Anesthesiafor CongenitalHeart Disease

Anesthesiafor CongenitalHeart DiseaseEDITOR IN CHIEF

Dean B. Andropoulos MD, MHCMAnesthesiologist-in-Chief Texas Children’s Hospital;Professor, Anesthesiology and Pediatrics;Vice Chair, Department of Anesthesiology;Baylor College of MedicineHouston, TX, USA

EDITORS

Stephen Stayer MDAssociate Chief of Anesthesiology and Medical Director of PerioperativeServices Texas Children’s Hospital;Professor, Anesthesiology and Pediatrics;Baylor College of MedicineHouston, TX, USA

Emad B. Mossad MDDirector, Arthur S. Keats Division of Pediatric Cardiovascular AnesthesiologyTexas Children’s Hospital;Professor, Anesthesiology and PediatricsBaylor College of MedicineHouston, TX, USA

Wanda C. Miller-Hance MD, FACC, FAAP, FASEAssociate Director, Arthur S. Keats Division of Pediatric Cardiovascular AnesthesiologyDirector of Intraoperative Echocardiography, Texas Children’s HospitalProfessor, Anesthesiology (Pediatric Anesthesiology) and Pediatrics (Cardiology)Baylor College of MedicineHouston, TX, USA

T H I R D E D I T I O N

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Cover design: From left to right: 1. (Left) Echocardiogram during fetal intervention for restrictive atrial septum ina fetus with hypoplastic left heart syndrome. Catheter with balloon can be visualized crossing atrial septum.Image courtesy of Shaine Morriss, M.D., Texas Children’s Hospital. 2. (Top Center) Neonate with dextrotransposition of the great arteries, after induction of anesthesia and placement of monitors and invasive catheters.Photo courtesy of Phillip Steffek, Texas Children’s Hospital. 3. (Bottom Center) Surgical field during regionalcerebral perfusion for aortic arch reconstruction for hypoplastic left heart syndrome. Aortic cannula is insertedinto the distal end of a 3.5 mm polytetrafluoroethylene shunt anastomosed to the right innominate artery toprovide cerebral blood flow. A bloodless surgical field is established by snaring brachiocephalic vessels anddescending aorta. Photo courtesy Charles D. Fraser, MD, Texas Children’s Hospital 4. (Right) Three-dimensionalreconstruction of a computed tomographic angiogram of a 12 year old with untreated coarctation of the aorta.Severe coarctation of the aortic isthmus, presumably at the site of ductal insertion, located 2.1-cm distal to thetakeoff of the left subclavian artery, with minimum caliber of 5.6 × 5.1 mm. Bilobed ductal aneurysm protrudingventrally at the site of the coarctation. Associated hypoplasia, tortuosity, and mild kinking of the distal transversearch. Mild stenosis of the origin of the left subclavian artery with poststenotic dilation. Significant dilation of themammary and intercostal arteries, which provide collateral blood flow to the body

Printed in the United States of America

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v

Contents

List of Contributors, vii

Preface, xi

List of Abbreviations, xiii

About the Companion Website, xix

Part I History, Education, Outcomes,and Science

1 History of Anesthesia for Congenital Heart Disease, 1Viviane G. Nasr, Paul A. Hickey and Dolly D. Hansen

2 Education for Anesthesia in Patients withCongenital Cardiac Disease, 16Sugantha Sundar, Lori Newman and James A. DiNardo

3 Quality, Outcomes, and Databases in CongenitalCardiac Anesthesia, 29Lisa Caplan, Ehrenfried Schindler and David F. Vener

4 Development of the Cardiovascular System andNomenclature for Congenital Heart Disease, 42Barry D. Kussman and Wanda C. Miller-Hance

5 Physiology and Cellular Biology of theDeveloping Circulation, 84Dean B. Andropoulos

6 Anesthetic Agents and Their CardiovascularEffects, 106Dean B. Andropoulos and Emad B. Mossad

7 Cardiopulmonary Bypass, 126Ralph Gertler and Dean B. Andropoulos

8 Multiorgan Effects of Congenital Cardiac Surgery, 156Gina Whitney, Suanne Daves and Brian Donahue

9 Anesthetic and Sedative Neurotoxicity in thePatient with Congenital Heart Disease, 184Richard J. Levy, Lisa Wise-Faberowski andDean B. Andropoulos

Part II Monitoring

10 Vascular access and monitoring, 199Kenji Kayashima, Shoichi Uezono andDean B. Andropoulos

11 Neurological Monitoring and Outcome, 230Ken Brady, Chandra Ramamoorthy, R. Blaine Easley andDean B. Andropoulos

12 Transesophageal Echocardiography inCongenital Heart Disease, 250Annette Vegas and Wanda C. Miller-Hance

13 Coagulation, Cardiopulmonary Bypass, andBleeding, 294Bruce E. Miller, Nina A. Guzzetta andGlyn D. Williams

Part III Preoperative Considerations

14 Preoperative Evaluation and Preparation, 314Emad B. Mossad, Rahul Baijal and Raj Krishnamurthy

15 Approach to the Fetus, Premature, and Full-TermNeonate, 336Annette Y. Schure, Peter C. Laussen andKirsten C. Odegard

16 Approach to the Adult Patient, 354Jane Heggie and Catherine Ashes

Part IV Management

17 Hemodynamic management, 375Mirela Bojan and Philippe Pouard

18 Arrhythmias: Diagnosis andManagement, 404Santiago O. Valdes, Jeffrey J. Kim and Wanda C.Miller-Hance

vi Contents

19 Airway and Respiratory Management, 436Stephen A. Stayer and Gregory B. Hammer

20 Early Tracheal Extubation and PostoperativePain Management, 451Alexander Mittnacht

Part V Anesthesia for Specific Lesions

21 Anesthesia for Left-to-Right ShuntLesions, 468Scott G. Walker

22 Anesthesia for Left–sided ObstructiveLesions, 497James P. Spaeth and Andreas W. Loepke

23 Anesthesia for Right-sided ObstructiveLesions, 516Michael L. Schmitz, Sana Ullah, Rahul Dasgupta andLorraine L. Thompson

24 Anesthesia for Transposition of the GreatArteries, 542Angus McEwan and Mariepi Manolis

25 Anesthesia for the Patient with a SingleVentricle, 567Susan C. Nicolson, James M. Steven, Laura K. Diaz andDean B. Andropoulos

26 Anesthesia for Miscellaneous Cardiac Lesions, 598Ian McKenzie, Maria Markakis Zestos, Stephen A. Stayerand Dean B. Andropoulos

27 Anesthesia for Cardiac and PulmonaryTransplantation, 636Glyn D. Williams, Chandra Ramamoorthy and AnshumanSharma

28 Anesthesia for Pulmonary Hypertension, 661Mark D. Twite and Robert H. Friesen

Part VI Anesthesia Outside the CardiacOperating Room

29 Anesthesia for the Cardiac CatheterizationLaboratory, 677Philip Arnold and Aarti Shah

30 Anesthesia for Non-cardiac Surgery andMagnetic Resonance Imaging, 705Erin A. Gottlieb and Stephen A. Stayer

31 Cardiac Intensive Care, 720V. Ben Sivarajan, Justin C. Yeh, Peter C. Laussen andStephen J. Roth

32 Mechanical Support of the Circulation, 751Adam Skinner, Stephen B. Horton, Pablo Motta andStephen Stayer

Appendix: Texas Children’s Hospital PediatricCardiovascular Anesthesia Drug Sheet(April 2015), 777

Lisa A. Caplan and Erin A. Gottlieb

Index, 782

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vii

List of Contributors

Dean B. Andropoulos MD, MHCMAnesthesiologist-in-ChiefTexas Children’s HospitalProfessor, Anesthesiology and PediatricsVice Chair, Department of AnesthesiologyBaylor College of MedicineHouston, TX, USA

Philip Arnold BM, FRCAConsultant Cardiac AnaesthetistAlder Hey HospitalRoyal Liverpool Children’s NHS TrustLiverpool, United Kingdom

Catherine Ashes MBBS, FANZCAAnaesthetistBrian Dwyer Department of AnaestheticsSt Vincent’s HospitalDarlinghurstNew South Wales, Australia

Rahul Baijal MDStaff Pediatric Anesthesiologist, Texas Children’s Hospital; andAssistant Professor, Anesthesiology and Pediatrics, Baylor College ofMedicine, Houston, TX, USA

Mirela Bojan MD, PhDConsultant Pediatric Anesthesiologist, Department of Anesthesiologyand Critical Care, Necker-Enfants Malades University Hospital, Paris,France

Ken Brady MDAssociate Professor of Pediatrics, Anesthesia, and Critical Care, TexasChildren’s Hospital, Baylor College of Medicine, Houston, TX, USA

Lisa Caplan MDStaff Pediatric Cardiovascular Anesthesiologist, Texas Children’sHospital; and Assistant Professor, Departments of Anesthesiologyand Pediatrics, Baylor College of Medicine, Houston, TX, USA

Rahul Dasgupta MDAssistant Professor of AnesthesiologyArkansas Children’s Hospital/University of Arkansas for MedicalSciencesLittle Rock, AR, USA

Suanne Daves MDAssociate Professor, Anesthesiology and Pediatrics, VanderbiltUniversity School of Medicine; Anesthesiologist in Chief, MonroeCarell Jr. Children’s Hospital; and Medical Director, PerioperativeServices, Pediatric Heart Institute, Nashville, TN, USA

Laura K. Diaz MDThe Children’s Hospital of PhiladelphiaDepartment of Anesthesiology and Critical Care MedicineAssistant Professor of Clinical Anesthesiology and Critical CarePerelman School of Medicine at the University of PennsylvaniaPhiladelphia PA, USA

James A. DiNardo MD, FAAPChief, Division of Cardiac AnesthesiaSenior Associate in Cardiac AnesthesiaBoston Children’s HospitalProfessor of Anaesthesia Harvard Medical SchoolBoston, MA, USA

Brian Donahue MD, PhDAssociate Professor of Anesthesiology, Division of Pediatric CardiacAnesthesiology, Vanderbilt University School of Medicine, Nashville,TN, USA

