Handbook of Neurocritical Care, Second Edition

Handbook of Neurocritical Care

Anish Bhardwaj, MD, FAHA, FCCM, FAAN Marek A. Mirski, MD, PhD Editors

Handbook of Neurocritical Care Second Edition

Editors Anish Bhardwaj Chairman Department of Neurology Tufts University School of Medicine Professor of Neurology Neurological Surgery, and Neuroscience Neurologist-in-Chief Tufts Medical Center Boston, MA, USA [email protected]

Marek A. Mirski Vice-Chair, Department of Anesthesiology and Critical Care Medicine Director, Neurosciences Critical Care Division Chief, Division of Neuro Anesthesiology Director, Anesthesia Perioperative Clinical Research Program Co-Director, Comprehensive Stroke Program Professor of Anesthesiology, Neurology, Neurosurgery Johns Hopkins Medical Institutions Baltimore, MD, USA [email protected]

ISBN 978-1-4419-6841-8 e-ISBN 978-1-4419-6842-5 DOI 10.1007/978-1-4419-6842-5 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2010934376 © Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in ­connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

Foreword

Neurocritical Care is a multi-specialty multi-disciplinary field dedicated to ­improving the care and outcomes of critically ill patients with neurological conditions. It has moved the central nervous system from being an innocent bystander in the management of critically ill patients to a major player. No longer is brain function all but ignored in managing critically ill patients, but rather critical care management is focused on optimizing brain function. This shift in focus has been driven as much by advances in medical knowledge and techniques as by the vision of its practitioners such as the editors and contributors to this second edition of Handbook of Neurocritical Care. Over the past 20 years I have watched the field grow in terms of perceived need, knowledge, and acceptance across a growing number of medical specialties and disciplines. This is clearly evident in this text with contributors from the specialties of neurology, vascular neurology, neurosurgery, interventional neuroradiology, anesthesiology, and medical critical care and the disciplines of nutrition and advanced practice nursing. By bringing together this breadth of expertise to update this concise focused handbook the editors have created a tool useful to practitioners from a wide range of specialties and disciplines who care for critically ill patients. The format of this handbook lends itself to being easy to use, concise, and to the point. While it is not meant to be comprehensive, it captures the most important key points that are necessary for thoughtful clinical decision making. The tables and figures provide easy to use tools that facilitate rapid evaluation and decision making both for trainees in neurocritical care as well as for experienced practitioners in related fields. This text provides concise practical review of the current state of this rapidly emerging field. Michael N. Diringer, MD, FCCM Professor, Neurology and Neurosurgery Section Chief, Neurological Critical Care Past President, Neurocritical Care Society Washington University School of Medicine.

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Preface

In the preface to the first edition of Handbook of Neurocritical Care, we commented that neurocritical care as a subspecialty has grown rapidly over the last two decades and has reached a level of maturity with the advent of newer monitoring, diagnostic, and therapeutic modalities in a variety of brain and spinal cord injury paradigms. This growth and maturation are clearly exhibited by the emerging fellowship training programs at various facilities, the recently instituted subspecialty certification examination by the United Council for Neurologic Subspecialties, and the increasing number of critical care units around the world. These major strides in the subspecialty that are commensurate with the goals of “decade of the brain,” coupled with the emerging data from clinical series and translational research, occasions another edition of this handbook. The overarching goal of the handbook remains the same. The operative tenet continues to be that “time is brain,” and rapid diagnosis and therapeutic interventions in these challenging patients cannot be overemphasized. The care provided to this subset of critically ill neurologic and neurosurgical patients continues to be interdisciplinary and includes care rendered by colleagues in emergency medical services and emergency medicine, neurologists, neurosurgeons, anesthesiologists, critical care physicians, critical care nurses, nurse practitioners, and physician assistants. The onus lies heavily on first-line physicians and other healthcare providers for early recognition, timely therapeutic interventions, and proper referrals in patients experiencing acute neurologic deterioration. This handbook is not meant to substitute for a full-length text, rather it is intended to serve as a quick-reference guide for those involved in the care of critically ill neurologic and neurosurgical patients. In response to feedback from the readership and colleagues regarding the previous edition, the first section of this edition, which covers general principles, logically progresses into a section regarding specific problems encountered in neurocritical care. We have focused further on management algorithms for making and confirming the clinical diagnosis with appropriate ancillary radiologic and laboratory tests and algorithms for managing acute neurologic diseases. Tables and illustrations provide quick and easy bedside reference. At the end of each chapter, key points and references highlight essential elements and should serve as quick summaries of salient features. We hope that this second edition of the handbook

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continues to provide a succinct and practical approach to the management of the critically ill patient population that we serve. We are indebted to the authors for their valuable contributions and thank Tzipora Sofare, MA, for lending her exceptional editorial skills. We would also like to particularly express our thanks to the Johns Hopkins Clinician Scientist Program, the American Heart Association, the National Stroke Association, and the National Institutes of Health extramural programs; their support has helped to advance our investigative work, aided in the establishment of fellowship training programs in neurosciences critical care, and augmented the much needed advancement of this field. Anish Bhardwaj, MD, FAHA, FCCM, FAAN Marek A. Mirski, MD, PhD

Special Introduction

This second edition of the Handbook of Neurocritical Care is a major revision of the first edition that appeared in 2004. As pointed out by the editors, since that time this field has grown and matured to include many more training fellowships as well as recent sub-specialty certification by the United Council for Neurologic Subspecialties. This handbook has also progressed forward: an expanded yet handy and easy to use reference manual for the management of patients with life threatening neurologic and neurosurgical illnesses. As in the first edition, all of the chapters are made up of bulleted teaching points followed by a list of Key Points and important references allowing for the rapid access to vital information critical for rapid and timely decision making. A major addition to the volume is the first section which covers a myriad of important general principles such as electrolyte derangements, fever and infection, cerebral blood flow, cerebral edema, brain and cardiovascular monitoring, ventilatory management, and sedation and analgesia to mention only a few. The second section covers the major diagnostic categories of neurocritical care with several new topics including neuroleptic malignant syndrome and malignant hyperthermia, meningitis and encephalitis, and intraventricular hemorrhage. Useful algorithms, tables, and illustrations throughout the book assist the decision making process. Whereas most of the contributors to the first edition were colleagues of the editors at the Johns Hopkins Hospitals, an impressive array of new authors has been added from all over the country reflecting the broad scope of this subspecialty. This handbook covers the current state of the art concisely and completely and should find itself into critical care units everywhere. It serves as a useful complement to other monographs in the Humana Press Current Clinical Neurology series such as Critical Care Neurology and Neurosurgery by Jose Suarez, Seizures in Critical Care by Panayiotis Varelas, and Status Epilepticus by Frank Drislane. This second edition is published by Springer, the new parent company of Humana Press. All books in the series can be found at www.springer.com. Daniel Tarsy, MD Professor Neurology Harvard Medical School Vice Chair, Department of Neurology Beth Israel Deaconess Medical Center ix

Contents

Part I  General Principles of Neurocritical Care   1 Establishing and Organizing a Neuroscience Critical Care Unit........ Marek A. Mirski

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  2 Electrolyte and Metabolic Derangements.............................................. Nikki Jaworski and Ansgar Brambrink

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  3 Fever and Infections................................................................................. Neeraj Badjatia

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  4 Cerebral Blood Flow and Metabolism: Physiology and Monitoring........................................................................................ Jeremy Fields and Anish Bhardwaj

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  5 Multimodality Monitoring in Acute Brain Injury................................ Kristine H. O’Phelan, Halinder S. Mangat, Stephen E. Olvey, and M. Ross Bullock

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  6 Cerebral Edema and Intracranial Hypertension.................................. Matthew A. Koenig

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  7 Cardiac Dysfunction, Monitoring, and Management........................... Andrew Naidech

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  8 Airway Management and Mechanical Ventilation in the NCCCU.......................................................................................... Paul Nyquist

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  9 Blood Pressure Management.................................................................. 115 Ameer E. Hassan, Haralabos Zacharatos, and Adnan I. Qureshi 10 Nutrition in Neurocritical Care.............................................................. 123 Tara Nealon xi

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11 Sedation, Analgesia, and Neuromuscular Paralysis............................. 145 Marek A. Mirski 12 Postoperative Care................................................................................... 173 W. Andrew Kofke and Robert J. Brown 13 Care Following Neurointerventional Procedures.................................. 217 Yahia M. Lodi, Julius Gene Latorre, Jesse Corry, and Mohammed Rehman 14 Ethical Issues and Withdrawal of Life-Sustaining Therapies............. 247 Wendy L. Wright 15 Collaborative Nursing Practice in the Neurosciences Critical Care Unit.................................................................................... 265 Filissa M. Caserta Part II  Specific Problems in Neurocritical Care 16 Coma and Disorders of Consciousness.................................................. 277 Edward M. Manno 17 Acute Encephalopathy............................................................................. 287 Robert D. Stevens, Aliaksei Pustavoitau, and Tarek Sharshar 18 Traumatic Brain Injury........................................................................... 307 Geoffrey S.F. Ling and Scott A. Marshall 19 Acute Myelopathy.................................................................................... 323 Angela Hays and Julio A. Chalela 20 Ischemic Stroke........................................................................................ 341 Neeraj S. Naval and Anish Bhardwaj 21 Intracerebral Hemorrhage...................................................................... 353 Neeraj S. Naval and J. Ricardo Carhuapoma 22 Intraventricular Hemorrhage................................................................. 365 Kristi Tucker and J. Ricardo Carhuapoma 23 Subarachnoid Hemorrhage..................................................................... 371 Eric M. Bershad and Jose I. Suarez 24 Brain Injury Following Cardiac Arrest................................................. 389 Romergryko G. Geocadin

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25 Meningitis and Encephalitis.................................................................... 409 Barnett R. Nathan 26 Cerebral Venous Sinus Thrombosis....................................................... 421 Agnieszka A. Ardelt 27 Neuroleptic Malignant Syndrome, Malignant Hyperthermia, and Serotonin Syndrome......................................................................... 435 Panayiotis N. Varelas and Tamer Abdelhak 28 Brain Tumors .......................................................................................... 445 Sherry Hsiang-Yi Chou 29 Hydrocephalus.......................................................................................... 469 Michel T. Torbey 30 Neuromuscular Disorders....................................................................... 475 Jeremy D. Fields and Anish Bhardwaj 31 Status Epilepticus..................................................................................... 489 Marek A. Mirski 32 Deep Venous Thrombosis and Pulmonary Embolism.......................... 505 Wendy C. Ziai 33 Neurocritical Illness During Pregnancy and Puerperium.................... 523 Chere Monique Chase and Cindy Sullivan 34 Brain Death and Organ Donation.......................................................... 533 Alexander Y. Zubkov and Eelco F.M. Wijdicks Index.................................................................................................................. 541

Contributors

Tamer Abdelhak  Departments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, MI, USA Agnieszka A. Ardelt University of Chicago, Departments of Neurology and Surgery (Neurosurgery), Division of Neurocritical Care, 5841 South Maryland Ave MC2030, Chicago, IL 60637, USA Neeraj Badjatia Departments of Neurology and Neurosurgery, Columbia University, New York, NY 10032, USA Eric M. Bershad Department of Neurology, Baylor College of Medicine, One Baylor Plaza, MS NB302, Houston, TX 77030, USA Anish Bhardwaj Department of Neurology, Tufts University School of Medicine, Tufts Medical Center, Box 314, 800 Washington Street, Boston, MA 02111, USA Ansgar Brambrink Department of Anesthesiolgy, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA Robert J. Brown Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA M. Ross Bullock Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

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J. Ricardo Carhuapoma Neurosciences Critical Care Division, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA Filissa M. Caserta Neurosciences Critical Care Unit, Johns Hopkins University School of Medicine, 600 N. Wolfe Street - Meyer 8-140, Baltimore, MD 21287-7840, USA Julio A. Chalela Medical University of South Carolina, PO BOX 250606, Charleston, SC 29425, USA Chere Monique Chase Forsyth Comprehensive Neurology, 2025 Frontis Plaza Boulevard, Greystone Professional Center, Suite 102, Winston-Salem, NC 27103, USA Sherry Hsiang-Yi Chou Division of Critical Care Neurology and Cerebrovascular Diseases, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA Jesse Corry Upstate Medical University, Syracuse, NY, USA Jeremy D. Fields Department of Neurology, Oregon Health and Science University, Portland, OR, USA Romergryko G. Geocadin Division of Neuroscience Critical Care, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA Ameer E. Hassan Zeenat Qureshi Stroke Research Center, Department of Neurology, University of Minnesota, Minneapolis, MN Angela Hays Medical University of South Carolina, Charleston, SC, USA Nikki Jaworski Department of Anesthesia and Peri-operative Medicine, Oregon Health and Science University, Portland OR Matthew A. Koenig Associate Medical Director of Neurocritical Care, The Queen’s Medical Center, Neuroscience Institute–QET5, 1301 Punchbowl Street, Honolulu, HI 96813, USA

Contributors

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W. Andrew Kofke Departments of Anesthesiology and Critical Care, Department of Neurosurgery, Hospital of the University of Pennsylvania, 3400 Spruce Street - 7 Dulles, Philadelphia, PA 19104, USA Julius Gene Latorre Neurosciences Critical Care Unit and Neurocritical Care Fellowship Program, Upstate Medical University, Syracuse, NY, USA Geoffrey S.F. Ling Critical Care Medicine for Anesthesiology and Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd. Bethesda, MD 20814, USA Yahia M. Lodi Division of Cerebrovascular Program and Services, Vascular/Neurological Critical Care Neurology and Envovascular Surgical Neuroradiology, Upstate Medical University and University Hospital, SUNY, NY and Department of Neurology, 813 Jacobsen Hall, 750 East Adams Street, Syracuse, NY 13210, USA Halinder S. Mangat Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA Edward M. Manno Mayo Clinic School of Medicine, 200 First St. SW, Rochester, MN 55905, USA Scott A. Marshall Uniformed Services University of the Health Science, Bethesda, MD, USA Marek A. Mirski Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA Andrew Naidech Department of Neurology, Northwestern University, Feinberg School of Medicine, Neuro/Spine ICU, Northwestern Memorial Hospital, Chicago, IL 60611-3078, USA Barnett R. Nathan Department of Neurology and Internal Medicine, University of Virginia School of Medicine, PO Box 800394, Charlottesville, VA 22908, USA Neeraj S. Naval Neurosciences Critical Care Fellowship Program, Oregon Health and Science University, Portland, OR, USA

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Contributors

Tara Nealon Johns Hopkins University School of Medicine, Baltimore, MD, USA Paul Nyquist Department of Neurology, Anesthesiology and Neurological Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street – Phipps 126, Baltimore, MD 21287, USA Stephen E. Olvey Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA Kristine H. O’Phelan Assistant Professor Director of Neurocritical Care Department of Neurology, University of Miami Miller School of Medicine, Miami, FL Tarek Sharshar Hospital Raymond Poincare, University of Versailles, Versailles, France Robert D. Stevens Neurosciences Critical Care Division, Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Division of Neurosciences Critical Care, 600 North Wolfe Street - Meyer 8-140, Baltimore, MD 21287, USA Jose I. Suarez Department of Neurology, Baylor College of Medicine, One Baylor Plaza, MS NB302, Houston, TX 77030, USA Kristine H. O’Phelan Department of Neurology, University of Miller School of Medicine, Miami, FL, USA Kristi Tucker Departments of Neurology and Anesthesiology/Critical Care, Wake Forest University Health Sciences, Winston-Salem, NC, USA Panayiotis N. Varelas Departments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, MI, USA Aliaksei Pustavoitau Johns Hopkins University School of Medicine, Baltimore, MD, USA

Contributors

Adnan I. Qureshi Zeenat Qureshi Stroke Research Center, Department of Neurology, University of Minnesota, Minneapolis, MN Mohammed Rehman Department of Neurology, Upstate Medical University, Syracuse, NY, USA Cindy Sullivan Neurocritical Care Program, Novant Health Systems, Forsyth Medical Center, Winston-Salem, NC, USA M.T. Torbey Department of Neurological Surgery and Neurology, Medical College of Wisconsin, Department of Neurology, 9200 W.Wisconsin Avenue, Milwaukee, WI 53226, USA Eelco F.M. Wijdicks Department of Neurology and Neurological Surgery, Mayo Clinic School of Medicine, 200 First Street SW, Rochester, MN 55905, USA Elco A. Widjicks Professor of Neurology Chair, Division or Critical Care Neurology Mayo Clinic and Mayo College of Medicine, Rochester, MN Wendy L. Wright Emory University School of Medicine, 1365B Clifton Rd., NE, Ste. 6200, Atlanta, GA 30322, USA Haralabos Zacharatos Zeenat Qureshi Stroke Research Center, Department of Neurology, University of Minnesota, Minneapolis, MN Wendy C. Ziai Department of Neurology and Neurological Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street – Meyer 8-140, Baltimore, MD 21287, USA Alexander Y. Zukbov Stroke Center, Fairview Southdale Hospital, Minneapolis Clinic of Neurology, Rochester, MN, USA

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Part I

General Principles of Neurocritical Care

Chapter 1

Establishing and Organizing a Neuroscience Critical Care Unit Marek A. Mirski

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Goals and benefits for subspecialty neuroscience critical care unit (NCCU) ♦ Focused specialty care for unique ICU population ♦ Special expertise required by professionals in NCCU – neuroscience ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

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background Greater case efficiency of neurosurgical and neurointerventional cases Efficient ICU management Hub of clinical neuroscience communication Academic clinical neuroscience concentration Hospital hub for stroke, acute brain, and spinal cord injury centers Neurocritical-trained nursing Cohesive and comprehensive rounds Neurologic monitoring – capable and savvy Sensitive neurologic evaluations Precisely match therapeutics to neurologic pathophysiology Shorter lengths of stay (LOS) for patient in both the ICU and hospital Improved patient outcomes Increased regional referral network Enhanced marketing strategy

NCCU requires consensus-driven support from medical center ♦ ♦ ♦ ♦ ♦

Medical center administration Neurology Neurosurgery Radiology Anesthesiology

M.A. Mirski, MD, PhD (*) Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_1, © Springer Science+Business Media, LLC 2011

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Probable conflicts must be defined and respected; strategies to overcome conflicts must be defined ♦ ♦ ♦ ♦ ♦ ♦

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Administrative and political goals of medical center Other ICU environments – patient selection processes Territorial issues within medical center Potential increase in cost of care per patient Sacrifice in overall ICU bed efficiency Dilution of ICU intensivist coverage pool; more resources are required by medical center

Physician argument for an NCCU ♦ Lines of evidence for improvement in patient outcomes

• Several published reports in neurologic and neurosurgical ICU patient populations • Neurology – for intracranial hemorrhage (ICH), data has been published that compared general ICU care versus NCCU; Cumulative survival enhanced in NCCU (Fig. 1.1) • Patients with ischemic stroke – data demonstrates reduced ICU and hospital LOS and improved the disposition of patients • Patients with ICH, improvement in outcome as defined by percent of mortality, percent to home, and rehabilitation versus nursing home, despite lower Glasgow Coma Scale score in comparative grouping in NCCU versus general ICU (Fig. 1.2)

Fig. 1.1  Cumulative survival curve demonstrating a benefit in lower mortality of patients suffering from acute intracerebral hemorrhage that are admitted to and cared for in a neuroscience speciality critical care unit. There is approximately an additional 10 percent survival benefit after a 10 day ICU length of stay. Data from Diringer 2001

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Fig. 1.2  Comparative hospital outcome data from patients with intracerebral hemorrhage (ICH) treated in general medical-surgery intensive care unit (ICU) versus a neuroscience subspecialty ICU (NSICU). GCS = Glasgow Coma Scale score; Rehab = rehabilitation; LOS = total hospital length of stay; SEM = standard error of the mean. Data from Mirski 2001

♦ Improvement in ICU efficiency of care and ICU LOS

• Shorter ICULOS leads to reduction in cost and increased case-load profitability • For neurology patients, reduction of LOS from 4.2 ± 4.0 to 3.7 ± 3.4 following development of an NCCU; another series reports a reduction in LOS to 2.0 ± 0.9 NCCU days compared to 3.0 ± 0.2 for comparable patients in MICU • For neurosurgery patients, LOS post-craniotomy for tumor and traumatic brain injury reduced post-implementation of specialty NCCU compared to general surgical ICU model of care: (DRG 001-craniotomy; DRG 002-; DRG 027-; DRG 028-) (Fig. 1.3) ■

Hospital argument for NCCU ♦ Improvement in ICU efficiency of care and cost of care

• Subspecialty intensivist can minimize cost of services due to recognition of patient condition and diagnoses based on precise and focused examination and interpretation of findings; e.g., reduction of imaging requisitions and lower cost of pharmaceuticals can be expected with expertise at bedside (Fig. 1.4) • Further subdivision among costs for imaging studies, pharmacy, and laboratory testing found reduction across all aspects of clinical management

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Fig. 1.3  National database [HBS International, Inc. (HBSI, Bellevue, WA)] comparative difference (%) in ICU length of stay from the benchmark standard (0 on axis) for neuroscience subspecialty ICU (NSICU) care and other hospital areas (Non-NSICU areas included acute care ward, telemetry unit, and general medical/surgical intensive care unit [ICU]) for principal neurosurgery severity adjusted Adjacent Patient Related Groups (A-DRGs). The cohort size ranged from 20 (A-DRG 028, NSICU) to 152 (A-DRG 001, NSICU). Each care area (ward, ICU, telemetry unit) is compared with its own national benchmark standard. A-DRGs 001 and 002 = craniotomy with or without intracerebral hemorrhage or coma; A-DRGs 027 and 028 = skull fracture with and without hemorrhage or coma; SEM = standard error of the mean. Data from Mirski, 2001

♦ Improvement in ICU efficiency of care and documentation

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• Data from a sampling of records with three diagnoses: traumatic brain injury, ICH, and subarachnoid hemorrhage – pre- and post-appointment of neurointensivist • Documentation improved from 32.5 to 57.5% [Odds Ratio 2.8; 95% Confidence Interval (CI), 1.9–4.2] in the after period; documentation using Glasgow Coma Scale, clot volume, Hunt & Hess scale, and Fisher grade also improved significantly in each of the diagnoses examined in the after period Nationally – Studies by Leapfrog Group support neurointensivists ♦ ICU data clearly demonstrate decreased mortality in intensivist-run ICU

model • Leapfrog group examined nine published studies on intensivist-driven ICU care and found that relative reductions in mortality rates associated with intensivist-model ICUs ranged from 15 to 60% • Leapfrog Group conclusion – using a conservative estimate of effectiveness (15% reduction), full implementation of intensivist-model ICUs would save ~53,850 lives each year in the US

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Fig.  1.4  National database [HBS International, Inc. (HBSI, Bellevue, WA)] comparative difference in cost per case in US dollars ($, fiscal year 1997) from the benchmark standard (0 on axis) for neuroscience subspecialty ICU (NSICU) care and non-NSICU hospital areas for principal neurosurgery severity adjusted Adjacent Patient Related Groups (A-DRGs). Each care area (ward, intensive care unit, telemetry unit) is compared with its own national benchmark standard. A-DRGs 001 and 002 = craniotomy with or without intracerebral hemorrhage or coma; A-DRGs 027 and 028 = skull fracture with and without hemorrhage or coma; SEM = standard error of the mean. Data from Mirski, 2001

♦ Further evidence

• A meta-analysis of 26 relevant observational studies of alternative staffing strategies revealed that high-intensity staffing was associated with a lower ICU mortality, with a pooled estimate of the relative risk for ICU mortality of 0.61 (95% CI, 0.50–0.75) • High-intensity staffing reduced hospital LOS in 10 of 13 studies and reduced ICU LOS in 14 of 18 studies without case-mix adjustment ♦ Neurointensivists – Support of staffing models and Leapfrog key standards

(http://www.leapfroggroup.org/media/file/Leapfrog) • Intensivists are present in the ICU during daytime hours 7 days/week, with no other clinical duties during this time • Return >95% of pages within 5 min • Rely on a physician (e.g., fellow or resident) or nonphysician extender who is in the hospital and able to reach ICU patients in <5 min during non-daylight hours

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Fig. 1.5  Hospital savings from implementation of The Leapfrog Group's Intensive Care Unit Physician Staffing standard. Savings are presented across 6-, 12-, and 18 bed intensive care units (ICUs). Increasing savings across larger ICUs are demonstrated based on conservative assumptions (squares) and the best-case scenario (triangles) sensitivity analysis. Comparatively small net costs are demonstrated for the worst-case scenario (diamonds) sensitivity analysis. Data from Pronovost 2006

♦ Cost savings of intensivist coverage

• Data demonstrate intensivist coverage renders considerable savings to medical center • Neurointensivists offer additional ICU staffing options for hospital in providing necessary expertise to critical care • Survey and analysis suggest savings across 6-, 12-, and 18-bed ICU designs (Fig. 1.5) ♦ Leapfrog ramification: Further need for additional intensivists

• US hospitals manage 5,980 US ICUs; ~55,000 patients/day p p p p p p

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Non-teaching, community hospitals (n = 4,245; 71% of hospitals) Hospitals of <300 beds (n = 3,710; 62%) Combined medical-surgical ICUs (n = 3,865; 65%) One in four ICUs are described as “high-intensity” (n = 1,578; 26%) Half have no intensivist coverage (n = 3,183; 53%) Remainder have some intensivist presence (n = 1,219; 20%)

Key components to NCCU successful staffing model ♦ Specialty-trained neurointensivists

• 2-Year accredited fellowship

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• Ideal: three intensivists for 8–12-bed NCCU; intensivists perform academic activity or other non-ICU clinical duty 2 of 3 weeks • On-service 1–2 weeks per shift; 24/7 responsibility most common current format • If one neurointensivist: typical model is as hospital/ICU consultant • Two neurointensivists: minimum to establish functional unit and offer 24/7 schedule • >3 Neurointensivists – provide opportunities for advanced academics or expanded clinical function – stroke unit, intermediate care unit coverage, neurology or neurosurgery hospitalist function ♦ Closed unit design

• Using several metrics of staffing and outcomes (see below), closed ICU model has been demonstrated to be more effective • 10–14 ICU beds considered ideal range for ICU physician management ♦ Specialty-trained NCCU nursing

• • • •

Expertise with neurologic examination Detect subtle neurologic findings consistent with deteriorating exam Comprehend and administer neurologically specialized therapeutics Familiar with long-term functional outcomes, accept patience in clinical management • Intelligent patient and family interaction; allay concerns and fears of difficult concepts inherent in neurologic disease ♦ ICU point-of-care pharmacist

• Important for patient safety and for cost savings (see below) ♦ Major recommendations from National Guideline Clearinghouse, US govern-

ment scientific review • Grades of Evidence (I–V) and Levels of Recommendations (A-E) are defined at the end of the Major Recommendations field (http://www. guideline.gov) p

p

p

p

p

Literature does not clearly support one model of critical care delivery over another Dedicated ICU personnel, specifically the intensivist, the ICU nurse, respiratory care practitioner, and pharmacist, all work as a team Multidisciplinary group-practice model should be led by a full-time critical care-trained physician who is available in a timely fashion to the ICU 24 h/day (Grade D recommendation) While leading the critical care service, the intensivist physician should have no competing clinical responsibilities (Grade E recommendation) ICUs with an exclusive critical care service and operating in the closed format, as described previously, may have improved outcomes; when

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p

p

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geographic constraints, resource limitations, and manpower issues allow, this organizational structure for the delivery of critical care services may be optimal (Grade E recommendation) The presence of a pharmacist as an integral part of the ICU team, including but not limited to making daily ICU rounds, improves the quality of care in the ICU and reduces errors; integration of a dedicated pharmacist into the ICU team is recommended (Grade C recommendation). Physician practitioners in the ICU should have hospital credentials to practice critical care medicine; these credentials should incorporate both cognitive and procedural competencies (Expert opinion)

Revenue sources ♦ Clinical ICU Professional Fee for typical ICU codes

• • • •

Critical care – 99291, 99292 Subsequent care – 99231–3 Consult codes Admission H&P (if attending physician)

♦ Clinical Procedural Fees for common procedures:

• • • • • • • • •

Arterial catheter Central venous catheter (>5 years age) Endotracheal intubation Lumbar puncture Pulmonary artery catheter Fiberoptic bronchoscopy and lavage CSF drainage/irrigation Transcranial-Doppler procedure and professional reading Other less common – chest tube, tracheostomy change, EEG report

♦ Academic support

• • • •

Clinical trial grants Investigator-initiated, industry-supported clinical studies Government grants (NIH RO1, R21, SBIR, others) Institutional awards

♦ Joint agreement – NCCU and hospital

• ICU supports efficiency in ICU resources, beyond professional fee; Argument used in support of data demonstrating improvement in LOS and patient outcomes (hence lower total cost of care), reduced hospital resource utilization, and higher turnover enabling greater case load per ICU bed ♦ Transcranial-Doppler and ultrasound laboratory for centers certified by the

Intersocietal Commission for the Accreditation of Vascular Laboratories

1  Establishing and Organizing a Neuroscience Critical Care Unit ■

Costs ♦ ♦ ♦ ♦

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Intensivist compensation package Nurse practitioner (possible) Nursing training for specialty nursing staff NCICU specialty equipment as needed – EEG, cranial Doppler, etc.

Overall hospital financial analysis ♦ Professional fees may but may not cover salary requirements

• Highly dependent on patient demographics (private insurance, Medicare, Medicaid) • Complexity of admissions – ICU procedural fees • ICU patient rate of turnover (LOS) ♦ However, hospital revenue based on income from:

• Hospital stay – often DRG based and under federal, state, or local regulated rates of return per DRG • Income from surgical and interventional procedures • Complexity of admissions – APR-DRG-based coding ♦ Hospital improves revenue to cost ratio by:

• • • • •

Lower LOS per each DRG; hence, from improved ICU efficiency Lower cost per patient day Fewer medical complications Solid referral pattern for high reimbursement DRGs and procedures Increase in high complexity procedures (operations, etc.) per ICU bed due to higher turnover potential by specialty neurointensivist-managed ICU

Key Points ■

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Neurointensivist-managed NCCU offers expertise to provide improved outcome with lower cost/patient and ICU LOS This model has historically been financially beneficial to hospital administration, despite increase in medical center ICU physician pool

Suggested Reading Angus DC, Shorr AF, White A et al. (2006) Committee on Manpower for Pulmonary and Critical Care Societies (COMPACCS).Critical care delivery in the United States: distribution of services and compliance with Leapfrog recommendations. Crit Care Med 34:1016–1024 Diringer MN, Edwards DF, Aiyagari V, Hollingsworth H (2001) Factors associated with withdrawal of mechanical ventilation in a neurology/neurosurgery intensive care unit. Crit Care Med 29:1792–1797

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Mirski MA, Chang CW, Cowan R (2001) Impact of a neuroscience intensive care unit on neurosurgical patient outcomes and cost of care: evidence-based support for an intensivist-directed specialty ICU model of care. J Neurosurg Anesthesiol 13:83–92 Pronovost PJ, Angus DC, Dorman T et al. (2002) Physician staffing patterns and clinical outcomes in critically ill patients: a systematic review. JAMA 288:2151–2162 Pronovost PJ, Needham DM, Waters H et al. (2006) Intensive care unit physician staffing: financial modeling of the Leapfrog standard. Crit Care Med 34:S18–S24 Suarez JI, Zaidat OO, Suri MF et  al. (2004) Length of stay and mortality in neurocritically ill patients: impact of a specialized neurocritical care team. Crit Care Med 32:2311–2317 Varelas PN, Spanaki MV, Hacein-Bey L (2005) Documentation in medical records improves after a neurointensivist’s appointment. Neurocrit Care 3:234–236 Varelas PN, Schultz L, Conti M et al. (2008) The impact of a neuro-intensivist on patients with stroke admitted to a neurosciences intensive care unit. Neurocrit Care 9:293-299 Young MP, Birkmeyer JD (2000) Potential reduction in mortality rates using an intensivist model to manage intensive care units. Eff Clin Pract 3:284–289

Chapter 2

Electrolyte and Metabolic Derangements Nikki Jaworski and Ansgar Brambrink

Acid – Base Disorders ■ ■

■

Acid – base disorders are very common in the NCCU The normal pH range is 7.35–7.45; alkalosis is defined as pH >7.45, and acidosis is defined as pH <7.35 pH is a measure of the hydrogen ion concentration in the extracellular fluids and is determined by the pCO2 and HCO3 concentration ♦ [H2] (meq/L) = 24 × (PCO2/HCO3)

■

■

■

■

The initial change in PCO2 or HCO3 is called the primary disorder; the subsequent change is called the compensatory or secondary disorder Compensatory changes frequently will not return the pH to the normal range but will serve to limit the effect of the primary derangement Acid – base disorders are of particular concern in neurophysiology because of their effects on cerebral blood flow (CBF) Acidosis (decrease in pH) results in cerebral vasodilation, whereas alkalosis (increase in pH) results in cerebral vasoconstriction ♦ As pH increases, cerebral vasoconstriction also increases, resulting in

decreased CBF and therefore decreased cerebral blood volume and ICP ■

■

Changes in acid – base status within the blood are transmitted across the bloodbrain barrier (BBB) via CO2 rather than by H+ ions; the BBB is impermeable to H+, but CO2 crosses freely The subsequent change in the CSF pH is a result of the conversion of CO2 + H2O to H+ and HCO3 by carbonic anhydrase

N. Jaworski, MD Department of Anesthesia and Peri-operative Medicine, Oregon Health and Science University, Portland OR A. Brambrink, MD (*) Department of Anesthesiolgy, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_2, © Springer Science+Business Media, LLC 2011

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N. Jaworski and A. Brambrink

The pH of the CSF returns to normal after 6–8 h, as HCO3 is either retained or extruded across the BBB despite ongoing hyper- or hypocapnia, respectively As the CSF pH returns to normal, CBF also trends toward normal

Primary Acid: Base Disorders ■

Respiratory acidosis – increased PaCO2 ♦ Compensation – subsequent increase in HCO3 ♦ Neurologic consequence

• CBF increases 1–2 mL/100 g/min for each 1 mmHg change in PaCO2 within the PaCO2 range of 20–80 mmHg • Hypoventilation and hypercapnia can exacerbate an already elevated intracranial pressure in a patient with cerebral edema ♦ Etiology

• Hypoventilation • Increased CO2 production from hypermetabolic state such as hyperthermia, fever, or seizures • Decreased cardiac output, resulting in accumulation of CO2 in blood and tissues ■

Respiratory alkalosis – decreased PCO2 ♦ Compensation – subsequent decrease in HCO3 ♦ Neurologic consequence

• CBF decreases 1–2 mL/100 gm/min for each 1 mmHg change in PaCO2 within the PaCO2 range of 20–80 mmHg • Decreased CBF due to hypocapnia/hyperventilation can be detrimental to brain tissue that is already suffering from ischemia ♦ Hyperventilation can be a useful method for temporarily decreasing CBF and

ICP in patients at risk for impending herniation ♦ Etiology

• Hyperventilation ■

Metabolic acidosis – decreased HCO3 ♦ Compensation – subsequent decrease in PaCO2 (hyperventilation) ♦ Neurologic consequence

• Primarily a result of the compensatory change in PaCO2 • Hypoxia (PaO2 <60 mmHg) rapidly increases CBF most likely due to cerebral vasodilation induced by lactic acid ♦ Differential includes anion gap vs. non-anion gap

2  Electrolyte and Metabolic Derangements

15

♦ Anion gap = Na – (Cl− + HCO3) = 12 (±4)

• Most of the normal anion excess is due to albumin ♦ An elevated anion gap is due to the addition of fixed anions

• Lactic acid, ketoacidosis, end-stage renal failure, methanol, ethanol, salicylate toxicity ♦ A normal anion gap acidosis is due to a net gain in chloride ions

• Diarrhea, early renal insufficiency, resuscitation with isotonic or hypertonic saline, renal tubular acidosis, acetazolamide ■

Metabolic alkalosis – increased HCO3 ♦ Compensation – subsequent increase in PCO2 (hypoventilation) ♦ Neurologic consequence

• Again, this is primarily due to the compensatory change in PaCO2, resulting in increased CBF ♦ Etiology

• Administration of NaHCO3 • Contraction alkalosis from overdiuresis (kidney retains HCO3 ions to maintain electrical neutrality while losing Cl- ions) • Any time the loss of chloride ions exceeds the loss of sodium ions (nasogastric suctioning)

Electrolyte Disorders ■

■ ■

■

Electrolyte disorders are common and important in any critically ill patient and are of particular concern in patients with CNS disturbances They may occur as a part of the disease process, or they may be iatrogenic If unrecognized or persistently severe, the consequences of electrolyte derangement may become life threatening Sodium ♦ Sodium cannot move freely across cell membranes and is the primary deter-

minant of tonicity or effective osmolarity ♦ Isosmotic solutions have the same number of dissolved particles, regardless

of the amount of water that would flow across a given membrane barrier • In contrast, solutions are isotonic when they would not cause water to move across a membrane barrier, regardless of the number of particles dissolved • Example – 150 mM NaCL added to plasma is approximately isosmotic & isotonic to brain, and little water is therefore passed between plasma and brain.

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N. Jaworski and A. Brambrink

• 150 mM alcohol in water, however, is isosmotic but hardly isotonic (it is quite hypotonic), as it readily passes into brain, with water also following, thus promoting edema ♦ Tonicity is the primary determinant of total body water as well as the distribu-

tion of body water between the intracellular and extracellular compartments • Hypernatremia and hyponatremia are disorders of water balance rather than disorders of sodium balance because it is the movement of water between the intra- and extracellular compartments that results in the change in serum sodium concentration • For any given serum sodium concentration (hypo-, eu-, hypernatremia), the actual amount of total body sodium may be low, normal, or high, which means that each state can actually be a hypo-, iso-, or hypertonic state, respectively ♦ During normal homeostasis, total body water is tightly coupled to total body

sodium; for example, an excess of total body sodium (eating a really salty meal) results in the kidneys retaining more free water, and thus eunatremia is maintained; however, in some disease states, the body’s compensatory mechanisms become disturbed and unable to fully compensate for sodium and water losses or gains • These states result in an uncoupling of total body water and sodium such that volume status must be assessed by physical exam independently of total body sodium and sodium concentration ♦ Some states are very common; others are very unlikely to occur, while others

are iatrogenic ■

Hyponatremia ♦ Defined as serum sodium <135 meq/L ♦ Hyponatremia always represents an excess of free water relative to sodium ♦ Hyponatremia in the neurocritical care patient most frequently occurs due to

inappropriate water retention or inappropriate sodium + water loss • Normal sodium stores – gain of free water with only minimal changes in sodium ▲

▲

▲ ▲

Hyperglycemia – non-sodium osmoles (glucose) in the extracellular fluid draw water from the intracellular space, creating hyponatremia; each 100 mg/dL glucose over 100 results in an approximate 1.6 meq/L decrease in serum sodium, representing a hypertonic state Azotemia – excess urea can result in an increase in total body water, leading to hyponatremia; however, as urea moves freely across cellular membranes this is actually an isotonic state Psychogenic polydipsia Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

2  Electrolyte and Metabolic Derangements

17

N ADH is normally secreted when an increase in plasma osmolarity is

detected by the hypothalamus or a decrease in plasma volume is detected by the peripheral and central baroreceptors N ADH secretion is considered inappropriate when the above criteria are not present or when it is secreted in the setting of low serum osmolarity N Findings include Urine is inappropriately concentrated (>100 mOsm/kg H2O) Urine volume will be normal or low Plasma is hypotonic (<280 mOsm/kg H2O) Patients demonstrate normal sodium handling by the kidneys, and urine sodium excretion remains >20 meq/L ° Extracelluar fluid volume remains normal or slightly elevated ° ° ° °

N Etiology ° Exact etiology is unclear ° SIADH may be associated with brain tumors, subarachnoid hemor-

rhage (SAH), traumatic brain injury, stroke, meningitis or encephalitis, or may be drug induced (e.g., carbamazapine) N Other reasons for excessive ADH secretion must be ruled out; e.g.,

hypothyroidism, mineralocorticoid insufficiency, hypotension, hypovolemia, positive-pressure ventilation, pain, stress, or lung malignancy • Low sodium stores – loss of sodium is greater than loss of water ▲

▲

▲

Diuretic overuse or diarrhea/vomiting followed by volume replacement with free water Adrenal insufficiency – decreased ACTH (adrenocorticotropic hormone) secretion or primary insufficiency (Addison disease), resulting in insufficient release of mineralocorticoid (aldosterone) Cerebral salt wasting (CSW) – a special form N Characterized by excessive sodium loss accompanied by excess

water loss; most likely due to impaired sodium reabsorption in the proximal renal tubule ° Theories are plentiful, but the impaired sodium reabsorption may

be due to decreased sympathetic input to the kidneys or due to the release of natriuretic peptides, such as brain natriuretic peptide, by injured brain N Laboratory evaluation is similar to that for SIADH, with exception

of extracellular fluid volume ° ° ° °

Urine volume will be normal or high Plasma is hypotonic (<280 mOsm/kg H2O) Urine sodium excretion remains >20 meq/L Extracellular fluid volume becomes increasingly depleted

18

N. Jaworski and A. Brambrink N Primary distinguishing features between CSW and SIADH are pres-

ence of hypovolemia and a negative sodium and fluid balance N CSW shares many of the same associated disease states as SIADH;

recent evidence suggests that many conditions previously thought to be associated with SIADH such as meningitis, SAH, TBI, and pituitary surgery are more likely to be associated with CSW due to the presence of hypovolemia N Restoration of a positive sodium balance requires the infusion of hypertonic saline and may require the use of fludrocortisone, a synthetic mineralocorticoid N SAH ° Hyponatremia is the most common and severe electrolyte abnor-

mality after SAH ° Hypovolemia and hyponatremia are likely due to CSW and occur

2–10 days after aneurysm rupture; they are frequently associated with cerebral vasospasm and are particularly concerning, as they further increase the risk of delayed cerebral ischemia • High sodium stores – excess of sodium and water, with the water gain exceeding the sodium gain ▲

Cardiac, renal, or hepatic failure

♦ Neurologic manifestations

• Symptoms usually do not develop until serum sodium drops to <120 meq/ dL; however, a rapid decrease in serum sodium concentration is more likely to be symptomatic than chronic hyponatremia • Symptoms include headache, anorexia, nausea, vomiting, malaise, confusion, or lethargy • If untreated, symptoms may progress to metabolic encephalopathy associated with cerebral edema, elevated ICP, and tonic-clonic seizures • As extracellular hypotonicity develops, water shifts intracellularly to reestablish equilibrium (cellular edema) ▲

During gradual development of hyponatremia, the brain compensates by extruding intracellular inorganic solutes; this is followed by water loss as the brain becomes hypotonic relative to its environment, helping to reduce the degree of cerebral edema

♦ Treatment

• Volume status should be assessed first • Patients with hypovolemia require immediate replacement with isotonic saline to maintain hemodynamic stability and restore intravascular volume • The sodium deficit may then be calculated to guide further therapy ▲

Na+ deficit (meq) = Normal TBW x (130 – Current Na+)

2  Electrolyte and Metabolic Derangements

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• In patients with isovolemia or hypervolemia, infusion of furosemide with isotonic fluids may be helpful • Euvolemic patients with asymptomatic hyponatremia may be treated with free water restriction alone or in combination with oral sodium supplementation • Severely symptomatic patients may require the use of hypertonic saline • Fludrocortisone ▲ ▲

▲

A synthetic mineralocorticoid May be used for mineralocorticoid replacement in patients with primary adrenal insufficiency May be considered in refractory CSW with ongoing losses of sodium and free water (0.1–0.2 mg daily)

• Important risk – osmotic demyelination syndrome ▲

▲

▲

Results from a too-rapid correction of serum sodium that triggers demyelination of susceptible neurons, particularly the pons Symptoms progress over hours to days and include spastic paralysis, pseudobulbar palsy, and decreased level of consciousness Correction of serum sodium should be limited to 0.5 meq/L/h and no more than 8–10 mmol/L over 24 h to limit risk

♦ Hypernatremia

• Defined as a serum sodium >145 meq/L • Hypernatremia always represents a deficiency in water relative to total body sodium ▲

Normal sodium stores – loss of free water with minimal or no loss of sodium N Diabetes insipidus (DI) ° Most frequently occurs after pituitary or diencephalic surgery ° May occur with brain neoplasms, anoxic brain injury, meningitis,

or cerebral edema ° Injury to the hypothalamus results in insufficient secretion of ADH,

rendering the kidneys unable to concentrate urine in the face of a rising serum osmolarity ° Diagnosis — High urine output — Serum Osm >290 mOsm/kg — Urine specific gravity <1.010 ° Associated with loss of other electrolytes due to high urine

output ° Is often temporary, lasting 3–5 days ° Treatment includes vasopressin (DDAVP); sodium and serum

osmolarity should be checked frequently, as the use of vasopressin in the setting of resolving DI may result in hypervolemia and hyponatremia

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N. Jaworski and A. Brambrink ° DI may be nephrogenic or neurogenic; however, nephrogenic DI

rarely occurs in the neuro ICU ▲

Low sodium stores – loss of water greater than the loss sodium (loss of hypotonic fluid) N Excessive sweating, vomiting, or diarrhea without volume replacement N Iatrogenic ° Mannitol is frequently used in the NCCU for treatment of acutely

elevated ICP and results in free water loss greater than sodium loss; serum osmolality and sodium should be monitored ▲

High sodium stores – gain of more sodium than water (gain of hypertonic fluid) N Frequently iatrogenic in the NCCU; hypertonic saline is used for

treatment of cerebral edema due to stroke or TBI as well as to replace sodium losses during CSW N To avoid development of symptoms, an upper limit to treatment must be set and the sodium levels must be frequently checked to ensure that levels are not rising too rapidly ♦ Neurologic manifestations

• Symptoms usually do not develop until Na >160 mmol/L, but a rapid increase in sodium concentration may cause symptoms at lower levels • Symptoms primarily include a decreased level of consciousness and confusion that may progress to tonic-clonic seizures • Intracellular fluid in the brain becomes hypotonic relative to the extracellular fluid during hyponatremia; water then shifts out of the cells along the osmotic gradient, resulting in a reduction of intracellular volume and symptoms (cellular contraction) ▲

This mechanism is frequently used to advantage in the NCCU for the treatment of cerebral edema and elevated ICP; hypertonic saline infusion creates an osmotic gradient to draw water out of brain cells

• The brain is able to compensate for acute hypernatremia over a matter of hours by accumulating electrolytes intracellulary; cerebral osmolality and brain volume are then restored • Chronic hypernatremia results in brain accumulation of organic osmolytes over several days (myoinositol, b taurine, small-chain amino acids); restoration of cerebral osmolality results in restoration of brain volume ▲

The brain is unable to rapidly eliminate the organic osmolytes; rapid correction of hypernatremia or rapid discontinuation of hypertonic saline therapy can therefore result in rebound cerebral edema as the osmolytes and the accumulated electrolytes continue to draw water into brain cells

2  Electrolyte and Metabolic Derangements

21

♦ Treatment

• Volume status should be assessed, and hypovolemia should be treated with isotonic fluids to maintain hemodynamic stability • Free water deficit is then calculated using the following formula: ▲ ▲ ▲ ▲

TBW = total body water TBW deficit = Normal TBW – Current TBW Current TBW = Normal TBW x (Normal PNa/Current PNa) Replacement Volume = TBW deficit × (1/1 – X) N X = concentration of sodium in the replacement fluid

• As described above, acute hypernatremia may be corrected over a few hours as the brain is able to rapidly eliminate accumulated electrolytes • To avoid the risk of cerebral edema, chronic hypernatremia should be corrected at a rate not greater than 0.5 meq/L/h and no more than 10 meq/L/ day, as the brain requires days to eliminate accumulated organic osmoles

Potassium ■ ■

■ ■

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Potassium is the major intracellular cation Only 2% of potassium stores are found extracellulary, and only 0.4% is found in plasma; therefore, serum potassium is a poor measure of total body potassium Total body potassium is ~50 meq/kg Large intracellular stores of potassium are very effective at replenishing extracellular potassium losses; as a result, the relationship between the changes in total body potassium and serum potassium is curvilinear such that serum potassium changes occur twice as rapidly when potassium stores are in excess than they do when potassium stores are depleted Hypokalemia ♦ Defined as serum K < 3.5 meq/L ♦ Etiology

