire à des infortunés que rongeait
cette démence qui prend son origine dans une soumission servile à
l’instinct : le culte idolâtrique de la femme. Mais l’exemple que me
fournissait mon pauvre frère surpassait tous les autres. A force de
ressasser cette idée, mon jugement se faussait ; je me sentais tout
faible, prêt, par instants, à lui faire savoir que, selon son désir, je ne
lui parlerais plus jamais de sa conduite. Mais alors il me semblait
entendre le sinistre éclat de rire du Malin désormais assuré que nul
ne libérerait cette âme du filet aux mailles de feu où il la tenait
captive. Et je m’écriais : — Si je renonce, que répondrai-je à Dieu
quand il me demandera : « Qu’as-tu fait de ton frère ? »
Ce réveil de conscience finit par l’emporter d’une façon décisive.
Je rejetai avec horreur toute velléité de m’avouer vaincu. Et,
aussitôt, l’inspiration me vint d’aller au front pour y mériter le salut de
Charles. Cette grâce me fut octroyée. Depuis, en assistant ceux qui
s’offrent au danger perpétuel d’une mort subite, je tâche de
compenser devant Dieu les égarements de mon frère bien-aimé…
Maintenant, voici mon rêve.
Ce soir-là, comme, couché sur la paille de l’écurie où cantonnait
notre ambulance, je commençais à m’assoupir, la dernière phrase
que Charles m’avait dite me revint fortement à l’esprit : Prie pour
moi, mon ami ! Elle signifiait, à coup sûr, qu’il n’était pas perdu sans
rémission puisque, malgré notre mésentente, il gardait assez de foi
pour admettre que mes prières plaideraient sa cause au tribunal de
Dieu. Cette pensée me fut un réconfort. J’en avais besoin car,
n’ayant aucune nouvelle de lui, depuis plusieurs semaines, sachant
seulement que son bataillon avait pris part à la victoire de la Marne
et combattait récemment sur l’Yser, je vivais dans une anxiété
continuelle à son sujet. Je m’endormis en formulant le désir
d’apprendre bientôt ce qui lui était advenu.
Alors, il me sembla que j’étais transporté ailleurs… dans une
plaine immense où il n’y avait ni routes, ni sentiers, ni fleuves ni
ruisseaux, ni arbres, ni végétations quelconques, ni le moindre
vestige d’un travail accompli par la main de l’homme. C’était une
effrayante solitude où régnait la chaleur d’une fournaise inextinguible
et sur laquelle s’étendait une morne lueur crépusculaire dont la
teinte rougeâtre donnait l’impression d’une nappe de sang diffusée
dans un océan de brouillard.
D’abord, une tristesse écrasante me ploya l’âme. Je me croyais à
jamais abandonné dans ce désert. Mais lorsque je regardai autour
de moi, je m’aperçus que je n’étais pas seul. Des apparences
diaphanes m’environnaient — pas tout à fait des ombres, car une
sorte de rayonnement très faible émanait d’elles, comparable au
reflet, mi-voilé par un nuage, d’un astre infiniment lointain. Toutes
étaient tournées ou plutôt tendues vers un segment de l’horizon
comme si, là-bas, allait naître la pleine lumière. Quelques-unes
paraissaient déjà l’entrevoir mais moi, mes regards se heurtaient à
des ténèbres qui bornaient les confins de la terre et du ciel.
Renonçant à les percer, j’examinai attentivement les ombres qui
m’étaient le plus voisines. J’avais le sentiment d’une corrélation avec
elles et pourtant je n’en reconnus aucune. Leurs visages étaient si
vagues ! On eût dit, à l’avers de très anciennes médailles, des
effigies rendues presque indistinctes par l’usure.
Je demandai : — Où suis-je donc ? Nulle parmi les ombres ne
manifesta qu’elle m’avait entendu. Mais une voix intérieure me
répondit : — Tu es en Purgatoire.
Je ne m’étonnai ni ne m’alarmai. Ainsi qu’il arrive dans les rêves,
je trouvais ce Surnaturel — tout naturel. Cependant un incident ne
tarda pas à se produire qui me remua jusqu’au plus intime de mon
être. Les ombres, sans paraître toutefois avoir soupçonné ma
présence, s’écartèrent de moi. Elles se mirent en marche vers ce
point mystérieux qui les attirait d’une façon irrésistible et elles se
fondirent dans l’atmosphère torride où nous étions immergés. Je me
disposais à les suivre lorsque j’en fus empêché par la survenue
d’une âme qui me barra le passage. Celle-ci me voyait. Elle s’arrêta
