Brain Protection in Cardiac Surgery

Robert S. Bonser • Domenico Pagano Axel Haverich(Editors)

Brain Protection in Cardiac Surgery

Prof. Robert S. Bonser MD, FRCP, FRCS, FESC, FACCProfessor and Consultant Cardiac SurgeonDepartment of Cardiothoracic Surgery, Queen Elizabeth Hospital,University Hospital Birmingham NHS Trust,Edgbaston, Birmingham, UK

Mr. Domenico PaganoCardiothoracic SurgeryBeaumont Road 208B30 1NX Birmingham BournvilleUnited Kingdom

Prof. Axel HaverichMedizinische HochschuleHannover (MHH) Klinik für Herz-, Thorax-,Transplantations- undGefäßchirurgieCarl-Neuberg-Str. 130625 Hannover Germany

ISBN: 978-1-84996-292-6 e-ISBN: 978-1-84996-293-3

DOI: 10.1007/978-1-84996-293-3

A catalogue record for this book is available from the British Library

Library of Congress Control Number: 2010937962

© Springer-Verlag London Limited 2011

Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers.

The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore free for general use.

Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature.

Printed on acid-free paper

Springer Science+Business Media (www.springer.com)

v

“You are old, Father William,” the young man said,And your hair has become very white;And yet you incessantly stand on your head –Do you think, at your age, it is right?”“In my youth,” Father William replied to his son,I feared it might injure the brain;But, now that I’m perfectly sure I have none,Why, I do it again and again.”1

These verses from the poem Father William1 were composed by Lewis Carroll, the author of Alice’s Adventures in Wonderland. They suggest that brain damage might be induced by serial insults – albeit in this case, by standing on one’s head!

The recognition that cardiac surgical operations might be associated with brain injury was reported by Fox et al. in 1954,2 the very year in which Gibbon reported the first successful clinical use of the heart-lung machine in cardiac surgery.3 Succeeding years saw numerous studies confirming the association between cardiac surgery and cerebral injury.

Although much research effort has been expended over the years, brain damage in cardiac surgical patients remains a significant and challenging problem, not least because of the increased susceptibility of our progressively ageing patients. Progress has been made, but perhaps not as much as in other areas of cardiac surgical morbid-ity and mortality. There are several reasons for this, not least the fact that the brain has proved to be a difficult organ to study. Much of the research has focused on either functional or structural cerebral damage. Studies which have attempted to increase the understanding of the potential importance and relative incidence of these two components of the overall cerebral pathology have been relatively few. It has to be said that a strong consensus providing a clear indication of the principal pathophysi-ology (or pathophysiologies) has yet to emerge.

This book focuses on a thorough review of where we are currently in our under-standing of brain injury in cardiac surgery and the strategies currently employed to lessen its incidence and severity in our patients. The editors have gathered together an impressive group of established experts and researchers in this field. The chapters are broad in the overall coverage of the subject, and commendably, they are also very forward-looking in their suggestions for future research and development, emphasiz-ing the potentially important contributions from new developments in basic science, pharmacology, imaging modalities, etc.

I congratulate the editors and authors for this informed and stimulating book, which deserves to find a place on the desk of all of us who, rightly, believe that the

Foreword

vi Foreword

understanding and ultimate prevention of serious brain injury in cardiac surgery patients remains a mountain yet to be conquered.

London Professor Ken Taylor

References

1. Father William verses are reprinted from The Hunting of the Snark and Other Poems and Verses. Lewis Carroll. New York: Harper & Brothers; 1903.

2. Fox HM, Risso ND, Gifford S. Psychological observations of patients undergoing mitral sur-gery. Psychosomat Med. 1954;16;186–208.

3. Gibbon JH. Application of a mechanical heart and lung apparatus to cardiac surgery. Minnesota Med. 1954; 37:171–185.

vii

Preface

We welcome the reader to the Monographs in Cardiac Surgery series. These mono-graphs have the objective to fully summarize the information available to date regard-ing particular facets of cardiac surgery – indications, operative techniques, pre-operative care, post-operative outcomes – so that the reader can have a full and up-to-date understanding of the history, current understanding, and future direction in a given area. As such, the series should be of interest to cardiac surgeons in practice or training, anesthesiologists, intensive care physicians, and potential researchers.