• Transmembraneous shift ▲ ▲

▲ ▲ ▲

Catecholamines (i.e., b agonists) stimulate Na+/K+ ATPase activity Alkalosis – hydrogen ions are shifted extracellularly in exchange for potassium ions Hypothermia Insulin enhances Na/K ATPase activity Hypertonicity – the increase in electricochemical gradient favors the movement of ions out of cells

♦ Potassium depletion

• Renal losses

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N. Jaworski and A. Brambrink ▲

Diuretic therapy increases the distal tubular flow and sodium delivery to the distal tubule, stimulating the secretion of potassium via Na+/K+ ATPase N Mannitol is a frequently used diuretic to treat elevated ICP in the

NCCU; because of its potassium wasting properties, serum K+ should be monitored and replaced as needed ▲

Mineralocorticoids N Aldosterone stimulates the reabsorption of sodium and the secretion

of potassium in the distal tubule N Fludrocortisone therapy is often employed in the NCCU in the treat-

ment of hyponatremia in the context of CSW; serum potassium levels should be monitored and replaced to avoid associated hypokalemia ▲

▲

ADH stimulates potassium secretion at the distal tubule independent from its water-retaining effects Magnesium depletion N Impairs potassium reabsorption across the renal tubules

▲

High-dose steroids used to treat spinal cord injury and mineralocorticoid therapy for CSW both potentiate renal losses of potassium

• Extrarenal losses ▲

Diarrhea

♦ Clinical relevance

• Initially often asymptomatic but important due to its role in cardiac conduction • Hypokalemia can be associated with nonspecific EKG changes, including U waves, flattening or inversion of T waves, and prolongation of the QT interval • Hypokalemia promotes cardiac dysrhythmia when combined with other pro-dysrhythmic conditions such as ischemia, digitalis toxicity, or magnesium depletion ▲

▲

SAH is frequently associated with EKG changes and sinus dysrhythmia; EKG changes generally disappear within 24 h and are considered a marker for the severity of the SAH rather than a predictor of potential cardiac complications or clinical outcome; nonetheless, one should be wary of hypokalemia in the setting of SAH-induced EKG changes, as the combination may potentiate a cardiac dysrhythmia Stroke patients frequently have coexisting cardiac disease; for example, the case of an embolic stroke due to atrial fibrilliation with a patient who not only has coexisting cardiac disease but also receives digoxin for adequate heart rate control

2  Electrolyte and Metabolic Derangements ■

23

Hyperkalemia ♦ Defined as serum K+ >5.5 meq/L ♦ Transmembraneous shift

• b antagonists/digitalis • Acidosis • Rhabdomyolysis ▲

Occasionally, patients with neurologic disease are found after being unconscious for an unknown period of time; a high level of suspicion for rhabdomyolysis is indicated in these patients, and serial creatinine kinase and potassium level checks are indicated

♦ Impaired renal excretion

• Renal insufficiency, renal failure • Adrenal insufficiency • Drugs ▲ ▲ ▲ ▲

▲

ACE inhibitors/adrenergic receptor binders K+-sparing diuretics NSAIDs Heparin – e.g., patients with ischemic stroke may be placed on a heparin infusion Antibiotics – trimethoprim-sulfamethozaxole, potassium penicillin

• Blood transfusion ▲ ▲

Potassium leaks from erythrocytes in stored blood The extra potassium is normally cleared by the kidneys, but in circulatory shock that requires transfusion greater than one blood volume, potassium can accumulate and result in hyperkalemia

♦ Clinical relevance

• Slowing of electrical conduction within the heart can begin at levels of 6.0 meq/L and is almost always present by 8.0 meq/L; progressive EKG changes occur ▲

Peaked T waves → flattened P waves → lengthened PR interval → loss of P waves with prolonged QRS → ventricular fibrillation → asystole

• Hyperkalemia is a relatively uncommon electrolyte abnormality in NCCU patients; however, it can occur, particularly in those who have coexisting renal failure

Magnesium ■ ■

Second-most abundant intracellular cation after potassium Only 1% of magnesium is located in the plasma; therefore, total body stores of magnesium can be low despite normal serum magnesium levels

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N. Jaworski and A. Brambrink

Magnesium acts as a cofactor for many enzymatic reactions involving ATP ♦ Regulates the movement of calcium into smooth muscle cells, rendering it

important for cardiac contractility and vascular tone ♦ Regulates calcium influx into neuronal cells via glutamate receptor – associated

ion channels; magnesium partially blocks the receptor and reduces calcium currents, thereby limiting calcium overload of neurons in ischemia/reperfusion; magnesium has been suggested to have neuroprotective properties ■

Hypomagnesemia ♦ Defined as serum Mg < 1.3 meq/L ♦ Etiology

• Diuretic therapy – loop diuretics >thiazide diuretics ▲ ▲

Urine magnesium losses parallel urine sodium losses Does not occur with potassium-sparing diuretics

• CSW ▲

Magnesium follows sodium in the renal tubules; therefore, large sodium losses in CSW also result in significant magnesium losses

♦ Clinical relevance

• Symptoms include exacerbation of neurologic dysfunction, apathy, delirium, muscle weakness, hyperreflexia, muscle spasms, ataxia, nystagmus, and seizures • Associated electrolyte abnormalities ▲

▲

Hypokalemia and hypocalcaemia can be refractory to replacement therapy in the setting of hypomagnesemia Low magnesium impairs the release of parathyroid hormone and endorgan responsiveness to parathyroid hormone

• Magnesium depletion results in prolonged cardiac cell repolarization and prolonged Qt intervals on EKG ▲

Torsade de pointes – a form of ventricular fibrillation most frequently associated with hypomagnesemia; the primary treatment is magnesium infusion

• Neuroprotective agent ▲

Magnesium may act as a neuroprotective agent in brain ischemia via several mechanisms N Acts as an endogenous calcium-channel antagonist N Inhibition of release of excitatory neurotransmitters such as

glutamate

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25

N NMDA-receptor antagonism N Direct vascular smooth muscle relaxation ▲

Currently, the use of hyperacute magnesium therapy to provide neuroprotection after stroke is under investigation

• SAH ▲

▲

▲

~30% of patients who present with SAH have coexisting hypomagnesemia upon admission Relationship between low magnesium levels, SAH, and myocardial stunning remains unclear Combination of low magnesium with stunned myocardium represents a pro-dysrhythmic state, and magnesium should be replaced in these patients

• Prevention of seizures – low magnesium levels reduce the seizure threshold, and magnesium is the primary agent used to prevent seizures during preeclampsia in pregnancy ■

Hypermagnesemia ♦ Defined as a serum Mg >2.0 meq/L ♦ Etiology

• Renal failure • Iatrogenic – magnesium infusion for neuroprotection or in the context of preeclampsia • Hemolysis • Adrenal Insufficiency • Lithium intoxication • Hyperparathyroidism ♦ Clinical relevance

• Hypermagnesemia becomes symptomatic at levels >4 meq/L • Progress of symptoms – hyporeflexia → first degree AV Block → complete heart block → respiratory failure → cardiac arrest • Not a common problem in the NCCU but should be on the differential of patients with hyporeflexia

Calcium ■

■

Primarily an extracellular cation that exists in protein-bound (inactive), anionbound (inactive), and ionized (active) forms Tightly regulated by parathyroid hormone (PTH) and vitamin D; PTH secretion by the parathyroid gland results in increased reabsorption of calcium in the thick ascending limb and the distal tubule of the nephron

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N. Jaworski and A. Brambrink

Calcium is the primary mediator of muscle contraction Calcium is of primary importance in the neurocritical care environment due to its central role in neuronal death after CNS injury ♦ Cytotoxic intracellular calcium movement is mediated via glutamate recep-

tors, voltage-gated calcium channels, and pH-dependent calcium channels ♦ Influx of calcium from the extracellular space and the endoplasmic reticulum

results in the activation of cellular injury and death cascades ■

Calcium-channel blockers ♦ The calcium-channel antagonist nimodipine has been shown to reduce the

incidence of cerebral ischemia due to vasospasm following SAH and should be initiated as soon as possible following hemorrhage and continued for 21 days; a similar benefit has not been seen in stroke patients ■

Hypocalcemia ♦ Defined as serum ionized Ca <1.1 mmol/L ♦ Rather uncommon in the NCCU patient population ♦ Relevant causes include phenytoin, phenobarbital, hypoparathyroidism after

neck surgery, renal failure, and blood transfusion (citrate anticoagulant in packed red blood cells binds calcium) ♦ Respiratory alkalosis as a result of hyperventilation (i.e., for treatment of ­elevated intracranial pressure) results in an increase in protein binding of calcium ♦ Clinical manifestations are related to cardiac and neuromuscular conduction and to depressed myocardial contractility • Cardiac findings include prolonged QT and ST intervals, decreased cardiac output, hypotension, and bradycardia, and can progress to ventricular dysrhythmias • Neuromuscular symptoms include tetany, parathesias, weakness, and seizures ■

Hypercalcemia ♦ Defined as serum ionized Ca >1.3 mmol/L ♦ Also relatively uncommon in the NCCU patients ♦ Relevant causes include malignancies, renal failure, prolonged immobi-

lization, phosphorus depletion, hyperparathyroidism, lithium, and thiazide diuretics ♦ Clinical manifestations involve the gastrointestinal, cardiovascular, renal, and neurologic systems • Cardiovascular – increased vascular resistance, QT shortening, occasional dysrhythmias • Neurologic – confusion, lethargy, memory impairment, weakness, ­hypotonia, and hyporeflexia leading to progressive obtundation and coma

2  Electrolyte and Metabolic Derangements

27

Phosphate ■

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■

The most abundant intracellular anion; phosphate is important for membrane structure, cellular energy, the production of ATP, cell transport, and intracellular signaling cascades Depletion of high-energy intracellular phosphates is considered crucial for the development of a delayed cerebral deficit in the context of cerebral vasospasm, as well as following acute cerebral ischemia Hypophosphatemia ♦ Defined as serum Phos <2.5 mg/dL or 0.8 mmol/L ♦ Etiology

• • • • •

TBI Malnutrition Hypomagnesemia or hypocalcemia Phosphorus-binding antacids – sucralafate, aluminum salts Drugs – diuretics, steroids, b agonists

♦ Clinical relevance

• Phosphate is a major component in the production of cellular energy (ATP); therefore, phosphate depletion is concerning but can be compensated for some time; hypophosphatemia is generally asymptomatic until severe; symptoms are generally manifested as impairment in production of cellular energy ▲ ▲ ▲ ▲ ▲ ▲ ▲

Cardiac failure Hemolytic anemia (decreased erythrocyte deformability) Depletion of 2,3-DPG, resulting in tissue hypoxia Muscle weakness, including respiratory insufficiency Neurologic symptoms – ataxia, tremor, irritability, and seizures Impaired enzyme function Immune system

• Refeeding syndrome ▲

▲

Can occur in any nutritionally depleted patient but is particularly common among chronic alcoholics Hypophosphatemia can be profound and occurs as tissues begin to rebuild themselves upon the initiation of nutritional support N May lead to muscle weakness, including respiratory muscle weak-

ness, and glucose intolerance N May be associated with other electrolyte abnormalities (hypocalce-

mia, hypokalemia, or hypomagnesemia), further exacerbating muscle weakness

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N. Jaworski and A. Brambrink

Hyperphosphatemia ♦ Defined as serum Phos >4.5 mg/dL or 1.45 mmol/L ♦ Etiology

• Renal insufficiency • Cellular necrosis – rhabdomyolysis, sepsis, multiple trauma, tumor lysis ♦ Rapid increases in serum phosphate can lead to development of severe

hypocalcemia; symptoms are related to the hypocalcemia

Metabolic Disorders and Endocrinopathies ■

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■

■

Metabolic disorders are more common in the medical ICU and may be the reason for admission; they remain important in the NCCU for two primary reasons Metabolic disorders and endocrinopathies should always remain in the differential diagnosis of encephalopathy Metabolic disorders may occur as comorbidities in any patient, including neurosurgical or neurologic patients Hyperglycemia ♦ Hyperglycemia (defined as blood glucose >150 mg/dL) in the setting of ischemic

brain injury has been shown to be an independent predictor of poor outcome ♦ In animal studies, hyperglycemia before or during ischemic injury has been

shown to increase severity of injury ♦ Elevation of blood glucose in the setting of severe ischemia or TBI is most

likely due to the physiologic stress caused by the injury ♦ The exact blood glucose level at which insulin therapy should be initiated

remains undefined; however, most practitioners aim to keep blood sugar ­levels <150 mg/dL and >80 mg/dL in critically ill patients with CNS disease ♦ Two specific conditions that may result in severe hyperglycemia and may be the reason for admission to the ICU are nonketotic hypersmolar coma (NKHC) and diabetic ketoacidosis • NKHC ▲ ▲ ▲

▲

▲

A form of hypertonic encephalopathy similar to that of hypernatremia Patients usually have enough endogenous insulin to prevent ketosis Patient may or may not have a prior history of diabetes, but onset is ­usually precipitated by physiologic stress Encephalopathy usually presents as altered mental status but may ­progress to focal deficits and seizures Findings N Blood glucose usually >1,000 mg/dL N Persistent osmotic diuresis leads to profound hypovolemia

▲

Treatment N Volume resuscitation with isotonic fluids or colloids

2  Electrolyte and Metabolic Derangements

29

N Replacement of free water once intravascular volume has been

restored; pseudohyponatremia is likely to be present, and resuscitation of hypovolemic state requires high degrees of NaCl, as the serum glucose level decreases with treatment N Restoration of brain cell volume may occur rapidly; therefore, volume replacement should occur slowly N Insulin therapy can be initiated after volume status has been restored ° Insulin therapy via infusion: start at 0.1 unit/kg bolus + 0.1 unit/

kg/h with goal of decreasing blood glucose by 50–70 mg/dL/h; decrease infusion of insulin to 0.05 units/kg/h when a serum glucose of 200 mg/dL has been reached • Diabetic ketoacidosis ▲

▲

▲

Usually seen in Type I (insulin-dependent) diabetics but may be the presenting sign of new-onset diabetes May be seen in a previously well-controlled diabetic who is experiencing acute physiologic stress such as infection or sepsis Findings N N N N

▲

Blood glucose usually > 250 mg/dL but <800 mg/dL Serum bicarbonate <20 meq/L Elevated anion gap Ketones in blood and urine

Treatment N Volume resuscitation with isotonic fluids; fluid deficit is usually 100

mL/kg N Insulin therapy via infusion: start at 0.1 unit/kg bolus + 0.1 unit/kg/h

with goal of decreasing blood glucose by 50–70 mg/dL/h; decrease infusion of insulin to 0.05 units/kg/h when serum glucose of 200 mg/dL has been reached N Replace potassium; correction of underlying acidosis in combination with insulin therapy will drive potassium intracellularly; as patients are generally potassium depleted at baseline; therefore, a large potassium deficit likely exists, and aggressive replacement may be needed ■

Hypoglycemia ♦ Hypoglycemia (defined as blood glucose <50 gm/dL) is important in the

NCCU for several reasons • It is known to cause direct neuronal cell injury due to alterations in metabolism; EEG changes can be seen at levels of 40 mg/dL, and the EEG begins to show suppression at 20 mg/dL; seizures may develop • Hypoglycemia increases CBF which may be detrimental to patients with elevated ICP

30 ■

N. Jaworski and A. Brambrink

Thyroid disorders ♦ Thyroid-releasing hormone is secreted by the hypothalamus, which stimulates

the anterior pituitary to release TSH (thyroid-stimulating hormone), which subsequently stimulates the thyroid gland to secrete T3, T4, and rT3 ♦ Free (non-protein bound) T3 is the active form of the hormone ■

Myxedema coma ♦ The most severe form of hypothyroidism, with mortality approaching 50–60%

even after early initiation of treatment ♦ Most likely to present in elderly women, but overall, a rare disease ♦ Most likely scenario is a patient with stable hypothyroidism who develops

one of these precipitating factors • • • • • • •

Hypothermia Sepsis from any source Stroke Congestive heart failure Pneumonia Hyponatremia Amiodarone exposure

♦ Findings

• • • •

Slowly declining mental status that progresses from lethargy to coma Respiratory failure (carbon dioxide retention + hypoxemia) Possible airway edema Cardiac – nonspecific ST changes, bradycardia, decreased contractility, decreased cardiac output, and cardiomegaly • Hyponatremia – kidneys are unable to properly secrete free water due to decreased GFR and increased vasopressin secretion • Hypoglycemia, hypoxemia, and hyponatremia may result in reduced CBF and seizures • Findings of chronic hypothyroidism are also likely to be present – dry skin, sparse hair, periorbital and pretibial nonpitting edema, macroglossia, ­moderate hypothermia, and delayed deep tendon reflexes ♦ Diagnosis

• Diagnosis may be evident by physical findings consistent with hypo­ thyroidism in the presence of stupor or coma and concomitant hypothermia • Urinary sodium excretion is normal • Elevated TSH and low total and free T4 and T3 • Be wary of patients with suspected myxedema coma and normothermia; may actually represent a “fever” and may be a sign of associated sepsis, as these patients are usually hypothermic

2  Electrolyte and Metabolic Derangements

31

♦ Treatment

• Ventilatory support • Cautious warming – rapid rewarming may result in vasodilation and refractory hypotension • Glucocorticoid therapy (50–100 mg hydrocortisone q 6 h) • Circulatory support with isotonic saline and vasopressors as needed • Volume restriction versus hypertonic saline to treat the hyponatremia, depending on severity; sodium levels <120 meq/L are considered more severe • Thyroid hormone therapy ▲ ▲

No optimal approach exists, although IV therapy is a common option High mortality of untreated myxedema coma must be considered versus risk of high-dose thyroid hormone therapy, which includes tachyarrhythmias and myocardial ischemia

Hashimoto Encephalopathy ■

■

■

■ ■

Hashimoto encephalopathy is an autoimmune disorder that is related to Hashimoto thyroiditis Also known as STEAT (steroid-responsive encephalopathy associated with autoimmune thyroiditis) Antithyroid antibodies are present in both disorders; however, it seems that other unknown antibodies are actually responsible for the damage to the CNS in Hashimoto encephalopathy Disorder is uncommon and present more frequently in females Findings ♦ Initial presentation is usually that of a rapidly progressive dementia similar to

prion disease; however, the encephalopathy may present as delirium or psychosis with a gradual or subacute onset ♦ Seizures, rigidity, movement disorders, and myoclonus may also be present, although these symptoms may develop months after initial presentation of dementia ■

Diagnosis ♦ Antithyroid antibodies, including antithyroid peroxidase (also known as anti♦ ♦ ♦ ♦

microsomal antibody) and antithyroglobulin antibody will be present TSH may be normal or elevated Free T4 may be normal or reduced No correlation between appearance of delirium or dementia and thyroid status EEG findings are similar to those of prion disease and include generalized slow-wave abnormalities

32

N. Jaworski and A. Brambrink ♦ Pathology findings include widespread vasculitis of the CNS ♦ MRI may show focal or diffuse nonenhancing abnormalities

■

Treatment ♦ Corticosteroids are effective in 50% of cases ♦ Immunosuppressants may be necessary for refractory cases

Thyroid Storm ■

■ ■

■

A severe form of thyrotoxicosis; the distinction between severe thyrotoxicosis and thyroid storm is somewhat subjective Mortality approaches 20–30% Most common etiology is Grave disease but may also occurs with solitary toxic adenoma or toxic multinodular goiter; exposure to iodine such as iodinated ­contrast or amiodarone may also precipitate thyroid storm Findings ♦ CNS dysfunction

• Agitation, delirium, lethargy, or psychosis • Progresses to seizures and coma ♦ Cardiovascular dysfunction

• • • • •

Dysrhythmia – frequently atrial fibrillation Congestive heart failure Tachycardia Hyperdynamic contractility Decreased systemic vascular resistance due to smooth muscle relaxation and release of nitric oxide from the endothelium

♦ Hyperthermia

• Increased metabolic rate (increased CO2 production/O2 consumption) ♦ Gastrointestinal dysfunction

• Nausea/vomiting • Jaundice • Hyperglycemia may be present ♦ Adrenocortical dysfunction

• Thyrotoxicosis accelerates the metabolism of exogenous and endogenous cortisol • Given the degree of physiologic stress, a normal cortisol level may actually represent a relative adrenal insufficiency

2  Electrolyte and Metabolic Derangements

33

♦ Diagnosis

• Elevated free T4 and free T3 with decreased level of TSH (<0.05 mU/mL) ♦ Treatment

• Goal of management is to stop synthesis and release of thyroid hormone and to block peripheral effects of the hormone • A thionamide (propylthiouracil or methimazole) should be given first to inhibit thyroid gland synthesis • Iodine therapy (potassium iodine) should be initiated no sooner than 30–60 min after thionamide therapy; iodine therapy inhibits release of thyroid hormone; however, if it is administered prior to thionamide therapy, it will actually stimulate the synthesis of new hormone, thus aggravating the condition • Acetaminophen and active cooling to treat hyperthermia • b blockade effectively treats effects of T3 on myocardial contractility • Glucocorticoids (hydrocortisone 100 mg q 8 h) ▲ ▲

Treats relative adrenal insufficiency if present Provides some inhibition of peripheral conversion of T4 to T3

• Avoid aspirin ▲

Salicylates decrease protein binding of thyroid hormone, thereby increasing the free fraction of circulating hormone

Adrenal Crises (Acute Adrenal Insufficiency) ■ ■

■ ■ ■

■ ■

Cortisol is the primary glucocorticoid in the body Corticoid-releasing hormone (CRH) is secreted by the hypothalamus and stimulates the anterior pituitary to release ACTH; ACTH subsequently stimulates the zona fasciculata of the adrenal gland to release cortisol Basal daily cortisol requirements = 15–25 mg hydrocortisone Cortisol requirements increase substantially under stress, trauma, or illness Cortisol is vital for cellular metabolism, homeostasis, and for the maintenance of vascular tone; insufficiency results in hypoglycemia and hypotension that is refractory to volume resuscitation and inotropic support This refractory hypotension can lead to decreased cerebral perfusion pressure Causes of adrenal insufficiency ♦ Primary (Addison disease)

• Destruction of adrenal gland commonly by an autoimmune process • Absence of mineralocorticoid and glucocorticoid • If left untreated, patients present with profound adrenal insufficiency manifesting as hypotension, hypovolemia, and shock

34

N. Jaworski and A. Brambrink ♦ Secondary (inadequate production of CRH or ACTH)

• Iatrogenic ▲

Chronic suppression N Cortisol naturally participates in a negative feedback loop with

ACTH secretion N Chronic administration of exogenous glucocorticoids results in

adrenal gland atrophy and chronic suppression of the hypothalamusanterior pituitary axis N The adrenal gland is then unable to mount an appropriate response to stress, resulting in profound hypotension, muscle weakness, and hypoglycemia ▲

Etomidate N Etomidate directly inhibits cortisol synthesis by the adrenal gland;

a single dose results in suppression for up to 12 h • Chronic subclinical adrenal insufficiency ▲

▲

Chronic disease that is asymptomatic or presents with nonspecific symptoms such as weakness, dizziness, lethargy, or GI complaints Manifests as refractory hypotension in the setting of physiologic stress or infection

• Pituitary injury due to hemorrhage, ischemia, surgery, compression, or trauma ■

Diagnosis ♦ Random serum cortisol level

• > 35 mg/dL is considered normal • <15 mg/dL is considered abnormal • 15–35 mg/dL may require corticotrophin stimulation test for further differentiation ■

Treatment ♦ “Stress-dose steroids” should be considered in any patient at risk for adrenal

insufficiency or any patient with refractory hypotension despite volume resuscitation and vasopressor support • Regimens include ▲ ▲

100 mg hydrocortisone q 8 h 10 mg dexamethasone q 8 h

• In patients with severe sepsis or septic shock, current Surviving Sepsis Guidelines recommend initiation of 200–300 mg/day of IV hydrocortisone

2  Electrolyte and Metabolic Derangements

35

therapy in 3–4 divided doses for 7 days in adult patients with hypotension refractory to adequate volume resuscitation and vasopressor therapy ▲

Use of ACTH stimulation test to identify potential “responders” prior to initiation of corticosteroids is no longer recommended by the campaign

Key Points ■ ■

■

■

Acid-base disorders are commonly encountered in the NCCU Consequences of electrolyte derangement may become life threatening if unrecognized or persistently severe Derangements of serum sodium are common, and etiologies include SIADH, CSW, and DI Metabolic disorders and endocrinopathies may occur as comorbidities with any patient in NCCU and should always remain in the differential diagnosis of encephalopathy

Suggested Reading Ginsberg M (2008) Neuroprotection for ischemic stroke: past, present, and future. Neuropharmacology 55:363–389 Kitabchi A, Nyenwe E (2006) Hyperglycemic crises in diabetes mellitus: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin North Am 35:725–751 Nayak B, Burman K (2006) Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am 35:663–686 Rabinstein A, Wijdicks E (2004) Body water and electolytes. In: Layon A, Gabrielli A, Friedman W (eds) Textbook of neurointensive care. Elsevier, Philadelphia, pp 555–577 Schäuble B, Castillo P, Boeve B et al. (2002) EEG findings in steroid-responsive encephalopathy associated with autoimmune thyroiditis. Clin Neurophysiol 114:32–37 Tymianski M, Tator C (1996) Normal and abnormal calcium homeostasis in neurons: a basis for the pathophysiology of traumatic and ischemic central nervous system injury. Neurosurg 38:1176–95 Van der Bergh W, Algra A, Ginkel G (2004) Electrolyte abnormalities and serum magnesium in patients with subarachnoid hemorrhage. Stroke 35:644–648 Wartenberg K, Mayer S (2006) Medical complications after subarachnoid hemorrhage: new strategies for prevention and management. Curr Opin Crit Care 12:78–84 Wartofshy L (2006) Myxedema coma. Endocrinol Metab Clin North Am 35:687–698

Chapter 3

Fever and Infections Neeraj Badjatia

Fever ■

Definition ♦ A core body temperature >38.3°C (101°F)

■

Measurement ♦ Pulmonary artery catheter most accurate method, followed by bladder and

esophageal probes; rectal temperature is least accurate ■

Risk factors ♦ ♦ ♦ ♦ ♦

■

Hemorrhagic injuries more likely, especially intraventricular blood Endotracheal intubation External ventricular drainage Central venous catheterization Older age

Primary evaluation ♦ Obtain thorough history from pre-hospitalization to present ♦ Physical examination

• • • •

Surgical wounds, drainage, and vascular access sites Pressure-induced skin ulceration Auscultation of lungs anteriorly and posteriorly Abdominal examination

♦ Obtain chest X-ray, looking for evidence of new infiltrates or effusions

N. Badjatia, MD, MSc (*) Departments of Neurology and Neurosurgery, Columbia University, New York, NY 10032, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_3, © Springer Science+Business Media, LLC 2011

37

38

N. Badjatia

♦ Obtain appropriate initial laboratory studies

• White blood cell count with differential • Cultures of blood, urine, sputum, CSF, stool ♦ Inspect insertion sites of central venous catheters that have been in place

for >96 h ♦ Stool sample for Clostridium difficile toxin in patients on antibiotics for >3 days ■ ■

Secondary evaluations based upon initial findings, persistent fever (Table 3.1) Treatment ♦ ♦ ♦ ♦

Begin appropriate antibiotics (see “Infections” below) Remove all IV and intra-arterial catheters in place for >96 h Discontinue drugs that may predispose to drug fever Administration of antipyretics • Acetaminophen 1,000 mg orally q 4–6 h OR • Ibuprofen 600 mg orally q 8 h

♦ Consider infusion of cold saline (4°C) as a 30 mL/kg IV bolus

• Do not use in patients with compromised cardiac function (low ejection fraction) • Not suitable for repetitive use within 24 h Table 3.1  Secondary e­ valuation of fever: ­noninfectious causes of fever

Cardiovascular Myocardial infarction Pericarditis Deep venous thrombosis Pulmonary Atelectasis Pulmonary embolism Hepatobiliary/Gastrointestinal Acalculous cholecystitis Acute pancreatitis Toxic megacolon Non infectious hepatitis Endocrine Hyperthyroidism Adrenal insufficiency Pheochromocytoma Other Drug reactions (“drug fever”) Transfusion reactions Tumors Malignant hyperthermia Neuroleptic malignant syndrome Serotonin syndrome Drug withdrawal (alcohol, heroin, opiates)

3  Fever and Infections

39

Table 3.2  The Bedside shivering assessment scale (BSAS) Score Definition 0 None. No shivering noted on palpation of the masseter, neck, or chest wall 1 Mild. Shivering localized to the neck and/or thorax only 2 Moderate. Shivering involves gross movement of the upper extremities (in addition to neck and thorax) 3 Severe. Shivering involves gross movements of the trunk and upper and lower extremities

♦ Induction and maintenance of normothermia (37°C)

• Utilized for patients with fever refractory to above interventions • Application of advanced therapeutic temperature-modulating device (intravascular or surface) set to 37°C • Monitoring for shivering with the bedside shivering assessment scale (Goal BSAS £ 1) (Table 3.2) • Stepwise anti-shivering protocol ▲

Step 1 – In all patients prior to initiation and throughout duration of normothermia N 30 mg buspirone orally q 8 h N Surface counterwarming (43°C) N 1,000 mg acetaminophen q 4–6 h

▲

Step 2 – For persistent shivering, utilize a combination of medications N MgSO4, 4 g IV bolus; then, 0.5–1.0 g/h; Goal Serum Mg level:

3–4 mg/dL

N Dexmedetomidine, 0.2–1.5 mg/h N Meperidine, 25–75 mg IV q 4–6 h as needed OR 0.5–1.0 mg/kg/h

infusion; do not administer in patients with renal insufficiency N Dantrolene, 2.5 mg/kg IV q 6 h as needed ▲

Step 3 – Uncontrolled, moderate to severe shivering (BSAS 2–3) N Propofol, 30–50 mg/kg/min continuous infusion N Re-evaluate need for ongoing therapeutic normothermia

Thoracic Infections ■

Community-acquired pneumonia ♦ Risk factors

• Older age • Coexisting diabetes mellitus, cardiac disease, immunosuppression

40

N. Badjatia

♦ Diagnosis

• • • • • • •

Hospitalized for £3 days at time of infection Presence of clinical features Fever (>38.0°C) Elevated WBC Purulent sputum Infiltrate on chest X-ray PaO2/FiO2 ratio <240 (not necessary)

♦ Microbiology

• • • • • • •

Streptococcus pneumonia – most frequent Haemophilus influenza Klebsiella pneumonia Staphylococcus aureus Legionella pneumophila Mycoplasma pneumonia Chlamydia pneumonia

♦ Treatment

• General principle – empiric broad antibiotic coverage to cover gram-positive, gram-negative, and atypical organisms until culture data available • Fluoroquinolone plus b-lactam • Macrolide plus third-/fourth-generation cephalosporin • Macrolide plus a carbapenem ■

Aspiration pneumonia ♦ Risk factors

• Altered mental status • Repeated or prolonged seizures • Diminished bulbar function ♦ Diagnosis – See above (under Community-acquired pneumonia) ♦ Microbiology

• Anaerobes and gram-negative organisms most common ♦ Treatment

• Ampicillin/sulbactam – 1.5 g IV q 6 h OR second-/third-generation cephalosporin ■

Hospital-acquired pneumonia ♦ Nonventilator associated (hospital acquired pneumonia)

• Prevention ▲

Nonpharmacologic N Hand washing, head of bed elevated to 30–45°

3  Fever and Infections ▲

41

Pharmacologic N Chlorhexidine mouth wash, ranitidine

• Diagnosis – See above (under Community-acquired pneumonia) ▲

Nonintubated and hospitalized for >3 days prior to infection

• Microbiology ▲

Gram-positive N Streptococcus pneumonia and Staphylococcus aureus

▲

Gram-negative N H. influenza, K. pneumonia, S. aureus, Pseudomonas aeruginosa,

Enterobacter spp., Klebsiella spp. • Treatment ▲

General principle N Empiric broad antibiotic coverage to cover methicillin-resistant

S. aureus (MRSA), gram-negative organisms ▲

Vancomycin plus aminoglycoside or fluoroquinolone

♦ Ventilator associated pneumonia (VAP)

• Prevention ▲

Nonpharmacologic N Early extubation, early tracheostomy, hand washing, head of bed

elevated 30–45° ▲

Pharmacologic N Chlorhexidine mouth wash, ranitidine

• Diagnosis ▲ ▲

See above under Community-acquired pneumonia Mechanical ventilation for at least 3 days prior to development of infection

• Microbiology ▲ ▲ ▲

See above under Hospital-acquired pneumonia, plus high incidence of: MRSA Multidrug-resistant P. aeruginosa, Enterobacter spp., Klebsiella species

• Treatment ▲

General principle N Empiric broad-spectrum antibiotics to cover for a high incidence of

MRSA and multidrug-resistant gram-negative organisms until culture results available

42

N. Badjatia ▲

Vancomycin plus a fluoroquinolone and aminoglycoside

♦ Empyema

• Risk factors ▲ ▲ ▲

Abscess Pneumonia Trauma

• Diagnosis – requires pleural fluid ▲ ▲ ▲

▲ ▲

Grossly purulent pleural fluid pH <7.2 WBC count >50,000 cells/mcL (or polymorphonuclear leukocyte count of 1,000/dL) Glucose level <60 mg/dL Lactate dehydrogenase level >1,000 IU/mL

• Microbiology ▲

S. aureus most common

• Treatment ▲

Broad-spectrum, gram-positive antibiotics and thoracostomy

♦ Lung abscess

• Risk factors ▲ ▲ ▲ ▲ ▲ ▲

Aspiration pneumonia Periodontal disease Gingivitis Bronchiectesis Septic emboli Pulmonary infarction

• Diagnosis ▲

Chest CT with contrast; sputum unreliable

• Microbiology ▲ ▲

Gram positive: Streptococcus pneumonia and Staphylococcus aureus Gram negative: Haemophilus influenza, Klebsiella pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter spp., Klebsiella spp.

• Treatment ▲

Drainage and prolonged antibiotic course specific to isolated organisms

♦ Infective endocarditis

• Risk factors ▲

Prosthetic valve

3  Fever and Infections ▲ ▲

43

IV drug abuse Bacteremia

• Diagnosis ▲

Clinical findings N N N N N

▲

New heart murmur Splinter hemorrhages Retinal hemorrhages (Roth spots) Red/purple nodules on toes/fingers (Osler nodes) Flat red lesions on palms/soles (Janeway lesions)

Laboratory findings N Persistent fever N Elevated WBC N Blood culture positive

▲

Echocardiography N TEE better than TTE in diagnosis of valvular vegetations, abscesses

• Microbiology ▲ ▲ ▲

▲

Most commonly caused by Streptococcus spp. S. aureus and enterococcus common in elderly and IV drug abusers Gram-negative organisms seen in IV drug abusers and prosthetic valves Common group – Haemophillus spp., Actinobaccillus actinomycetemocomitans, Cardiobacterium hominus, Eikenella corrodens, and Kingella spp (HACEK)

• Treatment ▲

Broad-spectrum gram-positive and gram-negative coverage with vancomycin and aminoglycoside, with weight-based dosages determined by trough levels

Abdominal Infections ■

Peritonitis ♦ Risk factors

• Perforated abdominal viscus, trauma, ascites ♦ Diagnosis

• Paracentesis and abdominal CT imaging ♦ Microbiology

• Enteric gram-negative bacteria most common, gram-positive cocci, anaerobes

44

N. Badjatia

♦ Treatment

• Vancomycin plus either ▲ ▲

■

Aminoglycoside Third-generation nonpseudomonal cephalosporin

Cholecystitis ♦ Risk factors

• Obstruction of biliary tract ♦ Diagnosis

• Abdominal ultrasound or CT scan ♦ Microbiology

• Enteric gram-negative bacteria, anaerobic bacteria ♦ Treatment

• Antibiotics with broad coverage for gram-negative and anaerobes • Surgical intervention for severe cases ■

Pseudomembranous colitis ♦ Risk factor

• Persistent antibiotic therapy for gram-negative organisms ♦ Diagnosis

• Stool examination ▲

Leucocytes, RBC, and C. difficile toxin positivity

• Persistent watery diarrhea >72 h after initiation of antibiotics for gramnegative organisms • Sigmoidoscopy visualization of “pseudomembranes” ♦ Treatment

• 500 mg metronidazole orally q 6 h • 125–500 mg vancomycin orally q 6 h • Discontinuation of gram-negative antibiotics (if possible) ■

Urinary tract infections ♦ Risk factors

• Prolonged catheterization • Neurogenic bladder • Nephrolithiasis

3  Fever and Infections

45

♦ Diagnosis

• Urinary sediment for leukocytes • WBC casts suggest tubular or kidney involvement • Culture positive for organisms necessary ♦ Microbiology

• Gram-negative rods most common followed by gram-positive and fungal organisms ♦ Treatment

• Replace urinary catheter • Broad-spectrum gram-negative antibiotic coverage pending culture results ■

Sinusitis ♦ Risk factors

• Facial trauma • Nasal intubation • Nasoduodenal or gastric tubes ♦ Diagnosis

• CT imaging of sinuses • Needle aspiration for culture ♦ Microbiology

• Gram-negative (most common), anaerobes, and S. aureus ♦ Treatment

• • • •

Nasal decongestion Removal of nasal tubes Broad-spectrum, gram-negative antibiotics Surgical drainage (rarely necessary)

CNS Infections ■

Bacterial meningitis ♦ Risk factors

• • • •

Community exposure Immunocompromised Trauma Post-craniotomy

46

N. Badjatia

♦ Diagnosis

• Clinical signs ▲ ▲ ▲ ▲

Headache Fever Alteration in mental status Seizures

• CSF findings ▲ ▲ ▲ ▲

Elevated WBC with PMN predominance Normal glucose Mild increases in protein PCR analysis for specific antigen

• Neuroimaging ▲

Contrast enhancement of meninges on MRI

♦ Microbiology

• Most common ▲ ▲ ▲

S. pneumonia Neisseria meningitidis H. influenza

• Listeria monocytogenes in elderly or immunocompromised ♦ Treatment

• Steroids ▲

Dexamethasone, 10 mg IV bolus, followed by 10 mg IV q 6 h for 96 h

• Antibiotics ▲

Empiric coverage of gram-positive, gram-negative organisms until culture data available N 2 g ceftriaxone IV q 12 h N 1 g vancomycin IV q 8–12 h N 50–100 mg/kg ampicillin IV q 6 h

■

Viral encephalitis ♦ Risk factors

• Environmental exposures • Immunocompromised ♦ Diagnosis

• Clinical signs

3  Fever and Infections ▲ ▲ ▲

47

Headache Fever Alteration in mental status

• CSF findings ▲ ▲ ▲ ▲

Elevated WBC with lymphocytosis Normal glucose Mild increases in protein PCR analysis for specific viruses

• Neuroimaging ▲

Mesial temporal edema/hemorrhages (unique for herpes simplex virus (HSV))

♦ Treatment

• Only specific treatment exists for HSV – 10 mg/kg acyclovir IV q 8 h • Symptomatic treatment for other forms of encephalitides ■

Bacterial ventriculitis ♦ Risk factors

• Ventricular catheterization • Intraventricular blood • Administration of chemotherapeutics ♦ Diagnosis

• Clinical signs/symptoms ▲ ▲ ▲ ▲

Headache Altered mental status Nuchal rigidity High fever

• CSF findings ▲ ▲ ▲ ▲

Elevated WBC with lymphocytosis Normal glucose Mild increases in protein PCR analysis for specific viruses

• Neuroimaging ▲

Contrast enhancement of lateral ventricles (low sensitivity)

♦ Microbiology

• S. aureus most common followed by gram-negative rods ♦ Treatment

• Removal of catheters

48

N. Badjatia

• Antibiotics ▲

Initial empiric broad-spectrum coverage for gram-positive and gramnegative organism N 1.0–1.5 g vancomycin IV q 12 h (goal trough, level >15) N Second- or third-generation cephalosporin with good CNS penetra-

tion (e.g., 2 g ceftriaxone IV q 12 h or 2 g cefepime q 8 h) ■

Catheter-related infections ♦ Risk factors

• Prolonged central vein catheterization • Multiple lumen catheters • Administration of parenteral nutrition ♦ Diagnosis

• • • •

Fever and elevated WBC count Purulence at insertion site Positive blood culture Positive culture of catheter tip

♦ Microbiology

• Coagulase-negative Staphylococcus most common • S. aureus • Gram-negative rods or fungal species ♦ Treatment

• Removal of central line catheter • Broad-spectrum gram-positive and gram-negative antibiotic coverage pending culture results

Special Considerations ■

Malignant hyperthermia and neuroleptic malignant syndrome (see Chap. 27)

Key Points ■ ■

Hyperthermia is deleterious to an injured brain Workup for fever should entail a systematic approach to primary and secondary (noninfectious) causes

3  Fever and Infections ■

■

49

Etiologic considerations for risk factors, clinical suspicion, ancillary laboratory and microbiologic data are required to institute appropriate therapies in a timely fashion Monitoring for shivering with the BSAS with appropriate therapeutic measures taken in an algorithmic approach are essential for management of patients with fever

Suggested Reading Badjatia N, Strongilis E, Gordon E et al (2008) Metabolic impact of shivering during therapeutic temperature modulation: the bedside shivering assessment scale. Stroke 39(12):3242–3247 Greer DM, Funk SE, Reaven NL et al (2008) Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive meta-analysis. Stroke 39(11):3029–3035 O’Grady NP, Barie PS, Bartlett JG et al (2008) Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med 36(4):1330–1349 Polderman KH (2008) Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet 371:1955–1969

Chapter 4

Cerebral Blood Flow and Metabolism: Physiology and Monitoring Jeremy Fields and Anish Bhardwaj

Cerebral Physiology ■

Cerebral blood flow (CBF) (Fig. 4.1) ♦ CBF is tightly regulated because the brain lacks its own stores of glucose and

oxygen. With normal blood glucose and oxygen content: • Normal CBF = ³50 mL/100 g/min • CBF 15–20 mL/100 g/min results in reversible ischemia • CBF <10–15 mL/100 g/min results in irreversible ischemia ♦ CBF is controlled by vasodilation or vasoconstriction of arterioles; autoregu-

lation of these vessels occurs in response to the following metabolic and physiologic parameters: • PaCO2 ▲ ▲

An acute 1 mmHg decrease in PaCO2 causes CBF to decrease by 4% Chronic (>12–24 h) changes in PaCO2 do not affect CBF due to changes in physiologic set points

• PaO2 ▲

CBF does not correlate with PaO2 when it exceeds 50 mmHg; however, when PaO2 is <50 mmHg, CBF increases dramatically

• Temperature ▲

CBF increases by 6–7% for each 1°C increase in temperature

J. Fields, MD Department of Neurology, Oregon Health and Science University, Portland OR, USA A. Bhardwaj, MD, FAHA, FCCM, FAAN (*) Department of Neurology, Tufts University School of Medicine, Tufts Medical Center, Box 314, 800 Washington Street, Boston, MA 02111, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_4, © Springer Science+Business Media, LLC 2011

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J. Fields and A. Bhardwaj

Fig. 4.1  Chemical autoregulation: Effect of PaO2 and PaCO2 on CBF

• Mean arterial pressure (MAP) ▲

CBF is maintained across a MAP of 50–150 mmHg by changes in blood vessel caliber N Below this range, cerebral vessels are maximally vasodilated and

CBF decreases passively with decreases in MAP N Above this range, cerebral vessels are maximally constricted and

CBF increases passively with increases in MAP • Blood viscosity ▲

▲ ▲

Blood viscosity is determined primarily by hematocrit and, to a lesser degree, by erythrocyte flexibility, platelet aggregation, and plasma viscosity Blood viscosity is inversely proportional to CBF CBF increases due to vasodilation in response to decreasing hematocrit N Under normal conditions, a decrease in hematocrit from 35 to 25%

leads to an increase in CBF by 30% N Below a hematocrit of 19%, compensatory vasodilation is

exhausted ■

Cerebral metabolism ♦ The brain is responsible for 20% of total body oxygen consumption and 25%

of total glucose consumption • ~55% of energy expenditure by the brain is related to dynamic brain function, particularly the generation of electrical signals; 45% is used for basal metabolic processes such as maintenance of ion gradients and synthesis of structural molecules

4  Cerebral Blood Flow and Metabolism: Physiology and Monitoring

53

• >90% of glucose is metabolized by aerobic oxidative phosphorylation in neurons; astrocytes utilize anaerobic metabolism predominantly; these two energy mechanisms are coupled: ▲

▲

▲

Astrocyte anaerobic glycolysis produces lactate, which is then released into the extracellular space Neurons take up lactate for aerobic metabolism and release glutamate, aspartate, and potassium into the extracellular space Glutamate, aspartate, and potassium are then taken up by astrocytes in an energy-dependent process fueled by anaerobic glycolysis, producing lactate and initiating the cycle again

♦ Under normal physiologic circumstances, CBF is coupled to metabolism;

thus, an increase in the brain’s activity (and therefore, an increase in its demand for oxygen and glucose) is accompanied by an increase in CBF ♦ Key cerebral metabolic parameters • Arterial venous difference in oxygen content (AVDO2) ▲ ▲

Difference between arterial oxygen content and venous oxygen content Increases with increased brain activity

• Oxygen extraction fraction (OEF) ▲

▲

Difference between arterial oxygen saturation and venous oxygen saturation Increases with enhanced brain activity, assuming constant CBF

• Cerebral metabolic rate of oxygen consumption (CMRO2) ▲

▲ ▲

Represents the total oxygen consumption by the brain in a given time period Calculated as CBF × AVDO2 Increases with increased brain activity

• Cerebral metabolic rate of glucose consumption (CMRGlu) ▲

▲

Represents the total glucose consumption by the brain in a given time period Increases with increased brain activity

Pathophysiology ■

General principles ♦ Loss of cerebral autoregulation

• In many disease states, cerebral autoregulation of CBF and metabolism is perturbed ▲

This may be global (for example, in diffuse head injury or severe SAH) or local (as in stroke or hemorrhage)

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• Important implications of loss of autoregulation include: ▲

▲

CBF changes passively with changes in MAP or cerebral perfusion pressure (CPP), resulting in hyperemia with high pressures and ­ischemia with low pressures CBF does not change in response to changes in CO2, O2, or hematocrit

♦ Uncoupling – When autoregulation is impaired, physiologic parameters that

are normally inter-related lose their predictable relationships ♦ Important examples of uncoupling include:

• Loss of relationship between metabolic energy expenditures (CMRO2 or CMRGlu) and CBF • Uncoupling of lactate utilization by neurons and uptake of excitatory neurotransmitters by astrocytes ■

Specific diseases ♦ Chronic hypertension

• Autoregulation in response to MAP is preserved; however, the range is shifted upward in proportion to the degree of chronic hypertension • Therefore, decreasing MAP to the lower range in a chronically hypertensive patient may cause CBF to decrease into the ischemic range ♦ Seizures

• During generalized seizures, CBF and metabolism increase and then decrease below normal during the postictal period • In focal seizures, the most common findings have been hyperperfusion and hypermetabolism ictally, and decreased CBF and metabolism postictally, which persists during the interictal period ♦ Traumatic brain injury (TBI)

• Metabolism ▲

▲

▲

Initially (hours to days) after severe head injury, the brain enters a hypermetabolic state Following this period, the brain becomes hypometabolic; the degree is correlated with the depth of coma Poorer clinical outcomes are associated with greater degrees of initial hypermetabolism, as measured by CSF lactate, and subsequent hypometabolism, as measured by CMRO2

• CBF becomes uncoupled from metabolism in TBI and often follows three hemodynamic phases: ▲

▲

Hypoperfusion (day 0–1) – CBF decreases to 50% of normal; decrease is severe enough to cause ischemia in ~25% of patients Hyperemia (day 1–3) – CBF normal or above normal; may lead to increased ICP