R. Blaine Easley MDAssociate Professor, Anesthesiology and Pediatrics, Baylor College ofMedicine; Fellowship Director, Pediatric Anesthesiology; andDirector of Education, Department of Pediatric Anesthesiology, TexasChildren’s Hospital, Houston, TX, USA

Robert H. Friesen MDProfessor of Anesthesiology,University of Colorado School of Medicine Vice Chair, Department ofAnesthesiology,Children’s Hospital ColoradoAurora, CO, USA

Ralph Gertler MDConsultant AnesthesiologistInstitute of Anesthesiology and Intensive CareGerman Heart Centre of the State of BavariaTechnical University MunichMunich, Germany

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viii List of Contributors

Erin A. Gottlieb MDStaff Cardiovascular AnesthesiologistTexas Children’s HospitalAssociate Professor of AnesthesiologyBaylor College of MedicineHouston, TX, USA

Nina A. Guzzetta MDAssociate Professor, Departments of Anesthesiology and Pediatrics,Emory University School of Medicine, Children’s Healthcare ofAtlanta, Atlanta, GA, USA

Gregory B. Hammer MDProfessor of Anesthesiology and PediatricsStanford University School of Medicine Attending Pediatric CardiacAnesthesiologist Associate Director, Pediatric Intensive Care UnitLucille Salter Packard Children’s HospitalPalo Alto CA, USA

Dolly D. Hansen MDEmeritus Associate Professor, Department of Anesthesia, BostonChildren’s Hospital and Harvard Medical School, Boston,MA, USA

Jane Heggie MD, FRCPAssociate Professor, Department of Anesthesia and PainManagement, University of Toronto and Toronto General Hospital,Toronto, ON, Canada

Paul A. Hickey MDAnesthesiologist-in-Chief and Professor of Anaesthesia, BostonChildren’s Hospital and Harvard Medical School, Boston, MA, USA

Stephen B. Horton PhD, CCP(Aus), CCP(USA),FACBSAssociate Professor /Director of PerfusionFaculty of Medicine, Department of Paediatrics – The University ofMelbourneHonorary Research Fellow, Murdoch Children’s Research InstituteCardiac Surgery Royal Children’s HospitalMelbourne, Australia

Kenji Kayashima MDChief, Department of Anesthesiology, Japan Community Health CareOrganization, Kyushu Hospital, Kitakyushu, Japan

Jeffrey J. Kim MDDirector, Electrophysiology and Pacing, Texas Children’s Hospital;and Associate Professor, Department of Pediatrics, Section ofCardiology, Baylor College of Medicine, Houston, TX, USA

Raj Krishnamurthy MDSection Chief, Radiology Research and Cardiac Imaging, TexasChildren’s Hospital; and Associate Professor, Radiology, BaylorCollege of Medicine, Houston, TX, USA

Barry D. Kussman FFA(SA), FAAPAssociate Professor of Anaesthesia, Harvard Medical School; andSenior Associate in Cardiac Anesthesia, Department ofAnesthesiology, Perioperative and Pain Medicine, Boston Children’sHospital, Boston, MA, USA

Peter C. Laussen MBBS, FCIMChief, Department of Critical Care Medicine, Hospital for SickChildren; and Professor, Department of Anaesthesia, University ofToronto, Toronto, Canada

Richard J. Levy MD, FAAPVice Chair for Pediatric Laboratory Research, Department ofAnesthesiologyDivision of Pediatric Anesthesia Professor of AnesthesiologyColumbia University Medical CenterNew York, NY, USA

Andreas W. Loepke MD, PhDStaff Anesthesiologist, Division of Cardiac AnesthesiaCincinnati Children’s Hospital Medical CenterProfessor of Clinical Anesthesia and PediatricsUniversity of Cincinnati College of MedicineCincinnati, OH, USA

Mariepi Manolis MA MB BChir (Cantab) FRCAClinical Fellow in Anaesthesia, Great Ormond Street Hospital forChildren NHS Foundation Trust, London, UK

Ian McKenzie MBBS, DipRACOG, FANZCADirector, Department of Anaesthesia & Pain ManagementThe Royal Children’s Hospital MelbourneMelbourne, Australia

Angus McEwan FRCAConsultant Paediatric Anaesthetist, Great Ormond Street Hospital forChildren NHS Foundation Trust, London, UK

Bruce E. Miller MDAssociate Professor, Departments of Anesthesiology and Pediatrics,Emory University School of Medicine; and Director of PediatricCardiac Anesthesiology, Children’s Healthcare of Atlanta, Atlanta,GA, USA

Wanda C. Miller-Hance MD, FACC, FASEProfessor of Anesthesiology and Pediatrics, Baylor College ofMedicine;Associate Director Division of Pediatric Cardiovascular,Anesthesiology and Director of Intraoperative, EchocardiographyTexas Children’s HospitalHouston, TX, USA

Alexander Mittnacht MDProfessor of Anesthesiology Icahn School of Medicine at Mount SinaiDirector Pediatric Cardiac AnesthesiaDepartment of Anesthesiology The Mount Sinai Medical CenterNew York, NY, USA

Emad B. Mossad MDDirector, Arthur S. Keats Division of Pediatric CardiovascularAnesthesiologyTexas Children’s Hospital;Professor, Anesthesiology and PediatricsBaylor College of MedicineHouston, TX, USA

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List of Contributors ix

Pablo Motta MDStaff Cardiovascular AnesthesiologistTexas Children’s Hospital Assistant Professor, Anesthesiology andPediatricsBaylor College of MedicineHouston, TX USA

Viviane G. Nasr MDAssistant in AnesthesiaBoston Children’s HospitalAssistant Professor in AnesthesiaHarvard Medical School

Lori Newman M.EdPrincipal Associate in Medical Education, Harvard Medical SchoolDirector of the Office for Professional, Development, Center forEducationCo-Director of the Rabkin Fellowship in Medical, Education, andCo-Chair of the Academy of Medical EducatorsBeth Israel Deaconess Medical CenterBoston, MA, USA

Susan C. Nicolson MDMedical Director, Cardiac Center Operations, The Cardiac CenterThe Children’s Hospital of PhiladelphiaDepartment of Anesthesiology and Critical Care MedicineProfessor of Anesthesia Perelman School of Medicine at theUniversity of PennsylvaniaPhiladelphia PA, USA

Kirsten C. Odegard MDSenior Associate in Anesthesia, Boston Children’s Hospital; andAssociate Professor in Anaesthesia, Harvard Medical School, Boston,MA, USA

Philippe Pouard MDHead of Intensive Care, Anaesthesia and Perfusion Unit, ReferenceCenter for Complex Congenital Heart Disease, University HospitalNecker Enfants Malades, René Descartes University, Paris, France

Chandra Ramamoorthy MB BS, FFA (UK)Professor of Anesthesiology, Stanford University School of Medicine;and Director, Pediatric Cardiac Anesthesia, Lucile Packard Children’sHospital, Stanford, CA, USA

Stephen J. Roth MD, MPHProfessor of Pediatrics (Cardiology) Chief, Division of PediatricCardiologyStanford University School of MedicineDirector, Children’s Heart CenterLucile Packard Children’s Hospital StanfordPalo Alto, CA, USA

V. Ben Sivarajan MD MS FRCPCAssistant Professor of Critical Care Medicine & PaediatricsDepartments of Critical Care Medicine & PaediatricsMedical Director, Organ & Tissue DonationThe Hospital for Sick Children, TorontoFaculty of Medicine, University of TorontoToronto, Ontario, Canada

Ehrenfried Schindler MDMedical Director, German Pediatric Heart Center, Department ofPediatric Anesthesiology, Asklepios Klink Sankt Augustin, SanktAugustin, Germany

Annette Y. Schure MD, DEAASenior Associate in Anesthesia, Boston Children’s Hospital andInstructor in Anaesthesia, Harvard Medical School, Boston, MA, USA

Michael L. Schmitz MDProfessor, Departments of Anesthesiology and PediatricsArkansas Children’s HospitalUniversity of Arkansas for Medical SciencesLittle Rock, AR, USA

Aarti Shah MB ChB FCARCSICardiac AnaesthetistAlder Hey Hospital Royal Liverpool Children’s NHS TrustLiverpool, United Kingdom

Anshuman Sharma MD, MBAProfessor, Department of AnesthesiologyWashington University School of MedicineSt. Louis, MO, USA

Adam Skinner BSC, MBChB, MRCP, FRCAConsultant Paediatric AnaesthetistDepartment of Anaesthesia Royal Children’s HospitalMelbourne, Australia

James P. Spaeth MDDirector of Cardiac AnesthesiaCincinnati Children’s Hospital Medical CenterAssociate Professor of Clinical Anesthesia and PediatricsUniversity of Cincinnati College of MedicineCincinnati, OH, USA

Stephen A. Stayer MDProfessor, Anesthesiology and Pediatrics, Baylor College of Medicine;and Medical Director of Perioperative Services, Texas Children’sHospital, Houston, TX, USA

James M. Steven MD, SMChief, Division of Cardiac AnesthesiaThe Cardiac CenterThe Children’s Hospital of PhiladelphiaDepartment of Anesthesiology and Critical Care MedicineAssociate Professor of Anesthesia Perelman School of Medicine at theUniversity of PennsylvaniaPhiladelphia PA, USA

Sugantha Sundar MB, BSProgram Director, Adult Cardiothoracic Anesthesia FellowshipProgramBeth Israel Deaconess Medical CenterAssistant Professor of AnaesthesiaHarvard Medical SchoolBoston, MA, USA

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x List of Contributors

Lorraine L. Thompson MDAssistant Professor of AnesthesiologyArkansas Children’s Hospital/University of Arkansas for MedicalSciencesLittle Rock, AR, USA

Mark D. Twite MB BChirAssociate Professor of AnesthesiologyUniversity of Colorado School of Medicine Director, CardiacAnesthesiology, Children’s Hospital ColoradoAurora, CO, USA

Shoichi Uezono MDProfessor and Chair, Department of Anesthesiology, Jikei University,Tokyo, Japan