Brain injury remains one of the most dreaded complications of cardiac surgery. The range of injury is broad; while a stroke may be easily defined and diagnosed, more subtle injuries most definitely occur. There remains debate as to how these are diagnosed and there is a lack of standard definitions allowing inter-study comparison. If we are to have confidence in strategies that may reduce brain injury, we need to have confidence in the end-points used to define that injury. We need to better under-stand the phenomena associated with neuropsychometric testing; we need to fully elucidate the relationship between structural brain injury, embolism counting, and surrogate biomarkers; and we need an improved understanding of the clinical signifi-cance of abnormalities detected on post-operative magnetic resonance imaging.

In this, the first of the series, we have tried to construct a detailed background of studies of neurological morbidity and neuroprotection from a range of experts in the field of neuroprotection, providing a detailed reference for clinicians in the field. We have attempted to inter-connect the different strands of injury – be it the pathology, the imaging, the clinical and cognitive examination, potential biomarkers – and have then provided summary reports of treatment strategies that may reduce such injury. One of our objectives was to provide a reference background to stimulate research. As we look to the future, the design of studies attempting to reduce such injury becomes increasingly important and we hope that the fundamental background infor-mation provided in these chapters will fuel interest, initiate novel prevention and therapeutic strategies, and inform the investigator how to develop and design their research study.

Robert S. Bonser Domenico Pagano

Axel Haverich

ix

Series Preface

This series is directed toward surgeons, physicians, and healthcare workers involved in the care of patients requiring cardiac, cardiothoracic, and cardiovascular surgery. The scientific developments in this field continue to be prodigious and are published in an ever-increasing journal base. We hope that the series will also provide an impor-tant resource to research workers in the quest to accelerate the translation of basic research findings into clinical study and practice. The knowledge base in our disci-plines is changing rapidly and there is an important requirement to consolidate the wide-ranging information on which clinicians must base their practice.

In the series, eminent experts, serving as editors or authors, offer their accounts of innovations within our areas of practice. In some, a thorough review of the available literature is undertaken to provide a balanced reference tool for investigators to pose future research questions and understand the studies that have been previously per-formed to best design subsequent studies and analyses. In others, state-of-the-art, technical advances are described, affording surgeons a platform to refine their prac-tice, providing information on thresholds of when to recommend interventions and guidance on which intervention might be appropriate.

Each and every anesthetic and surgical procedure carries a risk of mortality and complications. Much has been done in to define and quantitate risk and to establish which factors may predict adverse outcome. Although such definition and quantita-tion may allow us to improve our counseling of patients regarding the risks of proce-dures, it does not necessarily allow us to categorically decide whether patients should undergo an intervention or whether they are best served by continued medical treat-ment or alternative modes of therapy. One of the focuses of the series will not only be the reports of which patients are at risk of which complications but also concentrate on what avenues are available to reduce risk.

The series focuses on all aspects of cardiovascular patient care.Some volumes will focus on specific conditions or operative procedures while

others will focus on aspects of patient care, improvements in patient management, and reduction of complications. Developments in the field are continuous and, there-fore, clinicians need to understand which developments in basic research can be translated into improved patient care and how these can be investigated in clinical studies and trials. This series will continue to accelerate this process providing a detailed reference on which to base innovation and answer important clinical ques-tions in our disciplines.

x Series Preface

We have consciously emphasized the importance of future research direction within the series and, as co-editors, we pledge to support our professional colleagues and the series readers as they share advances within our field of practice.