4  Cerebral Blood Flow and Metabolism: Physiology and Monitoring ▲

55

Vasospasm (day 4–15) – CBF decreases below normal until consciousness is regained

♦ Ischemic stroke

• Four types of responses to focal ischemia may occur, depending on the degree of CBF ▲

▲

▲ ▲

Normal autoregulation – vasodilation and increased cerebral blood volume (CBV) to maintain CBF Oligemia – increased in OEF in response to a decline in CBF, with maintained CMRO2 Reversible ischemia – increase in OEF inadequate to sustain CMRO2 Irreversible ischemia – decrease in OEF, with very low CBF and CMRO2

• Loss of autoregulation occurs in the ischemic penumbra (the area of reversibly injured brain surrounding the core of irreversible damage), leading to passive dependence on blood pressure in this region for CBF; therefore: ▲

▲

▲

▲

Inadequate blood pressure in the region of the ischemic penumbra may result in extension of the area of irreversible injury In rare cases of persistent large-vessel occlusion with blood pressure dependence, it may be necessary to augment blood pressure with pressors (with MAPs in the 120–140 mmHg) to preserve CBF as collateral vessels form Some collateral circulation is available immediately after arterial occlusion; other vessels must be recruited – a process that takes days to weeks Excessive elevations in blood pressure may result in hyperperfusion injury, which leads to edema and hemorrhage

♦ Intracranial hypertension ▲

▲

Elevated ICP from brain injury or stroke is typically due primarily to vasogenic and cytotoxic edema with a smaller contribution from elevated CBF or CBV When ICP is elevated, CPP rather than MAP goals should be targeted, with typical CPP goals in the 60–80 mmHg range

♦ Subarachnoid hemorrhage

• CBF decreases progressively from 2 days after SAH to a trough at day 14, before returning to normal levels at day 21 • Vasospasm associated with SAH or systemic hypotension may decrease CBF still further, into the range of reversible or permanent ischemia • CMRO2 decreases during the first week and then normalizes; uncoupling of CBF and metabolism are most common during the first week • The rationale of hypertensive and hypervolemic therapy is, therefore, to increase CBF to avoid cerebral ischemia

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Monitoring ■

Electroencephalography (EEG) ♦ EEG slowing occurs with CBF 16–22 mL/100 g/min, and EEG amplitude

diminishes with CBF 11–19 mL/100 g/min ♦ EEG is limited by spatial resolution, electrical interference, and complexities

of real-time interpretation ■

Cerebral perfusion pressure ♦ ♦ ♦ ♦

CPP = MAP − ICP CBF = CPP/CVR (cerebral vascular resistance) CPP between 60 and 80 mmHg is commonly targeted CPP is targeted as a surrogate for CBF; this assumes that CVR is normal • With normal CVR, CBF should be preserved with CPP in the target range • If CVR is abnormal due to loss of autoregulation, a normal CPP may result in either hyperemia and edema (if CVR is low) or ischemia (if CVR is high)

■

Transcranial doppler (TCD) ♦ TCD involves direct insonation of cerebral arteries using Doppler ultrasound ♦ While TCD is commonly used to measure cerebral vasospasm, it can also be

used to assess cerebral vasoreactivity and the degree of cerebral autoregulation • Mean flow velocity (FVm), usually the MCA, is measured continuously or before and after a physiologic manipulation (typically MAP, CPP, PO2, or PCO2) • FV increases with vasoconstriction and decreases with vasodilation, allowing direct assessment of vasoreactivity ♦ TCD is limited by absence of temporal bone windows in 10–15% of patients,

high degree of operator dependence, and ability to image the proximal cerebral vessels only ■

Imaging (Table 4.1) ♦ Imaging of the brain using xenon CT, CT or MRI with perfusion, and PET

may be used to evaluate CBF and other measures of adequacy of CBF ♦ PET also allows for direct measurement of metabolism of oxygen and glucose ♦ Imaging modalities are compared in Table 4.2 ■

SjVO2 (jugular venous oxygen saturation) and PbrO2 (oxygen tension in brain tissue) (Table 4.3) ♦ Technique

• SjVO2 – Oxygen saturation probe inserted retrograde up the dominant internal jugular vein to the junction of the sigmoid sinus and internal ­jugular vein at the skull base (C1–C2)

4  Cerebral Blood Flow and Metabolism: Physiology and Monitoring Table 4.1  Bedside tests for evaluating CBF and metabolism Technique Parameters Test Increase MAP using CPP Change MAP pressor ICP or CPP to OR assess cerebral FV Decrease MAP with vasoreactivity vasodilator or progressive deflation of blood pressure cuff applied to leg AND Monitor ICP or TCD FV Change MAP or CPP Increase MAP using CPP to PbrO2 pressor and measure assess PbrO2 change in PbrO2

Oxygen challenge

PBrO2

Patient placed on 100% FiO2 for 15 min

57

Response Normal (autoregulation intact): increased CPP → decreased CBF within 5–15 s → decreased ICP, and increased FV Abnormal: increased CPP → increased ICP and little or no change in FV

Normal (autoregulation intact): small increase in PbrO2 Abnormal: substantial increase in PbrO2, suggesting either failure of autoregulation or inadequate CPP/CBF Normal: rapid rise in PbrO2 followed by plateau (intact autoregulation) Abnormal: prolonged rise in PBrO2

MAP mean arterial pressure; CPP cerebral perfusion pressure; ICP intracranial pressure; FV flow velocity; TCD transcranial Doppler; PbrO2 oxygen tension in brain tissue; FiO2 fraction of inspired oxygen

• PbrO2 – Microsensor (0.5 mm in diameter) introduced into the brain parenchyma through bolt or tunneled catheter to continuously measure brain oxygen tension (and in some cases, PbCO2 and pH) ♦ Interpretation

• A low value reflects a decrease in venous oxygen (or increased OEF), which may be due to: ▲ ▲

Increased metabolism (increased CMRO2), or Decreased oxygen delivery due to decreased arterial oxygen and decreased CBF

♦ An elevated SjVO2 is most often due to hypometabolism (or decreased OEF)

or equipment failure; elevated PbrO2 usually represents equipment failure

♦ Limitations

• SjVO2 measures mixed venous blood from entire hemisphere and is insensitive to more restricted ischemia • PbrO2 measures local oxygen tension in the area of the probe only (~15 mL volume) and does not reflect metabolism in other brain regions

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Table 4.2  Imaging techniques for measurement of CBF and brain metabolism Technique Measures Output/advantages Limitations 131 • Underestimates CBF Xenon CT Xenon concentration Quantitative map of in patients with lung after inhalation CBF in up to six CT disease slices CT perfusion Standard iodinated CT Qualitative map of CBV, • Qualitative measures of CBF relative to a IV contrast agent MTT, and CBF. specified arterial input Relatively function cheap, potentially • Contrast agents may widely available, cause renal failure and rapid • Accuracy depends on contrast not crossing the BBB Qualitative map of TTP, • Thresholds defining MR perfusion Standard gadolinium analysis of raw data CBV, and CBF. MR IV contrast not yet identified May be compared agent • Qualitative measures with DWI images to of CBF relative to a determine areas of specified arterial input reversible ischemia function • Difficult to transport patient to MRI emergently 15 PET • Poor spatial resolution O or 18FDG Quantitative. Can • Expensive and not measure both blood widely available for flow and metabolism, inpatient clinical use including CBF, CBV, CMRO2, OEF, and glucose metabolism CBF cerebrospinal fluid; CBV cerebral blood volume; MTT Mean transit time; BBB blood–brain barrier; TTP thrombotic thrombocytopenic purpura; DWI diffusion-weighted imaging; CMRO2 cerebral metabolic rate of oxygen; OEF oxygen ejection fraction

♦ Equipment issues

• Probes for measuring both parameters are subject to substantial drift • PbrO2 probe may cause hemorrhage or, rarely, infection • SjVO2 catheter and sheath may cause infection or thrombosis of internal jugular vein with increase in ICP if thrombosis is occlusive or near-occlusive ■

Cerebral microdialysis (Table 4.3) ♦ Technique – microdialysis catheter inserted through bolt or tunneled

catheter ♦ Depending on catheter, this technique can measure:

• Energy metabolites – lactate, pyruvate • Neurotransmitters – glutamate, aspartate • Markers of tissue damage – glycerol (a cell wall component), potassium

4  Cerebral Blood Flow and Metabolism: Physiology and Monitoring Table 4.3  Monitoring of brain metabolism in the neuro-ICU Technique Parameter Normal range Jugular venous SjVO2 50–75% oximetry

Brain tissue oxygen

PbrO2

20–50 mmHg in grey matter 35–40 mmHg in white matter 7.21.7 (SD 0.9) mmol/L 2.9 (SD 0.9) mmol/L 166 (SD 47) mmol/L 23 (SD 4) 82 (SD 44) mmol/L 16 (SD 16) mmol/L

59

Abnormal conditions >80% → reduced OEF/hyperemia <50% → increased OEF/ischemia <15 mmHg → ischemia

<7.0–7.15 → tissue acidosis/ischemia <0.66 → ischemia >25 → increased anaerobic metabolism 2–3× baseline → cell damage SjVO2 jugular venous oxygen saturation; OEF oxygen ejection fraction; PbrO2 oxygen tension in brain tissue

Cerebral microdialysis

pH Glucose Lactate Pyruvate Lactate/pyruvate Glycerol Glutamate

♦ Interpretation

• Injury pattern – decreased brain glucose, increased lactate and lactate/ pyruvate ratio, increased excitatory neurotransmitters (glutamate and aspartate), and increased tissue damage (glycerol, potassium) ♦ Limitations

• As with PbrO2, microdialysis technique measures local metabolic parameters in the area of the catheter only and does not reflect metabolism in other brain regions • Absolute values must be interpreted with great caution because considerable variation may exist across patients, depending on set-up; therefore, trends within a specific patient are generally more important • Invasive, and may cause hemorrhage or infection

Key Points ■

■

Understanding normal cerebral physiology and metabolism and in pathophysiologic states is critical in the management of critically ill neurologic and neurosurgical patients Conventional methods for measuring and monitoring CBF are not readily available and are tedious

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CPP is a surrogate for CBF that is commonly utilized at the bedside in the Neuroscience ICU (NSICU) Multimodality neuromonitoring provides important insights into cerebral metabolism and is increasingly being utilized to mitigate secondary insults in the NSICU; SAH carries a high risk of mortality and long-term disability

Suggested Reading Bhatia A, Gupta AK (2007a) Neuromonitoring in the intensive care unit I: Intracranial pressure and cerebral blood flow monitoring. Intensive Care Med 33:1263–1271 Bhatia A, Gupta AK (2007b) Neuromonitoring in the intensive care unit II: Cerebral oxygenation monitoring and microdialysis. Intensive Care Med 33:1322–1328 Briones-Galang M, Robertson C (2004) Cerebral metabolism: implications for neurocritically ill patients. In: Suarez JI (ed) Critical care neurology and neurosurgery. Humana Press, Totowa, NJ Rose JC, Neill TA, Hemphill JC (2006) Continuous monitoring of the microcirculation in neurocritical care: an update on brain tissue oxygenation. Curr Opin Crit Care 12:97–102 Tisdall MM, Smith M (2006) Cerebral microdialysis: research technique or clinical tool. Br J Anaesth 97:18–25 Torbey MT, Bhardwaj A (2004) Cerebral blood flow physiology and monitoring. In: Suarez JI (ed) Critical care neurology and neurosurgery. Humana Press, Totowa, NJ Wartenberg KE, Schmidt JM, Mayer SA (2007) Multimodality monitoring in neurocritical care. Crit Care Clin 23:507–538

Chapter 5

Multimodality Monitoring in Acute Brain Injury Kristine H. O’Phelan, Halinder S. Mangat, Stephen E. Olvey, and M. Ross Bullock

Introduction ■

Major advances in microelectronics have produced new techniques for monitoring the injured brain; some, such as ion sensitive microelectrodes and continuous single-photon microscopy, remain confined to animal studies; others have transitioned rapidly into clinical use, including: ♦ Microdialysis ♦ Thermal dilution blood flow monitoring ♦ Near-infrared spectroscopy (NIRS)

■

■

■

These techniques offer a wide array of sensor-based tools that permit continuous or semi-continuous measurement of various time-dependent parameters in small regions of the injured brain Combining these techniques with global cerebral mapping techniques such as PET, MRI, and MR spectroscopy offers enormous power in understanding the pathophysiology of the injured brain Most of these monitoring techniques have limited but growing clinical penetration ♦ Approximately 15 US hospitals are using microdialysis to guide neurocritical

care ♦ >40 Hospitals in the US regularly use brain tissue oxygen sensors for managing

patients with severe traumatic brain injury ■ ■

Certainly, optimal integration into the clinical care plan has yet to be fully realized Challenges for the future

K.H. O’Phelan, MD, H.S. Mangat, MD, S.E. Olvey, MD Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA M.R. Bullock, MD, PhD (*) Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_5, © Springer Science+Business Media, LLC 2011

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♦ Determine if any of these techniques have the potential to improve clinical

outcome ♦ Determine how to integrate these techniques into management protocols ■

■

The number of interventional procedures that are available to provide care for the patient at risk for secondary brain damage in the ICU is relatively limited Within the next 5 years, several clinical trials will be undertaken to evaluate the effect of ICP monitoring upon outcome ♦ NIH-sponsored Bolivian ICP monitoring trial ♦ NIH efficacy of PTiO2 monitoring phase II LICOX trial ♦ Proposed LICOX phase 3 study

■

Thus, the future role of these monitoring techniques in managing patients should become much more clear

When is Monitoring Helpful in the ICU? ■

■

Physiologic monitoring such as continuous arterial blood pressure, pulse oximetry, temperature, and end-tidal CO2 comprises the standard monitoring in the ICU; in the setting of acute brain injury, neurophysiologic monitoring can likely be useful in conditions such as traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), spontaneous intracranial hemorrhage (ICH), acute ischemic stroke, and large brain tumors with mass effect Structural and functional imaging can be useful for gaining a “snapshot” view of the brain ♦ MRI (STIR and FLAIR structural sequences, arterial spin labeling (ASL) or

MR perfusion for blood flow, BOLD for functional imaging), xenon CT for blood flow, and PET for information about blood flow and metabolism ♦ Intermittent monitors such as transcranial Doppler (TCD) and xenon¹³³ CBF are used in neurocritical care ■

■

■

Multimodality monitoring in the ICU is unique because it gives vital information about ischemia, changes in CBF, substrate delivery, energy metabolism, edema, electrolyte flux, and seizure activity Commonly used neuromonitors are variably invasive and can provide regional or global measurements (Table 5.1) The overarching goal of neuromonitoring is to detect alterations, which can lead to therapeutic changes to prevent detrimental events

Most Commonly Used Neurologic Monitoring Tools ■

Serial neurologic exam ♦ Neurologic exam is very sensitive in awake patients

Global

Level of alertness, wakefulness, consciousness Pressure

3–15, lower is worse Goal: ICP <20 mmHg

Parameters

Assets

Liabilities

Easy, quick, bedside, no cost, can be done by RN Invasive, EVD can clot; ICP Global Commonly used, easy to ventricular placement interpret, EVD can be may be difficult; 2% therapeutic and complication rate diagnostic PbtO2 Regional Partial pressure of oxygen Goal: PbtO2 > Easy to insert, may help to Poor data if tissue hematoma or in tissue 15–20 mmHg ascertain correct CPP too close to other monitors Frequent recalibration; artifact SjVO2 Global Saturation of venous blood Goal: 50–80% Can help identify episodes in 50%; requires experienced returning from brain of ischemia or nursing staff “desaturation” Difficult in agitated patients; Quantitative information Pupillometer Global? Pupil dynamics <1 mm anisocoria; not validated regarding changes in Constriction intracranial pressure velocity without invasive monitor <0.6 mm/s Microdialysis Regional Biochemical milieu of See Table 5.3 Information about metabolic High cost; labor intensive; extracellular fluid state of brain tissue not validated Difficult in agitated patients; Vary per Noninvasive, does not need Electrophysiologic EEG Global trained technicians required indication physician to perform – activity and and to perform; artifacts from only to read; can provide abnormal patterns regional electrical equipment in ICUs continuous data High cost; requires technical For seizure detection; Neurophysiologist may not Global Abnormal Spectral know-how be required to detect assessment of electrophysiologic analysis critical values level of activity patterns EEG Cost of machine; assesses only LR >3 – suggestive Easy to do in most patients; TCD Regional Cerebral arterial blood flow; proximal cerebral vessels; of vasospasm can be done by technician for vasospasm, can follow does not assess distal bedside; can be set-up Lindegaard ratio (ratio of vasculature for continuous intracranial flow velocity/ monitoring extracranial ICA velocity) GCS Glasgow Coma Scale; ICP intracranial pressure; EVD external ventricular drainage; PbtO2 parenchymal brain tissue oxygen; SjVO2 jugular bulb venous oxygen saturation; EEG electroencephalogram; TCD transcranial Doppler; LR Linnengard’s Ratio

GCS

Table 5.1  Commonly used neuromonitors Type Measures

5  Multimodality Monitoring in Acute Brain Injury 63

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♦ A MUST for neurologically injured patients ♦ Easy and quick to perform ♦ In comatose patients, the Glasgow Coma Scale (GCS) is useful; it is reliable,

reproducible, and can be taught to a wide variety of healthcare professionals ♦ Provides global and regional assessment ♦ Affected by sedation and paralysis, which are often used in modern practice

after acute brain injury; hence, the need for other monitoring methods ♦ May be performed by physicians as well as nursing staff ■

ICP monitoring (Fig. 5.1) ♦ Measures pressure in millimeters of mercury (mmHg) ♦ Invasive – can be placed in parenchyma or ventricle ♦ Placed through burr hole and secured with bolt; tunneled or placed at time of

craniotomy ♦ Requires expertise in placing monitor ♦ Provides global vs. regional Pressure data ●

●

Because brain is noncompressible, measured fluid pressure should represent pressure throughout cranial vault and is generally thought of as a global measurement However, gradients may develop within the cranial vault and the pressure measurement may be different in the two hemispheres or in the frontal vs. middle fossa by up to 20 mmHg for brief periods and 5 mmHg chronically

♦ External ventricular devices (EVD) can drain CSF and have the advantage of

being diagnostic and therapeutic ♦ Waveform analysis can provide information about brain compliance, with

higher slopes or increased P2 waves indicating decreased brain compliance ♦ Elevated ICP (>25 mmHg) that is nonreducible is associated with poor

outcome ♦ AANS Guidelines – Class II recommendation for ICP monitoring in patients

with TBI and GCS < 9 with abnormal brain CT, or patients with normal brain CT if age >40 years, motor posturing, or SBP <90 ♦ Low cost ■

Transcranial Doppler ♦ Uses ultrasound technology ♦ Cerebral arteries are insonated via thin temporal bone (window) or transor­

bitally ♦ Inadequate windows in 5–20% of patients ♦ Noninvasive and can be done bedside ♦ Use is widespread, can be performed by technician, machines can produce

numerical results that can be interpreted by neurointensivists ♦ Mean velocities measured are proportional to blood flow

5  Multimodality Monitoring in Acute Brain Injury

65

ICP MANAGEMENT PROTOCOL TARGETS Overall aim is to optimize brain perfusion and avoid secondary damage CPP, 60 – 70; ICP, <20; Temp, <37.5°C; CVP, 6 – 10 Maintain CPP with fluids and vasopressors as needed STAGE 1 Head up 30° Sedation with propofol, 40 mcg/kg/min, titrated to RASS-2 Analgesia with opiate infusion Ventilation with normocarbia—pCO2, 34–36 mmHg Normothermia—36–37.5°C EVD for 5 min at a time if ICP >20, for >5 min STAGE 2 Mannitol 20%, 0.5 g/kg bolus dose q 4 hr prn; ICP >20 mmHg Hold if plasma Osm is >315 mmol/L STAGE 3 Neuromuscular paralysis with cisatracurium and/or vecuronium Mild hyperventilation—pCO2, 32–35 mmHg Head CT (?)—if not recent, consider repeat. STAGE 4 Hypertonic saline 3%, 250 mL bolus dose q 4 hr prn; ICP >20 mmHg Hold if serum sodium is >150 mEq/L Mild hypothermia @ 34–35°C—using cooling catheter or surface cooling device, change propofol to benzodiazepine infusion before starting therapeutic cooling STAGE 5 Decompressive craniectomy STAGE 6 Barbiturate sedation—, thiopentone, 250 mg bolus; then, 4–8 mg/hr OR pentobarbital, 10 mg/kg bolus, followed by infusion of 1 mg/kg/hr titrated to burst suppression, with continuous EEG CPP, cerebral perfusion pressure; ICP, intracranial pressure; Temp, temperature; CVP, cerebrovascular pressure; RASS, Richmond Agitation-Sedation Scale; EVD, external ventricular drainage; Osm, osmolality.

Fig. 5.1  ICP monitoring

♦ Indicated to measure cerebrovascular reserve, detect vasospasm, and deter-

mine blood flow in occlusion (stroke), recanalization (after thrombolysis or embolectomy), vasospasm/stenosis, or circulatory arrest (brain death) ♦ Can estimate ICP via pulsatility index ♦ Can detect microemboli and paradoxic emboli via right–left shunt

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♦ AAN Guidelines – Type A, Class I–II, evidence for detection of vasospasm

in middle cerebral and basilar arteries after aneurysmal SAH ♦ AAN Guidelines – Type A Class II evidence for evaluation of cerebral circu-

latory arrest associated with brain death ♦ Cost is essentially associated with equipment and personnel ■

Electroencephalography (EEG) ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

Surface EEG measures electrical activity on the surface of the brain Noninvasive and can be done bedside Provides global monitoring Can be used with an “ICU montage” – fewer electrodes that are faster and easier to place than for traditional EEG Can be used for seizure detection 20% incidence of nonconvulsive status epilepticus or subclinical seizures in this at-risk population Can be used to detect other detrimental neurophysiologic changes such as ischemia and elevated ICP Interpretation difficult for untrained practitioners Can be used to titrate medication levels during metabolic suppression with barbiturates ICU electrical equipment frequently produces artifacts

Less Commonly Used Neuromonitoring Tools ■

Parenchymal brain tissue oxygen (PbtO2) (Table 5.2) ♦ Measures partial pressure of oxygen in brain tissue ♦ Placed through burr hole or tunneled or placed at time of craniotomy

Table 5.2  Neuromonitoring protocol using parenchymal brain tissue oxygen (PbtO2) PbtO2 <15 mmHg ICP <20 mmHg Administer FiO2 100% × 15 min to test probe ↑PaCO2 to 40–45 mmHg range as tolerated; carefully monitor both ICP and PbtO2 Optimize CPP Administer fluids to euvolemia; watch for signs and symptoms of fluid overload Give blood products for anemia Cooling measures for brain; temperature >37°C Optimize sedation/analgesia; consider paralytics

ICP >20 mmHg Administer FiO2 100% × 15 min to test probe Drain CSF Optimize CPP Administer fluids to euvolemia Give blood products for anemia Administer mannitol, 0.25–0.5 m/kg Administer hypertonic saline for ICP Optimize sedation/analgesia; consider paralytics Cooling measures for brain temperature of >37°C

5  Multimodality Monitoring in Acute Brain Injury

67

♦ “Flush test” can be performed after insertion to verify that sensor is function-

♦ ♦ ♦ ♦

♦ ♦ ♦ ■

ing properly, 100% FiO2 administered for 15 min, and PbtO2 documented before and after; hyperoxia should elicit a linear relationship with PbtO2 Placement of probe in more injured vs. less injured hemisphere greatly changes the values, with lower values typically seen in injured hemisphere Regional measurement – 14 mm3 of tissue reflected Value not reliable if placed in area of severe injury (contusion) or if hematoma forms at probe site Thresholds – after TBI with normal CPP and ICP, PbtO2 values are usually 25–30 mmHg; <15 mmHg likely represents tissue at significant risk of hypoxia; <10 mmHg suggests ongoing ischemia in animal studies; a threshold of <20 mmHg may provide a margin of safety to prevent ischemia Low PbtO2 has been associated with worse outcomes; a randomized trial to evaluate if targeted therapy improves outcome will begin soon AANS Guidelines – Level III recommendation for use in severe TBI, with a lower limit of 15 mmHg as threshold for treatment Expensive

Brain temperature monitoring ♦ Measures temperature with a thermocouple probe placed in brain

parenchyma Included in brain oximetry probes Invasive Used with other invasive monitoring such as ICP and PbtO2 Brain temperature is typically 1–1.5°C warmer than core temperature Fever has been associated with worse outcome in SAH, TBI, and acute stroke ♦ Brain temperature can be used to guide induced normothermia/fever control ♦ Potential benefit of hypothermia is less well established ♦ ♦ ♦ ♦ ♦

■

Pupillometry ♦ Measures pupillary diameter and constriction velocity via a handheld digital

♦ ♦ ♦ ♦ ♦ ♦ ♦ ■

device that can assess pupillary dynamics and provide objective data that can be tracked over time to determine trends Noninvasive Can detect pupillary constriction even in small pupils Correlates with ICP CV <0.6 mm/s; associated with ICP >20 mmHg or midline shift Difficult to perform on agitated patients Affected by pupillary changes caused by sedating medications Low cost, can be performed by nursing or medical staff Not validated with outcome or GCS

Continuous EEG (cEEG) with or without spectral analysis ♦ 24 h recording favored in TBI and poor-grade SAH patients for better yield

of seizure detection

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♦ Post-processing software facilitates bedside interpretation of cEEG data –

spectral analysis can quantify percentage of fast or slow rhythms ●

■

Percent a variability or a–d ratios can be calculated and displayed on bedside monitor

Bispectral index monitor (BIS) ♦ Four electrodes placed across forehead to measure frontal brain activity ♦ Numerical value displayed, higher implying higher level of consciousness

and lower level correlating with deeper sedation ♦ Can be used during anesthesia/OR to estimate depth of sedation ♦ Noninvasive, RN can place and remove probe ♦ Artifact common from movement and sweat; often unreliable in patients with

brain injury due to underlying abnormal frontal activity ■

Jugular bulb venous oxygen saturation (SjVO2) (Fig. 5.2) ♦ Measures oxygen saturation of venous blood returning from the brain in jugular

bulb, i.e., oxygen extraction ♦ Catheter is placed in the internal jugular in cephalad direction; sampling may

♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

be intermittent or continuous and gives online reading (Abbocath Oximetric System) Sensitively measures episodes of desaturations that worsen outcome “Relatively” noninvasive “Global” monitor, so that small areas of desaturation/ischemia may be missed due to wash out from better perfused areas Can be used in combination with a regional monitor such as PbtO2 Correlates well with PbtO2 when latter is placed in normal brain tissue Artifacts are common, frequent need for co-oxymetry for calibration and lateral c-spine films to verify placement May be affected by placement in dominant vs. nondominant internal jugular vein Some risk of venous thrombosis is associated with prolonged use Studies have shown 50% of values are inaccurate due to mixed venous contami­nation AANS Guidelines – Level II recommendation for use in severe TBI with a lower limit of 50% as threshold for treatment Low cost

Rarely Used Neuromonitoring Tools ■

Cerebral microdialysis ♦ Measures the concentration of analytes in brain tissue extracellular fluid ♦ Artificial CSF is circulated by a small pump and comes to equilibrium with

the extracellular fluid through a 20–100 kDa dialysis membrane; analyte

5  Multimodality Monitoring in Acute Brain Injury

69

SjVO2 Monitoring Goal Jugular Venous Saturation = 60% –85% IF SjVO2 is <50:

1. Draw jugular co-oximetry, and

→ (to check if calibration is necessary)

2. Send an ABG, and

→ (to assess for hypoxemia or hypocarbia)

3. Obtain an Hgb, and

→ (from the co-oximetry result; to assess O2 delivery capacity)

4. Note the light intensity, and

→ (poor SQI due to poor position of catheter in the jugular bulb)

• If PO2 is low—increase of FiO2 /PEEP to improve oxygenation • If PCO2 is <30—decrease respiratory rate/tidal volume to normalize PCO2 • If Hgb is <30—consider blood transfusion to improve oxygen delivery • If ICP/CPP are not within goals—administer therapies to maintain goals • If temperature is not within goals—administer therapies to maintain goals • If you have calibrated several times and actual OxyHgb is >50% and

PO2 /PCO2 /Hgb are within goals and patient was placed in last position where steady SjVO2 readings could be obtained and SjVO2 continues to falsely drop— consider replacing catheter IF SjVO2 IS >85

1. Draw a jugular co-oximetry, and

→

(to check if calibration is necessary)

2. Send an ABG, and

→

(to assess for hypercarbia or hyperoxia)

3. Note the catheter insertion depth at the cordis →

(depth should be ~21–23 cm)

• If PCO2 is > 45—adjust vent to normalize PCO2 • If catheter depth is <16–18 cm—SjVO2 may reflect the mixing of extracranial/intracranial blood, which gives false elevation; reposition catheter to proper position in jugular bulb and check lateral c-spine film

• If catheter is calibrated and PCO2 /PO2 is within goal and catheter depth is correct— elevated SjVO2 may be due to hyperemia (blood flow in excess of demand) caused by: 1. Cerebral metabolic suppression by sedation 2. Alteration in cerebral autoregulation 3. Cells not utilizing O2 due to reasons such as infarction and cell death *** If fluid is leaking at the Cordis or sheath site and/or blood cannot be drawn back from catheter— catheter may be clotted and may need to be replaced.***

Fig. 5.2  SjVO2 monitoring

concentration can be tracked hourly, and trends can be detected almost in real time (1 h delay) ♦ Invasive – small probe placed through burr hole or at craniotomy ♦ Regional – reflects cellular state in a small area of tissue surrounding probe ♦ Values are not absolute – they are relative concentrations; recovery rate is impacted by fluid perfusion rate; it may be difficult to compare data from different institutions

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♦ Probe placement is important; the injured hemisphere is metabolically distinct

from remote tissue ♦ Microdialysis can yield information regarding energy metabolism, cellular

integrity, and substrate delivery and could be used to sample larger proteins if larger pore size (100 kDa) membrane is used (Table 5.3) ♦ Microdialysis consensus statement suggests use in poor-grade SAH and severe TBI patients who require measurement of ICP and CPP ♦ Cost of equipment and training of staff is high ■

Laser-Doppler flowmetry (LDF) ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

■

Measures CBF Invasive – subcortical fiberoptic probe measures shift of reflected laser light Relative values are reported; therefore, not quantitative Xenon CT can be used simultaneously to “calibrate” the values on the LDF for a more accurate estimation of absolute value of CBF Regional information Expensive Needs expertise for placement Use is not validated in clinical care; remains research tool

Thermal dilution flowmetry ♦ Measures CBF ♦ Invasive – probe placed in grey or white matter, measurements based on ♦ ♦ ♦ ♦ ♦

■

c­ onductance of heat between two electrodes May reflect true CBF Regional Expensive Needs expertise for placement Use is not validated in clinical care; remains research tool

Near-infrared spectroscopy (NIRS) ♦ Estimates cerebral venous oxygen saturation ♦ Some instruments can measure cytochrome C levels, thereby estimating

redox state of underlying brain tissue ♦ Based on light absorption in near-infrared range transmitted from an emitting

source to a sensor nearby Not quantitative Noninvasive – probe is placed on forehead Regional (frontal) Used more commonly in neonates – more reliable with thin skull and open fontanelles ♦ Unreliable in presence of underlying hematoma or fluid collection ♦ Monitors and probes are expensive ♦ Not validated clinically; essentially, a research tool ♦ ♦ ♦ ♦

TBI

100 ± 200

8,900 ± 6,500

31 ± 47

458 ± 563

–

381 ± 236

SAH No ischemia 2,120 ± 150 3,040 ± 320 150 ± 11.4 19.7 ± 2 1.62 ± 0.17 19.4 ± 3.24 SAH Severe ischemia 540 ± 150 6,730 ± 1,090 84.2 ± 35.8 97.8 ± 32.2 16.7 ± 4.70 119 ± 58.4 Data for the single analytes are expressed in mmol/L and are presented as mean ± standard deviation. TBI traumatic brain injury; SAH subarachnoid hemorrhage; L/P lactate/pyruvate; L/G lactate/glucose

Pathologic values Stahl N et al ( 2001) Acta Anaesthesiol Scand 45:977–985 Schultz MK et al (2000) J Neurosurg 93:808–814

Table 5.3  Normal and pathologic concentrations of brain metabolic analytes in human microdialysis studies, as reported in the literature for perfusion rate of 0.3 mL/min Pathology Glucose Lactate Pyruvate L/P ratio L/G ratio Glutamate Normal values Reinstrup P et al (2000) Posterior fossa (awake) 1,700 ± 900 2,900 ± 900 166 ± 47 23 ± 4 – 16 ± 16 Neurosurgery 47:701–710

5  Multimodality Monitoring in Acute Brain Injury 71

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Key Points ■

■

■

■

Major advances in microelectronics have produced new techniques for monitoring the injured brain Most commonly used neuromonitoring tools include serial neurologic exams, ICP monitoring, TCD, and EEG Less commonly used neuromonitoring tools include parenchymal brain tissue and brain temperature monitoring, pupillometry, cEEG with or without spectral analysis, BIS monitoring, and jugular bulb venous oxygen saturation Rarely used neuromonitoring tools include cerebral microdialysis, NIRS, laser Doppler flowmetry, and thermodilution flowmetry

Suggested Reading Becker DP, Miller JD, Ward JD et  al (1977) The outcome from severe head injury with early diagnosis and intensive management. J Neurosurg 47:491–502 Bellander BM, Cantais E, Enblad P et al (2004) Concensus meeting on microdialysis in neurointensive care. Intensive Care Med 12:2166–2169 Damian MS, Schlosser R (2007) Bilateral near infrared spectroscopy in space-occupying middle cerebral artery stroke. Neurocrit Care 6:165–173 Kurtz P, Hanafy KA, Claassen J (2009) Continuous EEG monitoring: is it ready for prime time? Curr Opin Crit Care 15(2):99–109 Marmarou A, Anderson RL, Ward JD (1991) Impact of ICP instability and hypotension on outcome in patients with severe head trauma. J Neurosurg 75:s59–s66 Meixensberger J, Jager A, Dings J et al (1998) Multimodality hemodynamic neuromonitoring – quality and consequences for therapy of severely head injured patients. Acta Neurochir Suppl 1:260–262 Robertson CS (1993) Desaturation episodes after severe head injury: influence on outcome. Acta Neurochir (Wien) Suppl 59:98–101 Steifel MF, Spiotta A, Gracias VH et  al (2005) Reduced mortality rate in patients with severe traumatic brain injury treated with brain oxygen monitoring. J Neurosurg 103:805–811 Stochetti N, Canavesi K, Magnoni S et al (2004) Arterio-jugular difference of oxygen content and outcome after head injury. Anesth Analg 99:230–234 Valadka AB, Gobinpath SP, Contant CF et al (1998) Relationship of brain tissue PO2 to outcome after severe brain injury. Crit Care Med 26:1576–1581

Chapter 6

Cerebral Edema and Intracranial Hypertension Matthew A. Koenig

Etiology ■ ■

Cerebral edema is traditionally divided into two types: vasogenic and cytotoxic Vasogenic edema is defined as excess fluid within the interstitial space ♦ Common causes include malignant brain tumors or abscesses, surgical

manipulation, meningitis or encephalitis, and contusions ♦ Due to disruption of the blood – brain barrier (BBB) and diffusion of water

into the interstitial space ♦ Tends to be at least partially responsive to glucocorticoid and osmolar therapies ♦ Primarily white-matter edema with maintenance of grey – white junction on

brain CT and MRI ♦ Increased signal on T2, diffusion-weighted (DWI), and apparent diffusion

coefficient (ADC) MRI ♦ Mechanism believed to be disruption of perivascular endothelial tight junc-

tions, resulting in movement of water from the vascular space into the interstitium, possibly related to alteration of aquaporin channels ■

Cytotoxic edema is defined as excess fluid within the intracellular space ♦ Common causes include stroke, fulminant hepatic failure, and water

intoxication ♦ Due to disruption of normal cellular osmotic gradients across the cellular

membrane resulting in ingress of water into the intracellular space ♦ Not responsive to glucocorticoid therapy; minimally or transiently responsive

to osmolar therapy (except water intoxication) ♦ Involves grey and white matter and does not maintain grey-white junction on

brain MRI and CT M.A. Koenig, MD (*) Associate Medical Director of Neurocritical Care, The Queen’s Medical Center, Neuroscience Institute–QET5, 1301 Punchbowl Street, Honolulu, HI 96813, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_6, © Springer Science+Business Media, LLC 2011

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• Increased signal on T2 and DWI, but decreased signal on ADC MRI (restricted diffusion) • Mechanism in stroke is energy depletion, resulting in failure of the Na+-K+ ATPase to maintain transmembrane osmotic gradients • Mechanism in water intoxication and other hypoosmolar states is passive movement of water down diffusion gradient into the intracellular space • Mechanism in hepatic failure is unknown, but likely related to disruption of osmolar gradients by accumulation of glutamine and ammonia ■

■

■

Hydrocephalic edema, a specialized type of vasogenic edema due to transependymal dissection of cerebrospinal fluid (CSF) into the interstitium surrounding distended cerebral ventricles, occurs in the setting of an intact BBB Hydrostatic edema, a specialized type of vasogenic edema due to disruption of the BBB from malignant hypertension that results in transvascular diffusion of water into the interstitial space, predominantly occurs in the posterior circulation (occipital white matter) Intracranial hypertension is defined as sustained intracranial pressure (ICP) >20 mmHg ♦ Cerebral edema and intracranial hypertension may occur together or

independently ♦ Normal ICP 5–20 cmH2O or 3–15 mmHg (1.36 cmH2O = 1 mmHg) ♦ ICP is usually reported in millimeters of mercury (mmHg) to ease calculation

of cerebral perfusion pressure (CPP) ♦ CPP = mean arterial pressure (MAP) – ICP in mmHg ♦ Normal CPP = 50–70 mmHg ♦ Relatively constant cerebral perfusion can be maintained at MAP of

♦

♦

♦ ♦

50–150 mmHg due to cerebral autoregulation; MAP >150 mmHg results in hydrostatic edema from malignant hypertension, unless chronic compensated hypertension exists ICP elevation is an independent risk factor for bad outcomes after head trauma, with a direct association between duration of ICP >20 mmHg and outcomes Even if CPP is maintained within the normal range, sustained intracranial hypertension has been demonstrated to increase brain injury in animal models of head trauma Intracranial hypertension causes brain injury due to compression and shifts of brain tissues, resulting in mechanical injury and vascular compromise Normal intracranial contents – total intracranial volume 1,400–1,700 mL • • • • •

Brain parenchyma 80% (~1,200 mL) CSF 10% (~150 mL) Blood 10% (~150 mL) CSF is produced by choroid plexus at 20 mL/h (450–500 mL/day) CSF absorption primarily via arachnoid granulations in superior sagittal sinus

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♦ Monroe – Kellie Doctrine states that the skull is inelastic, the intracranial

c­ ontents are noncompressible, and the overall volume of the cranial vault must remain constant so that an increase in volume in one compartment must be offset by a decrease in volume in the other compartments and/or an increase in ICP • Compensatory mechanisms for increasing brain parenchymal volume due to cerebral edema or a space-occupying lesion include displacement of (in order): CSF into the thecal sac, venous blood into the jugular veins, brain tissue into the foramen magnum (central herniation), and arterial blood into the extracranial carotid arteries (cerebral ischemia) • Intracranial elastance (dV/dP) is nonlinear; Early in the pathologic process, increases in parenchymal volume minimally impact ICP; after compensatory mechanisms are exhausted, further small increases may dramatically increase ICP

Clinical Presentation ■

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■ ■

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Because clinical signs and symptoms of intracranial hypertension lack specificity and sensitivity, a high index of clinical suspicion should be maintained in the appropriate settings The classic Cushing triad of bradycardia, hypertension, and abnormal respirations is only present in ~50% of patients with intracranial hypertension and is most commonly observed in the terminal stages of herniation The earliest signs and symptoms include new onset of hypertension and headache Bradycardia may be masked by pain, agitation, or blood loss, resulting in paradoxic tachycardia Other signs and symptoms include decrease in mental status, abnormal periodic breathing patterns (e.g., central hyperventilation), vomiting, hiccoughs, diplopia from bilateral sixth nerve palsies, dysrhythmias, and pupillary abnormalities For acute lesions, level of consciousness is associated with the extent of shift of midline structures, as measured by lateral displacement of the pineal body (easily identified on head CT due to calcification) ♦ ♦ ♦ ♦

■

■

<3 mm displacement from midline is associated with alertness 3–5 mm displacement from midline is associated with drowsiness 6–8.5 mm displacement from midline is associated with stupor >8.5 mm displacement from midline is associated with coma

For chronic lesions, such as brain tumors, a much greater degree of midline shift can be tolerated without alteration of consciousness Cerebral herniation syndromes (Table 6.1) ♦ Cerebral herniation refers to displacement of brain tissue into an adjacent

compartment due to local gradients in ICP

Bilateral downward herniation of both medial temporal lobes through the tentorial notch, compressing the midbrain

Herniation of brain through skull breach from trauma or surgery Upward herniation of posterior fossa contents through the tentorial notch, usually due to excessive ventricular CSF drainage Downward herniation of cerebellar tonsils through foramen magnum with compression of medulla

Central

External

Cerebellar

Upward

Medial temporal lobe herniates under tentorium cerebelli into tentorial incisura, displacing the midbrain

Transtentorial (Uncal)

Table 6.1  Types of cerebral herniation syndromes Etiology Subfalcine Cingulate gyrus herniates under falx cerebri

Bilateral posterior cerebral artery compression, brainstem stroke

Brainstem stroke

Bilateral papillary dilation, extensor posturing, decrease in mental status

Respiratory arrest, episodic extensor posturing, decrease in mental status, cardiac dysrythmias

Findings related to etiology and location

Bilateral pupillary dilation, decreased mental status, and extensor posturing

Ipsilateral pupillary dilation due to third nerve compression and decreased mental status

Complications Ipsilateral or contralateral anterior cerebral artery compression Ipsilateral or contralateral posterior cerebral artery compression, obstructive hydrocephalus from compression of cerebral aqueduct, brainstem stroke or Duret hemorrhage Bilateral posterior cerebral artery compression, obstructive hydrocephalus from compression of cerebral aqueduct, brainstem stroke or Duret hemorrhage Hemorrhage or ischemia of herniating tissue

Clinical findings Contralateral leg weakness and decreased mental status

Decompression of posterior fossa lesion

Decompression of bilateral supratentorial lesions or CSF diversion if caused by obstructive hydrocephalus Decompression of mass lesion or extension of craniectomy Clamping of the ventriculostomy drain

Decompression of unilateral mass lesion

Treatment Decompression of unilateral mass lesion

76 M.A. Koenig

6  Cerebral Edema and Intracranial Hypertension

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♦ Herniation causes ischemic stroke and venous hemorrhages due to compression

of adjacent arteries and veins, often resulting in permanent, devastating neurologic injury, even if quickly reversed ♦ Although cerebral edema, intracranial hypertension, and herniation often occur in concert, it is important to recognize that herniation occurs in the absence of ICP elevation in one-third of patients

Diagnosis and Differential Diagnoses ■

ICP monitoring ♦ Indications for ICP monitoring

• In traumatic brain injury, Glasgow Coma Scale score is £8 and an abnormal head CT or a normal head CT and two-thirds of the following conditions: ▲ ▲ ▲

Age >40 Unilateral or bilateral motor posturing Systolic blood pressure <90 mmHg

• In other conditions, guidelines are lacking, but ICP monitoring is usually indicated in the following conditions: ▲ ▲ ▲

▲ ▲

Obstructive hydrocephalus Communicating hydrocephalus with signs of elevated ICP Subarachnoid hemorrhage with abnormal Glasgow Coma Scale score, generalized cerebral edema, or risk factors for neurologic decline Stroke involving >50% of the MCA territory Intraparenchymal hemorrhage with >5 mm midline shift

• External ventricular drain – gold standard for ICP monitoring ▲

▲

▲

▲

▲

▲

Fluid-coupled transducer placed in the lateral ventricle, with tip located in the foramen of Monroe Allows continuous ICP monitoring and intermittent drainage of CSF when ICP is elevated Alternative strategy is continuous CSF drainage at a given ICP “popoff” (the ICP threshold that must be reached for CSF drainage to occur) and intermittent measurement of ICP Major advantage is that it offers both an ICP monitor and a treatment option for intracranial hypertension (CSF drainage) Potential complications include hemorrhage into catheter tract ­(“tractoma”), infection, injury to eloquent tissue, CSF over drainage, catheter occlusion Catheter must be re-zeroed at the level of the foramen of Monroe (the tragus of the ear is the external landmark) when the patient is moved or repositioned or the bed height is changed

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M.A. Koenig ▲

▲

▲

▲

▲

Indicated for most patients who require ICP monitoring and may require CSF drainage, absolutely indicated for patients with intracranial hypertension secondary to obstructive hydrocephalus Relative contraindications include collapsed ventricles, coagulopathy (i.e., fulminant liver failure carries a 10% risk of catheter tract hemorrhage), and infection over insertion site Antibiotic impregnated catheters decrease the rate of iatrogenic meningitis and ventriculitis; systemic antibiotics are optional in standard ventriculostomy catheters CSF infection rates increase rapidly between days 5–10 and subsequently plateau CSF infection rates are decreased by aseptic insertion and access techniques, limiting the frequency of catheter access, tunneling the catheter beyond the insertion site, and early catheter removal

• Solid-state ICP monitors ▲

▲

▲

▲

Fiberoptic or microwire ICP transducers can be placed within the brain parenchyma or any other intracranial compartment May be coupled with brain tissue oximeter, microdialysis catheter, brain thermometer, ventriculostomy catheter, or other devices Advantages – small catheter size allows smaller craniotomy, lower risk of hemorrhage and infection than ventriculostomy drain, does not require re-zeroing with change in position, no risk of catheter occlusion, easily placed in patients with collapsed ventricles Disadvantages – cannot be used to drain CSF unless coupled with a traditional ventriculostomy drain, accuracy of ICP measurement may drift with time and cannot be re-zeroed after insertion

• Subarachnoid (Richmond) “bolt” ▲

▲

▲

Fluid-coupled ICP monitor is placed via a screw placed through a small ventriculostomy into the epidural space, followed by durotomy to allow communication with the CSF Advantages – low risk of infection or hemorrhage, easily placed in patients with collapsed ventricles Disadvantages – cannot be used to drain CSF, accuracy of ICP measurement tends to drift with time and device cannot be re-zeroed after placement, prone to occlusion or dampening of ICP waveform

• Lumbar catheter ▲

▲

Fluid-coupled catheter inserted via lumbar puncture into the lumbar thecal sac Advantages – avoidance of craniotomy, lower risk of hemorrhage and infection than is associated with ventriculostomy catheter, allows therapeutic drainage of CSF in addition to ICP measurement

6  Cerebral Edema and Intracranial Hypertension ▲

▲

▲

▲

79

Disadvantages – preferentially drains the subarachnoid space rather than intraventricular compartment; therefore, may be ineffective for patients with ventriculomegaly Contraindicated in patients with significant shift of midline structures due to unilateral supratentorial lesions or crowding of the basal cistern by generalized supratentorial edema In lateral decubitus position, lumbar ICP should be equivalent to ventricular ICP In upright position, ventricular ICP (in cmH2O) = lumbar ICP (in cmH2O) - distance from lumbar drain tip to tragus of ear in cm (in practice, this is difficult to measure)