Sana Ullah MB, ChBAssociate Professor of Anesthesiology University of TexasSouthwestern Children’s Medical Center of DallasDallas, TX, USA

Santiago O. Valdes MDAttending Physician, Electrophysiology and Pacing, Texas Children’sHospital; and Assistant Professor, Department of Pediatrics, Sectionof Cardiology, Baylor College of Medicine, Houston, TX, USA

Annette Vegas MD, FRCPC, FASEStaff Anesthesiologist and Director of Perioperative TEE, Departmentof Anesthesia and Pain Management, Toronto General Hospital andAssociate Professor of Anesthesiology, University of Toronto,Toronto, USA

David F. Vener MDStaff Pediatric Cardiovascular Anesthesiologist, Texas Children’sHospital; and Associate Professor, Departments of Anesthesiologyand Pediatrics, Baylor College of MedicineHouston, TX, USA

Scott G. Walker MDAssociate Professor of Clinical AnesthesiaGopal Krishna Scholar in Pediatric Anesthesiology, IndianaUniversity School of MedicineDirector, Division of Pediatric Anesthesiology, Chief of PediatricAnesthesiaRiley Hospital for Children at IU HealthIndianapolis, IN, USA

Gina Whitney MDAssociate Professor of Anesthesiology and PediatricsUniversity of Colorado School of MedicinePodiatric Cardiovascular AnesthesiologistChildren’s Hospital, ColoradoAurora CO, USA

Glyn D. Williams MBChB, FFAProfessor, Department of Anesthesiology, Perioperative and PainMedicine, Stanford University School of Medicine and Lucile PackardChildren’s Hospital, Stanford, CA, USA

Lisa Wise-Faberowski MDAssistant Professor of Anesthesiology, Perioperative and PainMedicine, Stanford University Medical Center, Stanford,CA, USA

Justin C. Yeh MDClinical Assistant Professor of Pediatrics (Cardiology)Stanford University School of MedicineDirector, Cardiac ECMO ProgramLucile Packard Children’s Hospital StanfordPalo Alto, CA, USA

Maria Markakis Zestos MDChief of AnesthesiologyChildren’s Hospital of MichiganAssociate Professor Wayne State UniversityDetroit, MI, USA

xi

Preface

The third edition of Anesthesia for Congenital Heart Dis-ease is a major update and expansion of the textbookthat reflects the ongoing development of the practiceof pediatric and congenital cardiac anesthesia, and theburgeoning knowledge base in this exciting field. Allchapters have been thoroughly revised and updated withnew sections and numerous recent references. Additionalchapters have been included in two important areas ofcritical knowledge and practice, addressing anestheticand sedative neurotoxicity in the patient with congenitalheart disease (Chapter 9) and anesthesia in the patientwith pulmonary hypertension (Chapter 28). Both of thesechapters are written by true experts in these fields andare worthy of their own separate treatment. Also, forthe first time, this edition of the textbook is in color, andnumerous new illustrations and figures have been addedto present a vibrant representation of cardiovascularanatomy and surgical approaches that are essential tothe knowledge base for the congenital cardiac anesthe-siologist. In addition, after each major section in everychapter, key learning points are presented to highlightimportant concepts and enhance knowledge retention.Each chapter is accompanied by five multiple-choicequestions covering the most crucial learning points in eachchapter, to optimize the learning experience for readers atall levels of training and clinical experience. These ques-tions can be found in the on-line book supplement at http://www.wiley.com/go/andropoulos/congenitalheart.

We are pleased to welcome our Texas Children’sHospital colleague, Wanda C. Miller-Hance, MD, asCo-Editor of this text. Dr. Miller-Hance is a fully trainedpediatric and congenital cardiac anesthesiologist, pediatriccardiologist, and recognized authority in intraoperative

echocardiography for congenital heart surgery. Reflectingthe international scope of anesthesia for congenital heartdisease and themany outstanding practitioners all over theworld, a number of new international authors have beenadded from Germany, the United Kingdom, Australia,France, Japan, and Canada.

Finally, caring for patients with congenital heart diseaserequires a team of dedicated professionals that includecongenital cardiac anesthesiologists, congenital heartsurgeons, pediatric and adult congenital cardiologists,cardiac intensivists, cardiac interventionalists and imagingspecialists, nurses, perfusionists, respiratory therapists,technicians, child life and social workers, and interpreters,amongmany others.We greatly appreciate the passion andcommitment of the people in these disciplines, withoutwhom we could not do our work. Finally, the patientand family are the focus of the team, and their courageand goodwill in the face of serious and complex illnessalways amaze and inspire us. It is to our patients andtheir families that Anesthesia for Congenital Heart Disease,third edition, is dedicated, in the hope that the knowledgecontained in these pages will contribute to better outcomesfor them.

It is the purpose of this, our third edition of Anesthesiafor Congenital Heart Disease, to contribute to the fund ofknowledge in our field and to enhance the care of childrenwith heart disease by individuals from various disciplinesworldwide.

Dean B. Andropoulos, MD, MHCM (Editor-in-Chief)Stephen A. Stayer, MDEmad B. Mossad, MD

Wanda C. Miller-Hance, MD

xiii

List of Abbreviations

α2M α2-macroglobulinAA aortic atresiaABC Aristotle Basic ComplexityABO-C ABO-compatibleABO-I ABO-incompatibleACE angiotensin-converting enzymeACGME Accreditation Council for Graduate

Medical EducationACHD adult congenital heart diseaseACT activated clotting timeACTH adrenocorticotropic hormoneAEG atrial electrogramAI aortic insufficiencyAICD automatic internal cardiac defibrillatorAIDS acquired immunodeficiency syndromeAKI acute kidney injuryAkt protein kinase BALCAPA anomalous left coronary artery arising

from the pulmonary arteryALI acute lung injuryANF atrial natriuretic factorANH Acute normovolemic hemodilutionAPAF-1 apoptotic protease activating factor 1APERP accessory pathway effective refractory

periodAPOE apolipoprotein EAPRV airway pressure release ventilationaPTT activated partial thromboplastin timeAPW aortopulmonary windowAR adrenergic receptorARCAPA anomalous right coronary artery from the

pulmonary arteryARDS acute respiratory distress syndromeARF acute renal failureASD atrial septal defectASE American Society of EchocardiographyASO arterial switch operationAT atrial tachycardiaATIII antithrombin IIIATP adenosine triphosphateAUC area under the curveAV atrioventricularAVC atrioventricular canal

AVNRT atrioventricular nodal re-entry tachycardiaAVSD atrioventricular septal defectBAV bicuspid aortic valveBax B-cell lymphoma-2-associated X proteinBCAS The Boston Circulatory Arrest StudyBCL-2 B-cell lymphoma-2BCL-xL B-cell lymphoma-extra largeBCPC bi-directional cavopulmonary connectionBDNF Brain-derived neurotrophic factorBiVAD biventricular ventricular assist deviceBNP brain natriuretic peptideBOS bronchiolitis obliterans syndromeBPA branch pulmonary arteryBPD bronchopulmonary dysplasiaBSA body surface areaBSID Bayley Scales of Infant DevelopmentBUN blood urea nitrogenC3PO Congenital Cardiac Catheterization Project

on OutcomesCABG coronary artery bypass graftingCALM congenital atresia of the left main coronary

arterycAMP cyclic adenosine monophosphateCAV coronary artery vasculopathyCAVC complete atrioventricular canalCAVF coronary arteriovenous fistulaCBF cerebral blood flowCBG corticosteroid-binding globulinCCA common carotid arteryCCAN Congenital Cardiac Anesthesia NetworkCCAS Congenital Cardiac Anesthesia SocietyCCB calcium channel blockerCCTGA congenitally corrected transposition of the

great arteriesCF cystic fibrosiscGMP cyclic guanosine monophosphateCHARM Catheterization for Congenital Heart

Disease Adjustment for Risk MethodCHD congenital heart diseaseCHF congestive heart failureCICU cardiac intensive care unitCIED cardiovascular implantable electronic

device

xiv List of Abbreviations

CIRCI critical illness-related corticosteroidinsufficiency

CL cardiolipinCLAD chronic lung allograft dysfunctionCMR cardiac magnetic resonanceCMRO2 cerebral metabolic rate for oxygen

consumptionCMV cytomegalovirusCO carbon monoxideCO cardiac outputCoA coarctation of the aortaCOP colloid osmotic pressureCOx cerebral oximetry indexCPAP continuous positive airway pressureCPB cardiopulmonary bypassCPVT catecholaminergic polymorphic

ventricular tachycardiaCRBSIs catheter-related bloodstream infectionsCRMDs cardiac rhythm management devicesCSA cross-sectional areaCSOR cerebral–splanchnic oxygen ratioCT computed tomographyCUF conventional ultrafiltrationCVC central venous catheterCVVH continuous veno-venous hemofiltrationCVVH/D continuous veno-venous hemofiltration

and dialysisdATP deoxyadenosine triphosphateDBD donation after brain deathDCD donation after cardiac deathDCM dilated cardiomyopathyDCRV double-chambered right ventricleDHCA deep hypothermic circulatory arrestDIC diffuse intravascular coagulationDIVA difficult intravenous accessDLCO diffusing capacity for carbon monoxideDLT double-lumen tubeDNA deoxyribonucleic acidDO2 oxygen deliveryDORV double outlet right ventricleD-TGA dextro-transposition of the great arteriesDVT deep vein thrombosisEA Ebstein’s anomalyEACA 𝜀-aminocaproic acidEACTS European Association for Cardio-Thoracic

SurgeryEAT ectopic atrial tachycardiaEBV estimated blood volumeECG electrocardiogramECMO extracorporeal membrane oxygenationECPR extracorporeal cardiopulmonary

resuscitationECPR extracorporeal membrane oxygenation as

part of cardiopulmonary resuscitationEDA end-diastolic areaEDV end-diastolic volumeEEG electroencephalogramEF ejection fraction