Robert S. BonserDomenico Pagano

Axel Haverich

xi

Contents

1 Molecular and Biochemical Basis of Brain Injury Following Heart Surgery – Interventions for the Future . . . . . . . . . . . . 1Eric S. Weiss and William A. Baumgartner

2 Cardiopulmonary Bypass Circuit and the Brain . . . . . . . . . . . . . . . . . . 11Michael A. Borger, George Djaiani, and Robert A. Baker

3 Neurological and Cognitive Sequelae of Cardiac Surgery . . . . . . . . . . . 19Guy M. McKhann, Rebecca F. Gottesman, Maura A. Grega, William A. Baumgartner, and Ola A. Selnes

4 Neurocognitive Decline Following Cardiac Surgery: Incidence, Risk Factors, Prevention, and Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . 29John W. Hammon and David A. Stump

5 Neuropathology of Brain Injury in Cardiac Surgery . . . . . . . . . . . . . . . 37Colin Smith

6 Biochemical Markers of Brain Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . 45Basel Ramlawi and Frank W. Sellke

7 Pitfalls of Neuropsychometric Assessment and Alternative Investigative Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57Yasir Abu-Omar and David P. Taggart

8 Imaging of the Brain in Cardiac Surgery as a Tool in Brain Protection Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65Martin Bendszus

9 Current Techniques of Emboli Detection and Their Utility in Brain Protection Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Sunil K. Bhudia, David A. Stump, and Timothy J. Jones

10 Intraoperative Brain Monitoring in Cardiac Surgery . . . . . . . . . . . . . . 83Joseph E. Arrowsmith and Maruthi S.S.R. Ganugapenta

xii Contents

11 Near-Infrared Spectroscopy Monitoring in Cardiac Surgery: Theory, Practice, and Utility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113John M. Murkin, Miguel F. Arango, Alain Deschamps, and André Y. Denault

12 The Design and Methodology of Clinical Studies of Neuroprotection in Cardiac Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . 131Reza Motallebzadeh and Marjan Jahangiri

13 Temperature and Brain Protection in Cardiac Surgery. . . . . . . . . . . . . 141George Djaiani, Harish Ramakrishna, and Alina M. Grigore

14 Studies of Nonpharmacological Interventions to Reduce Brain Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159Aaron M. Ranasinghe and Timothy J. Jones

15 Pharmacological Studies to Reduce Brain Injury in Cardiac Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177Deborah K. Harrington, Vamsidhar B. Dronavalli, and Robert S. Bonser

16 Off-Pump and On-Pump Coronary Artery Surgery and the Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191R. Peter Alston

17 Experimental Basis and Clinical Studies of Brain Protection in Pediatric Heart Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . 207Richard A. Jonas

18 Experimental Basis and Clinical Studies of Brain Protection in Aortic Arch Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219Gabriele Di Luozzo and Randall B. Griepp

19 The Future of Brain Protection in Cardiac Surgery. . . . . . . . . . . . . . . . 229Min Lou and Magdy Selim

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239

xiii

Contributors

Yasir Abu-Omar MBChB, DPhil, MRCS Specialist Registrar Department of Cardiothoracic Surgery, Papworth Hospital, Papworth Everard, UK

Robin Peter Alston MBChB, MD, FRCA Consultant Department of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK

Miguel F. Arango MD Anesthesiologist Department of Anesthesiology, London Health Sciences Centre, London, Ontario, Canada

Joseph E. Arrowsmith MB, BS, MD, FRCP, FRCA Consultant Department of Anaesthesia and Intensive Care, Papworth Hospital, Papworth Everard, Cambridgeshire, UK

Robert A. Baker PhD, BMedSci(Hons), Dip Perf, CCP (Aus) Director Cardiac Surgery Research and Perfusion Department of Cardiac and Thoracic Surgery, Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia

William A. Baumgartner MD Director of Cardiac Surgery Research Laboratory and The Vincent L. Gott Professor Department of Cardiac Surgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA

Martin Bendszus MD Director Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany

Sunil K. Bhudia MD, FRCS(CTh) Specialist Registrar West Midlands Cardiothoracic Rotation, Edgware, Middlesex, UK

Robert S. Bonser MD, FRCP, FRCS, FESC, FACC Professor and Consultant Cardiac Surgeon Department of Cardiothoracic Surgery, Queen Elizabeth Hospital, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, UK

Michael A. Borger MD, PhD Staff Surgeon Department of Cardiac Surgery, Leipzig Heart Center, Saxony, Leipzig, Germany