net pour me fixer. Deux flammes, jaillies de ses prunelles, lui
éclairèrent le visage d’une façon si intense que, sans erreur
possible, je reconnus mon frère Charles !…
Cloué sur place, la gorge serrée, le cœur tressautant, je
m’efforçai de crier son nom. D’un geste, il m’imposa silence. Alors,
non par l’ouïe mais au-dedans de moi, je l’entendis murmurer : — Je
suis mort cette nuit… Prie pour moi !
Simultanément, je fus averti que, jumeaux sur terre, en
Purgatoire nous n’avions qu’une âme. C’est pourquoi, bien que
Charles n’articulât plus une seule syllabe, j’éprouvais ses
souffrances comme lui-même les éprouvait. Elles étaient doubles.
D’une part, un feu, d’une ardeur toujours croissante le consumait,
rongeait, comme un vitriol implacable, les taches laissées par ses
péchés. D’autre part, l’amour de Dieu, le désir de le posséder dans
l’Absolu le calcinait au point qu’il n’est pas de soif d’ici-bas qui
puisse lui être comparée. Ensuite, je sentis la réalité de ce que
j’avais naguère appris par la foi — ceci : comme toutes les âmes du
Purgatoire, Charles ne pouvait rien pour abréger la durée de sa
pénitence. C’était uniquement par les prières des fidèles en état de
grâce et appartenant à l’Église militante qu’une telle faveur lui serait
consentie. Et l’attente éplorée de cette intercession constituait une
troisième torture…
Dès que je fus tout imprégné de son supplice, Charles leva la
main et me désigna l’horizon et, aussitôt, là où je n’avais perçu
qu’une muraille de nuit opaque, je vis se dresser une cathédrale tout
en or radieux. Elle brillait comme dut briller l’étoile qui conduisit les
Mages à la crèche de Bethléem. Il n’est pas de chiffre capable
d’évaluer l’effrayante distance qui nous en séparait. A ce moment,
notre fusion l’un dans l’autre prit fin. Charles eut un sourire de
gratitude mélancolique car il lisait en moi que, jusqu’à mon dernier
souffle, toutes mes énergies se voueraient à solliciter pour lui la
Miséricorde divine et à l’assister de mes oraisons durant son long, si
long voyage vers la Béatitude éternelle. Puis un rideau de brume
embrasée se déroula entre nous… Tout disparut et je me réveillai,
ruisselant de larmes.
Pendant toute cette journée et celle du lendemain, je restai sous
l’influence de mon rêve. Sans arrêt, je me posais des questions
douloureuses : ce songe figure-t-il un avertissement venu d’En-
Haut ? N’est-ce qu’un cauchemar où se condensèrent mes
préoccupations depuis des semaines ? Par-dessus tout, je me
demandais si mon frère était encore de ce monde.
Le matin du troisième jour, je reçus une lettre signée de
l’aumônier volontaire qui accompagnait son bataillon. Elle
m’apprenait la mort de Charles ! Menant ses hommes à l’attaque
d’une tranchée allemande, il avait été transpercé d’un coup de
baïonnette et il n’avait survécu que peu de temps à sa blessure. Et
cela s’était passé dans la nuit et à l’heure où lui-même m’annonçait
son entrée en Purgatoire…
La missive de l’aumônier se terminait par ces lignes qui se
gravèrent en moi de telle sorte que je puis les répéter sans crainte
d’en déformer le sens : « Je me suis tenu près de votre frère
jusqu’au dénouement. Tant que se prolongea son agonie, je lui ai
prodigué toutes les consolations religieuses dont je suis capable. Il
avait sa connaissance ; il m’entendait mais, le sang l’étouffant, il ne
pouvait me répondre. Pourtant, au moment suprême, il se souleva
de terre ; une expression d’humilité adorante lui éclaira la figure ; il
se frappa la poitrine et réussit à émettre ce seul mot : Confiteor !
Puis il retomba et tout fut fini… Je crois ne pas me tromper en
affirmant que Dieu lui a octroyé l’entière contrition de ses fautes… »
L’abbé Cerny inclina le front et entra dans une méditation
profonde que, pleins de sympathie et de respect, nous nous
gardâmes de troubler. Enfin, relevant la tête, il s’écria : — Louanges
à Dieu ! Charles expie mais il est sauvé. Il dépend de moi d’obtenir
pour son âme une réduction de peine, Maintenant, accourez
souffrances et occasions de sacrifices — je suis prêt !…
IV
LES HIRONDELLES
Le frère Placide a écouté avec la plus grande attention le récit de