♦ ICP waveform analysis

• ICP waveform is produced by transient increase in pressure from transmission of arterial pulse to the brain • P1; percussion (systolic) wave produced by transient increase in ICP from transmission of arterial systolic pressure to the choroid plexus, resulting in production of CSF • P2; elastance (tidal) wave due to restriction of ventricular expansion by rigid dura and skull, resulting in a transient increase in ICP • P3; dicrotic wave due to closure of the aortic valve associated with arterial dicrotic notch • With normal intracranial compliance, P1 has the highest pulse pressure, followed by P2 and P3 • Elevation of the P2 pulse pressure higher than the P1 is a sign of disturbed intracranial elastance, indicating that small increases in intracranial volume may dramatically increase ICP • Normal ICP pulse pressure is ~3 mmHg, increasing as high as 10–15 mmHg in patients with poor intracranial compliance • Lundberg A (Plateau) wave – periodic, sustained elevation of ICP >50 mmHg for 15 min or more, associated with poor intracranial compliance and poor prognosis • Lundberg B wave – periodic, self-limited elevation of ICP to 20–50 mmHg, occurring every 1–2 min and lasting several seconds • Lundberg C wave – periodic, self-limited elevation of ICP ~20 mmHg, occurring every 4–8 min, of uncertain significance

Management ■

Vasogenic cerebral edema due to tumor, abscess, or surgical manipulation ♦ 10 mg dexamethasone IV q 6 h rapidly decreases vasogenic edema but is

ineffective against cytotoxic edema

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M.A. Koenig

♦ Treat fever if present, using 650 mg acetaminophen PO q 4 h or external/

invasive cooling devices if required ♦ Maintain normoglycemia with aggressive insulin therapy to maintain glucose

<150 mg/dL ♦ 0.5–1 g/kg mannitol IV q 6 h to maintain serum osmolality 300–320 mOsm/L

or 2–3% NaCl infusion to maintain serum Na 145–155 mEq/L for severe or refractory cerebral edema ♦ If intracranial hypertension suspected, proceed to ventriculostomy for ICP monitoring and to ICP crisis treatment algorithm ■

Cytotoxic cerebral edema due to stroke or intracerebral edema ♦ Corticosteroids are ineffective and are not indicated ♦ Treat fever if present, using 650 mg acetaminophen PO q 4 h or external/

invasive cooling devices if required ♦ Maintain normoglycemia with aggressive insulin therapy to maintain glucose

<150 mg/dL ♦ Osmolar therapy with mannitol or hypertonic saline have never been demon-

strated to alter outcomes for cytotoxic edema and may produce rebound exacerbation of edema when discontinued; however, these agents may temporize for definitive therapy ♦ If intracranial hypertension suspected, proceed to ventriculostomy for ICP monitoring and to ICP crisis treatment algorithm ♦ Consideration should be given to early decompressive surgery or ­hemicraniectomy before significant clinical deterioration ■

Intracranial hypertension ♦ For ICP crisis or cerebral herniation syndromes, follow the treatment

­algorithm (Fig. 6.1)

ICP crisis or herniation

• Head of bed to 30° • Bag-mask ventilate to PaCO2 ~30 mmHg • Mannitol 1–1.5 g / kg or 23.4% NaCl 30 – 60 mL

Intubate and hyperventilate to PaCO2 ~30 mmHg Repeat dosing of mannitol or hypertonic saline to serum osmolality ~320 mOsm/L • Place ventriculostomy catheter and drain 5 –10 mL CSF • Place central line for hypertonic saline; goal Na, 145–155 mg/L

• Pentobarbital 3–10 mg/kg load; then, 0.5–3 mg/kg/hr for 48–72 hr • Hypothermia to 32°C Surgical decompression or hemicraniectomy

Fig. 6.1  Sample algorithm for management of intracranial hypertension

6  Cerebral Edema and Intracranial Hypertension

81

♦ Head of bed to 30°

• On average, raising the head of the bed to 30° decreases intrathoracic ­pressure and increases jugular venous drainage, thereby decreasing ICP by 3–4 mmHg • However, in patients with hypotension, the small decrease in ICP may be offset by a decrease in CPP, resulting in ischemia • Stroke patients may be optimally positioned with the head of bed at 0° due to loss of autoregulation and decreased CPP when the head of bed is raised • In practice, the effect of raising the head of bed should be tested while closely monitoring ICP and CPP, and the optimal height should be individualized to the patient • Of perhaps greater importance, the neck should be held in the upright ­position and obstructions such as cervical collars or endotracheal tube tape should be loosened or removed to allow jugular venous drainage

Sedation and Analgesia ▲

▲

▲

▲

▲

▲

Transient and sustained intracranial hypertension may result from untreated pain or agitation, coughing at the endotracheal tube, or shivering Pain should be treated with short-acting narcotics such as fentanyl or remifentanil, either by continuous infusion (with frequent interruptions for neurologic examination) or serial boluses Agitation should be treated with short-acting sedative/hypnotic medications such as midazolam, propofol, or dexmedetomidine, either by continuous infusion (with frequent interruptions for neurologic examination) or serial boluses Coughing at the endotracheal tube can be treated with systemic sedation alone or in combination with topical lidocaine solution in addition to checking for proper tube positioning and cuff inflation and adjusting the ventilator settings to patient comfort Shivering can be managed with a combination of 30 mg buspirone PO q 8 h, narcotics (morphine and meperidine are most effective), and surface counter-warming (either with a bear hugger blanket or selective counter-warming of the palms and face) Paralysis is rarely required but may be highly effective in treating refractory intracranial hypertension, but proper sedation must be ensured prior to initiation

• Hyperventilation ▲

▲

Rapidly reduces ICP by reflex cerebral vasoconstriction due to hypocapnic CSF alkalosis May provoke or worsen cerebral ischemia if PaCO2 <28 mmHg

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M.A. Koenig ▲

▲

▲

▲

▲

▲

▲

▲

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Prolonged hyperventilation (>4 h) will lead to rebound intracranial hypertension when discontinued due to CSF buffering Patients with refractory ICP elevation, especially those requiring sedation, should undergo early intubation to maintain control of the airway and PaCO2 Hyperventilation should not be applied prophylactically, and most patients should be maintained at a target PaCO2 ~35 mmHg In patients with ICP crisis or herniation, target PaCO2 should be 28–32 mmHg For patients on mechanical ventilation, manual bag breaths should be avoided because of the tendency for excessive ventilation, and hyperventilation should be accomplished by increasing the minute ventilation by ~20% and titrating to an end-tidal CO2 monitor Hyperventilation begins to reduce ICP within 10 min, with a peak effect in 20–40 min The effect of hyperventilation on ICP may last as long as 4–8 h, but rebound intracranial hypertension ensues thereafter If hyperventilation is required prior to intubation, controlled breaths should be delivered by bag-valve at a rate of ~20, and excessive volumes and rates should be avoided After definitive therapies are initiated, hyperventilation should be slowly weaned over 6–12 h by reducing the respiratory rate by ~2 every 2 h or similar serial reductions in minute ventilation

• Osmotic therapy ▲

▲

▲

▲

▲

▲

▲

Dehydrates brain tissue across an intact BBB by creating an osmotic gradient that draws water from the interstitium into the vascular space More effective against vasogenic than cytotoxic edema but may temporize malignant cytotoxic edema by selectively dehydrating uninvolved brain Prolonged infusions of osmotic agents may ultimately worsen cytotoxic edema by sinking across a degraded BBB into infracted tissue beds Rebound cerebral edema may occur with rapid discontinuation of osmotic therapy In stroke and intraparenchymal hemorrhage, selective osmotic dehydration of normal brain may actually worsen brainstem compression and shift of midline structures Serum electrolytes and osmolality must be closely monitored during osmotic therapy due to the potential risks of dehydration, hypokalemia, hypomagnesemia, hypernatremia, hyperosmolality, and renal failure Mannitol N Initiated as a 1–1.5 g/kg bolus of 20% mannitol for ICP crisis or

herniation N Not recommended for continuous infusion in stroke or head trauma

due to potential to worsen cerebral edema

6  Cerebral Edema and Intracranial Hypertension

83

N May repeat 0.5–1 g/kg boluses on an as needed or scheduled

N N N

N

N N

N

N

▲

basis q 6 h to maintain a target serum osmolality of 300–320 mOsm/L Two-stage mechanism of action – osmotic dehydration of brain followed by renal diuretic effect 90% excluded by an intact BBB (reflection coefficient, 0.9) May produce massive, rapid diuresis of dilute urine due to osmotic load on renal tubules, leading to volume contraction and hypotension, both of which may reduce CPP and produce ischemia in the setting of high ICP Urine output should be closely monitored in the first 4 h after administration and should be replaced by hypertonic or isotonic NaCl to maintain euvolemia Electrolytes and serum osmolality should be monitored q 6 h during therapy In addition to osmotic effects, other salutary effects include free radical scavenging, favorable rheologic effects, and neuroprotective mechanisms Side effects include acute tubular necrosis (which leads to renal failure if dehydration is permitted), hypokalemia, hypomagnesemia, hypotension Although serum osmolality should be targeted to be <320 mOsm/L due to the risk of acute tubular necrosis, in practice, osmolality as high as 360 mOsm/L is tolerated without apparent complications as long as dehydration is not permitted

Hypertonic saline N May be given as a bolus or continuous infusion of a variety of NaCl

concentrations, including 2, 3, 7.5, and 23.4% N Has similar osmotic effects as mannitol but is less potent diuretic N Serum osmotic load increases blood volume and MAP, contributing

to a net increase in CPP coupled with a decrease in ICP N Concentrations of NaCl >2% require administration via a central

N N

N N

venous catheter due to the risk of phlebitis when given through peripheral catheters In addition to osmotic effects, other salutary effects include an improved rheologic profile and neuroprotective properties Continuous infusion of hypertonic solutions may cause rebound exacerbation of cerebral edema and tissue sinking with cytotoxic edema and disruption of the BBB In the presence of an intact BBB, hypertonic NaCl is 100% excluded from the interstitium (reflection coefficient 1.0) Repeated doses or continuous infusion of concentrated NaCl leads to hyperchloremic acidosis unless buffered as a 50%/50% or 75%/25% solution of NaCl and NaHCO3

84

M.A. Koenig N For transtentorial herniation, bolus infusion of 30–60 mL of 23.4%

N

N

N

N

N N

N

▲

saline as part of a standard treatment algorithm will temporarily reverse clinical features of herniation and reduce ICP in 75% of patients For herniation or ICP crisis, a bolus infusion of 30–60 mL of 23.4% saline or 250–500 mL of 3% NaCl should be followed by a continuous infusion of 2–3% NaCl at 50–100 mL/h, with the goal of increasing serum Na+ by 5 mg/L within the first hour and maintaining Na+ at 145–155 mg/L thereafter The most feared potential complication, central pontine myelinolysis (CPM), has never been reported after use of hypertonic NaCl for treatment of intracranial hypertension or cerebral edema Risk factors for CPM, including alcoholism, malnutrition, and chronic hyponatremia, should be considered a relative contraindication for hypertonic NaCl 23.4% Saline should be infused via IV pump over at least 10 min because rapid hand infusion produced transient hypotension in a significant number of patients Other potential side effects include renal failure, dehydration, dysrhythmia, hemolysis, and congestive heart failure Typically, serum [Na] should be maintained at <160 mg/L; however, in practice, concentrations as high as 180 mg/L are tolerated without apparent complications With continuous infusion of hypertonic NaCl, most patients develop hypokalemia, requiring the addition of 20–40 mg of KCl per 1 L infusion

Choosing mannitol or hypertonic NaCl N Mannitol and hypertonic saline may be given serially or simultane-

N N

N N

ously and may have independent and complementary actions on erythrocyte morphology and secondary mediators of injury Because of its volume expansion effects, hypertonic NaCl is preferred in the setting of dehydration or hypotension In patients lacking central venous catheters, osmotic therapy should not be delayed, and mannitol should be administered until central access can be established Patients with significant risk for development of CPM should probably receive mannitol rather than hypertonic NaCl In patients with symptomatic congestive heart failure, mannitol is preferred due to the diuretic actions and the shorter duration of osmotic volume expansion

• Metabolic suppression ▲

Cerebral perfusion is dictated in part by metabolic demands of brain tissue in a phenomenon that is called vascular-metabolic coupling, which is exploited in the BOLD effect in fMRI

6  Cerebral Edema and Intracranial Hypertension ▲

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Suppressing brain metabolism by hypothermia and general anesthetic agents leads to decreased ICP by reducing cerebral blood volume Pentobarbital N Barbiturate anesthetic most commonly used for metabolic suppres-

sion for treatment of refractory ICP elevation N Half-life of 20 h compares favorably to phenobarbital (96 h) N 3–10 mg/kg IV load over 30–60 min followed by a continuous infu-

sion of 0.5–3 mg/kg/h N Continuous electroencephalogram (EEG) monitoring is recom-

N N

N

N

N

N N N

N

▲

mended while the infusion rate is being titrated, although the goal is to control ICP rather than to achieve an arbitrary degree of EEG suppression (i.e., burst-suppression frequency every 10 s) If ICP remains elevated despite complete EEG suppression, further increase in pentobarbital dose will not be effective After ICP control is established at a stable dose of pentobarbital, EEG monitoring can be performed periodically rather than continuously The neurologic exam will be completely suppressed during EEG burst suppression or generalized suppression, often including the pupillary light reflexes, potentially masking brain death Most patients experience hypotension, requiring vasopressor agents, immune suppression, hypothermia, generalized edema from third spacing, and ileus Patients are at high risk for infection and do not mount fever or other markers of inflammation; therefore, routine blood, sputum, and urine cultures should be obtained at least every other day during pharmacologic coma Pentobarbital should be maintained for 48–72 h, after which, it can be discontinued without weaning due to the long half-life Serum drug levels may be useful after discontinuation to determine the rate of drug clearance Brain death examination cannot be performed by clinical findings until the serum pentobarbital level is <5 mg/mL, requiring confirmatory testing (i.e., SPECT scan or angiography) at higher levels In clinical trials for head trauma, pentobarbital has never been demonstrated to improve neurologic outcomes or mortality despite proven efficacy in reducing ICP

Propofol N Propofol has become more popular as an alternative to pentobarbital

due to a shorter half-life (60–120 min after prolonged infusion)

N 150 mg/kg bolus, followed by 10–100 mg/kg/min infusion N More frequently causes severe hypotension N Patients often develop tachyphylaxis, requiring higher doses over

time to maintain burst suppression

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M.A. Koenig N Relatively contraindicated in children, dehydration, heart failure,

N

N

N N

▲

renal failure, hepatic failure, and elderly patients due to risk of propofol-infusion syndrome Patients receiving >50 mg/kg/h should undergo daily screening for metabolic acidosis and serum triglyceride and creatinine kinase levels Propofol infusion syndrome is a fatal syndrome of refractory ­metabolic acidosis (with or without elevated lactate levels), rhabdomyolysis, renal failure, and cardiovascular collapse Propofol may cause pancreatitis due to hypertriglyceridemia from the lipid carrier vehicle Other complications, including hypothermia and immune suppression, are similar to those associated with pentobarbital

Hypothermia N Presumably reduces ICP through metabolic suppression, but mech-

anisms remain unclear N Proven neuroprotective therapy for comatose survivors of cardiac

N N N

N N

arrest, but disappointing neuroprotection in clinical trials of stroke and traumatic brain injury External or invasive cooling devices used to maintain core temperature at ~32°C for 48–72 h Rewarming should occur in a controlled fashion over 12–24 h to prevent rebound intracranial hypertension Hypothermia masks the fever response to infection; therefore, ­routine blood, sputum, and urine cultures are recommended for surveillance Other side effects include coagulopathy and dysrhythmias Shivering must be suppressed as described above because it causes increased metabolism, CO2 production, and ICP

♦ Decompressive hemicraniectomy (Fig. 6.2)

• Large craniectomy and duroplasty to decompress the frontal, parietal, and temporal lobes as a rescue therapy for malignant cerebral edema • Demonstrated mortality and functional outcome benefit for patients <60 years of age with malignant MCA strokes who were treated prior to herniation and within 24–48 h of stroke onset • For MCA strokes, hemicraniectomy was equally beneficial in patients with dominant and nondominant strokes • Evidence for efficacy in intraparenchymal hemorrhage, subarachnoid hemorrhage, and head trauma is less strong • Should be performed early in disease process in patients at high risk for the development of malignant cerebral edema before neurologic decline or cerebral herniation occurs

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Fig. 6.2  Right MCA stroke treated with decompressive hemicraniectomy followed by cranioplasty at 3 months. Note the improvement in midline shift after hemicraniectomy.

• Bilateral hemicraniectomy can be performed for patients with bilateral cerebral edema due to head trauma or encephalitis, but large outcome studies are lacking • As with all salvage therapies, the possibility that hemicraniectomy may increase the chances of a patient (who would have otherwise died) surviving in a dependent state with severe neurologic deficits must be discussed with surrogate decision makers • Hemicraniectomy reduces the need for osmotherapy and other interventions for cerebral edema • The bone flap can be replaced or substituted with a prosthesis ~3 months after the initial surgery • Complications include persistent subdural hygromas, hydrocephalus, hemorrhage due to compression at the edge of the craniectomy, and infection • Patients must protect the brain under a helmet after replacement of the bone flap ♦ The Lund concept – physiologic approach to management of cerebral edema

• Although CPP-guided therapy has been the mainstay for management of cerebral edema for decades, competing treatment philosophies also exist • Therapy based solely on maintenance of CPP at >50–60 mmHg has inherent limitations - CPP is a global measure that does not necessarily account for focal ischemia • A rigid approach to maintaining CPP at all costs may result in systemic injury from volume overload and vasopressor use leading to ARDS • In patients with predominantly cytotoxic edema (stroke, contusions, etc.), the BBB and autoregulatory mechanisms are disrupted, leading to a linear relationship between MAP and cerebral edema formation • Therapy based on increasing MAP to augment CPP may, therefore, worsen cerebral edema and systemic complications

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• The Lund concept focuses on limiting cerebral edema by maximizing the capillary oncotic pressure and minimizing the capillary hydrostatic pressure ▲

▲

▲

MAP is controlled with beta blockers and clonidine to limit the contribution of hydrostatic pressure to cerebral edema formation Albumin is given to maintain the capillary oncotic pressure and draw water into the vascular space Tissue hydrostatic pressure is limited by reducing ICP through sedation and metabolic suppression

Key Points ■

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■

■

■

Cerebral edema, intracranial hypertension, and cerebral herniation may occur independently or may exist on a spectrum of disease Clinical signs and symptoms of intracranial hypertension are unreliable, and a high index of suspicion is required for relevant diseases The BBB is disrupted in cytotoxic edema, rendering it less amenable to treatment with osmotic agents or corticosteroids and more prone to worsening of edema with CPP augmentation Sustained ICP elevation and cerebral herniation are medical emergencies best managed by a protocol that includes osmotic therapy and hyperventilation Medical management of malignant cytotoxic edema has only temporary efficacy but can act as a bridge to definitive surgical management, if available

Suggested Reading Bardutzky J, Schwab S (2007) Antiedema therapy in ischemic stroke. Stroke 38:3084–3094 Bhardwaj A, Ulatowski JA (1999) Cerebral edema: hypertonic saline solutions. Curr Treat Opt Neurol 1:179–187 Hutchison P, Timofeev I, Kirkpatrick P (2007) Surgery for brain edema. Neurosurg Focus 22:E14:1–9 Jüttler E., Schwab S., Schmiedek P., Unteberg A., Hennerici M., Woitzik J., Witte S., Jenetzky E., Hacke W., DESTINY Study Group (2007) Decompressive surgery for the treatment of malignant infarction of the middle cerebral artery (DESTINY): a randomized, controlled trial. Stroke 38:2518–2525 Koenig MA, Bryan M, Lewin JL, Mirski MA, Geocadin RG, Stevens RD (2008) Reversal of transtentorial herniation with hypertonic saline. Neurology 70:1023–1029 Lescot T, Abdennour L, Boch AL, Puybasset L (2008) Treatment of intracranial hypertension. Curr Opin Crit Care 14:129–134 Marmarou A (2007) A review of progress in understanding the pathophysiology and treatment of brain edema. Neurosurg Focus 22(5):E1:1–10 Mayer SA, Coplin WM, Raps EC (1999) Cerebral edema, intracranial pressure, and herniation syndromes. J Stroke Cerebrovasc Dis 8:183–191 Raslan A, Bhardwaj A (2007) Medical Management of cerebral edema. Neurosurg Focus 22(5):E12:1–12

Chapter 7

Cardiac Dysfunction, Monitoring, and Management Andrew Naidech

Epidemiology ■ ■

Cardiac dysfunction is common in patients in the NCCU Incidence varies with disease ♦ Subarachnoid hemorrhage (SAH)

• • • •

~70% of patients have abnormal ECG or elevated cardiac troponin I (cTI) ~15–20% have systolic BP <100, requiring vasopressors ~15% have pulmonary edema ~5–10% have dysarrhythmia

♦ Intracerebral hemorrhage (ICH)

• ~20% of patients have elevated cTI ♦ Traumatic brain injury (TBI)

• ~10–20% of patients have pulmonary edema or cardiac dysfunction More common in patients with devastating TBI that leads to brain death ♦ Status epilepticus (SE) ▲

• Noted in both convulsive and nonconvulsive SE • Associated with persistent and life-threatening dysrhythmias ♦ Spinal cord injury (SCI)

• Varies with level of involvement of autonomic nervous system • Most common with altered autonomic system tone • Bradycardia and tachycardia common

A. Naidech, MD (*) Department of Neurology, Northwestern University, Feinberg School of Medicine, Neuro/Spine ICU, Northwestern Memorial Hospital, Chicago, IL 60611-3078, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_7, © Springer Science+Business Media, LLC 2011

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Etiology ■

Coronary artery disease ♦ Less common in patients with SAH, TBI, and SCI because these patients tend

to be younger and have fewer medical risk factors (hypercholesterolemia, hypertension, previous myocardial infarction (MI), peripheral vascular disease, etc.) ♦ More common in patients with ICH or spinal cord infarction ♦ Should be considered in patients with appropriate medical risk factors or history (e.g. spinal cord infarction after aortic stenting) ■

Neurogenic stunned myocardium (NSM), e.g., myocardial stunning. Reversible heart dysfunction (similar to Tako-Tsubo cardiomyopathy). Catecholamineinduced neurologic injury, especially SAH and SE ♦ Temporary increase in myocardial contractility, depressed myocardial function

1–2 days later, and recovery 7–10 days after that on serial echocardiography

♦ ↑cTI → ↑risk of vasospasm, cerebral infarction, hypotension, and death ♦ cTI levels are typically smaller than expected for MI ♦ Stunned myocardium is common with moderate elevations in cTI (0.1–2

mg/L)

■

Factors that increase the risk of NSM after SAH ♦ Worse neurologic grade ♦ Female sex ♦ Younger age

■

Vasopressors and hyperdynamic therapy ♦ Increased myocardial work from ↑BP, contractility, and myocardial oxygen

demand may provoke myocardial ischemia and dysrhythmias ♦ Subclinical NSM may be provoked by vasopressors for vasospasm or induced

hypertension (see Management, below) ■

Volume overload from volume loading, hypervolemic therapy, albumin

Clinical Presentation (Symptoms and Signs) ■

May be asymptomatic and detected by laboratory studies only ♦ cTI, CK, CK-MB, B-type naturitic peptide (BNP)

• Consider screen on admission and next calendar day in all patients with SAH, ICH, SE and TBI • cTI is more often positive than CK-MB • In SAH, early cTI elevation is associated with later complications and poor response to hyperdynamic therapy

7  Cardiac Dysfunction, Monitoring, and Management

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• Consider daily cTI screen in all patients receiving vasopressors ■

All NCCU patients should have continuous telemetry monitoring ♦ Many systems have automatic computer monitoring of rhythm, QRS dura-

tion, QTc, and ST-T waves ■

Hypotension ♦ May be refractory to volume supplementation ♦ NSM or neurogenic pulmonary edema (neurogenic pulmonary edema (NPE);

especially after SAH) is more likely if volume loading does not correct hypotension but worsens gas exchange, A-a gradient and leads to pulmonary edema ■

Abnormal echocardiogram ♦ Often shows regional wall motion abnormalities after 2–4 days after disease

onset, with improvement at 7–10 days in patients with SAH ■

Radiographic pulmonary edema ♦ Bibasilar infiltrates or atelectasis ± pulmonary effusions ♦ NPE

• SAH or SE may lead to NPE through catecholamine and inflammationmediated changes in alveolar and capillary cells • May require higher PEEP or increased mechanical support • Typically self-limited to a few days • Both hydrostatic (from increased left atrial filling pressures) and endothelial mechanisms have been implicated as causes of NPE • Typically prolongs ICU length of stay but does not increase mortality ■ ■ ■ ■

Impaired gas exchange or elevated A-a gradient Abnormal physiologic score (e.g., APACHE) Dysrhythmia, variable Dysrhythmias in SE may be more common, refractory to ACLS protocols, and fatal, especially in patients who are acidemic

Diagnosis and Differential Diagnoses ■

■

Direct effect of primary disease and catecholamine surge (diagnosis of exclusion after other diagnoses considered) Dysrhythmia or abnormal ECG ♦ Electrolyte abnormality

• Hypokalemia (↓K); hypertonic saline frequently leads to ↓K+ and may require standing supplementation • If abnormal Mg2+ is not corrected, ↓K+ cannot be normalized • ↑K+

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• Abnormal phosphate, magnesium, calcium should also be corrected ♦ Acidosis and academia

• Sepsis • Shock • Renal failure ■

Hypotension ♦ Myocardial ischemia (see below) ♦ Volume depletion ♦ Lack of autonomic (sympathetic) tone

• Common in cervical SCI, especially complete ■

Sepsis – consider screen for infection ♦ Ventriculitis/meningitis, especially if ventricular or lumbar drain is in place

• Few data to support prophylactic antibiotics for ventricular drains • Prophylactic antibiotics may lead to microbial resistance • Antibiotic-coated ventricular and central venous catheters probably reduce infection >1 week after insertion ♦ UTI and urosepsis ♦ Bacteremia

• Most common source in ICUs is related to central venous lines • Differentiate site of infection (central venous line, CSF, lung, etc.) • Reduce central line infection risk with strict sterile technique on insertion, full-body drape, use of gown/gloves/mask and discontinuation as soon as feasible • Antibiotic-coated central lines prevent infection >1 week after catheter insertion ♦ Pneumonia

• Ventilator associated if presentation is >48–72 h after intubation; antibiotics depend on sensitivities • Consider anaerobic coverage for suspected aspiration pneumonia ■

Pulmonary embolism – common in patients with immobility ♦ Consider minidose or low-molecular heparin for patients at low risk for hem-

orrhage but high risk for venous thrombosis (e.g., SCI with immobility, CNS tumor or metastatic disease, etc.). Controversial in patients with cerebral hemorrhage. ♦ Consider IVC filter for patients with PE when anticoagulation is ­contraindi­cated ♦ Consider routine compression stockings

7  Cardiac Dysfunction, Monitoring, and Management ■

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Hypovolemia ♦ In SAH, a common goal is CVP ³5 mmHg

• One trial showed CVP ³8 mmHg associated with similar outcomes as those associated with CVP ³5 mmHg • Some controversy about NS vs. albumin; trials under way ♦ It is possible to measure circulating blood volume, but technique and implica-

tions are not well validated • Some place a PA catheter to assess the effect of preload on cardiac output, but this is not well validated ■

Myocardial ischemia ♦ When cTI is 0.04–2 mg/L, differentiating myocardial ischemia from NSM is

difficult, but MI is more likely with typical risk factors (hypertension, high cholesterol, etc.) ♦ ECG abnormalities are common and varied in NCICU patients and may mimic myocardial ischemia or drug interactions ♦ cTI levels >10 mg/L are uncommon with NSM and are more likely to ­indicate MI ■

Adrenal insufficiency ♦ More likely after outpatient steroid use, up to 1 year later ♦ May present with volume and vasopressor refractory hypotension ♦ May screen with ACTH stimulation test (methods vary), repeated cortisol, or

free cortisol (best, but not widely available) ♦ Usually responds to high-dose glucocorticoid (e.g., hydrocortisone) and miner-

alocorticoid (e.g., fludrocortisone) ■

Drug interactions and side effects ♦ Pharmacist consultation and specialized computer software reduce drug-drug

interactions, medication utilization, and antibiotic resistance, and improve outcomes ♦ Anticonvulsants • Many anticonvulsants (valproic acid, barbiturates, benzodiazepines, etc.), and in particular, phenytoin may lead to hypotension, dysrhythmia, or prolonged QTc on ECG • Multiple anticonvulsants are especially challenging because of displacement from protein binding sites, changes in metabolism, and idiosyncratic side effects ♦ Aminoglycosides ♦ Propofol-infusion syndrome

• More common with:

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A. Naidech ▲ ▲ ▲ ▲

Younger age CNS disease Dose >100 mg/kg/min >24 h treatment

• Presents with: ▲ ▲ ▲ ▲ ▲

Acidemia Rhabdomyolysis (↑ CK) Renal failure Dysrhythmia Hypotension

• Consider screening with lactic acid or anion gap measurements for patients at risk • When suspected, discontinue propofol immediately and choose an alternative sedative • Consider alternative sedative to high-dose propofol often fatal

Management ■

General management (Fig. 7.1) ♦ ECG changes can usually be observed ♦ Telemetry monitoring for all but low-risk patients while in the ICU ♦ Hypotension

• Volume resuscitation if clinically appropriate; general goal CVP ³5 mmHg (best studied in SAH) • Consider echocardiography to assess left ventricular (LV) function; if LV function is depressed, fewer options exist for volume resuscitation and vasopressor use • Remove offending cause (antibiotics, propofol, anticonvulsants, etc.), if possible • Interruption of sympathetic tone in SCI ▲

▲

▲

■

Patients with SCI above the sympathetic output from the spinal cord (~C8) may have reduced sympathetic tone and decreased vascular resistance May require peripheral vasopressors to maintain adequate blood pressure; a-agonists (e.g., phenylephrine) most helpful May be vasopressor dependent indefinitely; consider midodrine and/ or fludrocortisone for refractory vasopressor-dependent hypotension

Sepsis ♦ Consider use of “sepsis bundles” to optimize preload, antibiotic use, etc.

7  Cardiac Dysfunction, Monitoring, and Management

95

Admission/Complication Physical exam Correct hypovolemia Telemetry Check e-lytes/ABG/cTI 12-lead ECG Echocardiography

Dysrhythmia

Hypotension

Acute coronary syndrome

Re-check electrolytes Re-check cardiac enzymes Refer to ACLS protocols

Re-check cardiac enzymes Consider echocardiography In SCI, consider α agonists Screen for infection Consider screen for PE Screen for causative Rx

Consider: b blocker ACE Inhibitor High-dose statin Oxygen Nitrates

Fig. 7.1  General cardiac monitoring in the NCCU

■

Dysrhythmias ♦ For life-threatening dysrhythmias, refer to the ACLS guidelines and protocols ♦ Few data on prophylaxis with anti-arrhythmics

■

Pulmonary embolism (PE) ♦ If clinically appropriate, consider CT angiography of chest for PE ♦ If present, consider anticoagulation or IVC filter placement for secondary

prevention ■

SAH and NSM ♦ cTI elevation usually resolves over a few days; no available data on b-blockade

or other medical treatment to prevent NSM ♦ Elevated cTI is associated with later vasospasm and poor response to hyper-

dynamic therapy, even with low levels (0.5–2 mg/L); vasopressors may lead to LV failure and lower blood pressure (Fig. 7.2)

• Be wary of using two or more vasopressors that increase vascular resistance (phenylephrine, norepinephrine, higher-dose dopamine, etc.) with worsening hemodynamics • Consider checking cTI at least daily while patient is on vasopressors • Increasing vasopressor requirements for BP goals or increasing cTI with vasopressors suggests worsening NSM; strongly consider angiographybased intervention in lieu of hyperdynamic therapy • Consider a PA catheter; caveats to PA catheter management: ▲

Several prospective randomized trials in critical illness found no benefit, and some found harm (pulmonary artery rupture or infection)

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Increased vasopressors

BP

Elevated cardiac enzymes

Depressed LV function

Fig. 7.2  Vicious cycle of neurogenic-stunned myocardium after SAH. Consider breaking cycle with angiography or inotropes, depending on the clinical scenario

▲ ▲

Providing management protocols did not improve outcomes Tests of interpretation of PA catheter values by operators have frequently been disappointing; consider intensivist consultation

• Severe LV failure may require milrinone or dobutamine; both increase cardiac output in SAH; milrinone leads to greater decreases in vascular resistance and blood pressure over the therapeutic range ■

Acute coronary syndromes (ACS) ♦ Aspirin, clopidogrel, heparin, and other anticoagulants

• Generally contraindicated after SAH and ICH; for similar reasons, emergent cardiac catheterization is generally contraindicated • Should be considered when the risk of ICH is low (e.g., lacunar ischemic stroke without tPA treatment) ♦ b-Blockers, ACE inhibitors, angiotensin receptor blockers, high-dose statins,

nitrates and oxygen can generally be used • Balance the hypotensive effect of b blockers and ACE inhibitors with desired cerebral perfusion • Cautious use of peripheral vasodilators in SCI

Outcomes ■

In SAH and ICH, elevated cTI is associated with a higher risk of death

7  Cardiac Dysfunction, Monitoring, and Management ■

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Death from cardiovascular collapse, dysrhythmia, or refractory hypotension is uncommon in SAH, ICH, TBI, and SCI, but well described in SE ♦ Cardiovascular compromise increases the risk for cerebral infarction,

depressed mental status, long-term neurologic disability, and probably later death from complications of disability (aspiration pneumonia, venous thrombosis, PE, etc.) ■

■

Cardiovascular instability and hypotension are associated with increased length of stay, resource utilization, and costs Most patients with ACS can be managed successfully, if not optimally, without anticoagulants or antiplatelet agents in the acute phase and can be reconsidered for anticoagulation in the future

Key Points ■ ■

■ ■ ■

Cardiac dysfunction occurs commonly in NCCU, especially SAH Cardiovascular dysfunction occurs more commonly in patients with SAH, status epilepticus and cervical spinal cord injury Telemetry monitoring should be routinely used in the NCCU Common precipitants include adverse drug events, infection and volume depletion Death from cardiovascular collapse, dysrhythmias, or refractory hypotension can occur in NCCU patients

Suggested Reading Colice GL (1985) Neurogenic pulmonary edema. Clin Chest Med 6:473–489 Daniele O, Caravaglios G, Fierro B, Natale E (2002) Stroke and cardiac arrhythmias. J Stroke Cerebrovasc Dis 11:28–33 Hays A, Diringer MN (2006) Elevated troponin levels are associated with higher mortality following intracerebral hemorrhage. Neurology 66:1330–1334 Kothavale A, Banki NM, Kopelnik A et  al (2006) Predictors of left ventricular regional wall motion abnormalities after subarachnoid hemorrhage. Neurocrit Care 4:199–205 Lehmann KG, Lane JG, Piepmeier KM, Batsford WP (1987) Cardiovascular abnormalities accompanying acute spinal cord injury in humans: incidence, time course and severity. J Am Coll Cardiol 10:46–52 Naidech AM, Kreiter KT, Janjua N et al (2005) Cardiac troponin elevation, cardiovascular mortality, and outcome after subarachnoid hemorrhage. Circulation 112:2851–2856 Parekh N, Venkatesh B, Cross D et al (2000) Cardiac troponin I predicts myocardial dysfunction in aneurysmal subarachnoid hemorrhage. J Am Coll Cardiol 36:1328–1335 Tung P, Kopelnik A, Banki N et al (2004) Predictors of neurocardiogenic injury after subarachnoid hemorrhage. Stroke 35(2):548–551 Wartenberg KE, Schmidt JM, Claassen J et al (2006) Impact of medical complications on outcome after subarachnoid hemorrhage. Crit Care Med 34:617–623

Chapter 8

Airway Management and Mechanical Ventilation in the NCCCU Paul Nyquist

Introduction ■

■

■

Neurologic disorders in general ICUs comprise the primary causative factor for intubation in 25% of all ventilated patients; in an NCCU this statistic is much higher (>80%) In neurologically impaired patients, practitioners are often required to incorporate novel ventilatory strategies due to a unique constellation of symptoms and neurologically based problems centering on the need to preserve brain function These ventilator strategies often operate outside the norms established for medical and surgical ICUs, and they often require solutions that are not well addressed by existing literature

Neurologic Conditions that Require Intubation in the NCCU ■

Diagnosis of patients intubated for primary CNS processes in the NCCU include: ♦ Strokes of all types: ischemic stroke, intracranial hemorrhage (ICH), and ♦ ♦ ♦ ♦ ♦ ♦

subarachnoid hemorrhage (SAH) Traumatic brain injury (TBI) Status epileptics Metabolic and septic encephalopathy CNS infections – meningitis, encephalitis Acute obstructive hydrocephalus Acute cerebral edema

P. Nyquist, MD, MPH (*) Department of Neurology, Anesthesiology and Neurological Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street – Phipps 126, Baltimore, MD 21287, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_8, © Springer Science+Business Media, LLC 2011

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100 ■

Primary neurologic disorders that result in primary neuromuscular disorders with type II respiratory failure and often require intubation include: ♦ ♦ ♦ ♦ ♦ ♦ ♦

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P. Nyquist

High cervical cord injury Guillain–Barré syndrome Myasthenia gravis Amyotrophic lateral sclerosis Acute inflammatory myopathy Unusual genetic peripheral neuropathies such as spinal muscular atrophy Intoxication from poisons

Often in the NCCU, patients require prolonged ventilation immediately postoperatively for issues pertaining to both neurologic and mechanical respiratory failure; this subset of patients include: ♦ Patients with spinal surgery ♦ Patients with altered mental status and coma after a brain surgery

Intubation ■

Comatose or obtunded patients often present with airway occlusion caused by their altered mental status; a number of mechanisms contribute to this problem: ♦ Tendency of the tongue to occlude the airway ♦ Dysregulation of ventilatory drive ♦ Mechanical consequences of temporary paralysis on the lungs and muscula♦ ♦ ♦ ♦

■

■

ture of the thorax and diaphragm in the setting of acute coma Loss of bulbar reflexes Inhibited cough reflexes Extinction of the gag reflex Impaired swallowing mechanisms

In general, any patient whom the practitioner feels is at risk for aspiration is a candidate for intubation Three factors should be considered when evaluating a patient’s need for intubation ♦ Are the gag and cough reflexes intact? ♦ Will the patient be neurologically impaired for a long period of time? ♦ Is the patient in a monitored setting where he can be easily intubated if necessary?

■

■

It is our observation that patients who meet these criteria can be safely observed and intubated at a later time if they deteriorate In our NCCU, the time limit for observation in the unintubated state is usually 24–72 h; if a patient’s mental status does not improve within that period, we often intubate and protect the airway

8  Airway Management and Mechanical Ventilation in the NCCCU ■

101

This practice is not data driven but is based on a clinical observation that patients who do not recover within 24–72 h usually need to be intubated for reasons other than airway protection, such as aspiration pneumonia

Central Control of Ventilation ■

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■

■

■

Most commonly observed patterns of breathing in patients with brain injury are tachypnea and hyperventilation; these patterns are frequently seen as a result of diffuse cortical and subcortical injury in awake and comatose patients Injury affecting these patients may be mild, and these alterations in breathing patterns can be seen in patients who appear to be neurologically intact Change in respiratory rate can be associated with a change in awareness and an improvement or decline in the neurologic exam During hyperventilation, the patient maybe more alert and may awaken if unconscious, and the pupils may change in configuration from miosis to dilation; this form of breathing is usually related to an increased dependency on the arterial carbon dioxide partial pressure (PaCO2) as a trigger for respiratory drive The Cheynes–Stokes pattern of disordered breathing is also a commonly observed centrally altered pattern of breathing; it is thought to be caused by the disruption between the bilateral cortical hemispheres and dysfunction of the medial forebrain structures Neural control of respiration depends on both conscious and automatic components integrated in nuclei in the pons and medulla; it is controlled by areas of: ♦ Dorsolateral tegmentum ♦ Pons ♦ Regions of the medulla, including:

• Nucleus tractus solitarus and retroambigualis • Descendingpathways in the ventrolateral columns of the spinal cord ■

Automatic respiration is a homeostatic mechanism by which ventilation is adjusted to regulate acid–base status to meet adequate oxygen demand ♦ Different patterns of respiration are observed in different neurologic injuries ♦ It has been observed that abnormal respiratory patterns associated with differ-

ent posterior fossa lesions may be of localizing value ■

Certain patterns of breathing are associated with specific lesion locations, often seen in ICU patients with intracranial mass lesions and elevated intracranial pressure (ICP) that lead to a herniation; these altered patterns of respiration include: ♦ Cheynes–Stokes breathing ♦ Apneustic breathing

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P. Nyquist

♦ Cluster breathing ♦ Ataxic breathing ■

These patterns are often seen in succession over minutes to hours, culminating in death, as the ICP steadily rises with progressive downward herniation ♦ Cheyne–Stokes respiration is typified by a changing ventilatory pattern that

alternates between hyperventilation and hypoventilation in a consistent and cyclical manner and is associated with lesions to the cortex ♦ Apneustic breathing is characterized by long respiratory pauses after which air is retained and then released; it occurs with lesions of the lower half of the tegmentum of the pons ♦ Cluster breathing consists of a group of quick breaths that occur in an irregular sequence in clusters and are regularly separated by long pauses; this pattern of breathing is often associated with low pontine or high medullary lesions ♦ Ataxic breathing is a form of respiration that is reflected by complete loss of rhythmicity of breathing • Breaths are irregularly timed, with variable tidal volumes usually of smaller sizes • Often called the atrial fibrillation of breathing • Associated with long pauses and can be confused with cluster breathing, except that the associated rhythm is irregular and is highly variable

Gas Exchange ■

Use of the ventilator affects ICP and the parenchyma of brain-injured patients in many ways ♦ One of the most important issues affected by the ventilator is brain oxygenation ♦ The ventilator is a major component of the strategies designed to address

brain oxygenation; however, no large studies have systematically examined the role of different ventilator strategies on brain oxygenation ■

Although strategies that emphasize maximal oxygen support with maximal fractional inspired oxygen (FiO2) have been proposed, no study has demonstrated benefit from the prophylactic use of high FiO2 in the setting of brain injury, and lung injury from exposure to high FiO2 in the setting of severe lung injury is a hypothetical consideration

Hyperventilation and ICP ■

Hyperventilation reduces ICP through its effect on PaCO2; hypocapnia induces vasoconstriction and reduces CBF by causing a reduction in the volume occupied by the vascular component of the cranial vault

8  Airway Management and Mechanical Ventilation in the NCCCU ■

103

Hyperventilation to induce hypocapnia is a rapidly effective strategy to acutely reduce ICP ♦ Hyperventilation is used to reduce PaCO2 from its normal range of 40–60

mmHg to a reduced range of 25–35 mmHg

♦ Acute ICP reduction through hyperventilation can be achieved in most intu-

♦ ♦ ♦

♦

bated patients by using bag breaths that result in doubling of the minute ventilation; this would most often require a bag breath rate of 18–24 breaths per minute Mediated by arterial responses to changes in pH and occurs in the perivascular space of the small arterioles of the brain Changes caused by hypocapnia can temporarily shift the autoregulatory curve to the right, resulting in lower ICP and lower CBF at higher MAP (Fig. 8.1) This involuntary mechanism produces a temporary change in the relationship of CBF to MAP and will resolve with time as a new PaCO2 set point is created by homeostatic pH regulatory mechanisms in the small vessels of the brain arterial system As bicarbonate concentration shifts intracerebrally, this autoregulatory system adapts to higher PaCO2 set points and will shift back to the left with higher CBF at lower MAP, at which point, the effects of hypocapnia will be lost • This adaptation usually occurs within 6–12 h after initiation of hypocapnia

♦ To induce hypocapnia, the patient must be intubated and sedated to allow for

aggressive control of his ventilatory cycle • No effective means of hyperventilation can occur in conscious patients who are not intubated ■

In a randomized prospective trial, hyperventilation, if continued chronically, was associated with increased morbidity and early mortality; to date, only one randomized prospective study has been conducted that addresses the effects of chronic hyperventilation on clinical outcomes in patients with TBI

Cerebral Blood Flow Increasing risk of hypertensive encephalopathy

Hyperventilation Normocapnia

Increasing risk of ischemia

0

50

100

150

MAP (mmHg)

Fig. 8.1  The cerebral autoregulation curve

200

250

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P. Nyquist

Present brain trauma guidelines recommend against any strategy that employs preemptive hyperventilation; however, the use of hyperventilation to induce hypocapnia and reduce ICP is effective for short periods in acute neurologic emergency cases that involve elevated ICP

Effects of Ventilatory Modes on ICP ■

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■

Clinical studies have documented the relationship of elevated positive endexpiratory pressure (PEEP) and ICP in brain injury; some have reported increases in ICP up to 14 mmHg in response to as little as 10 cm H2O of PEEP; these changes are reversible with the elimination of PEEP; however, most studies demonstrate that modest PEEP (5–15 mmHg) is tolerable in patients at risk for elevated ICP Close proximity of the thoracic cavity and the cranial vault allows the direct transmission of increased thoracic pressure caused by PEEP to the cranial vault due to the direct transmission of increases in intrathoracic pressure through the neck to the intracranial vault; this is of particular concern when the patient is prone PEEP increases ♦ Intrathoracic pressure ♦ Peak inspiratory pressure ♦ Mean airway pressure

■

PEEP decreases ♦ Venous return ♦ Mean arterial pressure ♦ Cardiac output

■

Most of these factors increase ICP via their effects on reduced venous outflow from the cranium and its effect on increased jugular venous pressure ♦ Rise in jugular venous pressure causes increased cerebral venous blood volume

• Rise in volume can be critical in situations in which the ventricular elastance is already elevated by a space-occupying lesion or traumatic injury • In this setting, even small changes in intracranial volume result in steep increases in ICP ■

■

The effects of PEEP on ICP appear to be significantly affected by reductions in the ventricular compliance of a brain-injured patient: the ability of the ventricle to buffer against changes in ICP in response to vascular pressure and venous outflow declines In patients with severe lung injury, the effects of PEEP on increases in intrathoracic pressure are often amplified ♦ Patients who experience changes in lung compliance and decline in ventricu-

lar compliance become PEEP sensitive with greater elevations in ICP in response to smaller increases in PEEP

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Effects of High-Frequency Ventilation on ICP ■

High-frequency ventilation (HFV) is an innovative mode of mechanical ventilation that may have a dramatic impact on the care of patients with severe lung injury of all types ♦ HFV has been documented to reduce ICP in certain circumstances and

has  never been demonstrated to increase ICP in studies in animals or in humans ■

TBI with both severe lung injury and severe brain injury may benefit from HFV ♦ These patients will have reduced pulmonary compliance and intracranial

compliance and are likely to be sensitive to the effects of intrathoracic pressure on ICP caused by mechanical ventilation ■

HFV incorporates high-frequency respiratory rates >150 breaths per minute with low tidal volumes, usually 1–5 mL/kg ♦ Allows for efficient ventilation and oxygenation with minimal induction of

ventilatory-induced lung injury (VILI) ♦ Produces reduced intrathoracic pressure and minimal effect on cerebral

venous outflow • Allows for a significant reduction of ICP when compared to conventional modes of ventilation ♦ HFV reduces:

• Mean peak airway pressure • Peak inspiratory pressure • Intrathoracic pressure ■

There are a number of variants of this ventilator mode: ♦ ♦ ♦ ♦ ♦

High-frequency oscillatory ventilation (HFOV) High-frequency jet ventilation (HFJV) High-frequency percussive ventilation (HFPV) High-frequency flow interruption (HFFI) High-frequency positive pressure ventilation (HFPPV)

Other Ventilation Issues that Affect ICP ■

Transition from controlled ventilation to spontaneous ventilation can be accomplished safely if the patient’s ICP is within the normal range ♦ In any situation in which patients have poor intracranial elastance, a spontane-

ous breathing trial may be associated with significant rises in ICP

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The cycle time of inspiration (I) and expiration (E) on changes in PEEP and ICP has been tested in humans and animals ♦ These inverted ratios appear to have no direct effect on ICP at any PEEP

setting ■

Fiberoptic bronchoscopy has been known to precipitate an elevation in ICP ♦ Occurs even with the patient paralyzed and with the use of cough suppres-

sants such as lidocaine

Ventilation Issues that Affect ICP and Brain Oxygenation ■

Two issues are of primary importance in dealing with brain-injured patients: cerebral oxygenation and ICP control ♦ In recent years, jugular venous oxygen sensors and intraparenchymal oxygen

sensors have been developed; they can yield direct measurements of whole brain and focal brain parenchyma oxygen levels ♦ Clinical studies have focused on two types of monitoring devices • Jugular bulb oximetry • Monitoring of brain tissue oxygen tension (PbrO2) ■