EFE endocardial fibroelastosisEJV external jugular veinELSO Extracorporeal Life Support OrganizationEMA European Medicines AgencyEMI electromagnetic interferenceEP electrophysiologicalEPDCs epicardially derived cellsEPO recombinant human erythropoietin alphaERA endothelin receptor antagonistERK extracellular signal-regulated protein

kinaseESA end-systolic areaESV end-systolic volumeET-1 endothelin-1EtCO2 end-tidal CO2ETT endotracheal tubeFAC fractional area changeFDA Food and Drug AdministrationFEV1 forced expiratory volume in 1 secondFFP fresh frozen plasmaFHF first heart fieldFiO2 fraction of inspired oxygenFOB fiberoptic bronchoscopeFRC functional residual capacityFTR failure to resuscitateFV femoral veinFVC forced vital capacityFVL FV LeidenGABA γ-aminobutyric acidGDP guanosine diphosphateGFR glomerular filtration rateGI gastrointestinalGLUTs glucose transportersGp glycoproteinGSK-3β glycogen synthase kinase-3βGTP guanosine triphosphateHAT heparin-associated thrombocytopeniaHCII heparin cofactor IIHct hematocritHEAL Health Education Assets LibraryHFOV high-frequency oscillatory ventilationHIT heparin-induced thrombocytopeniaHIV human immunodeficiency virusHLA human leukocyte antigensHLHS hypoplastic left heart syndromeHPA hypothalamic–pituitary–adrenal axisHPAH heritable pulmonary artery hypertensionHPV hypoxic pulmonary vasoconstrictionHR heart rateHTK histidine-tryptophan-ketoglutarateHUS head ultrasoundIAA interrupted aortic archIABP intra-arterial blood pressureIAS interatrial septumICE Intracardiac echocardiographyICH intracranial hemorrhageICU intensive care unitIE infective endocarditis

List of Abbreviations xv

IgG immunoglobulin GIJV internal jugular veinIM intramusculariNO inhaled nitric oxideINR international normalized ratioIO inflow occlusionIPAH idiopathic pulmonary artery hypertensionIPCCC International Pediatric and Congenital

Cardiac CodeISHLT Scientific Registry of the International Soci-

ety for Heart and Lung TransplantationIU international unitIV intravenousIVC inferior vena cavaIVH intraventricular hemorrhageJCAHO Joint Commission for the Accreditation of

Hospital OrganizationsJET junctional ectopic tachycardiaKIM-1 kidney injury molecule-1LA left atriumLAA left aortic archLAA left atrial appendageLAP left atrial pressureLAS lung allocation scoreLBBB left bundle branch blockLBW low birth weightLBWN low-birth-weight neonateLCOS low cardiac output syndromeLDLLT living donor lobar lung transplantLE lower esophagealL-FABP liver fatty acid-binding proteinLiDCO lithium dilution COLMA laryngeal mask airwayLMWH low-molecular-weight heparinLPA left pulmonary arteryLQTS long QT syndromeLSVC persistent left superior vena cavaL-TGA levo-transposition of the great arteriesLV left ventricle, left ventricularLVEDP left ventricular end-diastolic pressureLVEDV left ventricular end-diastolic volumeLVNC left ventricular non-compactionLVOT left ventricular outflow tractMAC minimum alveolar concentrationMAP mean arterial pressureMAS meconium aspiration syndromeMAT multifocal atrial tachycardiamBTS modified Blalock–Taussig shuntMCS mechanical circulatory supportMDI Mental Development IndexMMF mycophenolate mofetilMOD method of discsMPA main pulmonary arterymPAP mean pulmonary artery pressureMPTP mitochondrial permeability transition poreMR mitral regurgitationMRI magnetic resonance imagingMRSA methicillin-resistant Staphylococcus aureus

MSOF multisystem organ failuremTOR mammalian target of rapamycinMUF modified ultrafiltrationMV mechanical ventilationNAC N-acetylcysteineNEC necrotizing enterocolitisNGAL neutrophil gelatinase-associated lipocalinNICU neonatal intensive care unitNIRS near-infrared spectroscopyNMDA N-methyl-D-aspartateNOS nitric oxide synthaseOB obliterative bronchitisOEF oxygen excess factorOER oxygen extraction rateOHT orthotopic heart transplantationOPTN Organ Procurement and Transplant

NetworkOR operating roomp75NTR p75 neurotrophic receptorPA pulmonary arteryPA pulmonary atresiaPA/IVS pulmonary atresia with intact ventricular

septumPAA pharyngeal arch arteriesPAC premature atrial contractionPaCO2 partial pressure of carbon dioxide in

arterial bloodPAD preoperative autologous donationPAH pulmonary artery hypertensionPAH-CHD pulmonary artery hypertension associated

with congenital heart diseasePAI plasminogen activator inhibitorPAO2 alveolar oxygen tensionPaO2 partial pressure of oxygen in arterial bloodPAPVC partial anomalous pulmonary venous

connectionPAPVD partial anomalous pulmonary venous

drainagePAPVR partial anomalous pulmonary venous

returnPASP pulmonary artery systolic pressurePBF pulmonary blood flowPC protein CpCAS pediatric cardiopulmonary assist systemPCC prothrombin complex concentratePCWP pulmonary capillary wedge pressurePD peritoneal dialysisPDA patent ductus arteriosusPDC peritoneal drainage catheterPDE phosphodiesterasePDE-5 phosphodiesterase-5PDEIs phosphodiesterase inhibitorsPEEP positive end-expiratory pressurePEO proepicardial organPF4 platelet factor 4PFO patent foramen ovalePG pressure gradientPGE1 prostaglandin E1

xvi List of Abbreviations

PH pulmonary hypertensionPHT pulmonary hypertensionPI pulmonary insufficiencyPICC peripherally inserted central catheterPIP peak inspiratory measurementPI-PLC phosphatidylinositol-specific

phospolipase CPKA protein kinase APKC protein kinase CPLC phospolipase CPMP poly-(4-methyl-1-pentene)POCA Pediatric Perioperative Cardiac Arrest

RegistryPPL polypropylenePPS postpericardiotomy syndromePPV positive pressure ventilationPRA panel reactive antibodypRIFLE pediatric modification of the RIFLE scorePRISM Pediatric Risk of MortalityPS protein SPS pulmonary stenosisPS/IVS pulmonary stenosis with intact ventricular

septumPT prothrombin timePTLD post-transplant lymphoproliferative

disorderPTT partial thromboplastin timePV pulmonary valvePVCs premature ventricular contractionsPVD pulmonary vascular diseasePVP pulmonary valve perforationPVR pulmonary vascular resistancePVRI pulmonary vascular resistance indexQp pulmonary blood flowQs systemic blood flowRA right atriumRAA right aortic archRACHS-1 Risk Adjustment for Congenital Heart

SurgeryRAP right atrial pressureRBBB right bundle branch blockRBC red blood cellRCP regional cerebral perfusionRDS respiratory distress syndromerFVIIa recombinant activated factor VIIaRIFLE risk, injury, failure, loss and end-stage

renal diseaseRIPC remote ischemic preconditioningROS reactive oxygen speciesRPA right pulmonary arteryRV right ventricle, right ventricularRVDCC right ventricle-dependent coronary

circulationRVOT right ventricular outflow tractRVOTO right ventricular outflow tract obstructionRVSP right ventricular systolic pressureSAN sinoatrial nodeSaO2 arterial oxygen saturation

SCA Society of CardiovascularAnesthesiologists

SCPA superior cavopulmonary anastomosisSCV subclavian veinScvO2 central venous oxygen saturationSERCA sarcoplasmic reticulum Ca2+-ATPaseSF shortening fractionSGOT serum glutamic oxaloacetic transaminaseSHF second heart fieldSIRS systemic inflammatory response

syndromeSjvO2 jugular bulb venous oximetrySLV single-lung ventilationSPA Society for Pediatric AnesthesiaSpO2 pulse oximeter saturationSR sarcoplasmic reticulumSSI surgical site infectionSTAT Society of Thoracic Surgeons–European

Association for Cardio-Thoracic SurgeryCongenital Heart Surgery mortality score

STS Society of Thoracic SurgeonsSTS-CHSD Society of Thoracic Surgeons Congenital

Heart Surgery DatabasesubAS subvalvular aortic stenosisSV stroke volumeSVAS congenital supravalvular aortic stenosisSVC superior vena cavaSvO2 percentage of oxygen saturation of mixed

venous bloodSVR systemic vascular resistanceSVRI systemic vascular resistance indexSVT supraventricular tachycardiaT3 triiodothyronineT4 thyroxineTA tranexamic acidTA tricuspid atresiaTAFI thrombin-activatable fibrinolysis inhibitorTAPVC total anomalous pulmonary venous

connectionTAPVR total anomalous pulmonary venous returnTCAD transplant coronary artery diseaseTDI tissue Doppler imagingTEE transesophageal echocardiographyTEG thromboelastographyTF tissue factorTFPI tissue factor pathway inhibitorTGA transposition of the great arteriesTGC tight glycemic controlTI tricuspid valve (TV) insufficiencyTLC total lung capacityTNF-alpha tumor necrosis factor-alphaTOF tetralogy of FallotTOR target of rapamycin proteintPA tissue plasminogen activatorTPTD transpulmonary thermodilutionTR tricuspid regurgitationTRALI transfusion-related acute lung injuryTTE transthoracic echocardiography

List of Abbreviations xvii

TV tricuspid valveUFH unfractionated heparinUNOS United Network for Organ SharingURI upper respiratory tract infectionV/Q ventilation/perfusionVA ventriculoarterialVAA volatile anesthetic agentVAC video-assisted cardioscopyVAD ventricular assist deviceVATS video-assisted thoracoscopic surgeryVF ventricular fibrillation

VMI visual-motor integrationVO2 oxygen consumptionvPEO venous proepicardial organVSD ventricular septal defectVT ventricular tachycardiaVTI velocity time integralvWF von Willebrand factorWHO World Health OrganizationWMI white matter injuryWS Williams syndromeWUS Wake Up Safe Database

xix

About the Companion Website

Anesthesia for Congenital Heart Disease: Companion Website

Additional resources to accompany this book are available at:

www.wiley.com/go/andropoulos/congenitalheart

Included on the site:

MCQ questions to accompany each chapter

Full reference lists

1

CHAPTER 1

History of Anesthesia for CongenitalHeart DiseaseViviane G. Nasr, Paul A. Hickey and Dolly D. HansenDepartment of Anesthesia, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

Introduction, 1

The first years: 1938–1954, 1

The heart–lung machine:

1954–1970, 3

The era of deep hypothermic circulatory

arrest and the introduction of PGE1:

1970–1980, 5

PDA and the introduction of PGE1, 7

The story of HLHS: 1980–1990, 8

Fontan and the catheterization

laboratory: 1990–2000, 10

Emergence of technology, including

imaging (TEE, MRI) and ECMO:

2000–2010, 11

2011–2015 and the future, 12

CHD – a growing specialty from the fetus

to the adult patient, 13

Selected references, 15

Introduction

Over the last 70 years, pediatric cardiac anesthesia hasdeveloped as a subspecialty of pediatric anesthesia, or asubspecialty of cardiac anesthesia, depending on one’sperspective. It is impossible to describe the evolution ofpediatric cardiac anesthesiawithout constantly referring todevelopments in the surgical treatment of congenital heartdisease (CHD) because of the great interdependency ofthe two fields. As pediatric anesthesia developed, surgicaltreatments of children with CHD began to be invented,startingwith the simple surgical ligation of a patent ductusarteriosus (PDA), moving on to sophisticated, stagedrepair of complex intracardiac lesions in low-birth-weightneonates requiring cardiopulmonary bypass (CPB) andcirculatory arrest and then on to the most recent complexbiventricular repair. Practically every advance in the sur-gical treatment of CHD had to be accompanied by changesin anesthetic management to overcome the challengesthat impeded successful surgical treatment or mitigatedmorbidity associated with surgical treatment.

This history will mostly be organized around the themeof how anesthesiologists met these new challenges usingthe anesthetic armamentarium that was available to themat the time. The second theme running through this story isthe gradual change of interest and focus from events in theoperating room (OR) to perioperative care in its broadestsense, including perioperative morbidity. The last theme

Anesthesia for CongenitalHeartDisease, ThirdEdition. Edited byDeanB.Andropoulos, Stephen Stayer, EmadB.Mossad,WandaC.Miller-Hance.© 2015 John Wiley & Sons, Inc. Published 2015 by John Wiley & Sons, Inc.www.wiley.com/go/andropoulos/congenitalheart

is the progressive expansion in the age range of patientsroutinely presenting for anesthesia and surgery, from the9-year-old undergoing the first PDA ligation in 1938 [1]to the first fetus to have an intervention for critical aorticstenosis in utero, as reported in The New York Times in 2002[2], and, more recently, to the adult with CHD.

This story will be told working through the differenttime frames – the first years (1938–1954); CPB and earlyrepair (1954–1970); deep hypothermic circulatory arrest(DHCA) and introduction of prostaglandin E1 (PGE1)for PDA (1970–1980); hypoplastic left heart syndrome(HLHS) (1980–1990); refinement and improvement inmortality/morbidity (1990–2000); introduction of extra-corporeal membrane oxygenation (ECMO) and increasedemphasis on interventional cardiology and imagingmodalities (2000–2010); expansion to the fetus and adultwith CHD (2011); and on to the present time.

The first years: 1938–1954

This period began with the ligation of the PDA and con-tinuedwith palliative operations. The first successful oper-ation for CHD occurred in August 1938 when Robert E.Gross ligated the PDA of a 9-year-old girl. The operationand the postoperative course were smooth, but because ofthe interest in the case, the child was kept in the hospitaluntil the 13th day. In the report of the case, Gross mentions

2 Part I History, Education, Outcomes, and Science

that the operation was done under cyclopropane anesthe-sia, and continues: “The chest was closed, the lung beingre-expanded with positive pressure anesthesia just prior toplacing the last stitch in the intercostal muscles.”

A nurse using a “tight-fitting” mask gave the anesthetic.There was no intubation and, of course, no postoperativeventilation. The paper does notmention anyparticular pul-monary complications, so it cannot have been much differ-ent from the ordinary postoperative course of the day [1].

In 1952, Dr. Gross published a review of 525 PDAligations where many, if not all, of the anesthetics wereadministered by the same nurse anesthetist, under surgi-cal direction [3]. Here he states: “Formerly we employedcyclopropane anesthesia for these cases, but since abouthalf of the fatalities seemed to have been attributableto cardiac arrest or irregularities under this anesthetic,we have now completely abandoned cyclopropane andemploy ether and oxygen as a routine.” It is probablycorrect that cyclopropane under these circumstanceswith insufficient airway control was more likely to causecardiac arrhythmias than ether. An intralaryngeal airwaywas used, which also served “to facilitate suction removalof any secretions from the lower airway” (and, we mayadd, the stomach). Dr. Gross claims that the use of thisairway reduced the incidence of postoperative pulmonarycomplications. Without having a modern, rigorous reviewof this series, it is hard to know what particular anes-thetic challenges other than these were confronted bythe anesthetist, but we may assume that intraoperativedesaturation from the collapsed left lung, postoperativepulmonary complications, and occasional major blood lossfrom an uncontrolled, ruptured ductus arteriosus werehigh on the list.

The next operation to be introduced was billed as“corrective” for the child with cyanotic CHD and was thesystemic to pulmonary artery (PA) shunt. The procedurewas proposed by Helen Taussig as an “artificial ductusarteriosus” and was first performed by Albert Blalockat Johns Hopkins Hospital in 1944. In a very detailedpaper, Drs. Blalock and Taussig described the first threepatients to undergo the Blalock–Taussig shunt operation.Dr. Harmel anesthetized the first and third patients, usingether and oxygen in an open drop method for the firstpatient and cyclopropane through an endotracheal tubefor the third patient. The second patient was given cyclo-propane through an endotracheal tube by Dr. Lamont.Whether the first patient was intubated is unclear, but it isnoted that in all three cases, positive pressure ventilationwas used to reinflate the lung [4]. Interestingly, in this earlykinder and gentler time, the surgical and pediatric authorsreporting the Blalock–Taussig operation acknowledgedby name the pediatricians and house officers who tooksuch good care of the children postoperatively, but stilldid not acknowledge in their paper the contributionof the anesthesiologists Lamont and Harmel. Althoughintubation of infants was described by Gillespie as earlyas 1939, it is difficult to say when precisely intubationsbecame routine [5].

Drs. Harmel and Lamont reported in 1946 on theiranesthetic experience of 100 operations for congenital mal-formations of the heart “inwhich there is pulmonary arterystenosis or atresia.” They reported 10 anesthetic-relateddeaths in the series, so it is certain that they encounteredformidable anesthetic problems in these surgical proce-dures [6]. This is the first paper we know of published inthe field of pediatric cardiac anesthesia.

In 1952, Damman and Muller reported a successfuloperation in which the main PA was reduced in size and aband was placed around the artery in a 6-month-old infantwith a single ventricle (SV). They state that morphineand atropine were given preoperatively, but no furtheranesthetic agents are mentioned. At that time infants wereassumed to be oblivious to pain, so we can only speculateon what was used beyond oxygen and restraint [7].

Over the next 20 years, many palliative operationsfor CHD were added and a number of papers appeareddescribing the procedures and the anesthetic management.In 1948 McQuiston described the anesthetic techniqueused at the Children’s Memorial Hospital in Chicago [8].This is an excellent paper for its time, but a number of theauthor’s conclusions are erroneous, although theywere theresults of astute clinical observations and the knowledgeat the time. The anesthetic technique for shunt operations(mostly Potts’ anastomosis) is discussed in some detail, butis mostly of historical interest today. McQuiston explainedthat he had no experience of anesthetic management usedin other centers, such as the pentothal–N2O–curare usedat Minnesota or the ether technique used at the MayoClinic. McQuiston used heavy premedication with mor-phine, pentobarbital and atropine, and/or scopolamine;this is emphasized because it was important “to render thechild sleepy and not anxious.” The effect of sedation withregard to a decrease in cyanosis (resulting in making thechild look pinker) is noted by the authors. They also notedthat children with severe pulmonic stenosis or atresia donot decrease their cyanosis “because of very little bloodflow,” and these children have the highest mortality.

McQuiston pointed out that body temperature controlwas an important factor in predicting mortality andadvocated the use of moderate hypothermia (i.e., “re-frigeration” with ice bags), because of a frequently seensyndrome of hyperthermia. McQuiston worked from theassumption that hyperthermia is a disease in itself, but didnot explore the idea that the rise in central temperaturemight be a symptom of low cardiac output with peripheralvasoconstriction. Given what we now know about shuntphysiology, it is interesting to speculate that this “disease”was caused by pulmonary hyperperfusion after the open-ing of what would now be considered as an excessivelylarge shunt, stealing a large portion of systemic blood flow.

In 1950 Harris described the anesthetic technique usedat Mount Zion Hospital in San Francisco. He emphasizedthe use of quite heavy premedication with morphine,atropine, and scopolamine. The “basal anesthetic agent”was Avertin (tribromoethanol). It was given rectally andsupplemented with N2O/O2 and very low doses of curare.

Chapter 1 History of Anesthesia for Congenital Heart Disease 3

Intubation was facilitated by cyclopropane. The FiO2 waschanged according to cyanosis; and bucking or attemptsat respiration were thought to be due to stimulation of thehilus of the lung. This was treated with “cocainization” ofthe hilus [9].

In 1952 Dr. Robert M. Smith discussed the circulatoryfactors involved in the anesthetic management of patientswith CHD. He pointed out the necessity of understandingthe pathophysiology of the lesion and also “the expectedeffect of the operation upon this unnatural physiology.”That is, he recognized that the operations are not curative.The anesthetic agents recommendedweremostly ether fol-lowing premedication.

While most of these previous papers had been abouttetralogy of Fallot (TOF), Dr. Smith also described theanesthetic challenges of surgery for coarctation of theaorta, that was introduced by Dr. Gross in the U.S. andDr. Craaford in Sweden simultaneously in the year 1945.He emphasized the hypertension following clampingof the aorta and warned against excessive bleeding inchildren operated on at older ages using ganglionicblocking agents. This bleeding was far beyond what anes-thesiologists now see in patients operated on at youngerages, before development of substantial collateral arterialvessels [10].