l’abbé Cerny et le mien. Je ne m’en étonne point, sachant que la
communauté où il fit profession s’adonne spécialement à la prière
perpétuelle pour les âmes du Purgatoire. Je pressens que, dans la
sainte clôture qui le garda tout à Dieu depuis l’âge de dix-sept ans, il
a reçu des lumières de choix. Aussi, je ne tarde pas à lui dire :
— Maintenant, mon petit frère, c’est à votre tour de parler.
Il se trouble ; il rougit. Se mettre en évidence lui déplaît si fort que
mon invitation l’effarouche. Cependant, comme l’abbé Cerny vient à
la rescousse, il finit par nous répondre : — Je crois avoir appris
quelque chose sur les âmes du Purgatoire mais je suis tellement
gauche et je m’exprime si mal que je ne puis guère vous le rendre.
— Ne vous inquiétez pas. Dites-le comme vous l’avez senti et ce
sera très bien.
Visiblement, mon affirmation ne suffit pas à le rassurer. Toutefois,
pour ne pas nous désobliger, il fait un effort sur lui-même et c’est
avec une entière simplicité qu’il nous rapporte ce qui suit :
— Vous savez qu’au monastère, nous avons chacun notre
cellule. Nous n’y résidons guère que la nuit car, du réveil au coucher,
nous sommes pris par les offices liturgiques et le travail manuel. Eh
bien, un soir, à peu près un mois avant la guerre, je venais d’y
rentrer pour prendre mon repos. Ainsi qu’il est de règle, j’avais quitté
mes souliers et ma ceinture et je m’étais étendu sur la paillasse
piquée qui, avec un traversin de varech, constitue notre couchette…
— Je connais, interrompis-je, c’est à peu près aussi moelleux
qu’une table de granit !
Le frère rit doucement : — Peut-être, reprit-il, mais je puis vous
certifier que, d’habitude, cela ne m’empêche pas d’y dormir à poings
fermés. Ce jour-là, il n’en fut pas de même. Depuis le matin, régnait
une chaleur orageuse qui accablait et énervait à la fois. Des nuages
de plomb couvraient le ciel, pesaient de plus en plus bas et, comme
nous étions en pleine canicule, il n’y avait pas à espérer que quelque
fraîcheur naquît avec l’aube. Je suffoquais. Quoique je
m’appliquasse à ne pas bouger, j’avais le corps trempé de sueur. Je
l’avoue : j’aurais quitté bien volontiers ma tunique et mon scapulaire,
échangé ma grosse chemise de bure contre du linge sec. Mais ce
nous est interdit puisque nous sommes là pour réparer et que nous
avons fait vœu de pénitence à l’intention de secourir les défunts qui
expient, dans l’autre monde, le trop de complaisance qu’ils
donnèrent à leur bien-être ici-bas.
Je me sentis bientôt si mal à l’aise que je ne pus y tenir. Je mis
les pieds sur le carreau, je me traînai vers la fenêtre grande ouverte
et je m’agenouillai le front appuyé contre le bois vermoulu du
chambranle. J’aspirais d’une bouche avide l’air extérieur. Mais il ne
m’apporta nul soulagement car, au dehors comme dans la cellule,
l’atmosphère, d’une noirceur rigide, semblait provenir d’une forge où
l’on aurait entretenu un sombre brasier dont le souffle me calcinait
les poumons.
J’essayai de prier. Comme nos constitutions nous prescrivent de
le faire lorsque nous nous réveillons la nuit, je murmurai : —
Fidelium animae requiescant in pace… Mais ce ne me fut qu’une
formule machinale. Et même elle me parut si dépourvue de sens que
j’éprouvais une sorte de dégoût à la rabâcher. C’est que je passais
par une de ces minutes de dépression corporelle dont le Diable,
toujours aux aguets, sait si bien profiter pour nous lacérer l’âme et y
semer des orties.
Affaissé comme je l’étais, je ne réalisai pas le danger de cet
assaut. Sous l’influence démoniaque, d’un cœur débordant
d’amertume, je m’écriai : « A quoi bon ces prières ?… A quoi bon
cette pénitence ?… A quoi bon vivre ?…
Et je ne cherchais pas à enrayer l’esprit de révolte qui s’efforçait
d’abolir en moi la grâce de la vocation religieuse. Haché comme un
fétu par la grêle, je balbutiai : — Je ne peux pas, je ne peux pas
lutter davantage !… Et, je me laissai choir tout de mon long sur le
sol, répétant ce que me dictait la voix sardonique de l’Ennemi : —
Tout ce que tu entrepris, avec tant de joie, pour le salut des âmes,
est totalement inutile !…
Or, voyez la bonté de Dieu ! Tandis que, prostré de la sorte,
versant des larmes et me tordant les mains, je m’enfonçais, sans
réagir, dans ces ténèbres affreuses, voici qu’une lumière
éblouissante envahit tout à coup la cellule. J’ouvris les yeux, je me
relevai, d’un bond je courus à la fenêtre. Ce que je découvris alors
m’émerveilla jusqu’à l’extase.
La croisée donnait sur une partie assez limitée du jardin
entourant le monastère. Directement au-dessous, le regard se posait
sur des planches de choux et de salades. Vingt mètres plus loin se
dressait une rangée de cyprès si serrés qu’ils formaient une cloison
au delà de laquelle il était impossible de rien apercevoir. C’était, du
moins, l’aspect du lieu tel qu’il se présentait journellement à ma vue.
Mais, maintenant, ces choses avaient disparu. A la place, un
immense verger s’étendait où l’herbe d’un vert éclatant, moiré de
reflets vermeils, se parsemait de larges fleurs où chatoyaient toutes
les nuances du prisme. Çà et là, des arbres étendaient leurs
frondaisons. Je ne pus en déterminer l’espèce car ils étaient chargés
d’hirondelles au point qu’on ne distinguait plus le feuillage. Sur
l’ensemble, un ciel bleu d’une profondeur inouïe et une clarté solaire
si intense et si pure à la fois que je ne me souvenais pas d’en avoir
connu de semblable, même aux jours les plus beaux de l’été. Et ce
paysage et cette lumière me furent plus réels que toute réalité
perçue par les yeux du corps. En effet, j’avais l’intuition que c’étaient
les yeux de mon âme qui absorbaient cette féerie.
Les hirondelles chantaient éperdument. Oh ! ce chant !… Ce
n’était pas leur gazouillis coutumier, mais un hymne de joie qui
exprimait une reconnaissance infinie, une félicité sans bornes. Frais
comme l’eau d’une source sous-bois, pénétrant comme un parfum
de tubéreuse, aérien et subtil !… Mais pourquoi chercher des
comparaisons ? Cela dépassait tout ce que nos sens, rendus
infirmes par le péché, peuvent s’assimiler — tout ce que notre esprit,
entravé par la chair, peut concevoir.
Et le chant disait : Gloire à Dieu au plus haut des cieux !…
A écouter, dans le ravissement, cette action de grâces, il me fut
appris que ces hirondelles signifiaient les âmes du Purgatoire dont
les prières de la communauté avaient obtenu la délivrance. Avant
leur migration définitive vers la béatitude éternelle, Dieu permettait
qu’elles me révélassent que mes oraisons, ma vie pénitente, à moi
pauvre moine si imparfait, et jusqu’à mon agonie entre les griffes du
Démon, n’avaient pas été en vain.
Alors, mon cœur se dilata, s’épanouit comme une rose de mai ;
je riais, je pleurais des larmes d’allégresse, je chantais, moi aussi :
Gloire à Dieu !…
Enfin les hirondelles se levèrent toutes, déployèrent leurs ailes,
montèrent vers les hauteurs radieuses où, chantant toujours, elles
se perdirent en Dieu. Ah ! que j’aurais voulu les suivre !…
Le frère Placide n’ajouta rien. L’abbé Cerny et moi, nous ne fîmes
aucun commentaire. Et qu’aurions-nous pu dire ? Nous étions
transportés, comme lui, loin de ce triste monde : ce qu’il avait vu,
nous devenait sensible et nous prenions pleinement conscience qu’il
est salutaire, à quiconque se veut ami de Jésus, de souffrir avec nos
sœurs pathétiques : les âmes du Purgatoire.
La nuit a passé. Un petit jour blafard colle maussadement sa face