Recent guidelines of the Brain Trauma Foundation list suggested targets for brain parenchyma oxygenation (PbrO2), stating that the desired level should be >15 mmHg ♦ The brain in general cannot tolerate a level <10 mmHg for longer than 30

min, nor the lowest level of 6 mmHg regardless of duration ■

Jugular venous studies have demonstrated that hyperventilation can result in decreased global brain oxygenation ♦ A linear relationship between reduced oxygen availability and decreasing CBF

with increasing hyperventilation has been observed in animals and humans

Protocol of the Acute Respiratory Distress Syndrome Network and Permissive Hypercapnia ■

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are diagnosed frequently seen in the NCCU ♦ Many patients with a primary neurologic deficit present with disorders that

predispose them to ARDS and ALI, such as: • Head trauma • Sepsis

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• Neurologic surgery of the brain or back • Stroke of all types ■

The ARDS Network protocol is the only known ventilator strategy demonstrated to reduce mortality in the setting of ARDS ♦ Incorporates strategies that use high PEEP and elevated PaCO2

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In these settings, the low-tidal-volume strategy incorporated and published by the ARDS Network investigators incorporates two strategies designed to reduce ventilator lung injury ♦ Permissive hypercapnia ♦ Elevated PEEP

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Permissive hypercapnia has not been shown to induce brain injury and is frequently incorporated as a strategy to reduce ventilator lung injury in patients with head injury and in primarily neurologic patients in the NCCU to allow lower tidal volumes and less PEEP ♦ In neonates, permissive hypercapnia has been associated with more severe

injury from ICH ♦ Has not been verified in adult patients ■

Use of strategies that incorporate elevated PEEP is associated with increasing ICP ♦ In the context of the ARDS Network protocol, the lower tidal volumes and

reduced plateau pressures usually offset the effects of elevated PEEP on ICP and can be used safely

Direct Effects of Neurologic Injury on the Pulmonary System ■

In the NCCU, some subsets of patients with neurologic disease experience specific pulmonary complications caused by their neurologic illness; these associated pulmonary conditions are: ♦ Neurogenic pulmonary edema (NPE) ♦ Pulmonary edema from stunned myocardium

Neurogenic Pulmonary Edema ■ ■

NPE has been reported extensively in the setting of acute neurologic injury This disorder can occur rapidly, with onset at the initiation of injury, or it can occur at later stages of illness

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Early reports of the incidence of neurogenic pulmonary edema in neurologic illness suggested an incidence of 40% for all head injury subtypes and a 90% incidence in the setting of ICH Combat victims with pure head injuries have a high incidence of pulmonary edema; in these patients, the time to onset of edema appears to be almost instantaneous Supportive measures that incorporate the use of PEEP to maintain sufficient blood and brain oxygenation are usually quite effective in this disorder ♦ Recent case reports suggest that patients with NPE may be particularly

responsive to prone positioning ■

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NPE is caused by extravasation of a proteinaceous fluid across the alveolar membrane; this is secondary to injury to the alveolar membrane from the catecholamine storm associated with severe neurologic injury NPE is different from ARDS and ALI in that the mechanism of injury of ARDS and ALI is the result of an inflammatory reaction to lung injury, and the proteinaceous material is produced from the pneumocytes within the alveolar wall The diagnosis of NPE is often difficult to separate from other forms of lung injury, including ARDS, ALI, and heart failure from stunned myocardium While the diagnosis of NPE is one of exclusion, the clinician must employ his own knowledge to make the diagnosis by first excluding other causes of lung injury and then identifying characteristics that will help to include the diagnosis of NPE Other potential causes of NPE must be excluded, such as congestive heart failure of any type from: ♦ Stress myocardium ♦ Myocardial ischemia ♦ Other underlying causes of congestive heart failure present prior to injury

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Definition of ARDS and ALI can be quite similar to NPE ♦ Bilateral pulmonary infiltrates on chest X-ray ♦ Alteration of the PaO2/FiO2 ratio to <300 within 24 h for ALI and <200 over

48 h for ARDS

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In general, NPE is different from pulmonary edema from heart failure, ARDS, and ALI: ♦ ♦ ♦ ♦ ♦ ♦

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Wedge pressure usually is not elevated Ejection fraction on the echocardiogram is usually normal Onset occurs rapidly, with immediate onset at the time of neurologic injury Often involves only one lung field Temporary in duration Usually exquisitely PEEP responsive

Treatment of NPE involves supportive measures ♦ Intubation, if required ♦ PEEP

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♦ Elevated FiO2 ♦ The use of diuresis, if necessary

Stunned or Neurogenic Myocardium ■

Concept of stunned myocardium within the context of neurologic critical care has long been recognized ♦ Has been extensively described in the setting of SAH ♦ Has been associated with a number of neurologic diseases to include:

• • • • • ■

Brain tumor Seizure Ischemic stroke Hemorrhagic strokes of all types Guillain–Barré syndrome

Myocardial stunning in the setting of acute neurologic injury often results in acute fulminant pulmonary edema ♦ In SAH patients with cardiogenic shock, aggressive support with inotropic

agents to maintain adequate brain perfusion and avoid focal ischemia from vasospasm is sometimes required ■

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In ventilated patients with severe neurologic disease, this entity can often be confused with other syndromes such as NPE or ALI and ARDS; this issue is usually easily resolved with the use of echocardiography Diagnosis of stunned myocardium focuses on the detection of: ♦ Increased serum troponin and CK-MB, usually with disproportionately high

troponin levels ♦ EKG changes are typified by nonspecific ST changes in an apical distribution ♦ Diagnosis is easily achieved through the use of echocardiography

• Myocardial stunning is typified by global, as opposed to segmental, hypokinesis on the echocardiogram, usually with an apical distribution ■

Treatment of the stunned myocardium ♦ Inotropic support ♦ Fluid restriction ♦ Diuresis

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■

Early detection and appropriate treatment are required to avoid potentially fatal outcomes Intubation and appropriate ventilatory maneuvers to avoid hypoxia may be required supportive measures while the patient is treated, including intubation and PEEP, for underlying myocardial dysfunction and resolution of the stunning

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P. Nyquist

Liberation from Mechanical Ventilation in Neurologic Disorders ■

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Little data exist to guide the appropriate decision-making pathways in liberating patients with primarily neurologic injury from the ventilator The Society of Critical Care Medicine suggests that best evidence supports the weaning pathway that utilizes a standard breathing trial, with aggressive liberation from the ventilator if the patient passes this trial Weaning protocols that slowly wean by reducing the SIMV setting or by the use of CPAP without periods of rest are presently not supported by the literature Many practitioners will employ strategies that incorporate slow decreases in respiratory rate, CPAP, or pressure support to obtain FRC (functional reserve capacity) and NIF (negative inspiratory force) goals that potentiate liberation from mechanical ventilation Literature is limited concerning the effects of early ventilation on care in the NCCU ♦ When neurosurgical patients with GCS as low as 4 were extubated, no differ-

ences in outcome were reported; as long as the cough and gag were intact, patients had a relatively short period of predicted neurologic impairment ■

Weaning trials incorporating CPAP are often used in patients who are recovering from acute peripheral nervous disorders (e.g., myasthenia gravis and Guillain– Barré syndrome) and are intubated for prolonged periods; patients show a slow increase in strength, with a gradual increase in FRC and NIF over days to weeks

Strategies for Extubation of the Neurologically Impaired Patient ■

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Liberating patients who are mechanically ventilated in the setting of neurologic injury can be accomplished safely and quickly; predicting the success of liberation and the long-term viability of that process can be difficult Important considerations when evaluating the patient with respiratory impairment in the setting of neurologic injury ♦ Whether the damage is reversible ♦ In the case of reversible injury, whether the duration of injury will be short or

long ■

Patients who are intubated for a primarily neurologic reason can be classified into one of four categories ♦ Patients who suffer from the effects of a CNS process who are intubated

solely for airway protection; they can breathe and vent and have no signs of impending respiratory failure • These patients can usually be safely extubated if they have signs of active airway protection such as a cough and gag

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• If a patient will be neurologically impaired for an indefinite period, many practitioners will consider a tracheostomy as a bridging procedure that leads to earlier liberation from mechanical ventilation • Tracheostomy allows for safe suctioning and the immediate control of the airway in the advent of acute respiratory failure ♦ Patients who have a severe neurologic injury that inhibits the central neuro-

logic drive to breathe and who will experience acute respiratory arrest upon cessation of mechanical ventilation • Patients cannot be safely extubated until they demonstrate an autonomous respiratory drive • Often these patients will require tracheostomy and prolonged mechanical ventilation ♦ Patients who are experiencing some kind of mechanical failure induced by

their neurologic injury • Includes mechanical failure resulting from NPE, pulmonary edema from a stunned myocardium, and aspiration pneumonia • Patients cannot be safely liberated until they demonstrate both intact arousal and reversibility of their mechanical failure via standard protocols such as a standard trial of spontaneous breathing • Early liberation and early failure will result in dramatic setbacks (such as the acquisition of aspiration pneumonia) or exacerbation of the cause of mechanical ventilatory failure ♦ Patients who have primary peripheral mechanism of ventilatory failure identi-

fied as type II respiratory failure or pure neurogenic failure • Patients are inherently different from all classes of ventilated patients with a primary neurologic injury • Care must be taken to identify the mechanical limits caused by their neurologic injury prior to liberation • Patients in general should not be liberated until they have demonstrated a prolonged period of independent ventilation such as tolerance of a prolonged CPAP trial or T-piece trial

Weaning in Pure Type II Respiratory Failure ■

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Extubation of patients with severe peripheral nerve disease can be attempted when sufficient respiratory muscle recovery occurs Extubation should only be attempted when sufficient pulmonary recovery has occurred as indicated by: ♦ Signs of improvement in overall muscle strength ♦ Vital capacity (VC) >15–20 mL/kg

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P. Nyquist

♦ Mean inspiratory pressure <−20 to −50 cm H2O ♦ FiO2 requirement <40% and PEEP ³5 cm H2O ♦ No fever, infection, or other medical complications

Cervical Cord Injury ■

■ ■

High cervical cord injury represents a special case of pure type II neurogenic failure; in general, the same rules apply, but some special considerations apply as well High cervical spinal cord injury can inhibit many of the reflexes that protect the lung Respiratory failure usually involves a scenario of slow decline in which, due to alveolar hypoventilation, the patient progressively de-recruits alveoli; PaCO2 slowly rises with a concomitant decrease in oxygenation ♦ Causes slow progressive decline, often ending in intubation and ventilator

dependency ♦ Patients often exhibit a form of breathing known as paradoxical breathing ♦ The intercostal muscles often remain innervated, while the diaphragm is flaccid ♦ In this situation, the chest expands, while paradoxically, the belly contracts,

markedly inhibiting the efficiency of ventilation ■

Level of spinal injury may give insight into the severity of respiratory dysfunction; injury from C1 to C3 causes apnea ♦ Injury from C3 to C5 is often associated with a mixed presentation in which

the patient is able to initiate ventilation but not with enough efficiency to ventilate independently, or the patient lacks the stamina to remain ventilator independent ♦ Injury below C5 is usually associated with some form of recovery to ventilator independence; special concerns for these patients revolve around three key clinical obstacles • Avoiding atelectasis through maneuvers that promote alveolar recruitment and adequate inflation • Aggressive pulmonary toilet to avoid aspiration pneumonia • Education of the patient to use voluntary muscles of respiration and proper positioning to maximize pulmonary function and achieve the other goals outlined above ■

Strategies for liberation of ventilation include prolonged trials of spontaneous ventilation ♦ NIF >20 cm H2O ♦ Vital capacity >15–20 mL/kg of patient’s ideal body weight

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Pitfalls to be avoided involve the rapid extubation of patients with cervical spine injury within the first 72 h

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♦ Often these patients will perform well, only to fail as the edema at the site of

their injury expands and causes a more devastating injury, leading to respiratory failure ♦ Additionally, these patients utilize modified forms of respiration that lead to fatigue of the respiratory muscles over several days and result in reintubation ■

Spinal cord patients with high cervical cord injuries often require a tracheotomy as a permanent solution; if the injury results in quadriparesis and permanent respiratory paralysis, a tracheotomy should be pursued as early as medically possible and unnecessary weaning trial should be avoided

Key Points ■

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Airway management may be necessary to protect the lungs due to reflexes in coma or brainstem injury or to protect an agitated brain-injured patient and bedside personnel Intubation and extubation criteria depend on mental status examination and status of neuromuscular strength Certain patterns of breathing are associated with specific lesion locations, often seen in ICU patients with intracranial mass lesions and elevated ICP Neurologic injury causes direct effects on the pulmonary system that manifest as NPE and pulmonary edema from stunned myocardium A weaning protocol based on objective parameters is recommended in patients with neurologic injury prior to extubation

Suggested Reading Coplin WM, Pierson DJ, Cooley DJ et al (2000) Implications of extubation delay in brain-injured patients meeting standard weaning criteria. Am J Respir Crit Care Med 161;1530–1536 Ely EW, Meade MO, Haponik EF et al (2001) Mechanical ventilator weaning protocols driven by nonphysician health-care professionals: evidence-based clinical practice guidelines. Chest 120;454S–463S Esteban A, Anuzeuto A, Alia I et al (2000) How is mechanical ventilation employed in the intensive care unit? An international utilization review. Am J Respir Crit Care Med 161(5):1450–1458 Kerwin AJ, Croce MA, Timmons SD et al (2000) Effects of fiberoptic bronchoscopy on intracranial pressure in patients with brain injury: a prospective clinical study. J Trauma 48(5):878–882; discussion, 882–883 Muizelaar JP, Marmarou A, Ward JD et al (1991) Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 75:731–739 Namen AM, Ely EW, Tatter SB et al (2001) Predictors of successful extubation in neurosurgical patients. Am J Respir Crit Care Med 163:658–664 Pulm F, Posner LB (1980) The diagnosis of stupor and coma. Davis, Philadelphia The Acute Respiratory Distress Syndrome Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301–1308

Chapter 9

Blood Pressure Management Ameer E. Hassan, Haralabos Zacharatos, and Adnan I. Qureshi

Introduction ■

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The cerebrovascular system is highly vulnerable to fluctuations in systemic blood pressure (BP) through structural and functional alterations In a normal brain, cerebral blood flow (CBF) is autoregulated over a wide range of BP CBF remains relatively unchanged over a range of cerebral perfusion pressure (CPP) under normal circumstances secondary to changes in cerebrovascular resistance (CVR) via vasoconstriction and vasodilation CBF = CPP/CVR CPP is the difference between the mean arterial pressure (MAP) and the intracranial pressure (ICP) [CPP = MAP - ICP] Regarding hypertension – the overriding goal is to alleviate systemic hypertension while maintaining adequate CPP, thereby reducing hydrostatic forces to stimulate brain edema or vessel breakdown that may lead to intracranial hemorrhage Regarding hypotension – the goal is to prevent BP from falling below the threshold that maintains adequate CPP, thereby avoiding secondary ischemic brain injury A MAP in the range of 60–150 mmHg helps to maintain a constant CBF in normotensive individuals Mean arterial hypertension may be gradually reduced below 120 mmHg in persons with a history of chronic hypertension, but a reduction of >20% should be avoided in the acute setting

A.E. Hassan, DO, H. Zacharatos, DO, and A.I. Qureshi, MD (*) Zeenat Qureshi Stroke Research Center, Department of Neurology, University of Minnesota, Minneapolis, MN e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_9, © Springer Science+Business Media, LLC 2011

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Pathophysiology of Hypertension ■

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Chronic hypertension contributes to decreasing the elasticity of arteries, thereby increasing the likelihood of rupture in response to acute elevations in intravascular pressure The spectrum of lesions due to arterial hypertension, at the level of the intraparenchymal blood vessels, includes the following steps in vascular wall degeneration: ♦ Hypertrophy of smooth muscle layer ♦ Hyalinization of arterial wall ♦ Capillary walls demonstrating focal or circumferential thickening

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Long-standing and persistent hypertension leads to cerebral vascular wall damage that can be seen with the hyalinization of excessive fibrillar material from arteriolar wall or from basement membranes, otherwise termed sclerosis (arteriolar and capillary) with hyalinosis

Intracerebral Hemorrhage ■

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Hypertension is the most frequent and most important risk factor for intracerebral hemorrhage (ICH) After an acute ICH, BP initially reaches a maximum over 24 h and then declines spontaneously Hemorrhages that involve the putamen, globus pallidum, thalamus, internal capsule, periventricular white matter, pons, and cerebellum are often attributed to hypertensive small-vessel disease, particularly in a patient with known hypertension Elevated early-mortality rates have been clearly demonstrated in ICH patients who present with high arterial pressures Hematoma growth and acute hypertensive response: ♦ BP monitoring and treatment is a critical issue in the treatment of acute ICH

(Table 9.1) ♦ Reducing BP in acute ICH may prevent or slow the growth of the hematoma

and decrease the risk of rebleeding ♦ Emphasis on BP reduction is especially true for hemorrhage that results from

a ruptured aneurysm or arteriovenous malformation, in which the risk of continued bleeding or rebleeding is presumed to be highest ♦ Hematoma enlargement occurs more frequently in patients with elevated systolic BP. However, it is not known whether this represents a direct contributing cause to the hematoma expansion ♦ The risk of hemorrhagic expansion with mild BP elevation may be lower and must be balanced with the theoretical risks of inducing cerebral ischemia in the edematous region that surrounds the hemorrhage

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Table 9.1   Recommended AHA/ASA guidelines for treating elevated blood pressure in spontaneous ICH Suspicion and/or evidence BP check/clinical of elevated ICP CPP re-examination SBP/MAP Comment Every 5 min Consider aggressive BP If SBP >200 reduction with continuous mmHg IV infusion OR If MAP >150 mmHg >60–80 Consider monitoring ICP If SBP >180 Yes mmHg and reducing BP using mmHg intermittent or continuous OR IV medications to keep If MAP >130 CPP >60–80 mmHg mmHg Every 15 min Consider a modest reduction If SBP >180 No of BP (e.g., MAP of mmHg 110 mmHg or target BP OR of 160/90 mmHg) using If MAP >130 intermittent or continuous mmHg IV medications to control BP AHA American heart Association; ASA American Stroke Association; SBP systolic blood pressure; MAP mean arterial pressure; ICP intracranial pressure; CPP cerebral perfusion pressure; BP blood pressure; IV intravenous ■

Hypoperfusion in the perihematomal region ♦ Uncertainty exists as to whether a perihematomal area of critical hypoperfu-

sion may experience further perilesional ischemia as a result of the lowering systemic BP ♦ Decreased CPP secondary to the reduced BP could compromise CBF due to increased ICP ■

Decrease in perihematomal edema by reducing BP ♦ Reduction in the volume of the perihematomal edema, which has a direct

correlation to hematoma volume, may be associated with the decrease in BP ♦ Edema formation may possibly decrease with a reduction of BP, as a consequence

of reduced capillary hydrostatic pressures via an alteration of the Starling forces around the hematoma

Ischemic Stroke ■

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Patients with ischemic stroke often suffer from chronic hypertension, and their cerebral autoregulatory curve is shifted to the right The elevation in BP may be a result of many factors including the stress of the cerebrovascular event, anxiety, nausea, pain, baseline hypertension, a physiologic response to hypoxia, or a response to increased ICP

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Many patients have spontaneous declines in BP during the first 24 h after onset of stroke Higher MAP levels are better tolerated by hypertensive stroke patients Stroke patients with a history of hypertension are at risk of critical hypoperfusion for MAP levels usually well tolerated by normotensive individuals For every 10 mmHg increase >180 mmHg, the risk of neurologic deterioration is increased by 40% and the risk of poor outcome is increased by 23% Theoretical reasons for lowering BP include: ♦ Reducing the formation of brain edema ♦ Lessening the risk of hemorrhagic transformation of the infarction ♦ Preventing further vascular damage and forestalling early recurrent stroke

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AHA/ASA Stroke Treatment Guidelines (Fig. 9.1) ♦ Aggressive treatment of BP may lead to neurologic worsening by reducing

CPP to ischemic areas of the brain ♦ It is generally agreed that a cautious approach to the treatment of arterial

hypertension should be recommended

Clinical diagnosis of acute stroke

Reduce BP if >185/110 mm Hg using short acting IV medication∗

Emergent computed tomographic scan

Ischemic stroke

Candidate for thrombolysis

Intracerebral hemorrhage

Not a candidate for thrombolysis Suspect high ICP

Reduce BP if >185/110 mm Hg using short acting IV medication

Treated with thrombolysis

Reduce BP if >220/120 mm Hg using short acting IV medication and avoid and treat hypotension (<100/70 mm Hg)

Reduce BP if SBP>180 mm Hg or MAP >130 mm Hg using short acting IV medication; ICP monitoring recommended to maintain CPP>60 mm Hg

Maintain BP <180/105 mm Hg using short acting IV medication or infusions for 24 hours Oral ant hypertensive agents may be considered after 24 hours BP goal ≈160/110 mm Hg; titrate to more aggressive goals after neurological stability achieved

Fig. 9.1  Clinical diagnosis of acute stroke. Adapted from Qureshi (2008)

Do not suspect high ICP

Reduce BP if SBP>180 mm Hg or MAP >130 mm Hg using short acting IV medication; monitor neurological examination every 15 minutes

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♦ Patients eligible for treatment with thrombolytics need to have their BP low-

♦

♦

♦ ♦

ered so that their systolic BP is <185 mmHg and their diastolic BP is <110 mmHg before therapy is started If medications are given to lower BP, the clinician should be certain that the BP is below 180/105 mmHg for at least the first 24 h after IV thrombolytic therapy Consensus exists that medications should be withheld unless the systolic BP is >220 mmHg or the diastolic BP is >120 mmHg for the first 24 h of an acute ischemic stroke Research testing the effects of early treatment of arterial hypertension on outcomes after stroke is under way It is generally agreed that the cause of arterial hypotension in the setting of acute stroke should be sought: • Hypovolemia should be corrected with normal saline infusion • Cardiac dysrhythmias that result from reduced cardiac output should be corrected

Pharmacologic Treatment of Acute Hypertensive Response (Table 9.2) ■

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Drugs recommended for use in lowering BP in acute stroke include labetalol, hydralazine, nicardipine, and nitroprusside Due to the high rates of dysphagia and impaired consciousness within the acute neurocritical care setting, IV therapy is the route of choice for treatment Advantages of IV drugs are that they have a faster onset of action and the dose can be titrated to achieve a desired BP target

Table 9.2  Possible intravenous medications for control of hypertension in neurocritical care patients Drug Intravenous bolus dose Continuous infusion rate Hydralazine 5–20 mg IVP q 30 min 1.5–5 mg/kg/min Enalapril 1.25–5 mg IVP q 6 ha NA Esmolol 250 mg/kg IVP 25–300 mg/kg/min Nicardipine 5 mg/h IVP 5–15 mg/h Nitroprusside NA 0.1–10 mg/kg/min Nitroglycerin NA 20–400 mg/min Labetalol 5–20 mg q 15 min 2 mg/min (maximum 300 mg/day) Urapidil 12.5–25 mg 5–40 mg/h a  The enalapril first test dose should be 0.625 mg due to the risk of precipitous lowering of blood pressure

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Nicardipine ♦ Calcium-channel (L-subtype) antagonist ♦ Nicardipine demonstrates greater selectivity for binding of calcium channels

in vascular smooth muscle cells than in the cardiac myocytes; this relative tissue selectivity is important in the drug’s utility for the treatment of hypertension ♦ IV nicardipine has a rapid onset of action (1–2 min) with an elimination halflife of 40 ± 10 min, and the major effects last from 10 to 15 min ♦ It is rapidly distributed, extensively metabolized in the liver, and rapidly eliminated ■

Labetalol ♦ Labetalol is an a- and b-adrenergic antagonist (in a ratio of ~2:3) ♦ Labetalol can be administered either as intermittent boluses or as a continuous

infusion ♦ Given IV, its effect on BP begins within 2 min, peaks at 5–15 min, and lasts

2–4 h ♦ Both European and North American guidelines recommend IV labetalol as a

first-line agent in patients with ICH who require acute antihypertensive therapy ♦ IV labetalol treatment has the benefit of minimal side effects with a rapid onset of action and the disadvantage of sustained hypotensive effect with prolonged usage ♦ Labetalol is metabolized by the liver ■

Hydralazine ♦ Hydralazine, a peripheral vasodilator, acts by relaxing vascular smooth mus-

cle cells, leading to the reduction of arterial BP

♦ Hydralazine has a latency of £15 min following an IV dose and a therapeutic

duration of up to12 h ♦ Headache, hypotension, and palpitations are the common side effects associ-

ated with hydralazine ♦ Hydralazine has been used in conjunction with labetalol to lower systolic BP

to <160 mmHg ♦ Low rates of neurologic deterioration are associated with hydralazine usage

and it was well tolerated ■

Nitroprusside Sodium nitroprusside (SNP) is a nitric oxide donor Nitric oxide is a potent vasodilator and inhibitor of circulating platelets SNP reduces arterial BP because it reduces both pre-load and after load It acts within seconds and lasts for 1–2 min, with pretreatment BP levels being reached within 1–10 min after the infusion is stopped ♦ SNP is often not the antihypertensive of choice in patients with ICH due to its potent venodilatory effects, which may increase ICP in susceptible patients ♦ ♦ ♦ ♦

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Key Points ■

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Fundamental principles of BP management in neuro-critical care include avoidance of systemic hypotension and hypertension, maintaining CPP > 60–70 mmHg for preventing secondary brain and spinal cord injury Reduction of CPP below 70 mmHg can trigger reflex vasodilatation and ICP elevation Ideal agents should be short acting, can be administered intravenously and that have minimal effects on ICP and CBF autoregulation Drugs recommended for use in lowering BP in acute stroke include labetalol, hydralazine, nicardipine

Suggested Reading Adams HP Jr, del Zoppo G, Alberts MJ et al (2007) Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation 115:e478–e534 Broderick J, Connolly S, Feldmann E et al (2007) Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Circulation 116:e391–e413 Johnston KC, Mayer SA (2003) Blood pressure reduction in ischemic stroke: a two-edged sword? Neurology 61:1030–1031 Qureshi AI (2008) Acute hypertensive response in patients with stroke: pathophysiology and management. Circulation 118:176–187 Qureshi AI, Harris-Lane P, Kirmani JF et al (2006) Treatment of acute hypertension in patients with intracerebral hemorrhage using American heart association guidelines. Crit Care Med 34:1975–1980 Tietjen CS, Hurn PD, Ulatowski JA, Kirsch JR (1996) Treatment modalities for hypertensive patients with intracranial pathology: options and risks. Crit Care Med 24:311–322 Torbey MT (2004) Blood pressure management. In: Bhardwaj A, Mirski MA, Ulatowski JA (eds) Handbook of neurocritical care. Humana Press, Totowa, NJ Ziai WC, Mirski MA (2004) Blood pressure management in the neurocritical care patient. In: Suarez JI (ed) Critical care neurology and neurosurgery. Humana Press, Totowa, NJ, pp 247–266

Chapter 10

Nutrition in Neurocritical Care Tara Nealon

Epidemiology and Etiology ■

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Incidence of malnutrition in hospitalized patients has been shown to range from 30 to 55% Malnutrition is associated with longer hospital stay, slower recovery, more complications, and increased morbidity and mortality rates, all resulting in increased costs All patients admitted to the neurocritical care unit should be screened for risk or presence of malnutrition Critically ill patients with neurologic impairment often require specialized nutrition support because of intubation, dysphagia, or altered mental status Acute neurologic injury can result in metabolic and physiologic alterations and nitrogen wasting Early enteral nutrition (EN) support (within 48 h of injury or admission to the ICU) has been shown to attenuate the catabolic response and improve immune function and is associated with improved neurologic outcome Neurosurgical patients who require major spinal or intracranial interventions experience the same intense catabolism characteristic of major surgery patients Parenteral nutrition should be reserved for those patients with impaired gastrointestinal (GI) function or those who cannot meet their nutritional needs via EN alone

T. Nealon, RD, CNSC (*) Johns Hopkins University School of Medicine, Baltimore, MD, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_10, © Springer Science+Business Media, LLC 2011

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Clinical Presentation (Signs and Symptoms) ■

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A comprehensive nutritional assessment should be completed for any patient admitted to the neurocritical care unit who is malnourished, deemed at risk for malnutrition, or requiring specialized nutrition support Components of a nutritional assessment ♦ ♦ ♦ ♦ ♦ ♦ ♦

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Diet history Medical history Medication history Anthropometric measurements Laboratory data Nutrition focused physical exam Clinical Status

Assessment of premorbid nutritional status ♦ Assessment of weight status should be made using the patient’s pre-resuscitation

weight • Ideal body weight (IBW) ▲ Using the Hamwi method N Women – 100 lb (45 kg) for the first 5 ft (152 cm) and add 5 lb (2.3

kg) for each inch (2.54 cm) over 5 ft N Men – 106 lb (48 kg) for the first 5 ft (152 cm) and add 6 lb (2.7 kg)

for each inch (2.54 cm) over 5 ft N For both equations, a range of ±10 lb (4.5 kg) for large or small

frame size can be used for interpretation ▲ Classification of IBW N N N N

% of IBW = weight/IBW × 100 80–90% = mild malnutrition 70–79% = moderate malnutrition 0–69% = severe malnutrition

♦ If a patient is obese (>125% IBW), a common practice is to adjust weight

using a factor of 25% • [(Actual body weight – IBW)] × 0.25 + IBW ♦ Adjustments should also be made to IBW if amputations exist ♦ Paraplegia: subtract 4.5 kg from IBW; Quadriplegia: subtract 9 kg from IBW ♦ Body mass index (BMI)

• Used as a measure of obesity and malnutrition • Weight (kg)/Estimated surface area (m2) • Interpretation

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18.5–25 – Normal weight 25–29.9 – Overweight 30–34.9 – Obesity grade I 35–39.9 – Obesity grade II >/= 40 – Obesity grade III 17–18.4 – Protein-energy malnutrition grade I 16–16.9 – Protein-energy malnutrition grade II <16 – Protein-energy malnutrition grade III

♦ Recent weight loss is the best parameter to evaluate in classification of

malnutrition • % of usual body weight (UBW) = (current weight/UBW) × 100 ▲ Interpretation N 85–95% = mild malnutrition N 75–84% = moderate malnutrition N 0–74% = severe malnutrition

• Significant weight loss is defined as: ▲ ▲ ▲ ▲

³2% in 1 week ³5% in 1 month ³7.5% in 3 months ³10% in 6 months

♦ Malnourished patients may be at risk for refeeding syndrome (the metabolic

and physiologic shifts of fluid, electrolytes, and minerals (e.g., phosphorus, magnesium, and potassium) that occur as a result of rapid administration of nutrition or aggressive nutrition support – usually a sudden shift to carbohydrate metabolism from fat, which greatly alters insulin levels and concomitant serum electrolyte levels • The syndrome typically occurs within 4 days of refeeding; Hypophosphatemia is common as is a fall in potassium, magnesium, glucose, and thiamine • Visceral organ function (cardiac, neuromuscular, hematopoietic, etc.) is subsequently dysfunctional as a consequence • Special consideration should be given to this condition in the initiation and advancement of the nutritional support regimen ♦ Assessment of hepatic protein stores

• Serum transport proteins – albumin, transferrin, prealbumin ▲ Not directly linked to nutrition deprivation and should not be relied on

as indicators of nutritional status or nutritional recovery ▲ Negative acute-phase reactants because they decrease at least 25% in

response to chronic or acute inflammation ▲ In addition to inflammation, serum concentrations are affected by renal and

liver function, hydration status, blood loss, iron deficiency, and pregnancy

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T. Nealon ▲ Half-life N Albumin – 14–20 days N Prealbumin – 2–3 days N Transferrin – 8–10 days ▲ Can identify those patients who are at risk for malnutrition due to

hypermetabolism/hypercatabolism ▲ If monitored, evaluation should be patient specific; Serial measure-

ments may be helpful during the recovery phase of illness to help guide nutritional management ♦ Nitrogen Balance

• Used to evaluate the adequacy of protein intake • Nitrogen balance = nitrogen intake – nitrogen losses ▲ 1 g dietary protein = 6.25 g nitrogen ▲ Nitrogen intake = protein intake/6.25 ▲ Nitrogen losses = urinary urea nitrogen (UUN) + insensible losses (usu-

ally a factor of 2–4 g/day) ▲ Nitrogen balance = Nitrogen intake (g) - [UUN excretion (g) + (2–4 g

insensible skin and GI losses)] ▲ Goal for nitrogen balance is +2 to 4 g for repletion ▲ Not realistic to achieve this during catabolic phase of critical illness

• Limitations ▲ Invalid in the following conditions: N N N N

Urine output <1 L/day Renal or liver failure with nitrogen accumulating in the blood Nitrogen losses from large open wounds, fistulas, or diarrhea Urine collection <24 h

♦ Metabolic response to neurotrauma

• Initial “ebb” phase ▲ General decrease in metabolism, body temperature, cardiac output, and

energy expenditure ▲ Usually peaks 48–72 h after injury and lasts 3–4 days

• “Flow” phase ▲ Increase in metabolism, insulin production (resistance), increased pro-

teolysis, lipolysis, loss of lean body mass ▲ Can last anywhere from a few days to weeks, depending on severity

of injury ♦ Calculation of energy requirements

• Indirect calorimetry (IC) remains gold standard in ICU setting for determining energy requirements; IC obtains REE (resting energy expenditure)

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• Many factors limit the use of IC such as patient stability, inconsistent ventilator settings, air leaks, and calibration errors; therefore, it may be difficult to obtain accurate results • When IC is used, a 5 min steady state must be achieved to validate the use of data obtained • Traditionally, various multipliers are added to measured REE; however, recent research concluded that patients should be fed 100% REE without addition of factors • The respiratory quotient (RQ) has traditionally been used to determine substrate utilization. Recent research has determined that the RQ is an indicator of study validity and not substrate utilization. Physiologic range for RQ is 0.67–1.3 • Therefore, when using IC, care must be taken not to adjust a nutritional regimen based on the value of the RQ • When IC is not available, predictive equations and kcal/kg can be used to estimate energy requirements • Not all predictive equations that exist are appropriate for the critically ill patient. The Harris–Benedict equation (BEE) has traditionally been used; however, it has not been validated recently for use with the critically ill • If predictive equations are needed in non-obese critically ill patients, the equations listed in Table 10.1 (in order of accuracy) have been found to be the most accurate • For the obese critically ill patient, the Ireton–Jones (1992) or Penn State (1998) equation has the best prediction accuracy of equations studied (Table 10.1) • kcal/kg is often used in calculation of energy requirements, as it is simplistic; The American Society for Parenteral and Enteral Nutrition (ASPEN) Guidelines recommend 20–35 kcal/kg/day for adults • 25 kcal/kg is recognized as a starting point for the critically ill patient, as it is important to avoid overfeeding in this population • In those patients at risk for refeeding syndrome, nutritional needs may be estimated at 20 kcal/kg initially and, after slow advancement and determination of tolerance to feeding, will be adjusted appropriately; Careful monitoring and repletion of electrolyte levels is also recommended in these patients • Hypocaloric feeding or permissive underfeeding has been shown to benefit critically ill patients ▲ Evidence supports delivery of 14–18 kcal/kg/day or 60–70% of tube-

feeding goal in first week; this may be associated with decrease in length of stay (LOS), days on mechanical ventilation, and infectious complications ▲ Goal in the first week of illness is metabolic support; Avoidance of high calorie provisions with high protein intake (1.5–2.0 g/kg) is appropriate ▲ After the acute phase of critical illness, caloric provision can be evaluated on an individual basis to be increased to support the recovery phase

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Table 10.1  Estimation of energy requirements in critically Ill (in order of accuracy) For nonobese patients Penn State: Resting metabolic rate (RMR) (kcal/d) = HBE(0.85) + VE(33) + TM(175) – 6,433 Equation uses basal metabolic rate calculated with the Harris–Benedict equation (HBE), minute ventilation (VE) in liters per min (L/min), and maximum temperature (Tmax) in degrees Celsius. Swinamer: RMR (kcal/d) = BSA(941) – age(6.3) + T(104) + RR(24) + VT(804) – 4,243 Equation uses body surface area (BSA) in squared meters (m2), temperature (T) in degrees Celsius, and tidal volume (VT) in liters per minute (L/min). Ireton–Jones, 1992: Spontaneously breathing IJEE (s) = 629 – 11(A) + 25(W) – 609(O) Ventilator dependent IJEE (v) = 1,925 – 10(A) + 5(W) + 281(S) + 292(T) + 851(B) Equations use age (A) in years, body weight (W) in kilograms (kg), sex (S, male = 1, female = 0), diagnosis of trauma (T, present = 1, absent = 0), diagnosis of burn (B, present = 1, absent = 0), obesity >30% above initial body weight from 1959 Metropolitan Life Insurance tables or body mass index >27 (present = 1, absent = 0) For obese patient Ireton–Jones, 1992: Same as above Penn State, 1998: Resting metabolic rate (RMR) = Basal metabolic rate (BMR)(1.1) + VE(32) + Tmax(140) – 5,340 Equation uses basal metabolic rate calculated with the Harris–Benedict equation, minute ventilation (VE) in liters per min (L/min), and maximum temperature (Tmax) in degrees Celsius. Harris–Benedict Equation (BMR): Men: RMR = 66.47 + 13.75(W) + 5(H) – 6.76(A) Women: RMR = 655.1 + 9.56(W) + 1.7(H) – 4.7(A) Equation uses weight (W) in kilograms (kg), height (H) in centimeters (cm), and age (A) in years Adapted from American Dietetic Association Evidence Analysis Library; Critical illness evidencebased nutrition practice guideline, 2008 ▲ Consequences exist for both underfeeding and overfeeding critically ill

patients. A nutritional assessment by a registered dietitian or other nutrition support clinician is imperative for management of avoiding these consequences (Table 10.2) ♦ Estimation of protein requirements

• Goal during critical illness is to provide support for the body’s metabolic functions and to preserve lean body mass • Inflammatory response causes increased breakdown of protein stores. It is impossible to avoid some loss of lean body mass during critical illness secondary to inflammatory response, immobility, and inconsistent adequacy of nutritional intake • The current recommendation is to provide 1.5–2 g/kg/day of protein ♦ Fluid requirements

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Table 10.2  Possible consequences of underfeeding and overfeeding Underfeeding Decreased respiratory muscle strength Failure to wean from mechanical ventilation Poor wound healing Immunosuppression Impaired organ function Increased risk of nosocomial infection Overfeeding Hyperglycemia Failure to wean from mechanical ventilation Hypertriglyceridemia Hepatic steatosis Azotemia Immunosuppression Electrolyte imbalance Alterations in hydration status

• By weight – 25–35 mL/kg/day, depending on age, sex, activity, clinical condition • By caloric intake – 1 mL/kcal/day • Fluid intake will need to be limited in many conditions in the neurocritical care patient, such as with SIADH (syndrome of inappropriate antidiuretic hormone), hyponatremia, oliguria, intentional hypernatremia to avoid or limit cerebral edema, and congestive heart failure • Increased if abnormal GI, skin, or renal fluid losses • Consideration should be given to all sources of fluid: IV, enteral, oral, medications

Management ■

Enteral nutrition ♦ Most neurologically impaired critically ill patients will be vented initially and

require specialized nutritional support ♦ In the critically ill patient with a functioning GI tract who is hemodynami-

cally stable, EN is recommended over parenteral nutrition (PN) ♦ Potential contraindications to EN

• Complete mechanical obstruction or pseudo-obstruction below the duodenum that cannot be resolved • Severe GI bleed • Gut ischemia • Hemodynamically unstable: MAP <60–70 mmHg, ↑ dose of pressors

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• • • • • • •

Paralytic ileus of small bowel Severe short-bowel syndrome (<100 cm of small bowel) Fistulas – High-output midgut jejunal Severe GI malabsorption Intractable vomiting/diarrhea refractory to medical management Inability to gain access to GI tract Terminal illness

♦ Timing

• In the critically ill patient who is adequately resuscitated, EN should be started within 24–48 h following injury or admission to the ICU • Early EN is associated with a decrease in infectious complications and may reduce LOS ♦ Location

• Short term ▲ Nasogastric or orogastric tube N Commonly placed in the neurocritically ill patient N Made in various sizes (5–18 F), but 8–12 F most appropriate for

administration of enteral feeds N Easily placed at bedside ▲ Nasoenteric tube (nasal duodenal/Dobhoff, nasojejunal, nasogastric-

jejunal) N Placement of a feeding tube in the small bowel should be consid-

N N N N

ered when a patient is supine or under heavy sedation or when serial measurements of gastric residual volumes >250 mL are not responsive to prokinetic agents Nasogastric-jejunal tube can allow for gastric decompression with simultaneous small bowel feeding Can be more difficult to place – may need fluoroscopic or endoscopic placement X-ray verification of tube placement remains the gold standard The smallest bore feeding tube possible should be used for patient comfort

• Long term ▲ If anticipated that a patient will require enteral feeding for >4 weeks, a

gastrostomy or jejunostomy tube should be placed ▲ Gastrostomy (PEG, open G-tube) N Available in sizes from 14 to 28 F N Can be placed endoscopically, radiologically, and surgically N Allow for bolus feeding and administration of medication

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▲ Jejunostomy (PEJ, open J-tube, PEG/J, G-JT) N Smaller bore tubes (8–14 F); gastric port larger, if placed N Ideal for patients with gastroparesis, recurrent aspiration of gastric

contents N Can have a tube with both gastric and jejunal ports to allow for

gastric decompression and small bowel feeding ♦ Enteral formula selection

• • • •

Over 200 commercially made enteral formulas are available Each institution will have a formulary with selected products Caloric density of tube-feeding formulas range from 1 to 2 kcal/mL Types of formulas include polymeric, semi-elemental, and elemental

♦ Enteral formula composition

• Carbohydrate is primary macronutrient and principle energy source in most enteral formulations • Typically provided as 40–90% of total kcals • Most formulas are lactose free because of prevalence of lactose intolerance • Most contain oligosaccharides or polysaccharides • Fiber ▲ Fiber is a polysaccharide found in plant foods that is not digested by

humans and is often added to some enteral formulations ▲ May be soluble or insoluble N Soluble – can help to control diarrhea because of its ability to

increase sodium and water absorption. Enteral formulations with soluble fiber have been shown to reduce the incidence of diarrhea N Insoluble – may help to decrease transit time by increasing fecal weight. No studies to date have supported the decrease in incidence of diarrhea with insoluble fiber N Fiber-containing formulas should not be given to patients with decreased gastric emptying or who are at risk for bowel ischemia N Some enteral formulas contain FOS (fructo-oligosaccharides), a nondigestible oligosaccharide that is fermented in the colon to produce short-chain fatty acids that may aid in maintaining gut integrity and colon cancer prevention. Butyrate in particular, is important for the colonic mucosal enterocytes • Fat ▲ The fat component of enteral formulas can range from 1 to 55% and

mostly consist of a combination of long-chain triglycerides and medium-chain triglycerides (MCTs)

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T. Nealon ▲ The fat in enteral formulas serves as a source of concentrated energy

and prevents essential fatty acid deficiency ▲ Vegetable oils are commonly used as the fat source to provide essential

fatty acids ▲ Many formulas contain a percentage of fat as MCTs. MCTs are

absorbed right into the portal circulation and do not require bile salts or lipase for digestion. MCTs do not provide essential fatty acids. However, they may be useful in the presence of malabsorption ▲ Omega-3 fatty acids are thought to be anti-inflammatory, whereas omega-6 fatty acids are thought to be proinflammatory and immunosuppressive N Some enteral formulas contain a higher amount of omega-3s N While studies have shown promising results, it is not recommended

that they be routinely used at this time • Protein ▲ Enteral formulations may contain intact proteins, hydrolyzed proteins

▲ ▲

▲ ▲

or free amino acids. Protein content of enteral formulas ranges from 6 to 32% Intact proteins used are usually casein, soy or whey protein isolates, and milk protein Peptide-based formulas contain a protein source that has undergone enzymatic hydrolysis. Peptides are absorbed as efficiently as free amino acids Elemental formulas contain free amino acids Evidence is insufficient to determine whether small peptides or free amino acids are a superior protein source when using an elemental formula

• Water ▲ Water composes a large percentage of enteral formulations, ranging

from 70 to 85% ▲ In general, the more calorically dense the formula, the less water it

contains ▲ Percentage of water from enteral formulations should be included in

patients’ total fluid intake ▲ Most patients will require an additional source of fluid to meet their

fluid requirements • Modular components ▲ Traditionally diluted with water and flushed separately through the

feeding tube ▲ Should not be added directly to the tube feeding formula except if done

under sterile conditions ▲ Protein powders

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N Most commonly used modular product, contains 7–12 g protein per

serving N Used to add additional protein to tube feeding regimen without

significantly increasing caloric provision ▲ Carbohydrate powder N Polycose ▲ Fat N MCT oil ▲ Fiber N Soluble fiber supplement ▲ Micronutrients N When provided in a sufficient volume (usually 1,000–1,500 mL/

day), most enteral formulas meet 100% RDI for vitamins/minerals N Patients not receiving 100% RDIs from tube feeding should receive

a multivitamin and mineral supplement ♦ Formula selection

• The neurocritically ill patient will require special attention to fluid status and may initially require a more concentrated formula • Selection of an appropriate tube feeding formula should be based on GI function, fluid status, presence of renal failure, and needs for wound healing • While many specialty formulas exist for many different clinical conditions, the enteral formulary at each institution should be the first reference in deciding on an appropriate enteral product • Standard, polymeric formula ▲ Suitable for most patients; high protein, polymeric formula commonly

used in ICU setting • Concentrated formulas provide the same amount of calories and protein as a standard formula, except in less volume. Careful attention should be taken to address the protein content, as these formulas do not always meet the increased protein needs of the critically ill patient • Renal formulas may be appropriate for patients whose serum electrolyte and mineral levels are difficult to control • Diabetic formulas are not supported for routine use in the critically ill population. Published evidence that these formulas improve glycemic control is limited, and the high-fat content can contribute to delayed gastric emptying • Semi-elemental and elemental formulas should be used only in cases of malabsorption, maldigestion, short bowel syndrome, or pancreatic exocrine insufficiency

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• The use of immune-enhancing formulas is not recommended for routine use in the critically ill population ▲ American Dietetic Association (ADA) Analysis Library: N Immune-enhancing EN is not associated with reduced infectious

complications, LOS, reduced cost of medical care, days on mechanical ventilation, or mortality in moderately to less severely ill ICU patients N Their use may be associated with increased mortality in severely ill ICU patients, although adequately powered trials evaluating this question have not been conducted ♦ Initiation

• In critically ill patients, conservative tube feeding initiation and advancement is indicated • Gastric feeding is acceptable as a starting point and well tolerated by most neurocritically ill patients • Tube feeding should be started as a continuous drip, full strength at 10–40 mL/h, and advanced to goal rate in increments of 10–20 mL/h q 4–12 h • In the stable neurocritically ill patient who is tolerating gastric feeds, tube feeding regimens may be adjusted on an individual basis to a bolus or gravity controlled regimen to facilitate initiation of oral intake or to avoid drug– nutrient interactions, if indicated ♦ Tolerance

• Tolerance to EN is assessed by presence of abdominal distension, nausea, vomiting, and excessive diarrhea • Presence or absence of bowel sounds is not always a good indicator of bowel function; therefore, absence of bowel sounds is not a contraindication to enteral feeding • Diarrhea is the most commonly reported complication from enteral feeding ▲ Common causes of diarrhea include medications (liquid medications in

a sorbitol base, antibiotics, etc.), infection (Clostridium difficile and nonclostridial bacteria), and intolerance due to characteristics of the formula (osmolarity, fat content), or specific components in the formula (lactose) ▲ An infectious cause should be ruled out before implementing the strategies below ▲ Strategies to alleviate diarrhea N N N N