The heart–lung machine: 1954–1970

From 1954 to 1970 the development of what was thencalled the “heart–lung machine” opened the heart tosurgical repair of complex intracardiac congenital heartdefects. At the time, the initial high morbidity of earlyCPB technology seen in adults was even worse in children,particularly smaller children weighing less than 10 kg.Anesthetic challenges multiplied rapidly in associationwith CPB, coupled with early attempts at completeintracardiac repair. The lung as well as the heart receiveda large share of the bypass-related injuries, leading toincreased postoperative pulmonary complications. Braininjury began to be seen and was occasionally reported,in conjunction with CPB operations, particularly whenextreme levels of hypothermia were used in an attemptto mitigate the morbidity seen in various organ systemsafter CPB.

In Kirklin’s initial groundbreaking report of intracardiacsurgery with the aid of a mechanical pump–oxygenatorsystem at the Mayo Clinic, the only reference to anestheticmanagement was a brief remark that ether and oxygenwere given [11]. In Lillehei’s description of direct visionintracardiac surgery in humans using a simple, disposableartificial oxygenator, there was no mention of anestheticmanagement [12]. What strikes a “modern” cardiac anes-thesiologist in these two reports is the high mortality: 50%in Kirklin’s series and 14% in Lillehei’s series. All of thesepatients were children with CHD ranging in age from1 month to 11 years. Clearly, such mortality and the asso-ciated patient care expense would not be tolerated today.

At that time, pediatric anesthesia was performed withopen drop ether administration and later with ether usingdifferent non-rebreathing systems. Most anesthetics weregiven by nurses under the supervision of the surgeon. Thefirst physician anesthetist to be employed by a children’shospital was Robert M. Smith in Boston in 1946.

The anesthetic agent that came into widespread use afterether was cyclopropane; in most of the early textbooks,it was the recommended drug for pediatric anesthesia.Quite apart from being explosive, cyclopropane wasdifficult to use. It was obvious that CO2 absorption wasnecessary with cyclopropane to avoid hypercarbia andacidosis, which might precipitate ventricular arrhythmias.However, administration with a Waters’ absorber couldbe technically difficult, especially as tracheal intubationwas considered dangerous to the child’s “small, delicateairway.”

In all the early reports, it is noted or implied that thepatients were awake (more or less) and extubated at theend of the operation. In the description of the postopera-tive course, respiratory complications were frequent, in theform of either pulmonary respiratory insufficiency or air-way obstruction. This latter problemwas probably because“the largest tube which would fit through the larynx” wasused. Another reason may have been that the red rubbertube was not tissue-tested. The former problem was prob-ably often related to the morbidity of early bypass technol-ogy on the lung.

Arthur S. Keats, working at the Texas Heart Instituteand Texas Children’s Hospital with Denton A. Cooley,had much experience with congenital heart surgery andanesthesia from 1955 to 1960, and provided the mostextensive description of the anesthetic techniques usedin this era [13,14]. He described anesthesia for congenitalheart surgery without bypass in 150 patients, the mostcommon operations being PDA ligation, Potts’ operation,atrial septectomy (Blalock–Hanlon operation), and pul-monary valvotomy. Premedication was with oral or rectalpentobarbital, chloral hydrate per rectum, intramuscularmeperidine, and intramuscular scopolamine or atropine.Endotracheal intubation was utilized, and ventilation wasassisted using an Ayres T-piece, to-and-fro absorptionsystem, or a circle system. Cyclopropane was used forinduction, and a venous cutdown provided vascularaccess. Succinylcholine bolus and infusion were used tomaintain muscle relaxation. Light ether anesthesia wasused for maintenance until the start of chest closure,and then 50% N2O was used as needed during chestclosure. Of note is the fact that the electrocardiogram(ECG), ear oximeter, and intra-arterial blood pressure(IABP) recordings were used for monitoring during thisperiod, as well as arterial blood gases and measurementsof electrolytes and hemoglobin. The following year hepublished his experiences with 200 patients undergoingsurgery for CHD with CPB, almost all of whom were chil-dren. Ventricular septal defect (VSD), atrial septal defect(ASD), TOF, and aortic stenosis were the most commonindications for surgery. The anesthetic techniques were

4 Part I History, Education, Outcomes, and Science

the same as described earlier, except that d-tubocurarewas given to maintain apnea during the bypass. In 1957,in addition to ECG, IABP, and oximeter, Dr. Digby Leighnoted the importance of capnography in cardiac surgery.He described the effect of pulmonary blood flow onend-tidal CO2 (EtCO2) and the decrease in EtCO2 afterpartial clamping of the PA during the Blalock–Taussigshunt procedure. However, it was not until 1995 thatSmolinsky et al. reported the importance of EtCO2 duringPA banding [15–17].

Perfusion rates of 40–50 mL/kg/min were used ininfants and children, and lactic acidemia after bypass(average 4 mmol/L) was described. No anesthetic agentwas added during the bypass procedure, and “patientstended to awaken during the period of bypass,” butapparently without recall or awareness. Arrhythmiasnoted ranged from frequent bradycardia with cyclo-propane and succinylcholine to junctional or ventriculartachycardia, ventricular fibrillation (VF), heart block, andrapid atrial arrhythmias. Treatments included defibrilla-tion, procainamide, digitalis, phenylephrine, ephedrine,isoproterenol, and atropine. Eleven out of 102 patientswith VSD experienced atrioventricular block. Epicardialpacing was attempted in some of these patients but wasnever successful. Fresh citrated whole blood was used forsmall children throughout the case, and the transfusionof large amounts of blood was frequently necessary insmall infants. The mortality rate was 13% in the first series(36% in the 42 patients less than 1 year old) and 22.5%in the second series (47.5% in the 40 patients less than 1year old). Causes of death included low cardiac outputafter ventriculotomy, irreversible VF, coronary air emboli,postoperative atrioventricular block, hemorrhage, pul-monary hypertension, diffuse atelectasis, and aspirationof vomitus. No death was attributed to the anestheticalone. Reading these reports provides an appreciationof the daunting task of giving anesthesia during thesepioneering times.

Tracheostomy after cardiac operations was not unusualand in some centers was done “prophylactically” a weekbefore the scheduled operation. These practices werecertainly related to primitive (relative to the present)techniques and equipment used for both endotrachealintubation and CPB. Postoperative ventilatory supportdid not become routine until later when neonatologistsand other intensive care specialists had proved it couldbe done successfully. Successful management of pro-longed respiratory support was first demonstrated in thegreat poliomyelitis epidemics in Europe and the USA in1952–1954 [18].

Halothane was introduced in clinical practice in themid-1950s and it rapidly became the most popular agentin pediatric anesthesia, mostly because of the smoothinduction compared with the older agents. Halothane wasalso widely used for pediatric cardiac anesthesia in spite ofits depressive effect on themyocardium and the significantrisk of arrhythmias. Halothane is no longer available, andthe newer inhalational agents, isoflurane and sevoflurane,

are now the mainstays of pediatric cardiac cases in USacademic centers.

During this period, adult cardiac anesthesiologists,following the practice reported by Edward Lowenstein in1970 [19], began to use intravenous anesthesia based onopiates. Initially, morphine in doses up to 1 mg/kg wasgiven with 100% oxygen and this technique became theanesthetic of choice for adult cardiac patients, but vasodi-lation and hypotension associated with its use slowedthe incorporation of this technique into pediatric cardiacanesthesia until the synthetic opiates became available.

Before CPB was developed, or when it still carried highmorbidity and mortality, a number of modalities wereused to improve the outcome for infants. One was inflowocclusion (IO) and another was the hyperbaric chamber.IO was useful and, if well managed, an elegant technique.The secret was the organization of the efforts of the entireoperative team, and the technique required the closestcooperation between surgeons and anesthesiologists. Thetechnique was as follows.

The chest was opened in the midline. After pericar-diotomy, a side clamp was placed on the right atrial (RA)free wall and an incision made in the RA, or proximalon the PA, prior to placing the vascular clamps used toocclude caval return. Before application of the clamps,patients were hyperventilated with 100% O2. During IO,the superior vena cava (SVC) and inferior vena cava (IVC)inflow were occluded, ventilation held, and the RA orPA clamp released; the heart was allowed to empty andthe septum primum was excised or the pulmonic valvedilated. After excision of the septum or valvotomy, onecaval clamp was released initially to de-air the atrium. TheRA side clamp or the PA clamp was then reapplied andthe other caval clamp released. The heart was resuscitatedwith bolus calcium gluconate (range 30–150 mg/kg)and bicarbonate (range 0.3–3 mEq/kg). Occasionally,inotropes were administered, most often dopamine.It was important to titrate the inotropes so as not toaggravate rebound hypertension caused by endogenouscatecholamines. The duration of the IO was between 1 and3 minutes – terrifying minutes for the anesthesiologist,but quickly over.

Another modality used to improve the survival aftershunt operations, PA banding, and atrial septectomy wasto operate in the hyperbaric chamber, thereby benefitingfrom the increased amount of physically dissolved oxygen.It was a cumbersome affair operating in crowded andclosed quarters. There was room for only two surgeons,two nurses, one anesthesiologist, and one baby, as thenumber of emergency oxygen units limited access. Retirednavy divers ran the chamber and kept track of how manyminutes the personnel had been in the hyperbaric cham-ber in the previous week. Help was not readily availablebecause the chamber was buried in a sub-basement andpeople had to be sluiced in through a side arm that couldbe pressurized. The chamber was pressurized to 2–3atmospheres so it was unpleasantly hot while increasingthe O2 pressure and cold while decreasing the pressure;

Chapter 1 History of Anesthesia for Congenital Heart Disease 5

people with glasses were at a disadvantage. It did notseem to add to survival and was abandoned around 1974.

Anesthesia was a challenge in the hyperbaric chamber.The infants were anesthetized with ketamine and nitrousoxide. As the pressure in the chamber increased, theconcentrations of N2O had to be decreased to avoid thehypotension and bradycardia that occurred rapidly.