aux vitres. Le vent ne souffle plus, mais la pluie redouble. Étendus
côte à côte sur le plancher, nous commençons à nous assoupir
quand une canonnade enragée nous force de déclore les paupières.
Nos 75 lancent des aboiements secs. Au loin, dans le brouillard, les
grosses pièces allemandes leur répondent par de lourds
grognements enroués. Allons : le sang ruisselle comme il a ruisselé
hier, comme il ruissellera demain. Et les âmes des morts
tourbillonnent parmi les rafales homicides : — Priez pour nous !
Priez pour nous ! implorent-elles.
Nous prions…
BRÈVES ÉTAPES DU VOYAGEUR
ÉCLOPÉ
Portant ma croix, j’ai suivi la voie douloureuse

en mémoire du Maître. La trace de ses pas
restait empreinte en lumière sur les pavés
obscurs. Elle brillait si fort que souvent je faisais
halte pour l’admirer et la vénérer. Alors mon
cœur brûlait de Son Amour. Et me retournant
vers vous, je vous criais : « Ne monterons-nous
pas tous ensemble jusqu’au Calvaire ? »
Lapillus.
ARGUMENT
Amis très chers, dont la sollicitude m’assiste fraternellement

depuis tant d’années qu’il plut à Dieu de m’appliquer à Le servir par
des livres, variés quant aux sujets qu’ils traitent, semblables quant
au désir de Le faire aimer davantage, il faut que je vous confie ma
fatigue.
Lorsque je commençai le présent volume, j’avais conçu le projet
d’y réunir des narrations où des faits de vie intérieure vous seraient
exposés dans une forme analogue à celle choisie pour le chapitre
que vous venez de lire. Or, j’y dois renoncer et voici pourquoi : le mal
chronique dont je suis atteint va s’aggravant ; ses redoublements
journaliers m’enlèvent la possibilité de fournir un travail continu. Et,
sans continuité dans l’effort, comment mener à bien des récits où
tout s’enchaîne ? L’esprit le voudrait — le corps regimbe et reste
sourd aux injonctions d’une volonté qui, elle, ne fléchissait pas.
A vingt reprises, après avoir longuement réfléchi à la tâche que je
m’étais fixée, j’ai pris la plume. Mais à peine avais-je tracé quelques
lignes qu’une douleur lancinante m’obligeait de tout laisser pour
m’étendre, pendant des heures, sur ma chaise longue. D’autres fois,
une si grande faiblesse me tenait qu’il n’y avait même pas à tenter la
rédaction d’une page. C’était, tout au plus, si je pouvais me traîner à
la messe quotidienne. Et, au retour, je devais ou prendre le lit ou,
demeurant sur pied, me résigner à l’inaction.
Ce sont là, vous en conviendrez, des nœuds gordiens où le
glaive d’Alexandre s’ébrécherait. D’autre part, je respecte trop mon
art pour me contenter de vous soumettre des esquisses imparfaites
alors qu’il est de mon devoir de vous offrir des tableaux auxquels
j’aurais donné tous mes soins.
Vous donc, qui m’aimez comme je vous aime, qui priez pour moi
comme je prie pour vous, acceptez, faute de mieux, ces notes
éparses, disjecta membra, où je me suis efforcé de vous confirmer
dans la certitude que le Royaume de Dieu est en nous et qu’il serait
vain de le chercher ailleurs. Fruits spontanés de l’oraison,
méditations sur des textes sanctifiants, appréciations sur le temps
présent d’après des lectures profanes, je les assemble en une sorte
de petit calendrier dont les feuillets vous rappelleront votre
compagnon de route quand il vous aura quitté pour le Purgatoire. Et
ainsi, vous pourrez attester que, jusqu’à son dernier souffle, il
marcha les yeux fixés sur le Bon Maître lumineux et sanglant — tel
qu’il daigne nous apparaître au sein des ombres qui couvrent ce
monde en proie aux précurseurs de l’Antéchrist.
JUIN
Dans l’octave de l’Ascension. — Cette année, la fête de