Increasing fluid replacement Addition of soluble fiber Addition of anti-motility agent If possible, change of offending medication

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N Switch to tube feeding formula with lower osmolality or lower fat

content, if indicated N Change of formula to semi-elemental or elemental should be the last

resort and is only indicated if all other strategies have been exhausted and excessive stool output persists • Constipation is common in the neurocritically ill patient receiving narcotics • Neurocritically ill patients not experiencing diarrhea should be given a standing bowel regimen ♦ Aspiration

• Gastric residuals have traditionally been used to assess tolerance to tube feeding and aspiration risk. Recent research has shown no correlation between the presence of high gastric residual volumes and gastric emptying, regurgitation, vomiting, pneumonia, or mortality • In the critically ill patient population, risk of aspiration is thought to be increased due to endotracheal intubation, prolonged supine position, delayed gastric emptying, decreased level of consciousness, and/or misplacement of the tip of a feeding tube • Strategies to reduce risk of aspiration include elevation of the head of the bed to 45°, X-ray confirmation of feeding tube placement • An isolated incidence of a high gastric residual volume (>250 mL) should not prompt enteral feeding to be held without other signs and symptoms of intolerance ▲ Evidence suggests that a decision to stop tube feeding should be based

on a trend in serial measurements and on not a single isolated high volume ▲ Most institutions have a specific protocol regarding checking and monitoring gastric residuals in critically ill • The use of prokinetic agents (metoclopramide and erythromycin) in the critically ill population is recommended at first sign of elevated gastric residual volumes • If a patient is not responsive to the prokinetic agents, feeding tube placement beyond the ligament of Treitz may be beneficial • Blue dye has traditionally been added to enteral formulas to detect aspiration in the critically ill ▲ The current recommendations are that the risk of using blue dye

(FD&C Blue No. 1 and related dyes have toxic effects on mitochondria) outweighs any perceived benefit ▲ The presence of blue dye in tracheal secretions is not a sensitive indicator for aspiration and therefore should not be routinely used in the critically ill population

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♦ Mechanical complications

• Insertion of nasoenteric or oroenteric tube ▲ Esophageal or GI perforation ▲ Misplacement of the tube into the respiratory tract

• After insertion ▲ Migration of the tube, especially from the stomach to the esophagus or

from the small bowel to the stomach ▲ Kinking of the tube ▲ Clogging of the tube N Most common cause is inadequate flushing N Other causes include inadequately crushed medications, medica-

N N N N

tions administered together, inadequate amount of water given with each medication Tube should be flushed before, between, and after medication administration Warm water is the optimal choice for unclogging the tube Can use pancreatic enzymes if unsuccessful with warm water Tube feeding formula is rarely the cause of clogging

♦ Oral intake

• Candidates for oral intake should have a bedside swallowing evaluation before initiation of oral intake • Many patients may require concurrent administration of enteral feeds until able to meet caloric and protein requirements via oral intake alone • Enteral feeds can be changed to nocturnal, cyclic, or bolus in efforts to facilitate oral intake • Many patients will require a modified-consistency diet with thickened liquids. It can be challenging for these patients to meet their nutritional needs via oral intake alone and. without concurrent use of EN support. are put at severe risk for malnutrition • A registered dietitian or other nutrition support clinician should be closely monitoring the patient on transitional diets, and the use of calorie counts, if warranted, can help to guide the nutritional management of a patient ■

Parenteral nutrition ♦ Indications for use

• Impaired GI function ▲ ▲ ▲ ▲

Inability to absorb adequate nutrients via the GI tract Complete bowel obstruction or pseudo-obstruction Nonaccessible GI tract Documented intolerance to EN

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▲ Severe catabolism with or without malnutrition when GI tract is not

usable within 5–7 days ▲ Lengthy GI work-up, requiring NPO status for several days in malnour-

ished patient ▲ Acute abdomen; persistent ileus not responding to medical treatment ▲ High-output enterocutaneous fistula (>500 mL/day) and inability to

gain enteral access distal to the fistula site • Contraindications ▲ ▲ ▲ ▲ ▲

Functional GI tract Treatment anticipated for <5 days in patients without severe malnutrition Inability to obtain venous access A prognosis that does not warrant aggressive nutritional support When the risks of PN are judged to exceed the potential benefits

• Peripheral parenteral nutrition Appropriate for short-term use – at least 5 days but no more than 14 days Standard IV, 18–21 G needles IV site must be changed every few days to decrease risk of phlebitis Osmolality must be <900 mOsm. Final PN formulation should not exceed 10% dextrose and/or 5% amino acids ▲ Limitations on meeting nutritional needs ▲ Not the optimal choice for feeding patients with significant malnutrition, severe metabolic stress, large nutrient or electrolyte needs, fluid restriction and/or the need for prolonged IV support ▲ ▲ ▲ ▲

♦ Central parenteral nutrition (CPN) or total parenteral nutrition

• Preferred for use in patients who will require PN support for >7–14 days • Should be delivered through a catheter located with its distal tip in the superior vena cava or right atrium ▲ Peripherally inserted intravenous central catheter (PICC) is commonly

used in the hospital setting ♦ Formulations

• Protein ▲ Crystalline amino acid solution – contains all essential amino acids and

alanine and glycine, the major nonessential amino acids. Glutamine and taurine not included in adult formulas ▲ Available in concentrations from 3.0 to 10% ▲ Contains 4 kcal/g • Dextrose ▲ Has 3.4 kcal/g rather than 4 kcal/g, as in dietary carbohydrate, because

a noncaloric water molecule is added to dextrose molecules

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T. Nealon ▲ Available in concentrations from 5 to 70% ▲ Maximum dextrose infusion rate is 5–7 mg/kg/min; 3–4 mg/kg/min in

critically ill • Lipid emulsions ▲ Used as a source of essential fatty acids (EFA) ▲ Available in 10% (1.1 kcal/mL), 20% (2 kcal/mL), and 30% (3 kcal/mL) ▲ Consensus is that the triglyceride/phospholipid ratio is most favorable

for efficient metabolism in the 20% emulsions ▲ Total of 2.5 g/kg/day of lipids in healthy patients and 1 g/kg/day in the

critically ill should not be exceeded ▲ Propofol is a 10% lipid emulsion ▲ Contraindications include severe egg allergy, soy allergy, and hypertrig-

lyceridemia (>400 mg/dL) ♦ Additives

• Electrolytes ▲ Standard and individual additives based on normal requirements ▲ Higher amounts should be provided at initiation of PN if patient at risk

for refeeding syndrome ▲ Higher amounts may be required if patient has significant GI losses

• Multivitamin ▲ An aqueous multivitamin preparation is added to all PN solutions ▲ MVI-13 is the standard multivitamin added to PN solutions ▲ Amounts of each vitamin/mineral in MVI-13 are the recommended

amounts in adults ▲ Vitamin K is included in MVI-13; however, was not in previous

preparations • Trace elements ▲ A trace-element preparation is added to all PN solutions ▲ Contain the recommended parenteral amount for chromium, copper,

manganese, and zinc ▲ MTE-5 (5 mL) includes selenium ▲ Copper and manganese should be omitted if patient has elevated total

bilirubin (T-bili); other components can be added separately to PN solutions ▲ Iron not included in this preparation due to compatibility issues • Insulin ▲ Can be added to PN solution to achieve glycemic control ▲ Give 0.1 units/g CHO/24 h in patient with insulin-dependent diabetes

mellitus

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▲ 2/3 of previous 24 h coverage for non-insulin-dependent diabetes mel-

litus and iatrogenic hyperglycemia • H2 blockers ▲ Pepcid, Zantac, Tagamet

♦ Administration

• CPN should be administered through a clean, dedicated port or central line • Initiated as a continuous infusion (over 24 h) in hospitalized patient • Can be cycled in stable, long-term patients when anticipated to require continued therapy upon discharge from hospital • Can also be cycled in stable patients with PN-associated liver abnormalities to rest the liver • Cycled CPN must be tapered up and down to avoid rebound hypoglycemia • If CPN has to be stopped immediately, provide a 10% dextrose solution and monitor glucose levels ♦ Initiation

• May start PN at desired volume with 50–65% of CHO load (generally, 150–200 g dextrose), 50–100% protein needs, and 100% IV lipids (if triglyceride levels are <400 mg/dL) • May increase CHO load to 100% based on glucose tolerance ♦ Monitoring

• Initially – baseline chemistry panel taken before initiation of CPN and then daily until stable • Triglyceride level should be obtained before starting IV lipids; weekly thereafter • Fingersticks should be taken q 6 h until stable • Weight – 3×/wk ♦ Complications

• Catheter related • Electrolyte/metabolic disturbances • Hyperglycemia most common complication of PN ▲ Strategies to improve glycemic control N Avoid overfeeding N Limit dextrose in CPN to 150 g/day initially N Review other sources of IV dextrose that the patient is receiving

(antibiotic drips, continuous venovenous hemodialysis, peritoneal dialysis, etc.). Adjust PN if indicated N Tighten sliding-scale insulin coverage N Increase frequency of fingersticks

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T. Nealon N Start insulin drip N Stop CPN for 24 h; resume once glucose levels are under control

• Hepatic ▲ Fatty liver due to over infusion of dextrose, lipid, and/or total calories

• Biliary ▲ Cholestasis N Initiate enteral/oral intake as soon as possible, even with malabsorp-

tion to stimulate gallbladder • Metabolic bone disease ▲ Long-term complication; related to vitamin D metabolism

• Hypertriglyceridemia from lipid emulsions ♦ Transitioning

• No set guidelines regarding weaning or tapering of CPN • CPN should be discontinued once patient is meeting 50–75% of estimated nutritional needs enterally or via oral intake ■

Drug nutrient interactions ♦ Phenytoin

• Impaired absorption of phenytoin with patients on enteral feeding is probably the most commonly known drug–nutrient interaction • Many studies and case reports have been published, but few are prospective, randomized, controlled trials • The practice of holding tube feeding before and after phenytoin administration is cumbersome and often results in inadequate nutrient intake. This practice has not been validated • Many institutions are now choosing to adjust the phenytoin dose to achieve therapeutic concentrations, as too much potential exists for variation in feeding administration, resulting in inadequate delivery of EN when feedings are held for medications ♦ Carbidopa/Levodopa

• No trials have evaluated absorption of carbidopa/levodopa with concurrent enteral feedings • Extrapolations have been made from the data that show a decreased effect when the medication is taken with a high-protein meal • The current recommendation is that if a patient is receiving intermittent feedings, the doses be administered while the feeding is off ■

Nutritional considerations in specific diseases ♦ Traumatic brain injury (TBI)

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• TBI is characterized by a hypermetabolic response to injury • Indirect calorimetry can be useful in determining energy requirements • Hyperglycemia is a common complication after acute brain injury: Avoidance of overfeeding is essential • Nitrogen losses of up to 30 g/day have been documented in acutely ill patients with head injury • Goal for protein intake should be between 1.5 and 2.0 g/kg/day • Unrealistic to achieve nitrogen balance in the first few weeks after injury. Goal is to minimize losses • EN should be initiated as early as possibly, ideally within the first 48 h • Gastric function is altered after severe head injury. Elevation of head of bed and prokinetic agents should be utilized to increase tolerance to EN • If intolerance to gastric feeding is noted, placement of the tube should be advanced into the small bowel • Patients for whom EN was initiated rapidly had fewer infectious complications, earlier hospital discharge, and better neurologic outcomes at 3 months as compared to patients whose EN formula rate was slowly increased over time • For patients receiving barbiturate coma therapy, energy expenditure will be decreased. Small bowel feedings have been shown to be well tolerated • Propofol is formulated in a 10% egg-phospholipid emulsion, providing 1.1 kcal/mL. The calories from this should be taken into consideration when formulating a nutritional support regimen • PN should only be used in the absence of a functioning GI tract. Every effort should be made to facilitate EN tolerance when needed, such as postpyloric access or promotility agents • The more severe the brain injury, the less likely that normal swallowing function will return ♦ Spinal cord injury

• Patients with spinal cord injuries will often have a change in their nutritional requirements over the course of injury • In general, the higher the level of injury, the lower the calorie needs • EN support should be initiated within the first 48–72 h of injury • AANS/CNS guidelines favor small bowel feeding over gastric feeding; however, minimal complications have been reported when EN was implemented via nasogastric or nasojejunal tubes within the first 48 h • Immobilization leads to high nitrogen losses in acute phases of injury; however, over time, it may lead to an increase in body fat • Body weight should be adjusted by 4.5 kg for paraplegic and 9 kg for quadriplegic patients • Initial caloric guidelines for paraplegic patients are 28 kcal/kg/day; for quadriplegic patients, 23 kcal/kg/day. These levels may change depending on the clinical status of the patient at time of initiation of nutritional support • Many patients with spinal cord injuries will require a more permanent feeding device. Placement of tube may depend on location of injury

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• Constipation and fecal impaction are commonly associated with spinal cord injury ▲ Standing bowel regimen, adequate hydration and fiber intake (30 g/

day), and laxatives or prokinetic agents are recommended ♦ Stroke

• Depending on the location and severity of the injury, specialized nutritional support may be required • Enteral feedings via a nasogastric tube are often started at initiation. If EN support is necessary 2–3 weeks after onset of a stroke, placement of a PEG is likely warranted • Dysphagia is a common complication, and efforts to regain swallowing function should be implemented early • Even with demonstrated tolerance to oral intake, many stroke patients – especially those who are elderly – may not be able to meet nutritional needs via oral intake alone, and placement of a PEG is warranted ♦ Chronic phase of neurologic injury

• With the exception of TBI, energy requirements decrease as patients transition into the recovery (rehabilitation) phase of illness • Ongoing immobility and denervation continue to generate muscle losses; therefore, care should be given to maintain adequate protein intake • Hydration status should be closely monitored, as fluid intake is often compromised during acute phase of injury ♦ Alzheimers disease and Parkinson disease

• Weight loss and malnutrition is common in patients with either of these conditions due to difficulties in self-feeding • PEG placement may be a potential option for many of these patients; however, may not improve outcome

Key Points ■

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Malnutrition is associated with longer hospital stays, slower healing, more complications, and increased morbidity and mortality rates Nutritional support should be initiated in those patients unable to tolerate oral diet within 48 h of admission to the neurointensive care unit EN support is the preferred route in the neurocritically ill patient who requires specialized nutritional support Most neurocritically ill patients can tolerate gastric feedings; however, if intolerance is present, the use of prokinetic agents and placement of a tube past the ligament of Treitz should be utilized

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PN should be reserved for those patients with severe GI impairment or documented intolerance to EN Patients with TBI exhibit a hypermetabolic response that is proportional to the severity of injury and motor dysfunction Patients with spinal cord injuries will often have a change in their nutritional requirements over the course of injury and will require long-term specialized nutrition support A swallowing evaluation should be completed before initiating oral diet. Even when tolerance is established, many patients will also require long-term EN support to achieve adequate nutrient intake

Suggested Reading ADA Evidence Analysis Library (2006) Critical illness evidence-based nutrition practice guidelines. http://www.adaevidencelibrary.com. Accessed May 2008 ASPEN Board of Directors and the Clinical Guidelines Task Force (2002) Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enter Nutr 26:1SA–138SA Au Yeung SC, Ensom MHH (2000) Phenytoin and enteral feedings: does evidence support an interaction? Ann Pharmacother 34:896–905 Cook AM, Hatton J (2007) Neurological impairment. In: Gottschlich MM, DeLegge MH, Mattox T, Mueller C, Worthington P (eds) The ASPEN Nutrition Support Core Curriculum: a casebased approach – the adult patient. ASPEN, Silver Spring, MD, pp 424–439 Donaldson J, Borzatta M, Matossian D (2000) Nutrition strategies in neurotrauma. Crit Care Nurs Clin North Am 12465–12475 Frankenfield D (2006) Energy expenditure and protein requirements after traumatic injury. JPEN J Parenter Enter Nutr 21:430–437 Fuhrman PM, Charney P, Mueller CM (2004) Hepatic proteins and nutrition assessment. J Am Diet Assoc 104(8):1258–1264 Gleghorn E, Amorde-Spalding K, Delegge MH (2005) Neurologic diseases. In: Merritt R, DeLegge MH, Holcombe B, Mueller C, Ochoa J, Ringwald Smith K, Schwenk WF (eds) The ASPEN Nutrition Support Practice Manual, 2nd edn. ASPEN, Silver Spring, MD, pp 246–256 Hadley MN (2002) Nutrition support after spinal cord injury. Neurosurgery 50:S81–S84 Todd SR, Kozar RA, Moore FA (2006) Nutrition support in adult trauma patients. JPEN J Parenter Enter Nutr 21:421–429

Chapter 11

Sedation, Analgesia, and Neuromuscular Paralysis Marek A. Mirski

General Issues of ICU Sedation ■ ■ ■ ■

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Comfortable patient; ethical and good medical practice Relieves pain, anxiety, recall; enhances patient safety Mandated in 2000 by The Joint Commission Sedation may be particularly difficult to titrate in neurologically compromised patient Sedatives and analgesics may compromise exam and cerebral physiology More need for conscious sedation due to recent reduction in pharmacologically induced paralysis in ICU patients Emphasis on reducing length of ICU stay and cost of hospitalization Guidelines stress minimizing depth and duration of sedative regimens; overall beneficial for neurologic patient, as more likely to preserve neurologic functions

Identifying Need for “Sedation” ■

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Sedation – commonly used to indicate provision of analgesia, anxiolysis, antipsychosis, or a combination Correct diagnosis of a single or overlapping disturbance thus becomes starting point Medications may have narrow or broad overlapping therapeutic effects

M.A. Mirski, MD, PhD (*) Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_11, © Springer Science+Business Media, LLC 2011

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Management of Pain: Recognition ■

Prerequisite for analgesic therapy is discomfort ♦ Etiologies of pain in the ICU are depicted in Table 11.1 ♦ Not all pain should be entirely suppressed, particularly discomfort that provides

♦

♦

♦

♦

a clinical guide to the evolution of a pathologic process such as an acute abdomen or compartment syndrome Nevertheless, studies demonstrate that patients cared for in an ICU are apt to be in considerable discomfort during some portions of their stay and that overall management of pain during critical care has remained suboptimal In a recent large series of mechanically ventilated patients, procedural discomfort was specifically managed in <25% of the population, and the use of guidelines for analgesia and sedation promoted less – not more – therapy for pain management Specific to procedure, patients express differences between pre- and postprocedural levels of discomfort with interventions of drain removal, deep breathing and coughing exercises, suctioning, and line removal; often patients do not receive pre-procedural analgesia Important to note – routine monitoring of hemodynamic parameters such as heart rate and blood pressure often fail to serve as indicators of patient discomfort

Tools for Pain Assessment ■ ■

Adequate therapy requires assessment and titration guides (Tables 11.2 and 11.3) For patients unable to self-rate: ♦ Later scoring devices include measures of a variety of behavioral dimensions

to provide a comprehensive assessment in the nonverbal patient Table 11.1  Etiologies of pain in the ICU Localized pain Diffuse visceral Surgical wound Acute abdomen Bone fracture Myocardial ischemia Ulceration Pneumonia Pleurodynia Invasive procedure Local burn injury Compartment syndromes Ureteral stone Appendicitis

Myocarditis Pulmonary embolus Vascular ischemia Gastritis

Neurologic Intracranial hemorrhage Headache/migraine Elevated intracranial pressure Compressive neuropathy Subarachnoid hemorrhage Cranial neuritis Diabetic neuropathy

Pancreatitis Bowel obstruction

Reflex dystrophy Meningismus

Complex Mechanical ventilation Diffuse joint pain/ arthralgia Sickle cell Metabolic disorders Febrile/sepsis

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Table 11.2  Pain assessment scale for awake, responsive patients ICU pain scale Self-rating scale Numerical Rating Scale (NRS) 1–10 Visual Analog Scale (VAS) 1–100 Table 11.3  Pain assessment scales for noncommunicative patients ICU pain scale Behavioral Pain Rating Scale (BPRS) Behavioral Pain Scale (BPS) Critical-Care Pain Observational Tool (CPOT) Nonverbal Pain Scale (NVPS) Pain Assessment and Intervention Notation Algorithm (PAIN)

♦ The BPRS and the BPS have undergone complete content, criterion, and con-

struct validity testing, and the BPS has further documented inter-rater reliability testing ♦ Studies have demonstrated that self-reporting of discomfort has the greatest correlation with multi-domain behavioral ratings compared with single-item scoring ♦ Pain management regimens do risk diminishing overall level of arousal; hence, analgesia should be titrated to effect with preservation of responsiveness, typically to reduce the pain to <3 on a 0–10 ordinal scale

Classes of Analgesics ■

Many treatment options exist for pain management; some classes of drugs offer more than strictly analgesia; physicians should proceed with caution to offer the narrowest range of therapeutic action necessary ♦ Standard medications include nonsteroidal anti-inflammatory drugs (aspirin,

acetaminophen, ketorolac), narcotics [both pure and mixed agonists, a2 agonists (clonidine and dexmedetomidine)], steroids, ketamine, and the local anesthetics (Table 11.4)

Anxiolysis ■

■

Apart from the treatment of pain, anxiolysis represents the therapy most sought when delivering “sedation” Anxiolysis – provision of pharmacotherapy to lessen feelings of apprehension/ anxiety, diminish general nervous tension or “stress,” and treat the most severe form of excited disequilibrium, i.e., agitation

148 Table 11.4  Common classes of analgesic agents Analgesic Drug class Examples mechanism COX-1 or Nonsteroidal Aspirin, COX-2 acetaminophen, inhibition ketorolac µ-Receptor Opioids Morphine, agonists hydromorphone, fentanyl

M.A. Mirski

Other action Antiplatelet

Major toxicity Bleeding, hepatotoxicity

Respiratory control, Ventilatory sedation depression, addictive behavior a2 Agonists Hypotension, Clonidine, a2-Receptor Cardiovascular bradycardia dexmedetomidine agonist tone and heart rate control Motor weakness, Local Lidocaine, Nerve Na+ Sensory and motor cardiac arrest anesthetics bupivacaine blockade, cardiac channel conduction blockade Hallucinations, NMDA Ketamine NMDA Dissociative seizures, ICP antagonist antagonist anesthesia, elevation cerebral activation COX cyclooxygenase; NMDA N-methyl, d-Aspartic acid

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Psychologically demanding circumstances in critical care are numerous, with common general ICU stressors being the psychological responses to a lifethreatening illness, unfamiliar surroundings, near constant noise and activity, disturbed sleep-wake cycles, and overall sense of lack of control Pain and anxiety are commonly combined; important to discern if pain is paramount; several agents are very effective in anxiolysis such as the benzodiazepines or the sedative/hypnotic agents (e.g., the barbiturates and propofol); some provide both analgesia and anxiolysis: a2 agonists, ketamine, and some narcotics (morphine, meperidine) in low doses

Delirium ■

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Delirium is a dysfunctional cognitive state; recently gained great interest as a predictor of poor outcome in hospitalized patients, particularly in the ICU Not easily diagnosed unless the condition is specifically entertained Specific scoring batteries have been designed for diagnostic purpose; their introduction has led to data supporting that delirium is an independent predictor of longer hospital stay, greater mortality, and ICU costs However, it remains unclear whether all forms of delirium are equally hazardous; especially in the ICU setting, a breadth of conditions can incite the encephalopathic

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state and delirium in a transient or persistent manner, each with likely different effects on the patient’s physiologic state Several etiologies include metabolic dysfunction, electrolyte abnormalities, relative hypoxia, acid–base disturbances, drug-induced cognitive dysfunction, and loss of adequate sleep and sleep-wake cycling; it still remains to be seen whether effective treatment of delirium improves these indices

Therapy for Sedation ■

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Many classes of drugs exist, including the narcotics, benzodiazepines, barbiturates, propofol, neuroleptics, a2-adrenergic agents, ketamine, and several other lesser classes of chemical agents. Within each class are agents with varied pharmacokinetics, routes of administration, titratability, adverse reactions, and hemodynamic profile It is generally recommended that shorter-acting agents (Tables 11.5 and 11.6) be used in the critical care setting when serial neurologic examinations are important It is necessary to eliminate alternative explanations for agitation, confusion, or sympathetic hyperactivity prior to actively suppressing these potential symptoms and signs of a serious underlying condition (Table 11.7)

Monitoring of Sedation ■

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To monitor administration of sedatives, numerous sedation scoring systems have been crafted First scale popularized was the Ramsay Scale, introduced in 1974; focused primarily on patients post-cardiac surgery and emphasized deep levels of sedation Recent scoring tools include the Riker Sedation-Agitation Scale (SAS, 1999), Motor Activity Assessment Scale (MAAS, 1999), the Richmond AgitationSedation Scale (RASS, 2002), and recently, the ATICE (Adaptation to the Intensive Care Environment) and AVRIPAS (four components: agitation, alertness, heart rate, and respiration) Only the RASS has been validated for its ability to detect changes in sedation status over consecutive days Some intensivists have argued that representation of several domains of level of arousal, including cognitive state and degrees of anxiety or agitation, by a single numerical value diminishes the potential utility of an assessment tool Hence, two-domain instruments have been developed and validated and include the Vancouver Interaction and Calmness Scale (VICS) and the Minnesota Sedation Assessment Tool (MSAT) scale

Opioid

Opioid

Nonbarbiturate anesthetic/analgesic agent

Benzodiazepine

Benzodiazepine

Benzodiazepine

Morphine sulfate

Hydromorphone

Ketamine

Diazepam

Lorazepam

Midazolam

+++

+++

–

–

+

+++

+++

+++

+++

+++

+

+

GABAa-receptor agonist

GABAa-receptor agonist

GABAa-receptor agonist

NMDA agonist

µ-Receptor agonist

µ-Receptor agonist

µ-Receptor agonist

+++

Opioid

Remifentanil

+

Mechanism of action µ-Receptor agonist

Table 11.5  Pharmacologic profile of common ICU sedative agents Drug Type of medication Sedation Analgesia Fentanyl Opioid + +++

Reversible, short duration, titratable, water soluble

Reversible, longer duration

Reversible, longer duration Preserves ventilatory drive, pharyngeallaryngeal reflexes, and cardiovascular stability Reversible, short duration

Reversible, promotes sleep

Potent, reversible, rapid onset, short duration

Advantages Potent, reversible, rapid onset, short duration

Respiratory depression, hypotension, confusion, long-acting active metabolite Respiratory depression, hypotension, confusion Respiratory depression, hypotension, confusion

Adverse effects Respiratory depression, chest wall rigidity, gastric dysmotility, hypotension Respiratory depression, chest wall rigidity, gastric dysmotility, hypotension Respiratory depression, gastric dysmotility, hypotension, hallucinations Respiratory depression, gastric dysmotility Dissociative state, hallucinations, delirium, tachyarrhythmia

150 M.A. Mirski

++

++

+++

a2 Agonist

Clonidine

Dexmedetomidine a2 Agonist

Propofol

Non-barbiturate sedative hypnotic

+++

Neuroleptic (butyrophenone)

Droperidol

+++

Neuroleptic (butyrophenone)

Haloperidol

–

++

++

+

–

Unclear GABAareceptor agonist

Very short duration, titratable

Preserves level of Blocks dopamine, arousal, airway adrenergic, reflexes serotonin, acetylcholine, histamine receptors Combined sedation, Blocks dopamine, antipsychotic. adrenergic, serotonin, antiemetic, analgesia acetylcholine, in headache histamine receptors syndromes a2 Agonist (pre- and Useful in setting of post-synaptic) alcohol or drug withdrawal a2 Agonist (pre- and Short acting, little effect post-synaptic) on consciousness and blood pressure Dry mouth, bradycardia, hypotension, rebound hypertension Dry mouth, bradycardia, hypotension, adrenal suppression, atrial fibrillation Hypotension, respiratory depression, metabolic acidosis, rhabdomyolysis, anaphylaxis, sepsis, pain at venous site

Extrapyramidal signs, may lower seizure threshold, QT prolongation

Extrapyramidal signs, may lower seizure threshold

11  Sedation, Analgesia, and Neuromuscular Paralysis 151

30–60 h

10–20 h

1–2.5 h

12–36 h 4–12 h

Lorazepam

Midazolam

Haloperidol Droperidol

Half-life 30–60 min (single IV dose), if repeated is hours 3–10 min after single dose 1.5–4.5 h IV, IM, SQ

Diazepam

Morphine sulfate

Remifentanil

Drug Fentanyl

0.25–0.5 mg IV q 1–2 h 0.5–1 mg IV q 5–30 min 0.5–5.0 mg IV 0.625–2.5 mg IV

2 mg IV q 30–60 min

0.5–1.0 mg/kg IV bolus 5–20 mg IM q 4 h; 2–10 mg IV q 4 h

12.5–50 mg IV q 20–30 min

Starting dose

Table 11.6  Pharmacokinetics and dosing of common ICU sedatives

97%

Infusion 0.25–1.0 mg/kg/min – –

92% 92%

91–93%

99%

20–30%

92%

Protein binding 80–86%

–

Titration Infusion 0.01–0.03 mg/kg/min and titrate q 15–30 min, up to 50–100 mg/h Infusion 0.05–0.2 mg/kg/min Caution: metabolites may accumulate for postoperative pain (PCA): 0.2–3.0 mg and 5–20 min lockout intervals –

Hepatic Hepatic

Hepatic

Hepatic

Hepatic

Plasma esterases Hepatic

Metabolism Hepatic

– –

1-Hydroxymethylmidazolam

Desmethyl-diazepam, oxazepam, hydroxydiazepam –

Morphine-3glucuronide;morphine6-glucuronide

–

Active metabolite –

152 M.A. Mirski

12–16 h

Propofol

4–10 min

Dexmedetomidine 2 h

Clonidine

– 20–40% Hepatic (50%) – 0.1 mg PO q 8–24 h; and urine increase (unchanged, 0.1 mg/day q 1–2 50%) days up to 0.6 mg/day 1 mg/kg IV over Infusion 0.2–0.7 94% Hepatic – 10 min mg/kg/h Not found Hepatic and – Increase infusion 1.0–2.5 mg/kg IV extrahepatic by 5–10 mg/kg/min (anesthesia q 5–10 min to induction); maintenance 5 mg/kg/min for of 25–100 mg/kg/min 5 min IV (sedation) up to 100–300 mg/kg/ min

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M.A. Mirski Table 11.7  Physiologic etiologies for agitation Hypoxemia Hepatic or renal insufficiency Hypercarbia Myocardial ischemia Acidosis – metabolic, respiratory Cerebral ischemia Hyponatremia Hypotension Hypoglycemia Psychoactive medications Hyperammonemia Corticosteroids Hypercalcemia Anticonvulsants

Physiologic and Brain Function Monitors ■

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Neither heart rate nor blood pressure changes have been useful parameters for sedation guidance Neurologic monitors have their origin in the raw electroencephalogram (EEG) and typically have been variants of signal-processed EEG and, more recently, the BIS monitor The BIS is by far the most tested proprietary algorithm that compares the patient’s frontal EEG to processed data set from over 5,000 volunteer EEG samples to scale the output of the measured EEG to between 0 and 100; the “fully awake state” is scored 100, whereas 0 is an isoelectric EEG reading; a score <60 rates a high probability of unconsciousness; sedation targets are typified by ranges of 60–75 BIS suffers from several shortcomings; best used when administering a short-acting barbiturate anesthetic (thiopental) or barbiturate-like drug (propofol) on which the processed EEG algorithm is based, inducing stereotypic alteration in the EEG as a patient transitions from awake → sedated → unconscious/comatose states Agents such as the benzodiazepines, narcotics, or other classes of sedatives differentially influence the EEG; BIS is not programmed to interpret such changes as well: ♦ Benzodiazepines – rise in EEG frequency following modest to moderate doses ♦ Narcotics – little disturbance on the underlying cortical EEG ♦ Combination pharmacotherapy also makes it difficult to readily translate a

BIS “score” to a clinical state of arousal because different agents have such varying actions on the EEG, as they contribute to the sedation scheme ♦ Further limitation of BIS • Inability to fully eliminate the electromyographic (EMG) signal artifact that originates from the frontalis muscle underneath the electrode patch, contaminating the EEG signal input

Classes of Sedative Agents ■

Narcotics (opioids) ♦ Primarily as analgesics but also serve as sedative-hypnotics at low dosages

• Major disadvantage

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▲ Coincident action of suppressing ventilatory drive and gastrointestinal

motility • Advantages ▲ Easy titratability, provision of patient comfort, and reversibility; three opioids

are common in ICU setting – morphine, fentanyl, and remifentanil • An advantage ▲ Rapid reversibility with the antagonist naloxone; recommended dosage for

ICU reversal of narcotic overdose is 40–80 mg by IV push to avoid “overshoot” phenomena: hypertension, tachycardia, and emergence agitation

• Naloxone may need to be given as infusion if opioid half-life is long ♦ Mechanism of action

• Bind to m-opioid receptors in the central and peripheral nervous systems as agonists, partial agonists, or agonist-antagonists • Basis for pharmacologic effects – analgesia, decreased level of consciousness, respiratory depression, miosis, gastrointestinal hypomotility, antitussive effects, euphoria or dysphoria, and vasodilatation • Although all opioids bind to the m-receptor (MOR-1), physiologic response may vary from individual to individual, owing to receptor differences located inside the cell; interior cell portion of MOR-1 composed of several possible splice variants of exon fragments from MOR-1 gene; hence, variable physiologic response • Each therapy requires individualized approach – not one dose fits all ♦ Pharmacokinetics and dynamics (Table 11.8)

• Opioids are rapidly distributed to the brain, with the more lipophilic compounds (e.g., fentanyl, remifentanil) having shortest time of onset • Majority of morphine does not cross the blood–brain barrier • Peak effect – IV administration of morphine: 15 min; fentanyl: 5 min; remifentanil: 1–2 min • In recent randomized, double-blinded trial of remifentanil and fentanyl in ICU sedation found that analgesia-based sedation equals effective sedation ▲ Fentanyl – similar to remifentanil to achieve level of sedation and time

to extubation once the medications were discontinued following 12–72 h of continuous sedation (1–2 mg/kg/h) Table 11.8  Pharmacokinetics of opioids Opioid Peak effect (IV) Morphine 15 Hydromorphone 20 Fentanyl 5 Remifentanil 1–3

Half-life (min) 90–270 120–400 200 5–15

Clinical effect (min) 120–240 240–360 30–60 1–10

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M.A. Mirski ▲ Remifentanil incurred the risk of higher degrees and longer duration of

pain upon discontinuation than did fentanyl ▲ Emphasized need for proactive pain management when discontinuing

remifentanil • Fentanyl ▲ IV administration – recommended for ICU patients; starting dosage:

25–50 mg IV q 5–10 min until comfort is achieved

▲ Cumulative effect gradually occurs ▲ Alternatively, for more durable effect, a continuous infusion of

0.5–2.5µg/kg/h may be used, titrating to effect every 15–30 min

▲ Continuous infusions above 2 mg/kg/h – not recommended in narcotic-

naïve patients unless endotracheally intubated ▲ For deeper sedation, as adjunct to general anesthesia, or in narcotic-tolerant

patients, continuous infusions greater than those above may be advocated ▲ Not optimal for patient-controlled analgesia (PCA) – brief duration

leads to patient waking in pain prior to self-dose • Remifentanil ▲ Extremely short acting, effectively and quickly titrated by continuous

infusion

▲ Dosing range, ~0.02–0.05 mg/kg/min, to typical maximum of 0.1

mg/kg/min

▲ Larger doses rapidly lead to apnea and subsequently general anesthetic

doses ▲ No adjustment needed for renal or hepatic insufficiency ▲ Decreasing the dose by 50% is recommended for patients >65 years

of age • Morphine sulfate ▲ Time-to-peak – 20–30 min; duration of ~4 h; intermittent bolus delivery

is sensible dosing regimen ▲ For analgesic dosing, 5–20 mg IM q 4 h or 2–10 mg IV over 4–5 min q

2–4 h is recommended ▲ Preference to IV dosing in an ICU setting to minimize patient discomfort ▲ For oral dosing when appropriate, 15–30 mg of the immediate release

formula q 4 h is reasonable ▲ Appropriate for PCA ▲ High somnolence effect (potential good sleep aid in ICU)

• Hydromorphone (Dilaudid) ▲ Long acting: 4–6 h duration ▲ Minimal somnolence ▲ Appropriate for PCA

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♦ For narcotic-tolerant patients

• Best served by initial bedside titration of IV fentanyl until pain is relieved • Minimizes time to comfort • Not unusual to titrate upwards of 1,000 mg of fentanyl over a 30 min time span; thereafter, logical dose substitution for longer-acting agent – morphine, hydromorphone is warranted ♦ Rationale for ICU use and adverse reactions

• Advantages ▲ Opioids are relatively free of adverse physiologic effects; little or no

effect on chronotropy or systemic pressure ▲ Per se opioids have little effect on ICP or cerebral blood flow; hyper-

carbia related to respiratory depression by opiates may lead to cerebral vasodilatation and its sequelae • Adverse effects ▲ Very high doses of morphine and fentanyl induce seizure-like activity

▲ ▲

▲ ▲ ▲ ▲ ▲ ▲ ▲

in patients undergoing general anesthesia; none with documented electrographic seizure activity Meperidine is renally eliminated active metabolite; normeperidine associated with an excitatory syndrome that includes seizures Pruritus, excessive somnolence, respiratory depression, chest wall and other muscular rigidity (primarily fentanyl and other high-potency opioids) Dysphoria or hallucinations (primarily morphine) Nausea and vomiting Gastrointestinal dysmotility Hypotension Histamine release, causing urticaria and flushing (primarily meperidine and morphine) Anaphylaxis (rare) Immune suppression after repeated dosing

• Drug–drug Interactions ▲ Combined use of opioids + neuroleptics may decrease blood pressure ▲ Depressant effects of narcotics on respiration and level of conscious-

ness are potentiated by concurrent administration of phenothiazine neuroleptics, tricyclic antidepressants, and monoamine oxidase inhibitors ■

Benzodiazepines ♦ Most common agent used for ICU sedation ♦ Three principal agents – diazepam, lorazepam, and midazolam

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M.A. Mirski

♦ Predominant anxiolytic action; some analgesic effect has been suggested for

diazepam via GABAergic receptor function ♦ Mechanism of action

• Potentiation of inhibitory neurotransmitter, gamma aminobutyric acid (GABA); increase frequency of opening of the GABAa chloride channel in response to binding of GABA • Subsequent effects include anxiolysis, sedation, muscle relaxation, anterograde amnesia, respiratory depression (especially in children, patients with chronic pulmonary disease, hepatic insufficiency, or when combined with other sedatives), anticonvulsant activity (not all benzodiazepines), and analgesia (only IV diazepam) • Very high doses lead to coronary vasodilatation and neuromuscular blockade through interaction with peripheral sites ♦ Pharmacokinetics and dynamics

• Time to onset and offset of single IV doses determined by the agent’s relative lipophilicity • Rapidly distributed to the brain, followed by redistribution to muscle and fat • With multiple doses or continuous infusions, the time to offset is more dependent on the agent’s half-life and presence or absence of active metabolites • Diazepam ▲ Most rapid onset and most rapidly redistributed due to high lipophilicity,

followed by midazolam and lorazepam ▲ Longest half-life of >50 h; primary metabolite, dimethyl-diazepam,

retains considerable sedative potency; with elimination half-life of >90  h, may prolong recovery from repeated dosing or lengthy infusion • Midazolam ▲ Most easily titratable owing to shorter duration of action and shortest

half-life (1–4 h); most appropriate for use as a continuous infusion; midazolam does possess active metabolite (a-hydroxy-midazolam); renally eliminated; accumulation of this metabolite in the renally impaired may contribute to prolonged sedation • Lorazepam ▲ Most water soluble with smallest redistribution effect; enhancing dura-

tion of action; duration of 4–6 h following a single dose; compared to 5–20 min following either midazolam or diazepam; lorazepam does not possess any active metabolites • All benzodiazepines ▲ Highly bound to plasma proteins; all hepatically metabolized

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♦ Reversal

• Selective antagonist, flumazenil ▲ Used with caution – may precipitate rapid rises in ICP, systemic hyper-

tension, and lowering of seizure threshold, particularly in TBI and neurosurgical patients ▲ Because of short duration of action, re-sedation can occur ♦ Rationale for ICU use and adverse reactions

• Benzodiazepines provide often-needed relief from the stressful ICU environment • Small, titrated doses are effective without overt compromise of cognitive function • Anterograde amnesia is useful attribute for discomforting procedures, although analgesia should also be offered • Similar to the opioids, benzodiazepines provide positive effects without undo alteration in either blood pressure or heart rate, and respiratory drive is well preserved unless high doses are entertained • Alone, benzodiazepines have little or no effect on ICP; decreases in mean arterial pressure associated with midazolam administration may impair cerebral perfusion • As with opioids, high doses of benzodiazepines may induce respiratory dysfunction and apnea, and hypercapnia may stimulate an increase in ICP • Risk of benzodiazepines ▲ Frank delirium, which is diagnosed if: N Change occurs in features of acute onset of mental status, or N Fluctuating levels of consciousness occur, along with inattention, and N Either disorganized thinking or altered level of consciousness is

present • Recent developed measures for the screening of delirium ▲ Confusion Assessment Method for the Intensive Care Unit (CAM-

ICU) or ▲ Intensive Care Delirium Screening Checklist

• Apnea ▲ In conjunction with opioids – caution must be used when this combina-

tion therapy is pursued • Propylene glycol ▲ Solvent used for IV lorazepam and diazepam ▲ Implicated in development of hyperosmolar states, lactic acidosis, and

reversible acute tubular necrosis

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M.A. Mirski ▲ An absolute dosing threshold has not been identified, reported in

patients receiving higher doses (lorazepam infusion >18 mg/h) for prolonged periods of time ▲ Calculation of osmolar gap can be used as a surrogate for serum propylene glycol concentrations ▲ Should be monitored closely in patients receiving high doses, with an osmolar gap >10, suggestive of potentially toxic propylene glycol concentrations ▲ Other side effects of these agents include headache, nausea or vomiting, vertigo, confusion, excessive somnolence to obtundation, respiratory depression, hypotension, hypotonia/loss of reflexes, or muscular weakness ♦ Seizure therapy

• Benzodiazepines are primary therapy for treatment of acute seizures, including convulsive status epilepticus • Lorazepam is recommended drug for this life-threatening condition • Benzodiazepines inhibit many types of experimentally induced seizure activity but not all • When seizures are provoked by mechanisms other than antagonism of the GABA receptor, such as theophylline-induced seizures, benzodiazepine therapy is typically unsuccessful • However, in treating seizure disorders, however, tolerance develops rapidly and diminishes their efficacy with time ♦ Drug–drug interactions

• Both diazepam and midazolam are susceptible to numerous drug interactions; metabolized by cytochrome P450 family of enzymes; inducers (e.g., rifampin, carbamazepine, phenytoin, and phenobarbital) may enhance clearance of these agents, while inhibitors (e.g., macrolides, azole antifungals, non-dihydropyridine calcium-channel blockers) may inhibit clearance • Lorazepam has very few drug interactions; metabolized by glucuronidation ♦ Dosage recommendations

• Diazepam ▲ For sedation, doses of 1–2 mg IV every 10–20 min, incrementally

increasing up to 5 mg per dose ▲ For continuous IV infusion, possibility of prolonged sedation must be

considered • Lorazepam ▲ For sedation, 0.25–0.5 mg IV every 2–4 h ▲ 1–2 mg IV bolus provides moderately deep sedation for 4–8 h ▲ In acute withdrawal syndromes, higher dosing is often required, but

provisions for respiratory support must be made available

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• Midazolam ▲ Administer 0.5–2 mg IV every 5–10 min as needed ▲ Can be administered IM (0.07 mg/kg) in contrast to diazepam ▲ Maintenance infusions may be titrated 0.25–1 mg/kg/min ■

a2 Agonists ♦ Two agents now in use in the ICU – clonidine and dexmedetomidine ♦ Clonidine has long been used as an adjunct to general, neuraxial, and regional

anesthesia due to its sedative and analgesic properties; cardiovascular depressant effects limit its utility ♦ Dexmedetomidine is approved for postoperative and ICU settings; has shown promise in reducing discomfort of mechanical ventilation while permitting rapid patient arousal for neurologic examination ♦ Both agents markedly enhance efficacy of inhalational anesthetics and opioids, decreasing requirements for other substances ♦ Mechanism of action • Selective a2-adrenergic receptor agonists • Dexmedetomidine – a “super” selective a2 agonist, 8–10× more avid binding to a2 receptors than is clonidine • Sedative and analgesic properties – both presynaptic inhibition of descending noradrenergic activation of spinal neurons and activation of postsynaptic a2adrenergic receptors coupled to potassium-channel-activating G-proteins • Summation of effects – decrease in sympathetic outflow from the locus coeruleus, a decrease in tonic activity in spinal motor neurons and spinothalamic pain pathways, and subsequent decreases in heart rate and blood pressure; at recommended doses, respiratory drive is not compromised ♦ Pharmacokinetics and dynamics

• Clonidine ▲ Oral and transdermal formulations in the US ▲ Rapidly distributed to brain and spinal cord ▲ Decreases in blood pressure and heart rate noted within 30–60 min fol-

lowing oral dosing; peak effect, 2–4 h; half-life, 12–16 h, prolonged to 41 h with impaired renal function ▲ Only 5% of plasma clonidine is removed by hemodialysis; 50% of plasma clonidine is cleared by hepatic metabolism; remainder of drug is eliminated in urine; moderately bound to serum proteins (20–40%) ▲ Although initial action may be relatively rapid, effects may remain on heart rate and blood pressure for days after initiation of drug therapy ▲ Time of onset for transdermal clonidine – 24–72 h; not useful as a sedative agent; however, may be useful in setting of alcohol or drug withdrawal in ICU patients or as adjunct for reduction of sympathetic hyperactivity in severe TBI patients

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• Dexmedetomidine ▲ Given as IV infusion only; rapidly distributed to the brain; equilibrium

half-life of 6–9 min ▲ Elimination half-life is 2 h; may increase to 7.5 h in individuals with

hepatic insufficiency ▲ At recommended doses, elimination follows linear kinetics ▲ Due to short half-life, dexmedetomidine is easily titrated ▲ Excretion via kidney as inactive methyl and glucuronide conjugates

♦ Rationale for ICU use and adverse reactions

• Advantages ▲ Nominal effect on reduction of level of arousal; may induce sedation

without concomitant loss of attentive behavior and cognition following low levels of auditory or tactile stimulation; thus, ability to conduct neurologic assessment is preserved while achieving sedative goal ▲ Combined effect – sedative/anxiolytic and analgesic action may permit single-drug use for both sedation and modest pain control ▲ In the ICU, dexmedetomidine is demonstrated to possess advantageous characteristics for sedation in the critically ill • Adverse effects ▲ Bradycardia, hypotension, lightheadedness, and anxiety ▲ Acute withdrawal of chronic clonidine administration – rebound hyper-

tension and possible subsequent stroke or cerebral hemorrhage; thus, dosage should be tapered off after prolonged use ▲ In TBI patients, clonidine demonstrated no significant effects on ICP but did impair cerebral perfusion pressure via a reduction in systemic arterial pressure; similar data now exists for dexmedetomidine ▲ Paradoxical hypertension – following loading dose of dexmedetomidine ▲ With prolonged use, dexmedetomidine may lead to suppression of adrenocorticoid release ♦ Drug–drug interactions ▲ May exacerbate effects of other centrally acting depressants ▲ Hypotension and bradycardia may be worsened by concomitant admin-

istration of antihypertensive and antidysrhythmic medications ▲ In vitro studies suggest inhibition of P450 microsomal system by dexme-

detomidine; however, no clinically significant effects are noted

♦ Dosage recommendations

• Clonidine ▲ Initial oral dosing – 0.1 mg PO q 8–24 h, increasing by 0.1 mg/day

q 1–2 days to a maximum of 1.2 mg/day

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▲ Transdermal clonidine – 0.1 mg patch, changed q 7 days; dosage may

be incrementally increased to the 0.2 and 0.3 mg patches each week • Dexmedetomidine ▲ Dexmedetomidine infusions >24 h not approved by the FDA ▲ Loading prior to infusion may be given – 1 mg/kg over 10 min; not

mandatory (↑ risk of bradycardia with loading dose)