Also in this era, the first infant cardiac transplant wasperformed byKantrowitz in 1967 [20]. The recipientwas an18-day-old, 2.6 kg patient with severe Ebstein’s anomaly,who had undergone a Potts’ shunt on day 3 of life. Thedonor was an anencephalic newborn. The anesthetic tech-nique is not described, and the infant died of pulmonarydysfunction 7 hours postoperatively.

The era of deep hypothermiccirculatory arrest and theintroduction of PGE1: 1970–1980

Sometime around 1970 physiological repair of CHD, or“correction,” had begun to come of age. In the adultworld, coronary bypass operations and valve replacementspurred interest in cardiac anesthesia, which centeredincreasingly on use of high-dose narcotics and otherpharmacological interventions. As synthetic opiates withfewer hypotensive side-effects became available, their usespread into pediatric cardiac anesthesia in the late 1970sand 1980s.

Children were still treated as “small adults” becausemajor physiological differences were not yet well appre-ciated, particularly as they related to CPB morbidity. CPBwas rarely employed during surgery on children weighingless than 9 kg because of the very high mortality andmorbidity that had been experienced in the early years.The notion of repairing complex CHD in infancy wasgetting attention but was hindered by technical limitationsof surgical techniques, CPB techniques, and anestheticchallenges in infants. Theoretically, physiological repairearly in life provides a more normal development of thecardiovascular and pulmonary systems and might avoidpalliation altogether. The advantage of this was that thesequelae after palliation, for instance distorted pulmonaryarteries after shunts and PA banding, might be avoided.Pulmonary artery hypertension following Waterston andPotts’ shunts occurred as a result of increased pulmonaryblood flow and resulted in pulmonary vascular obstructivedisease. This would not develop if the defect were physi-ologically repaired at an early age. Furthermore, parentscould be spared the anxiety of repeated operations andthe difficulties of trying to raise a child with a heart thatcontinued to be impaired.

The perceived need for early repair, together withthe high mortality of bypass procedures, in infants andsmall children led to the introduction of DHCA. It wasfirst practiced in Kyoto, Japan, but spread rapidly toRussia, the west coast of the US at Seattle, Washington,and from there to Midwestern and other US pediatric

centers. One example of the difficulties this presented toanesthesiologists was the introduction of DHCA in prac-tice at Boston Children’s Hospital. The newly appointedchief of cardiovascular surgery at the Boston Children’sHospital was Aldo R. Castaneda, MD, PhD, one of thefirst supporters of early total correction of CHD, whoquickly embraced DHCA as a tool to accomplish his goalsfor repair in infants. In 1972, he immediately introducedDHCA into practice at Boston Children’s Hospital andthe rather shocked anesthesia department had to devisean anesthetic technique to meet this challenge, aidedonly by a couple of surgical papers in Japanese that Dr.Castaneda kindly supplied. Of course, these papers madelittle reference to anesthesia.

The first description of the techniques of DHCA fromJapan in the English literature was by Horiuchi in 1963[21]. This involved a simple technique with surface coolingand rewarming during resuscitation, using ether as theanesthetic agent, without intubation. In 1972 Mori et al.reported details of a technique for cardiac surgery inneonates and infants using deep hypothermia, again in asurgical publication [22]. Their anesthetic technique washalothane/N2O combined with muscle relaxant; CO2 wasadded to the anesthetic gas during cooling and rewarming(pH-stat) to improve brain blood flow. The infants weresurface-cooled with ice bags and rewarmed on CPB.

Surprisingly, given the enormity of the physiologi-cal disturbances and challenges presented by DHCA,very few articles describing an anesthetic technique forDHCA were published, perhaps because DHCA andearly correction were not widely accepted. A paper fromToronto described an anesthetic regime with atropinepremedication occasionally combined with morphine[23]. Halothane and 50% N2O were used, combined withd-tubocurare or pancuronium. CO2 was added to “im-prove tissue oxygenation by maintaining peripheral andcerebral perfusion.” The infants were cooled with surfacecooling (plastic bags with melting ice) and rewarmed onCPB. It was noted that six of the 25 infants had VF whencooled to below 30 ∘C.

Given the lack of any scientific data or studies to guideanesthetic management of such cases, a very simple tech-nique with ketamine–O2–N2O and curare supplementedby small amounts of morphine (0.1–0.3 mg/kg) wasused at Boston Children’s Hospital. This was the wayin which infants were anesthetized for palliative cardiacsurgical procedures in the hyperbaric chamber at BostonChildren’s Hospital. The infants were surface-cooledin a bathtub filled with ice water to a core tempera-ture of approximately 30 ∘C. The bathtub consisted ofa green plastic bucket (for dishwashing) bought at aSears-Roebuck surplus store, keeping things as simple aspossible (Figure 1.1). This method was used in hundredsof infants over the next couple of years and only one infantdeveloped VF in the ice water bathtub. This was an infantwith TOF who suffered a coronary air embolus either froma peripheral IV or during an attempted placement of acentral venous line. In retrospect, it is amazing that so few

6 Part I History, Education, Outcomes, and Science

Figure 1.1 Infant submerged in ice water.

papers were published about the anesthetic managementof this procedure, which was rapidly seen to be life-saving.The material that was published about these techniqueswas restricted to surgical journals and did not describe ormake any attempt to study the anesthetic techniques usedfor DHCA. The published surgical articles were largelyunknown to cardiac and pediatric anesthesiologists.

It was during this decade that the “team concept”developed, with cardiologists, cardiac surgeons, andanesthesiologists working together in the OR and theintensive care unit (ICU) in the larger centers. These teamswere facilitated by the anesthesiologists’ “invasion” ofweekly cardiology–cardiac surgeons’ conferences wherethe scheduled operations for the week were discussed. Dr.Castaneda, chief surgeon at Boston’s Children’s Hospital,was a leader in the creation of the cardiac team concept forpediatric cardiac surgery.

During the first year of using DHCA in Boston, itwas noticed that a number of the infants had “funny,jerky” movements of the face and tongue. A few also hadtransient seizures during the postoperative period, but asthey had normal electroencephalograms (EEGs) at 1-yearfollow-up, itwas felt that significant cerebral complicationswere not a problem. In view of the knowledge developedsubsequently, these clues to neurological damage occur-ring during and after pediatric cardiac surgery involvingDHCA were overlooked. In hindsight, it is perhaps moreaccurate to say these clues were ignored, and as a resulta great opportunity to study this problem was delayedfor almost two decades. The issue of neurological damagewith DHCA was raised repeatedly by surgeons such asJohn Kirklin, but was not really studied until the group atBoston Children’s Hospital led by Jane Newburger andRichard Jonas systematically followed a cohort of infantswho had the arterial switch operation in the late 1980susing DHCA techniques [24]. In the late 1980s and early1990s, Greeley and co-workers at Duke performed a seriesof human studies delineating the neurophysiologicalresponse to deep hypothermia and circulatory arrest [25].These studies provided the crucial data in patients fromwhich strategies for cooling and rewarming, length of

safe DHCA, blood gas management, and perfusion weredevised to maximize cerebral protection.

Those ongoing studies were followed by a number ofother studies comparing DHCA with hypothermic low-flow perfusion, with different hematocrit in the perfusateand with different pH strategies during hypothermic CPB,pH-stat versus alpha-stat.

During those years, the ketamine-morphine anes-thetic technique had been supplanted by fentanyl-basedhigh-dose narcotic techniques. For the neurological out-come studies, the anesthetic technique was very tightlycontrolled, using fentanyl doses of 25 μg/kg at induction,incision, onset of bypass and on rewarming, in addition topancuronium. From the beginning of this period, surgicalresults as measured by mortality alone were excellent,with steady increases in raw survival statistics. Becauseanesthetic techniques were evolving over this period oftime, it was difficult to definitely ascribe any outcomedifferences to different anesthetic agents. A 1984 studyof 500 consecutive cases of cardiac surgery in infants andchildren looked at anesthetic mortality and morbidity.Both were very low – so low in fact that they wereprobably not universally believed [26].

As the new synthetic opioids such as fentanyl andsufentanil were developed, they replaced morphine toprovide more hemodynamic stability in opiate-basedanesthetic techniques for cardiac patients. In 1981 Gregoryand his associates first described the use of “high-dose”fentanyl 30–50 μg/kg combined with pancuronium in 10infants undergoing PDA ligation. It is noteworthy thattranscutaneous oxygen tension was measured as part ofthis study. This paper was, in fact, the introduction ofhigh-dose narcotics in pediatric cardiac anesthesia [27].The technique was a great success; one potential reasonfor this was demonstrated 10 years later in Anand’spaper showing attenuation of stress responses in infantsundergoing PDA ligation who were given lesser doses offentanyl in a randomized, controlled study [28].

During this same period, synthetic opioids were replac-ing morphine in adult cardiac surgery. This techniqueslowly and somewhat reluctantly made its way into pedi-atric anesthesia [29], replacing halothane and morphine,which had previously been the predominant choice ofpediatric anesthesiologists dealing with patients withCHD. In the years from 1983 to 1995, a number of paperswere published showing the effect of different anestheticagents on the cardiovascular system in childrenwith CHD.Ketamine, nitrous oxide, fentanyl, and sufentanil weresystematically studied. Some misconceptions stemmingfrom studies of adult patients were corrected, such asthe notion that N2O combined with ketamine raises PApressure and pulmonary vascular resistance (PVR) [30].On the other hand, the role of increased PaCO2 or lowerpH in causing higher PVRwas also demonstrated and thatsubsequently became important in another connection[31]. A number of studies done at this time demonstratedin a controlled fashion the earlier clinical observation(Harmel and McQuiston in the late 1940s) [6,32] that in

Chapter 1 History of Anesthesia for Congenital Heart Disease 7

cyanotic patients the O2 saturation would rise duringinduction of anesthesia, almost irrespective of the agentused [33]. These events only serve to reinforce the value ofacute clinical observation and provide an example of howthe interpretation of such observations may well changeas new knowledge is discovered.