l’Ascension se célébra le 26 mai. Une impression reçue ce jour-là fut
si forte qu’elle persiste en moi après une semaine écoulée. Il faut
que je la note.
J’assistais à la messe dans la chapelle des Dominicaines gardes-
malades, humble petit sanctuaire où je sens si profondément que
Notre Seigneur aime à résider, pauvre parmi ses filles servantes des
pauvres ! Pour suivre la liturgie, je venais d’ouvrir mon paroissien.
Mais avant que mon regard se fût posé sur le texte, une phrase me
naquit dans l’âme et l’absorba totalement, de sorte qu’elle
m’empêcha de lire et même d’entendre le chœur des religieuses qui
chantaient l’Introït. La voici : « Quand j’aurai été élevé de terre,
j’attirerai tout à moi. »
On se souvient qu’elle se trouve au XIIe chapitre de l’Évangile
selon saint Jean. Jésus la formule, à cet endroit, pour annoncer son
crucifiement d’où résultera notre rachat. Mais l’office de l’Ascension
ne la cite nulle part. Du reste, ce n’est pas sur le moment que je fis
cette remarque. La phrase, se renforçant, se répercutant à tous les
échos de mon âme, ne me laissait pas le loisir de raisonner à son
sujet. Plus encore, elle me devint bientôt une image intérieure qui
me représenta le Christ s’élevant vers le ciel — en croix. Toutefois,
les ténèbres frémissantes qui surgirent lorsqu’il prononça la parole :
Tout est consommé ne l’environnaient point. Une calme lumière
émanait de lui et remplissait tout l’espace.
Cette image me demeura présente jusqu’à la fin de la messe.
Elle était là lorsque j’allai recevoir l’Eucharistie ; elle était là durant
mon action de grâces qui en fut exclusivement contemplative. Puis
elle occupa ma pensée, d’une façon presque continuelle, jusqu’au
dimanche dans l’octave où il me semble que le sens m’en fut donné.
En cette même chapelle, après la lecture de l’Épître, je me
remémorais ce que le chœur avait chanté le jeudi précédent :
Dominus, ascendens in altum, captivam duxit captivitatem… Et je
me dis : — Naguère, captif du monde, j’en fus délivré par la Croix.
Maintenant, captif heureux de la Croix, je sens que Jésus m’attire,
par elle, vers sa gloire. Si je reste l’homme de bonne volonté, elle
m’attirera de plus en plus parce que je ne puis m’élever au-dessus
de moi-même qu’en l’acceptant avec allégresse.
Alors je me mis à prier : — Seigneur, au temps de Noël, tandis
que je vous adorais à Bethléem, j’ai vu l’ombre de la Croix se
découper sur le mur de l’étable. Au temps de Pâques, j’ai vu les plis
du linceul, abandonné par vous dans le tombeau, dessiner la Croix.
Le matin de l’Ascension, je vous ai vu rayonner sur la Croix dans la
Lumière incréée. Daignez me maintenir uni à vous par le sentiment
que la grâce de votre présence est inséparable de la grâce de
souffrir pour l’amour de vous et, en corrélation, pour l’amour de ceux
qui vous ont perdu, de ceux qui vous cherchent et de ceux qui vous
ont trouvé. Car, vous venez de me l’apprendre, ces deux mots :
Rédemption, Ascension signifient une seule chose Là-Haut.
Pentecôte. — Voici une chambre plongée dans l’obscurité, la