▲ Maintenance infusions – 0.2–0.7 mg/kg/h; dosage adjustment may be

necessary in individuals with hepatic insufficiency ■

Neuroleptics – “antipsychotics” ♦ Drugs of choice for diagnosis of delirium ♦ Lack of respiratory depression makes these attractive alternatives to nonintu-

bated patients ♦ Discussion limited to two agents commonly used in the ICU – the butyrophe-

nones, haloperidol and droperidol ♦ Mechanism of action

• Block cerebral and peripheral (but not spinal) dopamine, adrenergic, serotonin, acetylcholine, and histamine receptors; variable selectivity, depending on agent • Effects include sedation (tolerance develops with repeated dosing), anxiolysis, restlessness, suppression of emotional and aggressive outbursts, reduction of delusions, hallucinations, and disorganized thoughts (over repeated dosing), antiemetic properties, hypotension (varies by agent), and extrapyramidal side effects • Haloperidol and droperidol – limited anticholinergic properties compared with other neuroleptics ♦ Pharmacokinetics and dynamics

• Haloperidol is highly lipophilic and plasma-protein bound; sedative effects within min of IV administration • Plasma half-life, 12–36 h; effective half-life may be much longer (³1 week) due to accumulation in brain • IV droperidol – rapid onset of action (1–3 min); peak effects, 30 min; duration of action varies from 2 to 12 h • Systemic elimination mirrors hepatic blood flow; metabolism is similar to haloperidol ♦ Rationale for ICU use and adverse reactions

• Advantages ▲ Major utility – treatment of acute agitation secondary to psychosis or

delirium ▲ Adverse effects negate use for mild sedation; however, where appropriate,

the effects can be dramatic and greatly enhance ICU management

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M.A. Mirski ▲ Recent studies have illustrated the adverse effect of ICU delirium on

patient ICU length-of-stay and mortality • Adverse effects ▲ Replete with potential physiologic and neurologic complications, limiting

ICU utility ▲ Extrapyramidal side effects (parkinsonism, acute and tardive dystonias,

tardive dyskinesia, akathesia, and perioral tremor) may be expressed; although less common than with phenothiazine antipsychotics, may still occur with both haloperidol and droperidol ▲ Possible other CNS effects N Droperidol has little effect on ICP, although cerebral perfusion pres-

sure can decrease via systemic hypotension N Lowering seizure threshold – neuroleptics induce slowing and syn-

chronization (with associated increased voltage) of the EEG; haloperidol and related butyrophenones (including droperidol) have unpredictable effects on seizure threshold; most studies suggest low risk; use with caution in patients with known seizure disorders ▲ Other side effects N Increased prolactin secretion, orthostatic hypotension (rare with

haloperidol and droperidol), neuroleptic malignant syndrome, and jaundice (rare with butyrophenones) N Both haloperidol and droperidol can induce QT prolongation and torsades de pointes; warnings have been issued with even low doses of droperidol, limiting its use N Droperidol is contraindicated in patients with preexisting QT prolongation, and should be used with extreme caution in those at risk for cardiac dysrhythmias N Significant hemodynamic side effects are rare with haloperidol and droperidol ♦ Drug–drug interactions

• Selective serotonin reuptake inhibitors (SSRIs) compete with neuroleptics for hepatic oxidative enzymes; may increase circulating levels of haloperidol and droperidol • Co-administration with any agent that can prolong the QT interval may increase the likelihood of torsades de pointes, and routine EKG monitoring is necessary ♦ Dosage recommendations

• Haloperidol ▲ For sedation, initial IV doses of 0.5–5 mg may be used; half-life is

12–36 h, but active metabolites may remain for longer period

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• Droperidol ▲ For sedation in the setting of agitation, a starting dosage of 0.625 mg to

a maximum of 2.5 mg IV is recommended N Additional dosages – not to exceed 0.625–1.25 mg every 2–4 h ■

Propofol ♦ Propofol, an ultra-short-acting alkylphenol, is extensively used both as a

sedative agent in critically ill patients and a general anesthetic ♦ Although structurally distinct, clinical action and effects on cerebral activity

♦ ♦ ♦

♦

and intracranial dynamics are similar to the short-acting barbiturates (e.g., thiopental) Extremely high rate of clearance results in even shorter duration of action, especially noted following prolonged infusions, as compared to barbiturates Other advantages include less emetic property than barbiturates and mood enhancer rather than frank depressant However, reports of fatal metabolic acidosis and myocardial failure following long-term administration of propofol (especially in children) has tempered these beneficial properties to a degree and in some cases has led to disfavor and a return to alternative methods of sedation Mechanism of action • GABAergic mechanism of action, according to both in vivo and in vitro binding studies; evidence that propofol directly binds to GABAa receptors and activates inhibitory chloride channels in absence of GABA • Other studies suggest nonspecific but structurally dependent effect on neuronal plasma membrane fluidity; thus, the specific mechanism(s) of action of propofol remain unclear

♦ Pharmacokinetics and dynamics

• Similar to thiopental in lipophilicity; propofol is rapidly distributed to brain following IV administration • Distribution half-life of 1–8 min; shorter in time than most sedative agents with equally rapid recovery following redistribution to other less-perfused tissues • Repeated or continuous dosing of propofol is cleared far more rapidly than is thiopental ▲ Due to high degree of clearance, calculated to approach or exceed

1.5–2 L/min, which is greater than that of hepatic blood flow; such kinetics suggest extrahepatic sites of metabolism • Brief elimination time – more rapid recovery following cessation of sedative infusions; propofol is also highly plasma-protein bound, with free circulating levels increased in hypoalbuminic states • Administered IV – premixed concentration of 10 mg/mL (1%), continuous infusion

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• Insoluble in water – suspended as emulsion of soybean oil, glycerol, and egg phospholipids; susceptible to bacterial contamination; despite presence of ethylene-diamine-tetra-acetate (EDTA) as a bacteriostatic agent, propofol must be handled in an aseptic manner, and unused solutions discarded within 6–12 h after seal is broken • Dosing ▲ Continuous sedation in the ICU – 5–80 mg/kg/min; for other ICU indi-

cations (burst-suppression EEG for refractory status epilepticus or refractory intracranial hypertension), general anesthesia doses such as 100–300 mg/kg/min may be required ♦ Rationale for ICU use and adverse reactions

• Ultra-short duration of action; readily titratable and rapidly eliminated • Produces stereotypic suppression of EEG activity similar to the barbiturates: increasing theta and delta to flat EEG pattern during deep general anesthesia • Can suppress all seizure activity at high doses • Provides sedation devoid of analgesia • Dose-dependent reduction on cerebral metabolism; niche in the control of intracranial hypertension ♦ Propofol – not ideal drug, especially in the ICU

• No analgesic action – should not be used alone during sedation for painful maneuvers • May cause hypotension – vasodilation and a negative inotropic effect, and impairs cardio-accelerator response to decreased blood pressure; may be especially pronounced in patients with reduced cardiac output, hypovolemia, in those on other cardiodepressant medications, or the elderly • For severe TBI patients, propofol may impair cerebral perfusion even as it induces a fall in ICP • Dose-dependent respiratory depression is a predictable result; to be used only in setting of a controlled airway or in the continuous presence of experienced critical care or anesthesia personnel • Continuous monitoring of pulse oximetry, respiratory rate and depth of respiration, and blood pressure is mandated; invasive monitoring of blood pressure and cardiac output may be necessary for high-dose propofol (e.g., burst-suppression EEG) • Pain on injection due to the carrier solution; may be lessened by administration through central or larger veins or pretreatment with IV lidocaine (0.5–1.0 mg/kg) • Far less common – potential anaphylactoid reactions with propofol due to the emulsion, which contains egg and soy products; thus, administration of propofol is contraindicated in individuals who have had a severe allergic reaction to these food substances

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• Given the lipid vehicle of propofol, hypertriglyceridemia may occur • High lipid content of propofol should be kept in mind when prescribing nutrition regimens; the lipid vehicle constitutes a significant source of calories (1.1 kcal/mL) from fat ♦ Cautionary note

• Syndrome of metabolic acidosis, hyperkalemia, rhabdomyolysis, and hypoxia has been described in children and, more recently, in adults receiving prolonged infusions of propofol; etiology of this syndrome is unclear • Most cases involve critically ill patients on multiple medications (may initiate the metabolic disarray) • Careful monitoring of electrolytes, lactic acid, creatine kinase, and triglycerides is highly recommended when doses >80 mg/kg/min are given for prolonged periods of time ♦ Drug–drug interactions

• Propofol may potentiate effects of alcohol, opioids, benzodiazepines, barbiturates, other general anesthetics, antihypertensives, and antiarrhythmics • Does not appear to alter the metabolism, elimination, or plasma-protein binding of other drugs; because of the scattered reports of rhabdomyolysis, metabolic acidosis, and myocardial failure following prolonged infusions of propofol, this agent should be used with caution when combined with other medications with similar potential ■

ICU neuromuscular paralysis ♦ General overview

• Purpose of neuromuscular blockers (NMB) – produce flaccid facial, thoracic, or extremity musculature, including muscles for ventilation • Unintended consequence of NMB use – inability for patient to communicate, ability to assess for pain, anxiety, or other discomfort, and removes patient from decision-making process • Other indirect consequences – loss of muscle tone (risk of pressureinduced injury, nerve palsies, joint misalignment), ophthalmic keratitis, diminished venous return • Use of NMB may directly contribute to increased ICU mortality • In 2002, the American College of Critical Care Medicine and the Society of Critical Care Medicine developed practice parameters for the use of NMB in the ICU; resulted in 50% decline in NMB use ♦ Common indications for NMB

• Endotracheal intubation ▲ Facilitates laryngoscopy, often via rapid-sequence induction; despite

risks of using NMB (especially succinylcholine), complications are greater if none are used

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M.A. Mirski ▲ Rocuronium provides an alternative to succinylcholine for rapid-sequence

induction but less reliable than succinylcholine in yielding optimal conditions • Optimizing mechanical ventilation ▲ NMB can improve pulmonary compliance and eliminate ventilator-

patient dyssynchrony ▲ Improve alveolar ventilation, decrease barotrauma ▲ Reduce the work of breathing and, thus, oxygen consumption

• Control of ICP ▲ Prevent ICP elevations associated with ventilator-patient dyssynchrony ▲ NMB may reduce airway and intrathoracic pressure, enhancing cere-

brovenous outflow • Reduction of muscle tone ▲ Treatment of muscle spasms, contractures ▲ Status epilepticus-associated tonic–clonic activity (not seizure itself!)

♦ Pharmacology of NMB

• Include depolarizing and nondepolarizing NMB • Depolarizing NMB bind and activate nicotinic acetylcholine receptors (AChR) • Nondepolarizing NMB antagonize receptor binding of ACh ♦ Depolarizing agent

• Succinylcholine used almost exclusively for rapid laryngoscopy for intubation; drug of choice due to rapid onset of action (30–60 s) • Brief duration of activity – 5–10 min • Metabolized by plasma and hepatic pseudocholinesterase • Risks of hyperkalemia and dysrhythmias (tachycardia and bradycardia) ♦ Nondepolarizing agents (Table 11.9)

• Classifications – short, intermediate, and long acting ▲ Mivacuriuim – short (10 min) ▲ Vecuronium and atracurium – intermediate (20–30 min) N No cardiovascular side effects; a preferred NMB in ICU ▲ Cisatracurium – long (60 min) ▲ Pancuronium – long (120 min)

♦ Complications of ICU use of NMBs

• Potentiation of NMB ▲ Antibiotics (gentamycin) ▲ Ca2+ blockers, b blockers, magnesium sulfate

11  Sedation, Analgesia, and Neuromuscular Paralysis Table 11.9  Properties of common NMBs Nondepolarizing Bolus dose Continuous infusion NMB (mg/kg) (mg/kg/min) Mivacurium 0.2 N/A Atracurium 0.4 2.5–3 Vecuronium 0.08 0.8–1.5 Rocuronium 0.6 8–10 Cisatracurium 0.2 2–8 Pancuronium 0.08 N/A

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Metabolized Plasma esterases Plasma esterases Hepatic Hepatic Plasma esterases Renal excreted

Adverse effects Minimal Histamine Minimal Minimal Minimal Vagolytic

▲ Hypokalemia, hypocalcemia, and hyponatremia ▲ Acid–base and electrolyte disturbances ▲ Hypothermia

♦ ICU-acquired, NMB-related myopathic disorders

• Syndrome of persistent muscle weakness – 5–10% if NMB use >24 h • AQMS (acute quadriplegic myopathy syndrome) – triad of acute paresis, myonecrosis with an elevated creatine phosphokinase level, and abnormal electromyographic results; rare • Steroid-induced myopathy can be as high as 30% in patients who receive both corticosteroids and NMB ♦ Succinylcholine-induced hyperkalemia

• Hyperkalemia can occur in patients with stroke, spinal cord injury, burn, prolonged immobility, and congenital muscle diseases • Due to loss of cortical and NM junction connectivity • Sensitization process, muscle end plate synthesizes many AChR (immature fetal) complexes • Sensitization to succinylcholine and resistance to nondepolarizing NMB • AChRs exposed to depolarization of succinylcholine – documented ↑ serum K+, as high as 12–15 mEq/L • Proportional risk to muscle mass involved; clinical risk if two or more limbs with paresis • Often resuscitative attempts successful • Sensitization manifests at >48 h after injury; peaks at about 1 week • Duration of sensitivity – estimate of 6 months to >1 year • Prudent to avoid succinylcholine in patients with residual weakness from spinal cord injury or nonlacunar stroke

Key Points ■

Preservation of the neurologic exam is paramount when considering choice of analgesics, sedatives, and paralytics; shorter-acting and reversible agents are preferable

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Patients with preexistent neurologic impairment are more sensitive to the sedative effects of multiple medications and may take a prolonged time to awaken from sedation or general anesthesia Cause of any acute change in mental status must be investigated for new intracranial pathology, metabolic or toxic disarray, infection, or adverse reaction to medications before treating symptomatically Any medication that impairs respiratory drive may lead to hypercarbia and concomitant elevations in ICP Nondepolarizing NMB must be used with great caution in patients with neuromuscular pathology Depolarizing NMB (i.e., succinylcholine) may cause elevations in intracranial, intraocular, and intragastric pressures

Suggested Reading Avripas MB, Smythe MA, Carr A et  al (2001) Development of an intensive care unit bedside sedation scale. Ann Pharmacother 35:262–263 DeJonghe B, Cook D, Griffith L et  al (2003) Adaptation to the Intensive Care Environment (ATICE): development and validation of a new sedation assessment instrument. Crit Care Med 31:2344–2354 de Lemos J, Tweeddale M, Chittock D (2000) Measuring quality of sedation in adult mechanically ventilated critically ill patients: the Vancouver Interaction and Calmness Scale. J Clin Epidemiol 53:908–919 Devlin JW, Boleski G, Mlynarek M et al (1999) Motor Activity Assessment Scale: a valid and reasonable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit. Crit Care Med 27:1271–1275 Ely EW, Truman B, Shintani A et al (2003) Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA 289:2983–2991 Gelinas C, Fillion L, Puntillo K et al (2006) Validation of the Critical-Care Pain Observation Tool in adult patients. Am J Crit Care 15:420–427 Jacobi J, Fraser GL, Coursin DB et al (2002) Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 30:119–141 Mateo O, Krenzischek D (1992) A pilot study to assess the relationship between behavioral manifestations and self-report of pain in postanesthesia care unit patients. J Post Anesth Nurs 7:15–21 Murray MJ, Cowen J, DeBlock H et al (2002) Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 30:142–156 Odhner M, Wegman D, Freeland N et al (2003) Assessing pain control in nonverbal critically ill adults. Dimens Crit Care Nurs 22:260–267 Payen J, Bru O, Bosson J et al (2001) Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med 29:2258–2263 Payen JF, Chanques G, Mantz J et  al (2007) Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology 106:687–695 Phillips DM (2000) JCAHO pain management standards are unveiled. JAMA 284:4–5 Puntillo K, Miaskowski C, Kehrle K et al (1997) Relationship between behavioral and physiological indicators of pain, critical care patients’ self-reports of pain, and opioid administration. Crit Care Med 25:1159–1166

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Riker RR, Picard JT, Fraser GL (1999) Prospective evaluation of the sedation-agitation scale for adult critically ill patients. Crit Care Med 27:1325–1329 Riker RR, Fraser GL, Simmons LE et al (2001) Validating the sedation-agitation scale with the bispectral index and visual analog scale in adult ICU patients after cardiac surgery. Int Care Med 27:853–858 Sessler CN, Gosnell MS, Grapp MJ et al (2002) The Richmond Agitation-Sedation Scale. Validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 166:1338–1344 Weinert C, McFarland L (2004) The state of intubated ICU patients. Development of a twodimensional sedation rating scale for critically ill adults. Chest 126:1883–1890

Chapter 12

Postoperative Care W. Andrew Kofke and Robert J. Brown

Postoperative care of patients in the NCCU generally encompasses management after neurosurgery but can also encompass issues associated with non-neurosurgical procedures; proper management requires an understanding of general post-anesthesia care and issues specifically related to the neurosurgical procedure.

General Issues ■

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■

Problems can be categorized as those that develop in the first 24 h after surgery and those that develop after 24 h Important issues can arise during transport; report must be made in the proper manner, and new and ongoing general medical issues must be managed Post-anesthesia and post-surgery issues deal with perturbations of the CNS by both anesthesia and surgery ♦ Transport from OR to NCCU

• Two team members, one from anesthesia and one from neurosurgery • Anesthesiologist focuses on the patient, and the surgeon focuses on transport and provision of medical assistance as needed • Common problems ▲ ▲ ▲ ▲

Hypoventilation from airway obstruction Hypoxemia from a variety medical and pharmacologic issues Alterations in mental status Hemodynamic abnormalities

W.A. Kofke, MD, MBA, FCCM (*) Departments of Anesthesiology and Critical Care, Department of Neurosurgery, Hospital of the University of Pennsylvania, 3400 Spruce Street - 7 Dulles, Philadelphia, PA 19104, USA [email protected] R.J. Brown, MD Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_12, © Springer Science+Business Media, LLC 2011

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• Continuous monitoring of the airway, gas exchange, oxygen saturation, and blood pressure (BP) is mandatory • Bring appropriate equipment and drugs to manage any problems that may arise en route; failure to anticipate problems can result in unacceptable events, such as a need for mouth-to-mouth ventilation or madcap runs through corridors • If a ventriculostomy is in place ▲

▲

▲

Generally best to clamp it so that no untoward ingress or egress of CSF occurs Do not allow CSF in the collection chamber to touch the filter at the top of the collection chamber Inadvertent overdrainage can cause a subdural hemorrhage or predispose an unprotected aneurysm to rupture; don’t let it happen!

♦ Report – the report received from the anesthesia and surgery team on arrival

is an extremely important element of care • History ▲

▲ ▲ ▲ ▲ ▲ ▲

Age, gender, presenting symptoms, and history that mandated the surgical procedure The surgical procedure(s) Recent medications and current infusions Important recent and preoperative lab data Intraoperative problems Fluid loss and fluid replacement Past medical history, including medical problems, relevant past surgeries, home medications, allergies, cigarette or drug use, and any other relevant social issues

• Physical examination should be performed and documented ▲ ▲ ▲ ▲

■

Vital signs and any ongoing vasoactive infusions Strength and sensation in all four extremities Level of consciousness and orientation Status of the wound and drains

General medical care – basic principles of postoperative management after any surgery ♦ Frequent check of vital signs ♦ Frequent neurologic checks; specifically request any special neurologic

findings that need to be documented (e.g., visual fields) ♦ Fluids – typical infusion is half normal saline at 85–100 mL/h, or calculate

as 40 mL/kg for the first 10 kg, 20 mL/kg for the next 10 kg, and 10 mL/kg for each 10 kg thereafter ♦ Anticipate the need for fluid boluses (typically, 500–1,000 mL normal saline) for decreases in BP or urine output

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Pain medications ♦ Some prefer prn codeine, whereas others may employ morphine, fentanyl, or

nonopioid analgesics, e.g., acetaminophen ♦ Patient-controlled analgesia after neurosurgery is controversial ♦ Tylenol alone is occasionally effective ♦ NSAIDS and aspirin are generally avoided in the first few postoperative days

because of concerns about drug-induced platelet dysfunction ■

Sedation ♦ Minimize sedative use so as to not obfuscate the neurologic examination ♦ Sometimes serious dysphoric anxiety, sedative-hypnotic addiction, or inabil-

ity to cooperate with care mandates the use of postoperative sedation ♦ If delirium arises in the first 1–2 h after surgery, physostigmine (1–2 mg IV)

should be considered, especially in the elderly ♦ Sedative hypnotic drugs given before anesthetic drugs have been fully elimi-

nated may prompt a return to unconsciousness ♦ Benzodiazepines may exacerbate agitation before they induce sedation or

unconsciousness, but the effects can be reversed ♦ Antipsychotic drugs (e.g., haloperidol or atypical antipsychotics) may produce

a very cooperative settled patient – or one who does not follow commands • Extrapyramidal side effects can be problematic • Cannot be reversed pharmacologically ♦ Dexmedetomidine is a reasonable alternative ♦ If patient is still intubated, propofol is reasonable

• Provides good sedation-hypnosis while allowing for serial, frequent, intermittent decrement or cessation in drug infusion to permit neurologic examination ♦ Provision of safe effective sedation in neurocritical care remains a challeng-

ing and problematic area (see Chap. 11) ■

Diet order should be entered; typically keep patient NPO until fully awake and able to swallow without aspiration; then start with liquid diet, which is advanced as tolerated ♦ Nausea and vomiting may delay diet advancement, as may the use of opioids ♦ Uncommon for a full diet to be implemented before postoperative day one ♦ If in doubt about dysphagia risking aspiration, have speech pathologist

evaluate ■

Indwelling tubes, drains, and catheter orders ♦ Transduce arterial, central venous, and pulmonary artery catheters ♦ Foley to drain ♦ Ventriculostomy orders (Fig. 12.1)

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Fig. 12.1  Ventriculostomy setup. Reproduced from Kofke WA, Yonas H, Wechsler L (1997) Neurointensive care. In: Albin MS (ed) Textbook of neuroanesthesia. McGraw-Hill, New York

• Clamp or keep open • If kept open, indicate height (in cm) above the tragus • With an open ventriculostomy, careful attention must be paid to the relationship of bed height to ventriculostomy height; if patient decides to sit up more than the bed height, overdraining can occur with potentially serious consequences (subdural or subarachnoid hemorrhage) ♦ Daily evaluation of need for each indwelling device should be performed;

typically after routine craniotomy, most indwelling catheters are removed by postoperative day 1, except for peripheral IVs ■ ■

■

Medication reconciliation must be performed Laboratory studies, X-rays, and brain imaging studies should be considered with the immediate postoperative orders, as this impacts ICU bed flow the next day Prophylaxis – consider: ♦ GI prophylaxis

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• H2 antagonist, proton pump inhibitor, or sucralfate, especially with use of steroids or continued intubation ♦ Deep venous thrombosis prophylaxis

• Sequential compression devices must be ordered • Typically for uncomplicated surgery, subcutaneous heparin can be started after brain imaging on postoperative day 1 shows no intracranial bleeding; this is particularly important after tumor surgery ♦ Seizure prophylaxis depends on whether cortical structures have been vio-

lated or irritated; if so, phenytoin is a mainstay, although use of levetiracetam is increasing

Procedure-Related Issues ■

■

A summary of neurosurgical procedures and their main associated complications are listed in Table 12.1 Craniotomy or craniectomy for tumor ♦ Posterior fossa – be vigilant for neurogenic issues in consciousness, circula-

tion, and respiration ♦ A variety of positions may be used for these procedures

• A sitting position entails risk of venous air embolism (VAE) but is associated with less blood loss and easier exposure for the surgical procedure ▲

These patients often arrive with antecubital CVP catheters in place N Catheters should be treated as normal central lines; they predispose

to ectopy, as they are typically purposely placed inside the heart to aspirate air during surgery (Fig. 12.2) • Prone position has risks with visual loss and airway edema ♦ Immediate potential issues are cerebral edema, cerebral hemorrhage, sub-

♦ ♦ ♦ ♦ ♦ ♦

dural hemorrhage, and seizure, all complicated by interactions with subsiding effects of anesthetic drugs Subsequent problems may include infection and CSF leak from the wound BP should be kept at <160 mm Hg systolic A slow steroid taper should be initiated Fluids must be strictly controlled CT scan and/or MRI must be obtained to quantitate the extent of surgical effects ICP monitoring may be needed if major issues arise, related to edema or hemorrhage with significant otherwise unexplained decrement in level of consciousness

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Table 12.1  Neurosurgical procedures and associated complications Complication Operation Immediate 24–48 h Craniotomy/ •  Cerebral edema •  Subgaleal CSF leak Tumor resection •  Intracranial hemorrhage •  Infection •  Cerebral edema Aneurysm clipping •  Stroke from prolonged temporary clip or permanent clip misplacement •  Vasospasm (day 5–10 after SAH) AVM resection •  Hemorrhage or cerebral edema •  Hemorrhage or cerebral edema Transsphenoidal •  Diabetes insipidus •  Diabetes insipidus hypophysectomy •  Visual loss •  CSF leak Carotid •  Myocardial ischemia •  Myocardial infarction endarterectomy •  Hypotension •  Cerebral edema •  Cerebral edema •  Cerebral hemorrhage •  Neck hematoma Posterior fossa •  Posterior fossa hemorrhage •  Hydrocephalus tumor resection •  Apnea •  Aspiration •  Bradycardia Back surgery •  Transfusion complications •  Visual loss •  Visual loss •  Spinal hematoma •  Spinal hematoma •  Retroperitoneal hemorrhage •  Retroperitoneal hematoma Cerebral arteriography •  Embolic stroke •  Arterial dissection •  Inguinal hematoma •  Femoral psuedoaneurysm •  Retroperitoneal hematoma •  Leg ischemia

■

Craniotomy for aneurysm clipping ♦ Entail a craniotomy with careful dissection down to expose and clip a prob-

lematic intracranial arterial aneurysm ♦ Typically, neurosurgeons expose the proximal feeding artery first; then, if

needed, the surgeon may induce temporary occlusion of the feeding artery after which the aneurysm is then quickly clipped ♦ Problems that can arise during surgery • Difficulty getting aneurysm properly clipped with associated prolonged temporary focal ischemia • Possible need for brain protection with anesthetic drugs or hypothermia • Aneurysmal rupture; presence or absence of prior SAH determines management • With aneurysmal SAH ▲

Concerns – first 24 h

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Fig. 12.2  Antecubital CVP catheter typically employed for sitting craniotomy. Often placed inside cardiac chamber or can move to intracardiac or intraventricular with associated ectopy. Reproduced from Freis ES (1986) Vascular cannulation. In: Kofke WA, Levy JH (eds) Postoperative critical care procedures of the Massachusetts General Hospital, 1st ed. Little, Brown, & Co., Boston

N Stroke from vascular manipulation or clip, cerebral edema, cerebral

hemorrhage, subdural hemorrhage, and hydrocephalus N Rebleeding is also a concern if residual unclipped aneurysm or other

aneurysms exist N If patient had a significant decrement in consciousness preopera-

tively, it can be expected after surgery as well ▲

Delayed problems N Vasospasm with stroke or cerebral edema, among others, is dis-

cussed in Chap. 23 ♦ Management

• Control BP to <160 mmHg systolic in first 24 h, but after that, allow to rise permissively up to 200 mmHg • Standard therapy for SAH (Chap. 23) • With no SAH ▲

▲

▲

Similar issues as with SAH intraoperatively, except patient is less inclined to aneurysmal rupture before and during the procedure If no intraoperative ischemia or aneurysmal rupture, most of the issues resemble those of patients after craniotomy for tumor Concerns – first 24 h N Stroke from vascular manipulation or clip misplacement N Cerebral edema

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W.A. Kofke and R.J. Brown N Cerebral hemorrhage N Subdural hemorrhage ▲ ▲

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Delayed problems are related to cerebral edema and ischemic stroke BP must be controlled at <160 mmHg systolic in postoperative day 1; thereafter, have BP treated per routine according to patient’s baseline medical problems

Craniotomy for ICH ♦ These procedures are fraught with controversy and uncertainty as to indica-

tions for surgery • ICHs that are peripherally located tend to do well • Patients with massive ICH, with heroic efforts, may undergo craniotomy to remove ICH (sometimes with hemicraniectomy); wide variation exists in this practice • Concerns – first 24 h – related to rebleeding • Concerns – after 24 h ▲ ▲ ▲

Cerebral edema Rebleeding Managing underlying medical problems that precipitated hemorrhage

♦ Management

• Strict control of BP at <140–160 mmHg systolic • Fix preoperative coagulation abnormalities • ICP management (Chap. 6) if significant persistent edema is associated with original ICH ■

Major back surgery that may require NCCU admission includes cervical corpectomy and multilevel fusions ♦ Cervical corpectomy

• May entail a one-level or multilevel resection of the vertebral body, usually followed by fusion • Approach is typically anterior • Patient’s return from the OR with cervical collar or, occasionally, halo frame • Concerns – first 24 h ▲

Bleeding in the surgical site that may become severe enough to compromise the airway N May be particularly problematic with multilevel corpectomy and if

a halo frame is in place ▲

Neurologic changes; arm and leg sensation and strength must be assessed every 2 h

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• Management ▲ ▲

Control systolic BP (SBP) at <160 mmHg Close monitoring of airway for development of stridor or desaturation N This is an emergency N Secure airway; then evaluate for surgery N Simply opening the wound at the bedside can be lifesaving

♦ Multilevel thoracic fusion

• Tend to be done in patients with trauma or malignancy • Anterior or posterior approach, or occasionally both • If anterior approach, a double-lumen endotracheal tube may have been employed with a one-lung anesthesia technique, which may present issues with gas exchange postoperatively • High blood loss is common • Concerns – first 24 h ▲ ▲ ▲ ▲

▲

Bleeding that may compromise neurologic function Pain management, often in context of chronic pain issues Respiratory function Massive transfusion-associated coagulopathy or thrombocytopenia, which may beget more bleeding Cardiovascular problems related to thoracic sympathectomy if thoracic neural injury occurs, as discussed in Chap. 19

• Management ▲

If one-lung anesthesia was done, unilateral pulmonary pathology may be present N Administer oxygen with serial oxygen saturation measurement and,

as needed, arterial blood gas evaluation and chest X-ray ▲

▲

▲

Imaging studies must be ordered, including a chest X-ray for possible pneumothorax Detection of a change in neurologic function mandates immediate evaluation and possible surgical intervention Orders related to vertebral column stability may be required, e.g., logrolling, c-spine collar, brace placement, physical therapy evaluation

• Postoperative visual loss ▲

Rare event associated with the prone position (including prone craniotomy/ectomy in pins)

• Risk factors ▲ ▲

Prolonged procedure, hypotension, anemia Intraocular pressure increases during these procedures

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Glaucoma Periorbital edema can result in a delay in diagnosis

• Pathogenesis is unclear, and no therapy is established • Common-sense management approach ▲

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Reduce intraocular pressure, ophthalmologic consultation stat, avoid postoperative anemia and hypotension

Pituitary Surgery ♦ Several different types of syndromes may be encountered ♦ Acromegaly

• Growth hormone-secreting tumors, which can result in a variety of secondary problems • Airway management problems related to redundant tissue in the hypopharynx and glottis • Obstructive sleep apnea • Hypertension • Cardiomegaly • Diabetes • Renal problems • Non-acromegaly procedures may have other associated endocrine issues, particularly if there is an ACTH oversecreting lesion, which leads to Cushing disease and the sequelae of chronic oversecretion of glucocorticoids • Craniopharyngioma • Embryonic tumors can be slow growing and present problems related to their mass • Tend to be difficult dissections, not shelling out easily, and can be associated with bleeding and unexpected neurologic deficits postoperatively ♦ Issues common to all pituitary surgeries

• Diabetes insipidus (DI) ▲

▲

▲

Can occur at any time in these patients (10–20%) or may not occur at all if a surgery has been isolated to the anterior pituitary Polyuria in patients having undergone pituitary surgery raises the possibility of DI However, it is not necessarily automatically DI

• DI after pituitary surgery is associated with one of three patterns ▲ ▲ ▲

Transient DI Permanent DI A triphasic pattern N An initial polyuric phase of several days’ duration is thought to be

related to posterior pituitary injury; urine volume increases with concomitant decrease in urine osmolarity and specific gravity

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N A second antidiuretic phase of 4–6 days arises; thought to be related

to release of supraoptic stores of ADH; urine volume decreases as urine osmolarity and specific gravity increase N The third, possibly permanent phase of polyuria then occurs with decreased urine osmolarity and specific gravity • The diagnosis of DI conceptually is made when dilute high volume urine is being produced in the context of hypertonic serum; a variety of definitions exist for this condition, which is made more problematic because the patient may have partial DI syndrome • Classic signs of DI ▲

▲

Inappropriate polyuria, often >1 L/h, urine specific gravity <1.005, and urine osmolarity <200 mOsm/L; to be sure of the diagnosis, these signs must occur in the context of hypertonic serum Differential diagnosis includes N Normal physiologic response to intraoperative fluids and/or N N N N

overhydration Hyperglycemia Mannitol or other diuretic administration Nephrogenic DI Partial DI, perhaps complicated by any of the above singly or in combination

• Postoperative DI can be managed in two ways ▲

Let patient drink N Water is placed at awake patient’s bedside, and drinking is allowed

ad libitum N Presupposes that patient is awake enough to manage drinking, that

thirst mechanisms are intact (i.e., no hypothalamic injury), and that water will indeed be kept close to the patient at sufficient volume to maintain normal serum sodium concentration N Sleep deprivation may arise ▲

Administer desmopressin (DDAVP) or ADH; doses are as follows: N DDAVP can be given 1–2 mg IV/SC q 12 h with close monitoring of

serum sodium, urine output, and urine specific gravity N If urine output increases with specific gravity falling below 1.005–1.008,

the dose is inadequate and should be increased; alternatively, the DDAVP can be given as needed when these criteria are met N Urine losses must be replaced if oral intake is inadequate, with ¼–½ normal saline adjusted as needed and adjusted according to urine output and serum sodium response N Postoperative intranasal administration is not possible; if permanent DI develops, the patient may be transitioned to this route

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W.A. Kofke and R.J. Brown N Vasopressin (ADH) can also be used with similar monitoring caveats;

it can be given in adults 5–10 U IM/SQ q 6–12 h as needed; alternatively, an IV infusion can be used 0.0005 U/kg/h (0.5 milliU/kg/h); double dosage q 30 min to a maximum of 0.01 U/kg/h • Accurate fluid intake and output is essential to diagnosis and treat DI; a Foley catheter is usually required • Serial sodium determinations must be made as frequently as q 4–6 h during the initial management phase and whenever sodium homeostasis changes • The changing nature of DI after pituitary surgery makes a uniform protocol difficult to establish • Bedside vigilance is required for changing therapeutic requirements, as extremes in serum sodium or sudden changes can be deadly complications ♦ CSF Leak

• Typically, a pack is placed in the nasopharynx after surgery to prevent leaking • If CSF leak arises, a lumbar drain may be necessary to decrease ICP • Instrumentation of the nasopharynx is contraindicated after packing has been removed ▲

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Attempts to place a nasogastric tube, for example, can lead to intracranial placement and infection, fistula, or patient death If reintubation or another anesthesia is required, try to avoid positive pressure to the nasopharynx to prevent pneumocephalus and the possibility of introducing an infection

Hemicraniectomy ♦ This procedure has been employed for >50 years but has achieved popularity

♦

♦ ♦

♦

with evidence that supports its use for ischemic stroke with associated malignant brain edema and for traumatic brain injury Entails removing most of the cranium on the most severely affected side of the brain to allow the brain to swell without further increases in pressure that may compromise blood flow or produce herniation syndromes A more difficult procedure, which is occasionally employed, is a bifrontal craniectomy Typically, the bone is kept in a sterile refrigerated or frozen place in the hospital, or the bone may be placed in the abdomen; if no infectious issues ensue, the bone will be placed back when the patient recovers from the acute illness Concerns in the acute phase include: • • • •

Cerebral hemorrhage Subdural hemorrhage CSF leak Herniation syndromes

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• Progressive edema and malignant intracranial hypertension notwithstanding hemicraniectomy ♦ Management principles are the same as those throughout this handbook for

the patient with elevated ICP (see Chaps. 5 and 6) ■

Epilepsy surgery ♦ Procedures include intracranial depth electrode placement, epidural electrode

placement, electrode removal, or definitive resective epilepsy surgery ♦ Concerns – first 24 h

• • • • • •

Cerebral edema Cerebral hemorrhage Subdural hemorrhage Bleeding in the area of the electrode insertion Seizures Visual field deficits after temporal lobe resection

♦ Management

• All antiepileptic drugs must be continued; those patients having electrodes placed will eventually have their antiepileptic drugs stopped in order to provoke seizures, but not on the first postoperative day • Potential drug interactions of common epileptic drugs need to be considered and reviewed (Chap. 31) • SBP <160 mmHg • Order appropriate imaging studies • Patients generally go to an epilepsy monitoring unit if they have had electrodes placed ■

Carotid endarterectomy ♦ Done from the anterior approach for an incompletely occluded carotid artery ♦ An arteriotomy is performed, atheroma is removed, and the artery is stitched

closed ♦ The carotid artery is clamped and unclamped, leading to the following intra-

operative events that may be postoperative concerns: • Cerebral ischemia with injury if prolonged or not recognized • Showers of emboli • Reperfusion cerebral hyperemia, which may predispose to brain edema or ICH ♦ Immediate concerns after this procedure:

• • • •

Hypotension if the carotid sinus was not blocked with local anesthetic Neck hematoma with airway compromise Neurologic dysfunction related to thrombus, emboli, or hemorrhage Myocardial infarction; a common cause of death after carotid endarterectomy

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Careful attention to myocardial supply-demand is essential

♦ Management

• Strict avoidance of hypertension and tachycardia • Treating hypotension with pressor and/or fluid (check EKG!) • Monitoring for evidence of myocardial ischemia, cerebral ischemia, or cerebral hyperemia • Myocardial ischemia may not be accompanied by chest pain (as after any surgery) ▲

▲

Myocardial ischemia diagnosis is complicated by immediate postoperative carotid sinus dysfunction producing low vascular resistance and bradycardia Myocardial ischemia is detected by bedside EKG and/or echocardiography and myocardial injury/infarction by cardiac enzyme

• Cerebral ischemia is detected by serial bedside neurologic examination ▲

▲

▲

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Cerebral hyperemia is suggested by presence of a unilateral headache; if this is noted, even more scrupulous attention to maintaining low to low normal BP is warranted ICH, in situ thrombosis, and cerebral emboli are also important complications for which monitoring is required In situ thrombosis may warrant a rapid return to surgery

Arteriovenous malformation (AVM) resection ♦ To resect an AVM, a craniotomy is performed ♦ This dissection can be very tedious and bloody ♦ Commonly, an embolization is done before the procedure to minimize the

cerebral vascular effects of abrupt occlusion and to minimize bleeding ♦ Occasionally it can be difficult to ascertain whether a specific vein is an

important drainage vein; if it is occluded, massive edema and bleeding can arise as a consequence ♦ Immediate postoperative concerns

• Hemorrhage or edema related to venous occlusion • Hemorrhage or edema related to normal perfusion pressure breakthrough (NPPB) ▲

▲

▲

Prior to AVM resection, the patient survived with a state of AVMinduced intracranial hypotension; theoretically, this leads to a lower CBF autoregulatory curve Normal BP, as typically defined, may produce a state of malignant hypertension if the “normal” BP exceeds the upper autoregulatory range of a given patient NPPB is associated with resection of large AVMs and can lead to edema and bleeding

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A day or more of postoperative intubation with an IV drug-induced state of anesthesia/deep sedation may be required to enforce the strategy of no hypertension/induced low normotension for large AVMs

Anesthetics and Anesthetic Techniques ■ ■

May be used in neurosurgery or in the NCCU IV drugs ♦ Opioids

• All have multiple issues ▲

▲

Delayed respiratory depression, especially if used in higher doses and after movement to the NCCU with cessation of painful, proprioceptive, and psychic stimuli Decrease in BP and heart rate from loss of pain

• Fentanyl ▲

▲

▲ ▲

Typical dose, 1 mg/kg per dose, and for an entire craniotomy procedure, ~5–10 mg/kg Effective half-life (b) of 19 min and an 8 h elimination half-life, during which most of the drug is extravascular A favorite neuroanesthesia drug Can be used in the NCCU in a dose of 25–100 mg IV push or as an infusion starting with 25–200 mg/hr, with dosage adjusted according to patient tolerance and needs

• Alfentanil ▲ ▲

~1/10 potency of fentanyl with b half-life of 23 min Less commonly used both in the OR and in the NICU

• Remifentanil ▲

▲

▲

▲

▲ ▲

Typically given as an infusion of 0.1–1.0 mg/kg/min, with general anesthesia being induced at the higher dosage Metabolized by plasma esterases and has an extremely context-insensitive half-life, i.e., duration of effect is not affected by prior dosing history Discontinuation of a low or high dose infusion results in emergence within min Associated with hyperalgesia on discontinuation, especially if inadequate long-acting analgesic drugs were given during the procedure Ensure that other longer-acting pain meds have been given Has many attractive attributes for ICU use as a titratable infusion, but extensive experience is lacking (NB: both etomidate and propofol were

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used in ICU after OR introduction, and patients died from adrenal ­suppression and propofol infusion syndrome, respectively) • Morphine sulfate ▲

▲

▲

▲

OR dose may be 5–30 mg as a bolus, with that loading dosage used for the entire case (4–6 h) and immediately postoperatively Postoperative doses are 1–5 mg IV, with dosage adjusted according to patient tolerance and needs Histamine release can arise, with concerns that central histamine is neurotoxic in animals Least lipophilic of the common opioids, with a terminal half-life of ~3 h

• Hydromorphone ▲

▲ ▲

Similar to morphine but ~5 times as potent with slightly shorter duration of action No histamine release Postoperative doses are 0.1–0.5 mg IV with dosage adjusted according to patient tolerance and needs

♦ Hypnotic drugs

• Propofol ▲ ▲

▲ ▲ ▲ ▲

Can be given by bolus or infusion Induction dose 1–3 mg/kg, with onset <30 s and duration 3–8 min; infusion dose is typically 25–80 mg/kg/min Lower bolus doses occasionally helpful as sedative Produces hypotension and respiratory depression Short duration of action and antiemetic Propofol-infusion syndrome N N N N N N

High dose or prolonged use Lactic acidosis Hypertriglyceridemia Rhabdomyolysis with very high CPK levels Difficult to predict susceptibility Thought to be more likely in children and young adults

• Thiopental ▲ ▲ ▲

▲

Induction dose 4 mg/kg, with onset of <30 s and duration of 3–10 min Seldom used as an infusion Thiopental has a somewhat longer duration of action than does propofol, with no antiemetic effect Lower doses can predispose to seizure, airway hyper-reactivity, or hiccups

• Etomidate ▲

Etomidate has minimal hemodynamic or respiratory effects

12  Postoperative Care ▲ ▲

▲

▲

▲

189

Good option when low BP can be an issue Induction dose 0.2–0.3 mg/kg with onset of <30 s and duration of 5–10 min Adrenal suppressant; when used in high doses or as an infusion, this may be a concern postoperatively Contains propylene glycol, which can produce toxicity manifest as lactic acidosis when used as a prolonged infusion Commonly used when intraoperative motor-evoked potentials are used

♦ Neuromuscular blocking drugs

• Depolarizing drug (cholinergic agonist) is succinylcholine • Nondepolarizing drugs (competitive cholinergic antagonists) include pancuronium, vecuronium, rocuronium, and cis-atracurium • Nondepolarizing drugs interact with most of the first-line anti-epileptic drugs, with a significant shortening of their action • All can be deadly in untrained hands, as they can all stop breathing and require skill with airway management • Succinylcholine ▲ ▲

Fast on, fast off Caution…caution…caution…caution !!!!! N Lethal hyperkalemia when used with ° Crush injuries ° Up regulation of nicotinic cholinergic receptor situations, such as

paralysis, chronic immobility, various muscle-wasting diseases N Increases ICP, likely related to fasciculations N Excessive infusion dosing produces type II block similar to that seen

with nondepolarizing agents N Repeat dosing can produce bradycardia N 1 in 10,000 do not have plasma cholinesterases ° Prolonged effect ° Elimination only by renal excretion, probably in the NCCU N If in doubt, don’t use it!