André Y. Denault MD Anesthesiologist Department of Anesthesiology, Montreal Heart Institute and Université de Montréal, Montréal, Quebec, Canada

xiv Contributors

Alain Deschamps MD, PhD, FRCPC Anesthesiologist Department of Anesthesiology, Montreal Heart Institute, Montreal, Quebec, Canada

Gabriele Di Luozzo MD Cardiothoracic Surgeon Department of Cardiothoracic Surgery, Mount Sinai School of Medicine, New York, USA

George Djaiani MD, DEAA, FRCA, FRCPC Associate Professor of Anesthesia Department of Anesthesia and Pain Management, Toronto General Hospital, UHN, University of Toronto, Toronto, Ontario, Canada

Vamsidhar B. Dronavalli MBBS, MRCS Research Fellow and Honorary Registrar Department of Cardiothoracic Surgery, Queen Elizabeth Hospital, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, UK

Maruthi S. S. R. Ganugapenta MBBS, MD(Anaesthesia), FCARCSI Clinical Fellow Department of Anaesthesia and Intensive Care, Papworth Hospital, Papworth Everard, Cambridgshire, UK

Rebecca F. Gottesman MD, PhD Assistant Professor Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Maura A. Grega MSN, CCRP Research Nurse and Program Coordinator Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA

Randall B. Griepp MD Cardiothoracic Surgeon and Director of Aortic Surgery Department of Cardiothoracic Surgery, Mount Sinai School of Medicine, New York, USA

Alina M. Grigore MD, MHS Associate Professor of Anesthesiology Department of Anesthesiology, Mayo Clinic Hospital, Phoenix, Arizona, USA

John W. Hammon MD Professor of Surgery Department of Cardiothoracic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

Deborah K. Harrington MD, MRCS Registrar Cardiothoracic Surgery Department of Cardiothoracic Surgery, Queen Elizabeth Hospital, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, UK

Marjan Jahangiri MBBS, FRCS, FRCS CTh, MS Professor of Cardiac Surgery Department of Cardiothoracic Surgery, St. George’s, University of London, London, UK

Richard A. Jonas MD Chief Children’s National Medical Center, Washington, DC, USA

Timothy J. Jones MD, FRCAS (CTh) Paediatric Cardiac Surgeon Cardiac Unit, Birmingham Children’s Hospital, Birmingham, UK

Contributors xv

Min Lou MD, PhD Assistant Professor Department of Neurology, The 2nd Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China

Guy M. McKhann MD Professor of Neurology Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA

Reza Motallebzadeh MA, MB, BChir, MRCS, MD Specialist Registrar and Wellcome Trust Clinical Research Fellow Department of Surgery, Addenbrooke’s Hospital, Cambridge, Cambridgeshire, UK

John M. Murkin MD, FRCPC Director Cardiac Anesthesiology Research, Department of Anesthesiology and Perioperative Medicine, University of Western Ontario, London, ON, Canada

Harish Ramakrishna MD, FASE Senior Associate Consultant, Section Chief Cardiothoracic Anesthesiology, Department of Anesthesiology, Mayo Clinic Arizona, Phoenix, Arizona, USA

Basel Ramlawi MD, MMSc Chief Resident Division of Cardiac Surgery, University of Western Ontario and London Health Sciences Center, London, Ontario, Canada

Aaron M. Ranasinghe MD, MRCS Clinical Lecturer Department of Cardiovascular Medicine, University of Birmingham, Birmingham, UK

Magdy Selim MD, PhD Associate Professor Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

Frank W. Sellke MD Chief Cardiothoracic Surgery Research, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Ola A. Selnes PhD Professor Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Colin Smith MB ChB, MD, FRCPath Senior Lecturer Department of Pathology, University of Edinburgh, Edinburgh, Scotland, UK

David A. Stump PhD Professor Department of Anesthesiology and Cardiothoracic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

David P. Taggart MD (Hons), PhD, FRCS Professor Cardiovascular Surgery, Nuffield Department of Surgery, University of Oxford, Headington, Oxford, UK

Eric S. Weiss MD, MPH Resident General Surgery, Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Brain Protection in Cardiac SurgeryForewordReferences

PrefaceSeries PrefaceContentsContributors