fenêtre et ses volets étant tenus rigoureusement clos. L’homme qui
l’habite, s’il ne passe ses jours à rêvasser en une morne torpeur,
s’occupe de ranger le pêle-mêle de meubles poussiéreux dont elle
est encombrée. Vaine besogne car, comme il ne voit pas clair, il
n’arrive qu’à augmenter le désordre. D’ailleurs il se rebute vite,
d’autant plus qu’il respire mal en ce logis follement calfeutré où
l’atmosphère, jamais renouvelée, se charge d’une myriade de
corpuscules nuisibles qui lui encrassent les poumons. Et quelle
odeur de renfermé ! Haletant et morose, il s’acagnarde alors devant
le foyer, tout noir de suie ancienne, où un tison chétif achève de
s’éteindre sous un amas de cendres.
Il dit : — Ce feu va mourir… Ensuite, je claquerai des dents mais
je n’ai ni brindilles ni copeaux pour réveiller la flamme, ni bois pour
l’entretenir. Et, je me l’avoue, je suis trop paresseux pour prendre la
peine de refaire ma provision de combustible. Foin de l’effort !…
Cependant, à l’extérieur, le grand soleil darde de longues flèches
d’or dont quelques-unes pénètrent par les fentes des volets et filtrent
à travers la buée malpropre qui rend les vitres opaques. Si l’homme
ouvrait tout, il recevrait, en surabondance, chaleur et clarté. Mais —
foin de l’effort !…
Au dehors, souffle un vent joyeux tout embaumé des parfums de
la vie. Si l’homme le laissait entrer, comme il assainirait la chambre,
comme il en chasserait les miasmes, comme il stimulerait le
prisonnier volontaire qui s’y engourdit et s’y hébète ! Mais — foin de
l’effort !…
L’homme a soif. Il soulève sa cruche afin de se désaltérer et
s’aperçoit qu’elle est vide. Devant la maison coule une fontaine
intarissable dont le murmure parvient jusqu’à lui. Il n’aurait qu’à
descendre et se pencher sur la vasque. L’eau qui la remplit
jusqu’aux bords lui rafraîchirait la bouche et le cœur pour longtemps.
Mais — foin de l’effort !…
Ainsi de l’âme que la grâce sanctifiante répandue par le Saint-
Esprit sollicite et qui refuse de l’accueillir. Elle est en proie — comme
dit Bossuet, — « à cet inexorable ennui qui fait le fond de la nature
humaine ». Elle languit faute de lumière, faute de chaleur, faute d’air
pur, faute de l’eau où s’imbiberait son aridité. Le Saint Esprit lui
apportait toutes ces richesses et plus encore puisqu’il entretient en
nous ce sentiment de la présence du Père et du Fils sans lequel
nous ne pouvons être qu’un terroir infécond. Qu’on se rappelle cette
strophe de l’admirable séquence au Paraclet conçue par Thomas
d’Aquin :
Sine tuo numine

Nihil est in homine
Nihil est innoxium.
Elle définit en sa vigueur concise, l’état effrayant de l’âme
réfractaire au Saint-Esprit. Bientôt, celle-ci devient inapte à le
recevoir. Elle est désormais cet animal rivé à ses instincts pervers
dont parle saint Paul dans la première épître aux Corinthiens. Et
cela, parce que, tel jour où la Grâce se faisait plus pressante, son
libre-arbitre ayant à choisir, en pleine conscience, entre Dieu et le
diable, a choisi délibérément le diable. C’est aussi parce qu’elle a
commis ce péché contre le Saint-Esprit dont Notre-Seigneur nous
prévient qu’il ne sera jamais pardonné. Voilà l’histoire de bien des
conversions avortées.
Mais la charité du Saint-Esprit est infatigable. Fût-ce au lit de
mort, fût-ce à la dernière minute, il s’offre encore à l’homme qui se
verrouillait, lui-même, dans le cachot de son orgueil. Que l’âme
pécheresse, sentant alors son indicible solitude, invoque, avec la
simplicité d’un enfant, le secours qu’elle avait si longtemps méprisé,
Jésus lui dit : — Je ne te laisserai pas orpheline. Et il lui envoie le
Consolateur.
Immédiatement, la pauvre âme découvre que les oripeaux
bariolés, dont elle se glorifia durant tout son voyage sur terre,
n’étaient que de sales guenilles. Elle s’en dépouille avec allégresse
et — quelle que soit la date de son revirement — elle revêt la
tunique de pourpre et d’or, tissée par les anges, que la Grâce
illuminante lui tenait en réserve pour une suprême Pentecôte. Car ne
vont en enfer que ceux qui l’ont voulu — jusqu’au bout…
Le lundi de la Pentecôte, je médite ces choses, un livre ouvert
sur ma table : Vie de Marguerite du Saint-Sacrement, Carmélite de
Beaune qui fut, au XVIIe siècle, la servante privilégiée de l’Enfant
Jésus. Mes yeux s’arrêtèrent sur une page dont je transcris
l’essentiel :
« Marguerite vit le double mouvement par lequel le cœur de
Jésus se resserre afin de s’imprégner du divin Esprit dans le sein du
Père puis se dilate afin de communiquer à l’Église, qui est son corps,
la chaleur vitale qu’il avait produite pour lui-même. »
Glose magnifique d’une parole de Jésus rapportée au chapitre XII
de saint Luc : — Je suis venu répandre le feu sur la terre et que
veux-je sinon qu’il s’allume ?
Oui, c’est par une effusion du Sacré-Cœur que ce Feu vivifiant :
le Paraclet, s’épanche dans nos âmes. Mais qu’arrivera-t-il le jour,
peut-être proche, où presque tous les baptisés prendront pour guide
Celui d’En-Bas, où il n’y aura plus qu’un petit troupeau pour suivre le
Pasteur unique ? Il arrivera la fin du monde par embrasement. Et ce
même Feu qui allumait en nous un foyer d’amour allumera l’incendie
vengeur de la Justice divine…
Fructum in nobis. — En cette Fête-Dieu où le fruit de la