PDA and the introduction of PGE1In the mid-1970s, several discoveries were made and intro-duced into clinical practice that turned out to be of greatimportance to the pediatric cardiac anesthesiologist andthe rest of the cardiac team, the most important being thediscovery that PGE1 infused intravenously prevented thenormal ductal closure [34]. These developments revolvedaround the role of the PDA in the pathophysiology ofboth cyanotic and acyanotic CHD. The critical role of PDAclosing and opening in allowing early neonatal survivalof infants with critical CHD began to be appreciated andclinicians sought methods of either keeping the PDA openor closing it, depending on what type of critical CHDthe neonate was born with and the role of patency of theductus arteriosus in the CHD pathophysiology. In somecases, particularly in very small neonates, the importanceof closing the PDA was increasingly appreciated and, inother cases, the critical importance of maintaining thepatency of a PDA was appreciated.

As the survival of very small premature infants (“pre-emies”) began to improve, mostly because of technicalimprovements with the use of a warmed isolette andimproved mechanical ventilation, it became apparent thatin many of these infants the PDA would not undergothe normal closure over time. As the understanding ofthese infants’ physiological problems improved and moreinfants survived, the role of continued patency of the PDAin neonates needing mechanical ventilation was appreci-ated. This led to medical therapy directed at promotingductal closure using aspirin and indomethacin.

When such attempts failed, it was increasingly under-stood that necrotizing enterocolitis in the preemie wasassociated with decreased mesenteric blood flow sec-ondary to the “steal” of systemic blood flow into thepulmonary circulation through a PDA. Thus, in caseswhen the PDA failed to close in premature infants, theneed for operative treatment of the PDA in preemies aroseas prophylaxis for necrotizing enterocolitis.

Pediatric and cardiac anesthesiologists were now facedwith the task of anesthetizing these tiny preemies safely.This involved maintaining body temperature in infants of1 kg or less with very large surface area/volume ratios.Intraoperative fluid restriction was important and lowlevels of FiO2 were used to decrease the risk of retinopathyof prematurity. As the decade progressed, these issuesemerged and were addressed. In 1980, Neuman [35]described the anesthetic management of 70 such infantsusing an O2/N2O muscle relaxant anesthesia techniquewith no mortality. Low FiO2 was used to reduce the riskof retrolental fibroplasia and precautions were taken to

prevent heat loss. In those days before human immunod-eficiency virus (HIV) became a wide concern, 40% of theinfants received blood transfusion. Interestingly, the ques-tion of whether to operate in the neonatal intensive careunit (NICU) or theOR for closure of the PDA in the preemiewas debated at that time and remains unsettled today.

The PDA lesion presents an interesting story. In 1938 itwas the first of the CHD lesions to be successfully treatedsurgically [1]. In the mid-1970s it was closed with medicaltherapy, first with aspirin and later with indomethacin. Itwas the first CHD lesion to be treated in the catheterizationlaboratory using different umbrella devices or coils [36].Presently, if surgical closure is necessary, it is often doneusing a minimally invasive, thoracoscopic video-assistedtechnique [37]. Thoracoscopy has the benefit of usingfour tiny incisions to insert the instruments, avoiding anopen thoracotomy and limiting dissection and trauma tothe left lung. At the same time, this latest developmentof surgical technique required the anesthesiologist onceagain to change the anesthetic approach to these patients.Unlike adult anesthesiologists, who can use double-lumenendotracheal tubes for thoracoscopic procedures, pediatricanesthesiologists caring for 1–3 kg infants undergoingPDA ligation do not have the luxury of managing the leftlung [37]. Another problem posed by thoracoscopic PDAligation in the infant is the emerging need for neurophys-iological monitoring of the recurrent laryngeal nerve’sinnervation of the muscles of the larynx to avoid injury, aknown complication of PDA surgery [38]. The last issue istailoring the anesthetic so that the children are awake atthe end of the operation, extubated, and spend an hour orso in the post-anesthesia care unit, bypassing the cardiacICU. In fact, in 2001, a group led by Hammer at Stanfordpublished the first description of true outpatient PDA lig-ation in two infants aged 17 days and 8 months [39]. Thesepatients were managed with epidural analgesia, extubatedin the OR, and discharged home 10 hours postoperatively.This report brings PDA closure full circle from a 13-dayhospital stay following an ether mask anesthetic for anopen thoracotomy to a day surgery procedure in an infantundergoing an endotracheal anesthetic for a thoracoscopicPDA ligation.

Maintaining patency of the PDA using PGE1 is probablynow of considerably greater importance than its closureboth numerically and in terms of being life-sustainingin neonates with critical CHD. The introduction of PGE1suddenly improved the survival rate of a large number ofneonates, with CHD having ductal-dependent lesions toimprove pulmonary blood flow, or to improve systemicblood flow distal to a critical coarctation of the aorta. Theintroduction of PGE1 into clinical practice for therapy ofneonatal CHD substantially changed the lives of pedi-atric cardiac surgeons and anesthesiologists, as frequentmiddle-of-the-night shunt operations with extremelycyanotic infants almost immediately became a thing of thepast. These operations were particularly daunting whenone realizes that these procedures were most commonbefore the availability of pulse oximetry; the only warning

8 Part I History, Education, Outcomes, and Science

signs of impending cardiovascular collapse were the verydark color of the blood and preterminal bradycardia. Toget an arterial blood gas with a PaO2 in the low teens wasnot uncommon and PaO2 measurements in single digitsin arterial blood samples from live neonates during suchsurgical procedures were recorded. Even more dramaticwas the disappearance of the child with critical post-ductalcoarctation. These infants were extremely acidotic, witha pH of 7.0 or less at the start of the procedure (if itwas possible to obtain an arterial puncture); they lookedmottled and almost dead below the nipples. With theadvent of PGE1 therapy, they were resuscitated medicallyin the ICU and could be operated on the following dayin substantially better condition than was previouslythe case.

But the introduction of PGE1 had an effect that was notclearly foreseen except possibly by some astute cardiolo-gists. Survival of a number of these neonates presentedpediatric cardiologists and cardiac surgeons (and thenanesthesiologists) with rare and severe forms of CHDthat had hitherto been considered a “rare” pathologicaldiagnosis. Foremost among these were the infants withHLHS and some forms of interrupted aortic arch. Asfurther experience was gained, it became obvious thatthese forms of disease were not so rare, but infants whohad survived with those forms of CHD were very rare.

The story of HLHS: 1980–1990

As mentioned in the previous section, the introduction ofPGE1 brought major changes to pediatric cardiac anesthe-sia, solving some problems and at the same time bring-ing new challenges for the cardiac team. New diagnoses ofCHD presented for treatment and were recognized; somehad been known previously but had until then presentedinsurmountable obstacles to any effective therapy.

One of thesewasHLHS. It had been accurately describedin 1958 by Noonan and Nadas but only as a pathologicaldiagnosis [40]. The syndrome is a ductus lesion, with 100%mortality within a few days to weeks when the ductusunderwent physiological closure. HLHS was therefore ofno practical interest from a therapeutic standpoint untilductal patency could be maintained. When it becamepossible to keep the ductus arteriosus patent with PGE1,these neonates rapidly became a problem that could noteasily be ignored. In the beginning, most of the infantswere misdiagnosed as having sepsis and being in septicshock, and few babies reached the tertiary center withouta telltale Band-Aid, indicating a lumbar puncture to ruleout sepsis.

But even with the ability to diagnose the defect in alive neonate temporarily kept alive with a PGE1 infu-sion, the outlook was not much better. There was nooperation devised, and in some centers such neonateswere kept viable on a PGE1 infusion for weeks andeven months in the (usually) vain attempt to get themto grow large enough for some surgical procedure to

be attempted. In subsequent years, several centers trieddifferent approaches with ingenious conduits, attemptingto create an outlet from the right ventricle to the aorta andthe systemic circulation.

Those were also the years during which PresidentRonald Reagan’s Baby Doe regulations were in effect.Anyone who thought an infant was being mistreated(i.e., not operated upon) could call a “hotline number”which was posted in all neonatal ICUs to report thephysicians’ “mistreatment” of the infant. Fortunately,these regulations died a quiet death after a few chaoticyears [41].

In the meantime, the search for a palliative operationwent on, also spurred by the increasing success of theFontan operation, which had been introduced in 1970 [42].This meant that there now was a theoretical endpoint forHLHS as well as for other forms of SV physiology. It wasWilliam Norwood at Boston Children’s Hospital who wasthe first person to devise a viable palliation and also tocomplete the repair with a Fontan operation the followingyear [43]. The publication of this landmark paper spurredconsiderable discussion. Many cardiologists and surgeonstook the position that this operative procedure representedexperimental and unethical surgery and that these infants“were better off dead.”

The current approach to these infants varies frommultistage physiological repair with palliation followedby Fontan operation. Another alternative is neonataltransplantation as proposed by the group at Loma Lindain California [44]. Some cardiologists are still advocatesof conservative “comfort care” for neonates with HLHS.With eventual survival of about 70% being achieved inmany centers, these infants can no longer be written offas untreatable. Now the question is more about qualityof survival, especially intellectual development. It isalso recognized that many have both chromosomal andnon-chromosomal anomalies that affect the cerebral andgastrointestinal systems [45].

As was the case from the beginnings of pediatric cardiacsurgery, this new patient population presented a manage-ment dilemma for the anesthesiologists; they posed a newset of problems that required a solution before acceptableoperative results could be achieved. It was obvious thatpatients with HLHS were hemodynamically unstablebefore CPB because of the large volume load on the heartcoupled with coronary artery supply insufficiency. Thecoronary arteries in HLHS are supplied from the PDAretrograde through a hypoplastic ascending and trans-verse aorta that terminates as a single “main” coronaryartery. A common event at sternotomy and exposure ofthe heart was VF secondary to mechanical stimulation.This fibrillation was sometimes intractable, necessitatingemergent CPB during internal cardiac massage. This wasnot an auspicious beginning to a major experimental openheart procedure.

It was during these years that there was a transitionfrom morphine–halothane–N2O to a high-dose narcotictechnique with fentanyl or sufentanil combined with 100%