Rédemption qui a nom : Sainte Hostie mûrit en nos cœurs d’une
façon plus sensible, où son arome dissipe l’arrière-goût de la pomme
vénéneuse que notre mère Ève cueillit au jardin d’Éden, j’éprouve
une joie paisible à recenser les jours les plus heureux que j’ai
connus ici-bas. Je me rappelle qu’ils me furent départis dans la
solitude. Ce n’est pas du tout que je sois, comme quelques-uns se le
figurent et même le publient, un être atrabilaire et peu abordable, un
Alceste reclus dans une caverne dont les abords se hérissent
d’orties contre le prochain et qui chérit la retraite misanthropique
Où d’être un ronchonneur on ait la liberté.
J’aime mes frères d’humanité et je plains ceux d’entre eux qui

tâchent d’oublier qu’ils ont une âme en se mêlant, avec une folle
persévérance, aux tumultes et aux sarabandes d’un monde dont la
règle de vie se formule en ces mots : « Il faut être de son temps. »
Or si une époque se caractérise par l’agitation dans le vide, c’est
bien la nôtre. Jamais le précepte de saint Paul : Nolite conformari
huic saeculo ne fut davantage méconnu.
Pour moi, la grâce de Dieu — et non point mon mérite car je ne
vaux pas grand’chose — fait que je ne me sens aucunement porté à
prendre contact avec les gens d’affaires, les gens de sport, les gens
de lettres, les gens du monde en général. De loin, je les regarde et
cela fait que je prie pour eux fort souvent et avec le plus de ferveur
qu’il m’est possible. Il arrive aussi que je ne puisse m’empêcher de
rire un peu lorsque j’observe leur application à poursuivre des bulles
de savon soufflées par le Diable et leur physionomie désappointée
dès qu’elles leur crèvent entre les doigts. Mais que mes
contemporains m’attristent ou qu’ils m’égaient, je suis en mesure de
certifier qu’il n’entre point d’acrimonie dans les sentiments que je
nourris à leur égard. Nous ne nous plaçons pas au même point de
vue, eux et moi, et voilà ce qui nous sépare. Eux croient qu’il y a des
réalités en dehors de Jésus-Christ, moi, la souffrance habituelle et
l’amour de la solitude me maintiennent dans la conviction qu’il n’y a
de réalité qu’en Lui. Je l’ai déjà dit et c’est, en somme, ce que
signifient tous mes livres depuis plus de vingt ans qu’il plut à Dieu de
m’ouvrir la porte de son Église. Permettez-moi de le répéter et de
vous le démontrer une fois de plus en vous traçant un fusain des
jours heureux que j’ai vécus dans la forêt, sur la route de Lourdes et
dans les monastères. Ce faisant, je ne me donne pas comme un
modèle à suivre. J’expose les raisons pour lesquelles je me
conforme sans peine à la volonté de Dieu sur moi. Et rien de plus.
Dans la forêt. — Dès que mon âme eut reçu la Lumière

unique, je pus m’écrier avec Dante : « Je me trouvais dans une forêt
obscure ayant perdu la voie droite. Ah ! qu’il m’est pénible de dire ce
qu’elle était cette forêt sauvage, âpre, épaisse, dont le souvenir
renouvelle mon effroi. » Cela, c’était la forêt symbolique, la forêt aux
taillis délétères où j’errais halluciné par ces bêtes fauves : mes
passions et mes vices.
Lorsque les rayons de la Grâce illuminante chassèrent, ainsi
qu’un brouillard empoisonné, les mirages qui constituaient cette
sylve implacablement ténébreuse, quelle allégresse j’éprouvai, moi
aussi, à saluer « l’heure où commence le matin, où le soleil monte
avec ces étoiles qui l’accompagnaient quand le divin Amour leur
donna, pour la première fois, le mouvement ! » Alors, je conçus
l’espoir d’échapper « au lion, à la louve, à la panthère » qui m’avaient
fasciné.
Toi, forêt palpable, forêt de Fontainebleau qui, même au temps
de mes pires égarements, entretenais en moi le goût de la solitude,
je te vis avec des yeux nouveaux. Tes sites, gracieux ou sévères, ne
me furent plus seulement un ensemble de formes changeantes
selon les saisons. Ils me devinrent des miroirs où se reflétait
l’éternelle Beauté — la face de Notre Seigneur Jésus-Christ.
Ils vivent dans ma mémoire ces jours de félicité, ces jours de
transfiguration et d’oraison brûlante. Je ne cesse d’entendre les
profonds feuillages chanter, d’une voix unanime, la gloire de mon
Dieu. Voici les bouleaux qui frémissent comme des lyres éoliennes ;
voici les chênes et les hêtres qui prolongent leurs graves accords ;
voici les pins pensifs qui résonnent comme de grandes lyres ; voici
toutes les frondaisons qui s’émeuvent au souffle du Saint-Esprit.
Forêt, je suis loin de toi dans l’espace, mais tu peuples toujours ma
vie intérieure et c’est par ton cantique perpétué que se grave
souvent dans mon âme l’image de Jésus.
Comprenez-vous maintenant pourquoi rien ne m’est plus hors de
cette radieuse présence du Bon Maître, pourquoi je me tiens à
l’écart du monde, pourquoi j’ose répéter — moi, poussière et
vermisseau — la parole de l’Apôtre : Je connais celui en qui j’ai cru
et j’ai l’assurance qu’il me gardera en dépôt jusqu’à l’heure où il me
jugera en juge équitable ?…
J’aime le Christ et le Christ daigne m’aimer, malgré mes
imperfections innombrables. Et je me réjouis d’être compté parmi
ceux de qui les gens du siècle disent avec un sourire méprisant : —
Ils sont fous à cause du rêveur galiléen…
Sur la route de Lourdes. — En juin 1908, j’accomplis, du

monastère de Ligugé, près de Poitiers, à Lourdes, le pèlerinage à
pied dont j’avais fait le vœu dix mois auparavant. J’en ai raconté les
étapes dans un livre qui, paraît-il, me suscita quelques imitateurs et

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Smith's Anesthesia for Infants and

Children 10th Edition Peter J. Davis -

Smith’s Anesthesia for Infants and Children 9th Edition

(eBook PDF) Infants Children and Adolescents 8th

(eBook PDF) Infants, Children, and Adolescents 9th

(eBook PDF) Infants and Children Prenatal through

(eBook PDF) Wong's Nursing Care of Infants and Children

(eBook PDF) Mothers, Infants and Young Children of

Infants, Toddlers, and Caregivers 10th Edition (eBook

Critical Heart Disease in Infants and Children 3rd

Infants and Children

Infants and Children

Franklyn P. Cladis, MD, FAAP

SMITH’S ANESTHESIA FOR INFANTS AND CHILDREN, ISBN: 978-0-323-69825-2

Chapter 30: Barry. D. Kussman retains copyright.

Library of Congress Control Number: 2021939106

Content Strategist: Sarah Barth

Last digit is the print number: 9 8 7 6 5 4 3 2 1

Peter J. Davis, MD Branden M. Engorn, MD Jessica A. George, MD, MEd

Mary Landrigan-Ossar Ronald S. Litman, DO, ML* Lynn Martin, MD

Mark A. Rockoff, MD Donald H. Shaffner, MD Deborah Studen-Pavlovich, DMD

The appendices, which can be found online at

Finally, this edition, like the previous edition, also

In summary, considerable developments and prog-

Peter J. Davis, MD, FAAP

Peter J. Davis, MD, FAAP

Contributors, vi 22 Transfusion Medicine, 455

PART I Basic Principles and Physiology PART IV Pain Management

4. Airway Physiology and Development, 78

Although pulse oximetry greatly improved patient monitoring,

ID, Inner diameter; OD, outer diameter.

The pharmacology of anesthetics and adjuvant drugs and their differ-

Surface area in square meters

Formula of Gehan and George (1970 )

Functional endocrinology from birth through adolescence. Cambridge, MA:

BSA (m2 )  ( 0.02  kg)  0.40.

The caloric need in relation to BSA of a full-term infant is about

Relative Size or Proportion

TABLE 1.3 Relation of Age, Height,

Chest, and a Large Abdomen.

Central and Autonomic Nervous Systems

exceptionally reactive to hypoxia and acidosis. The heart remains ex-

(Gesell and Amatruda 1951). For example, immobility caused by a

Infant Being Pushed Laterally. Note the extended contralateral arm.

1–2 Months 11–12 Months

Fig. 2.2 ​Gross Motor Skills Development Chart.

2006, Pathways Awareness Foundation.)

1–2 Months 11–12 Months

Fig. 2.4 ​Fine Motor Skills Development Chart.

TABLE 2.3 Cognitive and Language Communication Skills Development

understand detailed explanations, so procedures should be told in

TABLE 2.5 Age-Appropriate Instruments Across Cognitive Domains

Speech and Language

TABLE 2.5 Age-Appropriate Instruments Across Cognitive Domains—cont’d

Attention and Processing Speed

Learning and Memory

healthcare database of children from Taiwan (Tsai et al. 2018). These

30 broader definition of ADHD with longer follow-up times (Tsai et al.

10 Neuropsychological Testing and Behavioral Surveys

before 3 years of age were found to have an increase in deficits in recep-

Les jours suivants, ma pensée revenait sans cesse à Charles.

Le frère Placide a écouté avec la plus grande attention le récit de

La nuit a passé. Un petit jour blafard colle maussadement sa face

BSA (m2 ) ( 0.02 kg) 0.40.

Fig. 2.2 Gross Motor Skills Development Chart.

Fig. 2.4 Fine Motor Skills Development Chart.