• Vecuronium and rocuronium ▲ ▲ ▲

Steroid-based muscle relaxants 30 min duration usually Vecuronium may have prolonged effect with renal failure

• Cisatracurium ▲ ▲ ▲

30 min duration usually Metabolized in the plasma by Hoffman elimination Good drug to use in multiorgan failure

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W.A. Kofke and R.J. Brown

• Pancuronium ▲ ▲

▲

Steroid-based muscle relaxant Duration is ~60 min, with mostly renal elimination but some hepatic elimination Produces an ~10% increase in heart rate and does not decrease BP

• Neostigmine ▲ ▲ ▲ ▲ ▲ ▲

▲

■

Cholinesterase inhibitor Reverses the effects of the nondepolarizing muscle relaxants Produces a diffuse increase in acetylcholine in synapses everywhere Antidote must be given to prevent effects on the muscarinic receptors Glycopyrrolate or atropine must be given concomitantly Typical dose is 0.05–0.06 mg/kg neostigmine and 0.01–0.02 mg/kg glycopyrrolate Alternate cholinesterase-inhibitor drugs are pyridostigmine and edrophonium

Volatile anesthetic agents ♦ All of the volatile agents tend to elevate ICP, especially at higher doses ♦ Except for nitrous oxide, they also tend to decrease BP ♦ Sevoflurane

• Relatively fast on and fast off • Minimal irritation to the airway • Emergence delirium and epileptiform activity have been associated with it ♦ Desflurane

• Relatively fast on fast off • Can be somewhat irritating to the airway ♦ Isoflurane

• A standard volatile anesthetic with mild airway irritating effects ♦ Nitrous oxide

• • • • •

NMDA antagonist Neuroexcitatory effects may be problematic MAC (ED50) in humans is 100%; typical dose is 50–70% during surgery May enlarge pneumocephalus Inhibits methionine synthase; prolonged use may cause a syndrome similar to folate deficiency • Diffusion hypoxia for the first few minutes after it is turned off ■

Regional-awake anesthetics ♦ Given in neurosurgery predominantly for carotid endartectomy and some-

times for so-called “awake” craniotomies, where motor and speech mapping is required

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♦ Local anesthetic issues

• Potential local anesthetic toxicity • Bupivacine, ropivacine, and lidocaine can produce neuroexcitatory phenomena with seizure • Bupivacine toxicity also occurs with cardiovascular depression ▲ ▲

Difficult to resuscitate Intralipid infusion can increase chances of a successful resuscitation

♦ Awake craniotomy

• Not really awake – sedated • Requires excellent regional anesthesia with use of ample local anesthesia for scalp block • Patient is in deep sedation or asleep for beginning of procedure, allowed to wake up for middle portion, when speech facility is required, after which sedation is deepened • Drugs typically employed are remifentanil, propofol, and dexmedetomidine ♦ Awake, sedated carotid endarterectomy

• Patient is maintained responsive to determine if regional brain ischemia has arisen during the procedure, manifest by weakness or speech difficulties • Light sedation is employed combined with a superficial and possibly deep cervical plexus block ■

Perioperative airway issues (see Chap. 8) ♦ Mallampati grade has become a popular way to describe the difficulty of

airway management • Mallampati 1 is an expected easy intubation, with posterior pharyngeal structures easily visualized on physical examination • Mallampati 4 is an expected difficult intubation, with posterior pharyngeal structures difficult to visualize on physical examination • Typically part of the preoperative evaluation ♦ Laryngoscope view and ease of ventilation should have been documented by

the anesthesia team ♦ Ease of ventilation and ease of intubation are important pieces of history to

obtain, as each has independent implications for any subsequent airway management that will be required in the NCCU or for subsequent operative procedures ♦ Difficult intubation techniques that may be employed during or after surgery include: • Mask ventilation ▲

A mask is employed, and a triple-airway maneuver is performed, with placing the head in the sniffing position

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W.A. Kofke and R.J. Brown ▲

If this does not work, a nasopharyngeal or oropharyngeal airway may be placed to remedy an upper airway obstruction from the tongue or other oropharyngeal tissue

• Laryngeal mask airway ▲

Technique that allows bypassing an upper airway obstruction (such as a large tongue or redundant tissue) to ventilate the airway but from above the glottis

• Fiberoptic intubation ▲

▲

▲

Used for a patient with difficult anatomic airways, unstable neck, or immobilized neck from natural causes or prior surgery Patient is sedated, topical anesthesia is applied, and a fiberoptic scope is used to identify and enter the trachea The previously mounted endotracheal tube is then advanced

• Variety of other methods are described and are beyond the scope of this chapter ♦ Post-intubation intraoperative and postoperative problems can arise; these

may include: • Problems with the endotracheal tube cuff • Malpositioning of the endotracheal tube (bronchus, esophagus, supraglottic) • Dislodgement of the endotracheal tube • Kinks in the endotracheal tube • Ventilator circuit leaks, improper setup, faulty valves, etc. • All of these can pose major emergencies during surgery, and any causes, remedies, or sequalae of such problems must be ascertained in the NCCU • Some institutions place specific identification bands on patients with history of difficult airway; accompanying documentation should be available in the medical record ■

Fluid management ♦ Estimated blood loss

• Significant blood loss has several complications • More than a blood volume was lost and replaced may suggest potential problems with postoperative coagulopathy, thrombocytopenia, temperature issues, and rarely, transfusion-associated lung injury • Hypotension associated with intraoperative blood loss may indicate increased risk of multiorgan dysfunction ♦ Mannitol

• Frequently given during neurosurgical procedures to facilitate brain exposure

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• Significant diuresis during surgery • Determine if urine output was replaced • If mannitol-induced polyuria has not been replaced, patient will be arriving in the NCCU hypovolemic, which must be immediately corrected ♦ Fluid replacement issues

• Crystalloid is commonly used for intraoperative fluid replacement • If normal saline has been employed, the advantage of maintaining osmolarity is secured but at the cost of hyperchloremic acidosis; this usually resolves on its own and requires no specific therapy ♦ In the postoperative period, fluid shifts often result in low urine output or low

BP; unless another obvious reason is present, giving 500–1,000 mL of balanced crystalloid or normal saline usually resolves the problem

Intraoperative Problems that May Impact on Patient Management in the NCCU ■

■

Problems can arise that are related to the neurosurgery, the anesthetic, or the underlying medical problems; following are the major problems that can impact postoperative care Intraoperative brain ischemia ♦ Causes include edema, retractors, hemorrhage, arterial inflow obstruction,

head position, or global blood flow and blood pressure problems; residual effects may persist postoperatively ♦ Neuroprotective therapy may have been employed during procedure • Burst suppression with high doses of propofol or barbiturates ▲

▲ ▲ ▲

Prolonged effects of these drugs may be anticipated into the postoperative period Prolonged CNS depression can result BP may be low If etomidate was used, be aware of possible adrenal suppression

• Induced hypothermia ▲

▲

■

Data that support the benefits of induced hypothermia have now become less secure Can delay emergence and potentiate the effects of remaining anesthetic drugs

Intraoperative brain swelling ♦ Arises from problems typically related to tumor, trauma, ischemia with rep-

erfusion, intracranial hemorrhage, or venous occlusion

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W.A. Kofke and R.J. Brown

♦ Management typically entails stopping volatile anesthetic agents and switching

over to IV agents such as thiopental or propofol as well as with hypertension control, hyperventilation, mannitol, and furosemide • Decreased temperature may also be employed, but it is difficult to do acutely during surgery • All of these modalities will impact on postoperative management and require consideration in postoperative care ♦ When severe, resection of the swollen brain may be required as a life-saving

measure, or a hemicraniectomy may be employed ■

Intraoperative hemorrhage ♦ Arises from the operative bed itself, or it can arise from deeper structures

within the brain that may not be obvious; can appear as swelling, when in fact it is intraparenchymal hemorrhage ♦ Bleeding from arterial structures is managed by gaining proximal control; may produce arterial ischemia with residual postoperative deficits ♦ Bleeding from large venous structures brings the risk of venous occlusion, venous thrombosis, and VAE, all of which require consideration in the postoperative period ♦ Extensive bleeding is generally replaced by blood products • Blood loss and its replacement that exceed a blood volume (~75 mL/kg) can be associated with massive transfusion sequelae ▲ ▲ ▲ ▲ ▲

■

Hypothermia Coagulopathy Thrombocytopenia Infection Pulmonary problems

Intraoperative seizure ♦ Relatively unusual ♦ Suggests an increased risk of postoperative seizure ♦ Intraoperative seizure may have been treated with thiopental, propofol, or

midazolam, acutely followed by administration of more traditional antiepileptic drugs such as phenytoin or levetiracetam ♦ If patient’s skull is in pins when a motor seizure arises, laceration to the skull may occur, which may require attention postoperatively ♦ Attention to ensure antiepileptic drug levels is required intra- and postoperatively ■

Veneus Air Embolism (VAE) ♦ When the head is above the heart and a large vein or venous sinus has been

incised and the central venous pressure is less than the distance of the surgical site above the heart, air will be entrained into the vein

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♦ Significant VAE can produce an airlock in the heart and produce hypotension

or cardiac arrest ♦ With less severe (and much more common) VAE, patient may have a decrease

♦ ♦ ♦ ♦

■

in BP, a decrease in end-tidal CO2, increased PaCO2, and increased end-tidal nitrogen If a precordial Doppler was employed, the anesthesiologist will report having heard the air transit through the heart VAE can be precipitated in a previously stable case by hypovolemia from blood loss or diuresis Postoperative management requirements may include hemodynamic support with ventilatory support and 100% oxygen Paradoxical air embolism can arise either from a transit from right to left through a patent foramen ovale or other atrial or ventricular septal defect or from transit directly through the lungs to produce arterial ischemia syndromes; therapy for this condition, during and after surgery, is 100% oxygen; if the facility and time permit, hyperbaric oxygen can be considered

Awareness during surgery ♦ Incidence is ~1 in 1,000 to 1 in 10,000; can produce posttraumatic stress to

the patient; if it occurs, consideration is required postoperatively ■

Hypoxemia ♦ Causes include but are not limited to low FiO2, V/Q mismatch, diffusion

abnormalities, and low cardiac output in the context of pulmonary parenchymal abnormalities ♦ Consideration must be given to continuation of these problems and their causes postoperatively ■

Hypercapnia ♦ Produced by an imbalance between CO2 elimination and CO2 production ♦ Causes include ventilator malfunction, high physiologic or anatomic dead

space, or high CO2 production

♦ Causes of high anatomic dead space include excessive positive end-expira-

tory pressure (PEEP), air embolism, or low cardiac output ♦ Causes of low minute ventilation include equipment problems or problems

with the patient ♦ Consideration must be given to continuation of these problems and their

causes postoperatively ■

Hypotension ♦ Caused by interplay of anesthetic drugs, which by themselves will decrease

BP, and the stress of surgery, which will act to increase BP, in the context of ongoing blood loss ♦ Most common causes are blood loss and relative anesthetic drug overdose; if hypotension persists on arrival in the ICU, these are the leading candidates

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♦ Other important causes of hypotension must also be considered, such as

quadriplegia, myocardial problems, sepsis, etc. ■

Hypertension ♦ Major cause is insufficient anesthesia or analgesia, and these are the main-

stays of intraoperative therapy ♦ Anesthesia level and analgesia may be adequate, and the patient may still

be hypertensive; it may be necessary to consider and seek other medical causes ■

Anaphylaxis ♦ Causes include any of the many drugs that are given in the OR (or latex!) ♦ Can be a cause for immediate cancellation of a surgery even if it is underway

and will result in the patient possibly arriving to the NCCU on mechanical ventilation with vasoactive support on an epinephrine infusion and having received H1 and H2 antagonist therapy, along with steroids ♦ If any of these drug therapies were omitted, administering them may be among the first steps to be taken in the postoperative period ♦ If potentially offending drugs are still infusing on arrival to the NCCU, they must be stopped immediately (or the latex foley removed) ■

Malignant hyperthermia (MH) ♦ Occurs in ~1 in 10,000 anesthetics ♦ Produces a gradual or sudden increase in temperature to a lethal range during

or shortly after surgery ♦ Associated problems include hypercapnia, hypertension, tachycardia, shock,

rhabdomyolysis, and renal failure ♦ MH mandates immediate cessation of offending anesthetic agents and stop-

ping the surgery as soon as possible ♦ Therapy must be continued into the postoperative period and includes

supportive measures of fever reduction, adequate hydration, treatment of acid–base, abnormalities, mechanical ventilation, and infusion of dantrolene as a specific antidote (3–10 mg/kg); the MH hotline should be contacted for assistance with postoperative management (1-800-644-9737 in the US and 0011–315-464-7079 outside the US) ■ ■

Hemorrhage – this has been discussed previously Coagulopathy ♦ Manifests through abnormalities in the coagulation cascade or in platelet

number or function ♦ Causes include transfusion, prior antiplatelet or antithrombotic (warfarin)

therapy, or as a result of preexisting disease processes ♦ Scrupulous attention must be given to maintaining all of clotting factors at

normal during and after neurosurgery

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197

Intraoperative injuries ♦ A variety of injuries can occur during surgery that are unrelated to the surgery

itself ♦ Ocular injuries

• Visual changes after anesthesia for nonocular surgery are relatively infrequent, with an incidence of 0.0008% for all noncardiac surgery and 0.2% following spine surgery • Transient blurring of vision can be due to cycloplegia from anticholinergic medicines, use of ocular lubricants • Ophthalmologic consultation may be required if the problem persists ♦ Prolonged or permanent visual loss can occur after prone procedures (as

described elsewhere in this chapter) ♦ Oropharyngeal injuries

• Sore throat, hoarseness, and dysphagia are common postoperative complaints after intubation and laryngeal mask airway (LMA) ▲

▲

Usually a minor problem; resolves without treatment or with just symptomatic therapeutics such as gargling with viscous lidocaine or other such local anesthetics Severe or persistent pain, dysphagia, or hoarseness may suggest laryngeal injury or polyp, and otorhinolaryngology consultation may be required

• Trauma to the airway ▲ ▲

Can occur from laryngoscopy or from LMA placement Injuries can include epithelial loss, glottic hematoma, submucosal tears and formation of granulomas; LMA insertion can produce neural injury, arytenoid dislocation, epiglottis, and uvular bruises

• Dental injury ▲

▲ ▲

▲

Perioperative dental injury has an incidence of 1 in 4,500 general anesthetics Obtain dental consultation If a tooth is missing and cannot be found, a radiographic search is required If a tooth is observed on chest X-ray, it may need to be removed bronchoscopically

• Nerve injury ▲

▲ ▲

Anesthesia-related nerve injuries accounted for 16% of claims in the ASA Closed Claims Project The etiology of nerve injury is not clear During neurosurgery, extreme positioning for prolonged periods may predispose to this problem, particularly in the peroneal or ulnar nerves

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• Extravasation injury ▲

▲

▲

▲

▲

Results from injection or leakage of IV fluids or medications into the extravascular space Injury can be related to chemical effects of drugs or the pressure that was employed in injecting them If drugs like vasopressors are extravasated, an ischemic narcosis may result, whereas if normal saline is injected under high pressure into the arm or leg, a compartment syndrome could result Extravasation of vasopressors might be treated by early infiltration with phentolamine Surgical consultation is required for severe cases

Common Postoperative Problems ■

Postoperative nausea and vomiting (PONV) ♦ Extremely common problem ♦ Exacerbated by the use of narcotics and by intracranial procedures, especially

posterior fossa procedures ♦ Factors that increase the risk of PONV

• • • • • • • • • •

Female gender Nonsmoking History of PONV Motion sickness Narcotics Nitrous oxide Volatile anesthetics Neostigmine ENT surgery, neurosurgery, or strabismus surgery Prolonged surgery

♦ Management of PONV

• If polypharmacy approach, best to use drugs with disparate mechanisms ▲ ▲

Serotonin antagonist: Ondansetron, 4 mg IV Phenothiazines N Trimethobenzamide, 100 mg IM or PR N Prochlorperazine, 5–10 mg IV or 25 mg PR

▲ ▲ ▲

D2 antagonist – metoclopramide, 10 mg IV or IM Glucocorticoid – dexamethasone, 4 mg IV Butyrophenone neuroleptic – droperidol, 0.625–2.5 mg IV

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N Black box warning for possible QT prolongation N Not a recommended first-line drug because of this warning, notwith-

standing years of widespread use as a first-line agent N Can produce sedated appearance but with anxiety ▲

H-1 antihistamine – hydroxyzine, 25–100 mg IM N Sedative side effect

▲

Central anticholinergic – scopolamine, topical patch (best used prophylactically) or 0.2–0.6 mg IM, SQ, or IV N Can produce delirium; reversible with physostigmine

■

Airway issues ♦ A variety of airway problems can arise immediately after surgery, and these

issues and their management follow ♦ Upper airway obstruction

• Contributors – anesthetics; neurologic problems; anatomic abnormalities, injuries, or edema; or residual neuromuscular blockade • Anatomic origins ▲ ▲ ▲

Oropharynx from tongue displacement to the back or soft tissue collapse Hypopharynx from edema or redundant tissue Glottis from laryngospasm, laryngeal edema, or vocal cord paralysis

• Large airways due to external compression from, e.g., hematoma ▲

Presentations and management N Orohypopharyngeal obstruction N Snoring type respirations N Triple airway maneuver (i.e., chin lift, head extension, open mouth)

usually fixes obstruction N Oropharyngeal or nasopharyngeal airway insertion can help N Decrease sedative level if possible or await subsidence of anesthetic

effects N Nasopharyngeal airway use contraindicated with pituitary surgery

and can produce a nose bleed but tends to be better tolerated if successfully inserted N Oropharyngeal airway helps but requires blunted or absent gag ▲

Laryngeal obstruction N Stridor presentation N Airway swelling with glottic edema; consider this cause after pro-

longed surgery with the head down or in prone position N Laryngospasm; reflex closure of the glottis associated with light

anesthesia with lower airway stimulation; it can also be a posterior fossa injury sign

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W.A. Kofke and R.J. Brown N Vocal cord paralysis; can be due to nerve or brainstem injury related

to the surgery or may be preexisting; when bilateral, it can mimic laryngospasm ▲

Extrinsic airway compression N Stridor or bronchospasm presentation N Consider after neck or cervical vertebral surgery with a neck

hematoma. N Especially consider after: ° Carotid endarterectomy ° Multilevel cervical corpectomy N A rapidly expanding hematoma can cause marked tracheal deviation

and airway compromise ° Intubation from above can be extremely difficult; anesthesia or

neuromuscular blockade can create a situation of “can’t ventilate can’t intubate” ° If possible, the wound should be opened and the clot removed manually ° Tracheostomy or needle cricothyrotomy may be needed ° Return to surgery for repair will be needed ■

Pulmonary dysfunction ♦ Pulmonary problems after neurosurgery can manifest as both hypoxemia and

hypercapnia ▲

Hypoxemia (Fig. 12.3) Hypoxemia is caused by one of four things N N N N

▲

▲

Low alveolar O2 concentration VQ mismatching Anatomic shunt Diffusion abnormalities

These may be further exacerbated by alterations in cardiac output if the pulmonary shunt is high Common medical problems that may arise in the immediate postoperative time to produce hypoxemia N Low FiO2 ° Ensure adequate supplemental oxygen and that paCO2 is not so

high as to displace O2 from the alveoli with CO2

° Another short-lived cause is diffusion hypoxia as nitrous oxide

leaves the blood to flood the alveoli and displace oxygen N Small airway closure ° Can be related to any combination of factors, such as preexisting

lung disease, habitus, or drug-induced hypoventilation

12  Postoperative Care

201 Diagnostic Approach to Hypoxemia Assess ABC’s Check ABG increased Aa Gradient* Confirm FiO2 Check CXR

Normal**

Focal infiltrate

Consider Chest CT for PE

Pneumonia

Atelectasis

Blunted hypoxic vasoconstriction: Sepsis Vasodilators Liver failure

Consider Upper or Lower Airway Obstruction

Decreased NIF/FVC

Sedatives/ anesthetics

Neuropathy - Critical illness - GBS

Pneumothorax

Consider SwanGanz catheterization

CHF Assess respiratory drive and/or negative inspiratory force

Decreased respiratory drive Brainstem lesion - mass - hemorrhage - herniation

Diffuse infiltrates

elevated PCWP

V/Q mismatch Micro Atelectasis: Obesity Hypoventilati on Chest wall pain

Abnormal

normal PCWP ARDS/ ALI Fibrosis

Residual Neuromuscular Blockade Myopathy - Critical illness - Hypophosphatemia - ALS or MG - Disuse atrophy

Fig. 12.3  Algorithm for assessment of hypoxemia and increased alveolar gradient (A-a gradient). A-a gradient can be estimated by simply multiplying the FiO2 by 6 and comparing that expected paO2 with the actual paO2. The alveolar gas equation is pAO2 = 713 *fiO2 – paCO2/RQ. RQ is respiratory quotient, usually 0.8. Note that low pAO2 can arise with hypercapnea without any intrinsic lung abnormalities. **Normal chest X-ray also includes situations of minor atelectasis. Also note that low cardiac output in the context of inefficient pulmonary gas exchange can exacerbate hypoxemia due to low mixed venous oxygen level ° Consider residual neuromuscular blockade; added neostigmine may

be needed; however, one paradoxic cause of weakness is excessive neostigmine use, in which case, the only solution is endotracheal intubation and mechanical ventilation N V/Q mismatch from blunted hypoxic vasoconstriction; can occur with: ° Vasodilator infusion ° Early sepsis ° Liver failure N Infiltrates or atelectasis – ° Check the chest X-ray and treat as appropriate ° New infiltrates may be associated with position or aspiration

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W.A. Kofke and R.J. Brown ° Atelectasis may be related to endotracheal tube position or post-

operative hypoventilation N Diffusion problems ° Evaluate for and treat pulmonary edema ° High cardiac output can worsen diffusion-related hypoxemia ° Consider preexisting problems such as pulmonary fibrosis or

sarcoid N Low cardiac output ° In presence of an intrapulmonary shunt condition, low cardiac out-

put will decrease mixed venous O2 content; in the inefficient lung, this will contribute to hypoxemia; therapy to increase CO can help • Hypercapnia arises from too much CO2 production relative to CO2 elimination ▲

Increased CO2 production; consider and treat, if present: N Fever N MH N Thyrotoxicosis

▲

Decreased CO2 elimination N Decreased minute ventilation ° Evaluate for drug-induced causes (residual propofol, volatile

anesthetics, opioid, etc.) ° Naloxone may be helpful to diagnose and treat opioid-induced

depression ° Flumazenil can be used to reverse benzodiazepine contributions ° Central nonpharmacologic decreased control of breathing should

be considered; if related to a recent procedure, intubation may be required; if related to prior sleep apnea, use of nasal or oral CPAP may help N Increased dead space ° Can be produced through alveolar distension caused by excessive

PEEP; therapy is to decrease PEEP ° VAE, if still present from surgery, can contribute; it should

diminish with O2

° May also be caused by preexisting disease such as severe emphysema ° Ventilator or tubing aberrations can also cause an increase in

anatomic dead space; should be considered and fixed ♦ Preexisting lung disease

• Important risk factor for developing postoperative pulmonary complications • Patients on oxygen preoperatively tend to need it postoperatively

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• With severe chronic obstructive pulmonary disease and administration of fluids, a suboptimal state may be present • Do not extubate until medically optimal • Treat bronchospasm and airway inflammation • Treat excessive fluid administration with diuretics (carefully!) • Correcting hypoxemia and respiratory acidosis ▲ ▲

Hypercapnia is only a problem if associated with elevated ICP or acidosis Consideration must be given to continuation of these problems and their causes postoperatively

• Institute maneuvers to clear secretions ▲ ▲ ▲ ▲ ▲

Chest physiotherapy Bronchodilators Encourage deep breathing and coughing Suctioning as indicated and needed Postural drainage as feasible in context of recent neurosurgery

♦ Aspiration of gastric contents

• Protective airway reflexes may be depressed after general anesthesia and surgery, predisposing patients to aspiration of orogastric secretions • Gastric contents can enter the trachea during induction or emergence or even after emergence from anesthesia in the NCCU • Seizure activity may also be associated with an increased risk of aspiration • Presenting signs ▲ ▲ ▲ ▲ ▲ ▲

Bronchospasm Hypoxemia Atelectasis Tachypnea Tachycardia and/or hypotension X-ray evidence of aspiration with infiltrates, usually on the right side, which may take hours to mature radiographically

• Aspiration pneumonitis is a chemical injury caused by inhalation of gastric acid, whereas aspiration pneumonia refers to inhalation of contents that are colonized by bacteria and produce bacterial pneumonia • Treatment of significant aspiration ▲ ▲ ▲

▲ ▲

Supplemental oxygen Suctioning Bronchoscopy may be helpful to remove particulate matter; unclear value if nonparticulate matter aspiration Bronchodilators as needed Empiric antibiotics are not recommended unless the material aspirated has a high bacteria load such as maybe seen if there has been a small bowel obstruction with aspiration; this contrasts with other recommendations

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based on better outcome with earlier institution of antibiotic therapy of pneumonia N Some risk-benefit judgment may be needed, as each decision has asso-

ciated morbidity (resistant bacteria and fungal superinfection from superfluous antibiotics versus worse pneumonia from undertreatment) ▲ ▲

Steroids are not thought to be beneficial Intubation and ventilation per usual indications (Chap. 8)

♦ Pulmonary edema

• The accumulation of fluid in the alveoli and interstitium of the lungs, which hinders gas exchange; can arise postoperatively from cardiac or noncardiogenic causes ▲

Cardiogenic edema N Arises from increased pulmonary capillary pressure N Can be treated by measures to improve cardiac function and to

decrease capillary pressure with dieresis, along with supportive measures such as oxygen and sedation N When severe, mechanical ventilator support and PEEP may be needed N Consideration for myocardial ischemia as a contributing cause may be indicated ▲

Noncardiogenic edema N Usually due to increased permeability of pulmonary capillaries N Treatment includes supplemental oxygen, sedation as needed,

diuretics, mechanical ventilator support, and PEEP N If due to sepsis, pressors may be needed, along with appropriate anti-

microbial therapy ▲

Negative pressure pulmonary edema N Caused by upper airway obstruction with forceful inspiratory efforts

against a closed glottis ♦ Pulmonary embolism

• Arises when a clot from the periphery transits to the lung and produces significant hypoxemia • Important postoperative problem, and efforts to prevent deep venous thrombosis are required • The diagnosis is challenging but generally entails the existence of hypoxemia out of proportion to the abnormality on chest X-ray with confirmatory evidence by CT angiography or formal angiography • Treatment of pulmonary embolism is supportive, with volume infusion, vasopressors, and mechanical ventilation as needed, as anticoagulation or thrombolytic therapy generally is not an option immediately after neurosurgery • An inferior vena cava filter may be warranted urgently

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♦ Pneumothorax

• Accumulation of air in the plural space with collapse of a lung and impaired gas exchange with hypoxemia • Tension pneumothorax occurs when air leak forms a one-way valve, allowing air to flow into but not out of the plural space; a rapid increase of intrathoracic pressure develops, which can compromise venous return and produce hypotension • Therapy for pneumothorax is placement of a chest tube • Tension pneumothorax can be treated urgently with a needle thorocostomy in the second intercostal space ■

Cardiovascular dysfunction ♦ Postoperative hypotension

• Has a variety of possible causes and treatments • Hypovolemia ▲

▲ ▲

Most common cause in the postoperative period and is diagnosed most often by the intake-output records and the clinical context Causes include inadequate fluid replacement or ongoing hemorrhage Therapy is a trial infusion of fluids; if hemoglobin level is low, the fluids may include blood

• Vasodilation ▲ ▲

Produced by drugs, spinal cord or brainstem injury, or sepsis Reverse the cause; if feasible, drug treatment includes administration of fluids and vasopressors such as phenylephrine or norepinephrine

• Myocardial ischemia ▲ ▲

▲

▲

▲

▲

Common cardiogenic cause of postoperative hypotension Diagnosis is based on EKG abnormalities, echocardiographic findings, and cardiac enzyme elevations Absence of chest pain does not rule out postoperative myocardial ischemia Occurs because of an imbalance in myocardial oxygen supply and demand (which generally did not exist preoperatively) Determine what has changed in the postoperative period, as coronary artery thrombosis is seldom the cause Management includes N N N N N N

Treat hypoxemia, tachycardia, anemia, and hypotension Serial ECG, enzymes, echocardiography b blockade when BP permits Aspirin when feasible after surgery Nitroglycerin may be helpful if hemodynamically permissible Cardiology consultation; note – do not withhold the above therapy waiting for the cardiologist to arrive

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• Dysrhythmias ▲

▲ ▲ ▲ ▲ ▲

▲

Most perioperative dysrhythmias are benign, but if pathologic, precipitating factors must be considered and treated Electrolyte imbalance Hypoxemia Increased circulating catecholamines Altered acid-base status, etc. Specific anti-arrhythmia therapy in the NCCU is similar to that in other contexts, with the exception that specific perioperative precipitating factors must be identified and treated Tachycardia N Can be supraventricular or ventricular (Chap. 9) N Immediately after surgery, consider and treat ° ° ° °

Pain Hypovolemia Anxiety Intrinsic dysrhythmia

N Atrial fibrillation is a common SVT after neurosurgery ° If hemodynamically stable, b blockers, diltiazem, or amiodarone

can be given for rate control and/or conversion ° Hypervolemia can stretch the atrium to precipitate atrial fibrilla-

tion; if this is the case, a diuretic trial is reasonable, with electrolyte replacement ° If hemodynamically unstable, cardioversion is indicated ° Magnesium may be helpful N Glycopyrrolate or atropine given with the reversal of neuromuscular

blockade should also be considered in genesis of postoperative tachycardia ▲

Bradycardia N Consider causes, and as feasible, treat: ° Neostigmine administration (atropine or glycopyrrolate are

antidotes) ° Sinus node dysfunction ° Excessive b-blocker use ° Inferior wall myocardial ischemia N Bradycardia in the absence of hypotension is probably not really a

problem

N Possible therapies include atropine, b-agonist therapy, or transtho-

racic pacemaker

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207

Postoperative ECG changes N Extremely common after anesthesia and surgery N If nonspecific, changes generally do not suggest a problem with myo-

cardial ischemia; 18% incidence of T-wave changes reported in the postoperative population and not associated with evidence of myocardial ischemia or injury; most ECG changes resolve within 24 h N Nonetheless, if an ischemic process is suspected, the T-wave changes should be treated as a potential myocardial ischemia with an appropriate workup to follow, as previously outlined ♦ Postoperative hypertension

• Very common after neurosurgery • SBP >160 mmHg has been associated with intracranial hemorrhage • In neurosurgical patients, a variety of drugs is available to treat hypertension; antihypertensive drugs can be chosen, to a large extent, based on their side effects, including their propensity to have neuroprotective side effects and their impact on ICP and myocardial ischemia (Table 12.2) ▲

Sympatholytic categories of drugs have been associated with brain protection in both animals and humans; thus, labetalol, esmolol, clonidine, and propranolol become reasonable therapeutic options N Clonidine can produce unwanted sedation N b blockers can produce bronchospasm and excessive bradycardia

Table 12.2  Antihypertensive medications Drug Mechanism Labetalol, b-adrenergic and Metoprolol, a- adrenergic Propanolol (labetalol) blockade

Neuro side effects •  Neuroprotective

Other side effects •  Bradycardia

•  Bronchospasm •  Tachycardia •  Myocardial ischemia •  Increased catecholamines Renal ischemia if renal artery stenosis •  Tachycardia •  Myocardial ischemia •  Increased catecholamine •  Cyanide with high doses Coronary vasodilation

Hydralazine

Systemic vasodilation

•  No ICP effects Increase ICP

Enalopril

ACE inhibitor

No ICP effects

Sodium nitroprusside

Systemic vasodilation

Increase ICP

Nicardipine

Systemic vasodilator

•  Possibly neuroprotective •  Modest ICP effect

ICP intracranial pressure, ACE angiotensin-converting enzyme

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W.A. Kofke and R.J. Brown ▲

ACE inhibitors also exhibit neuroprotective qualities in animals and do not produce the intracranial hypertension or tachycardia that might exacerbate myocardial ischemia N Use with caution with preexisting renal ischemia

▲

▲

Nicardipine, a theoretical brain protectant, can be easily titrated to control BP, has coronary-vasodilating side effects, and does not increase ICP to a significant extent Hydralazine can be used if there are no issues with coronary artery disease or intracranial hypertension N Can increase ICP N Can cause tachycardia and exacerbate myocardial ischemia

■

Urinary and renal dysfunction ♦ Bladder distension

• May induce pain, hypertension, restlessness, and delirium • If severe and untreated, can lead to prolonged problems with bladder function • Can be diagnosed with ultrasound bladder scanning and treated with urethral catheterization ♦ Oliguria

• Defined as urine output <0.5 mL/kg/h • Very frequent after surgery • Pre-renal is usually postoperative ▲ ▲

▲

Caused by decreased renal perfusion due to hypovolemia Management consists of restoring blood volume, usually initially, with a 500–1,000 mL balanced crystalloid infusion Blood can be used if anemia or ongoing bleeding is present

• Postrenal acute renal failure ▲ ▲

▲

Caused by obstruction of urine drainage or outflow Placement of a urinary catheter usually helps to diagnose and treat this condition if due to urethral obstruction Catheterization of the urethra will miss bilateral ureteral obstruction, which requires ultrasound to diagnose

• Intrinsic acute renal failure ▲ ▲

Caused by acute tubular necrosis or other interstitial processes One important cause of intrinsic acute renal failure in the neurosurgical population is the use of radiocontrast dye and gadolinium N Pretreatment with acetylcysteine or bicarbonate may be helpful

prophylaxis

12  Postoperative Care ▲

209

The only practical therapy is to maintain normal-to-slightly elevated intravascular volume status and avoid vasoconstricting drugs N Diuretics have not been proven to affect outcome, although they

may attenuate progression to oliguric renal failure by converting the situation to nonoliguric renal failure ■

Postoperative CNS dysfunction (Fig. 12.4) ♦ Manifests as either excitation or depression; both can be serious postopera-

tive problems ♦ Delirium

• A transient fluctuating disturbance of consciousness, attention, cognition, and perception • May delay recovery and prolong hospital stay • Often has accompanying cardiovascular abnormalities and behavioral abnormalities that may endanger the patient and staff • Nutrition becomes nearly impossible to implement

Diagnostic approach to postoperative mental status change

Assess ABC’s

Perform neurologic exam

Focal deficits present*

Obtain stat brain imaging

Normal imaging

Labs unremarkable

Consider EEG

Focal deficits absent

Signs or symptoms of ↑ ICP absent

Consider stat brain imaging

Signs or symptoms of ↑ ICP present

Obtain stat brain imaging

Consider the following: - ABG: look for hypercapnea, hypoxia - serum glucose measurement - serum chemistry analysis – Sodium, Ca/Mag/Phos, Cr/BUN, LFTs/ammonia - infectious workup (consider CSF studies) - EKG, cardiac enzymes - review of medical history: look for drug withdrawal potential (EtOH, benzodiazepines) - review of medication history (sedatives, antipsychotics, anticholinergics) - Residual anesthetics (See Table 3)

Fig. 12.4  Algorithm for evaluation of altered mental status after neurosurgery. *Residual anesthesia can temporarily unmask predisposition to focal deficit. If this is the case the focal neurologic change with improve with dissipation of anesthetic effects

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W.A. Kofke and R.J. Brown

• Sometimes efforts to treat delirium create other problems as serious as the inciting event • Occurs in 3–5% of adults after anesthesia • Preoperative risk factors ▲ ▲ ▲ ▲ ▲ ▲ ▲

Elderly age group Organic brain disease Dementia Alcohol and sedative withdrawal Anxiety and depression Anticholinergic, barbiturate, and benzodiazepine drug intake ApoE4 genotype status

• Major problem area in neurocritical care, and management protocols are unsatisfying, producing obfuscation of neuro assessment and numerous systemic side effects • Management approach to delirium ▲

▲ ▲

▲

▲

▲

Rule out contributing physiologic abnormalities such as hypoxemia, hypotension, and acidosis Adequately evaluate and treat pain (including bladder distension) Evaluate for and treat metabolic causes such as blood sugar abnormalities, electrolyte disturbances, and sepsis Physostigmine is helpful when delirium is believed to be the result of central anticholinergic drugs; often worth giving empirically, as side effects are minimal Haloperidol or an atypical antipsychotic such as quetiapine may provide symptomatic relief, although probably does not treat cause, and an overdose cannot be reversed Benzodiazepines can be helpful if delirium is related to drug or alcohol withdrawal or anxiety; however, this can exacerbate the delirium or produce an unresponsive patient

♦ Delayed awakening after general anesthesia for neurosurgery

• Caused by either prolonged drug effects, metabolic abnormalities, or neurologic injury related to the recent neurosurgery • Metabolic abnormalities ▲

Evaluate and treat problems such as N N N N N N N

Hypoglycemia/hyperglycemia Severe azotemia Severe anemia Hyperammonemia related to hepatic failure Severe sodium imbalance Severe hypercapnia (PaCO2 >80 mmHg) or Hypoxemia (PaO2 <60 mmHg)

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211

Table 12.3  Residual anesthetic effects – 1 h after surgery Drug Effect Volatile anesthetics Blunt hypoxic drive to breathe Nitrous oxide Pneumocephalus Opioids Respiratory depression: Hypoxemia Hypercapnia Vecuronium, Rocuronium, Residual blockade: Pancuronium, Cisatracurium Dyspnea Proximal twitching (chorea-like) movement of extremities Hypoxemia Hypercapnia Propofol Propofol infusion syndrome Hypotension Metabolic acidosis Rhabdomyolysis Residual CNS depression Thiopental

Residual CNS depression

Droperidol

Residual CNS depression Extrapyramidal immobility and anxiety

Treatment options Oxygen Oxygen Stimulation Naloxone Oxygen Neostigmine/ glycopyrrolate Noninvasive ventilation Oxygen Endotracheal intubation Physiologic support (stop propofol)

Observation and physiologic support Observation and physiologic support Observation and physiologic support Reassurance

• Residual anesthetic drug effects (Table 12.3) ▲ ▲ ▲

▲

Most common cause of delayed awakening after neurosurgery Time-limited At some point, based on joint judgment of the surgeons and anesthesia team, this is eventually ruled out as a contributory factor Antagonist drugs may be employed in an effort to reverse some anesthetic drugs if it is important to have a faster wake-up; antagonist drugs may include N N N N

Physostigmine (1–2 mg) Naloxone (serial boluses of 40 mg IV) Flumazenil (0.2 mg q 1 min × 5 titrated) If neuromuscular blockade is a potential problem, neostigmine and glycopyrrolate can be given – but in consultation with the anesthesiologist

• If anesthetic drug factors or metabolic factors are deemed unlikely, brain imaging with CT or MRI is urgently required to evaluate for structural treatable problems such as intracranial hemorrhage; ischemic stroke may not be apparent for several hours on head CT

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W.A. Kofke and R.J. Brown

♦ Perioperative stroke

• Incidence ranges from 0.1 to 1% and varies according to type and complexity of surgery and preexisting cerebrovascular condition ▲

▲

▲

▲

After neurosurgery, many apparent ischemic stroke syndromes are related to retractor injury and will self-resolve Sometimes, vascular structures are injured (either expected or not), which can produce an ischemic stroke syndrome (Chap. 20) Occasionally, head position can produce compromise of vertebral artery flow, leading to brainstem vascular insufficiency In patients with ischemic stroke, management early on is similar to principles outlined in Chap. 20 N Risks and benefits of antiplatelet therapy and anticoagulation must

be seriously weighed after neurosurgery ▲

Hemorrhagic stroke can also occur N Common types are subdural and intraparenchymal in area of the

surgery; occasionally see epidural and distant intraparencymal sites N SBP > 160 mmHg has been associated with post-neurosurgery

intracranial hemorrhage N Other problems with associated intracranial vascular dysautoregula-

tion (e.g., after AVM surgery or carotid endarterectomy) also must be individually considered and may lead to judgment-based variation of the 160 mmHg guideline ■

Temperature abnormalities ♦ Hypothermia

• Common postoperative problem, particularly in neurosurgery • Occasionally therapeutically induced • Hypothermia with shivering with emergence from anesthesia has been associated with adverse outcomes ▲ ▲ ▲ ▲ ▲ ▲

Myocardial ischemia Dysrhythmias Coagulopathy Wound infection Delayed drug metabolism Very uncomfortable for the awake patient

• Shivering management ▲ ▲ ▲

▲

External warming blankets Small doses of meperidine (12.5 mg doses) Clonidine, dexmedetomidine, and ondansetron have also been reported to be effective to treat shivering If patient is still intubated, propofol infusion can also be effective

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213

♦ Hyperthermia

• Uncommon after surgery • May be caused by cytokine release associated with sepsis or surgery • MH is an important consideration during or after surgery; if untreated, MH is a lethal condition (see Chap. 27) • Diagnosis of MH ▲

▲

▲

Clinical diagnosis with no specific stat lab test available, although observation of an extremely high CPK may be helpful Diagnosis primarily based on observation of extremely high CO2 production and an extremely high temperature Associated problems can include N N N N N

▲

Metabolic acidosis Respiratory acidosis Extreme shivering and consequent rhabdomyolysis Renal failure Hemodynamic lability leading to shock state

Therapy for MH N Symptomatic control of temperature ° Cold saline infusion IV and, if needed, nasogastric irrigation and

enemas ° Ice bags topically placed ° Cooling blankets N Intubation with neuromuscular blockade and high minute volume, if

needed N Dantrolene (10 mg/kg IV) (block the ryanodine receptor) N Treatment of renal failure and rhabdomyolysis with fluid infusion;

treatment of acidosis N Call for help N Call MH hotline for assistance (1-800-644-9737 in US and 0011-

315-464-7079 outside the US) ▲

■

If patient has been in the hospital for >1 or 2 days, evaluation and possible therapy for infection are also required

Hyperglycemia ♦ Neurosurgical patients, many of whom have preexisting diabetes or receive

steroids for a neurosurgical procedure or disease, commonly become hyperglycemic after surgery ♦ In context of anaerobic conditions in brain, hyperglycemia is associated with worse neurologic outcome due to excessive lactic acidosis (Fig. 12.5) ♦ Although controversial, data suggest that hyperglycemia is associated with worse ICU outcomes

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Fig. 12.5  Glycolysis. Downstream oxygen is required to permit conversion of pyruvate to AcCoA in the Krebs cycle. Lack of oxygen promotes generation of lactate. Increased glucose availability promotes increased lactate production in an anaerobic situation. This has been associated with exacerbation of brain damage

♦ Overly aggressive treatment of hyperglycemia may produce deleterious

hypoglycemia; thus, treatment must be aggressive but careful ♦ Patients who have blood sugars >180–200 mg/dL who have ongoing evi-

dence of anaerobic metabolism in the brain and are not responding well to SC insulin coverage should be placed on an insulin infusion with frequent blood glucose checks to obtain tight control during the acute phase of their illness ♦ Acceptable blood glucose goals vary from 110 to 180 mg/dL probably best to aim for 150 mg/dL at this time ■

Postoperative cognitive dysfunction (POCD) ♦ Emerging problem and active research area ♦ Tends to be worse early postoperatively

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♦ Patients may complain of cognitive or personality changes early on, which

improve over the months after surgery ♦ 10–15% of elderly patients continue to have POCD at 6 months or later after

noncardiac surgery ♦ POCD has not been prospectively evaluated specifically after neurosurgery;

exact causative factors have not been elucidated; however, they include surgical and anesthesia factors • Surgical factors are related to physiologic stress response • Anesthesia theories relate to ▲ ▲ ▲ ▲ ▲

Use of hyperventilation and possible consequent ischemia Apoptosis induced by anesthetic drugs Neuroexcitation induced by anesthetics Genetic predisposition Hypoxia has not been linked to POCD

♦ No reliable preventive therapy

Key Points ■

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Care of the postoperative neurosurgical patient begins with a comprehensive report from the anesthesia and surgery team on arrival In caring for the postoperative patient, knowledge of the neurosurgical procedure and its common complications is vital to rapidly evaluating and reversing any adverse event In order to not confound the neurologic examination, sedatives in the NCCU should be used judiciously Successful preservation of neurologic status requires prompt resuscitation of systemic complications Hypertension increases the risk of ICH following craniotomy; in this setting, SBP >160 mmHg should be treated using agents with favorable side-effect profiles Postoperative hypotension may be caused by hyovolemia, vasodilation, or decreased cardiac dysfunction and should be treated accordingly Hyperglycemia and hyperthermia have deleterious effects on neurologic outcome and should be treated intensively Because of the myriad causes of postoperative CNS dysfunction, including residual anesthetic effects, metabolic derangements, and intracranial pathology, a systematic diagnostic approach is essential

Selected References Beauregard CL, Friedman WA (2003) Routine use of postoperative ICU care for elective craniotomy: a cost-benefit analysis. Surg Neurol 60:483–489 Bittner E, Grecu L, George E (2008) Postoperative complications. In: Longnecker D, Brown D, Newman M et al. (eds) Anesthesiology. McGraw-Hill, New York

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Coplin WM, Pierson DJ, Cooley KD et  al. (2000) Implications of extubation delay in braininjured patients meeting standard weaning criteria. Am J Respir Crit Care Med 161(5):1530–1536 Feely T, Macario A (2005) The postanesthesia care unit. In: Miller RD (ed) Anesthesia. ChurchillLivingstone, Philadelphia Geerts WH, Bergqvist D, Pineo GF et al. (2008) Prevention of venous thromboembolism: american college of chest physicians evidence-based clinical practice guidelines (8th ed). Chest 133: 381S–453S Grecu L, Bittner E, George E (2008) Recovery of the Healthy Patient. In: Longnecker D, Brown D, Newman M, Zapol W (eds) Anesthesiology. McGraw-Hill, New York Kam PC, Cardone D (2007) Propofol infusion syndrome. Anaesthesia 62(7):690–701 Manninen PH, Raman SK, Boyle K et  al. (1999) Early postoperative complications following neurosurgical procedures. Can J Anaesth 46(1):7–14 Ortiz-Cardona J, Bendo AA (2007) Perioperative pain management in the neurosurgical patient. Anesthesiol Clin 25(3):655–674 Ropper A, Kennedy S (1993) Postoperative Neurosurgical Care. In: Ropper A, Gress DR, Diringer MN et al. (eds) Neurological and neurosurgical intensive care, 3rd edn. Raven Press, New York Sesler JM (2007) Stress-related mucosal disease in the intensive care unit: an update on prophylaxis. AACN Adv Crit Care 18(2):119–126

Chapter 13

Care Following Neurointerventional Procedures Yahia M. Lodi, Julius Gene Latorre, Jesse Corry, and Mohammed Rehman

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Postoperative management following interventional procedures is equally as important as the procedure itself Postprocedural management must be coordinated with intraoperative management to optimize outcomes and avoid complications Meticulous preoperative and intraoperative planning leads to streamlined postinterventional care A preset postoperative management algorithm must be created for better early implementation

Carotid Occlusive Disease and Stent-Assisted Revascularization Incidence ■

Extracranial internal carotid occlusive disease is responsible for 8–10% of ischemic stroke

Y.M. Lodi, MD (*) Division of Cerebrovascular Program and Services, Vascular/Neurological Critical Care Neurology and Envovascular Surgical Neuroradiology, Upstate Medical University and University Hospital, SUNY, NY and Department of Neurology, 813 Jacobsen Hall, 750 East Adams Street, Syracuse, NY 13210, USA e-mail: [email protected] J.G. Latorre, MD Neurosciences Critical Care Unit and Neurocritical Care Fellowship Program, Upstate Medical University, Syracuse, NY, USA J. Corry, MD Upstate Medical University, Syracuse, NY, USA M. Rehman, MD Department of Neurology, Upstate Medical University, Syracuse, NY, USA A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_13, © Springer Science+Business Media, LLC 2011

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Y.M. Lodi et al.

More common in men than women Affects more Whites than Blacks

Etiology ■

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Atherosclerotic process is most common cause of extracranial carotid artery stenosis and associated with reduced ratio of lipoprotein B:A Other minor causes are trauma, tumor invasion, and radiation-induced stenosis

Classification of Carotid Stenosis ■ ■ ■

Mild stenosis, 15–49%; moderate, 50–69%; and severe, >70% Any stenosis >70% is considered hemodynamically significant Transcranial Doppler (TCD), CT, and MRI perfusion studies may help identify potential hemodynamically significant carotid stenosis

Clinical Presentation ■ ■

Carotid stenosis may be asymptomatic or symptomatic Symptoms may be due to hypoperfusion or dislodgement of emboli from carotid plaque ♦ Ipsilateral impairment of vision due to retinal ischemia (amaurosis fugax) ♦ Contralateral hemiparesis or sensory loss ♦ Aphasia or dysarthria

Recurrent Events ■

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Recurrent events depend on the severity of the stenosis and morphology of the plaque Highest recurrence rate (35%) is observed in cases of severe stenosis, especially with occlusive stenosis of between 90–94% Recurrence rate decreases to 11% with near-complete occlusion (95–99%) Plaques with ulceration and/or thrombus are associated with higher rate of recurrence Presence of collateral circulation is protective and associated with fewer events

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Management ■

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Prompt diagnosis and treatment of carotid stenosis is mandatory to prevent lifethreatening disabling stroke and recurrent events Treatment of carotid artery stenosis consists of revascularization of carotid artery, either by carotid endarterectomy (CEA) or carotid artery stenting (CAS), and reduction of risk factors by standard medical management For symptomatic carotid stenosis ³70%, revascularization is associated with 13.5% absolute risk reduction (RR), and number needed to treat to observe benefit is 8 For symptomatic carotid stenosis ³50%, revascularization is associated with 6.5% absolute RR, and number needed to treat to observe benefit is 15 Women and patients with diabetes mellitus were less benefited than men To observe benefit for a symptomatic carotid artery stenosis, the perioperative complications of CEA must be £6% For asymptomatic carotid stenosis, CEA is associated with reduction in recurrent events and good outcome if perioperative complication remains £3%

Cas ■

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CAS is an alternative to CEA, especially for those who have high risk of perioperative complications associated with CEA Angiographic criteria are considered to be high perioperative risk for CEA ♦ Contralateral occlusion of carotid artery ♦ Ipsilateral intracranial carotid stenosis ♦ Ipsilateral external carotid artery stenosis

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Clinical characteristics that are considered as high risk ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

Active congestive heart failure Active coronary artery disease Myocardial infarction in 30 days Chronic obstructive lung disease Uncontrolled diabetes Re-stenosis from previous CEA Dialysis dependent renal failure Unfavorable anatomy After radical neck surgery After radiation therapy Surgically inaccessible lesions Spinal immobility Tracheostomy stoma Contralateral laryngeal nerve paralysis

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Preparation of patient begins with obtaining following preoperative testing ♦ Electrocardiography to assess for active cardiac ischemia; in case of active

♦ ♦ ♦ ♦

cardiac ischemia, CAS must be deferred until stability of active cardiac ischemia is accomplished Most common perioperative complication of CAS is cardiac ischemia Chest x-ray for identification of any active pulmonary disease, which must be addressed prior to the CAS procedure Basic metabolic panel, including glucose and creatinine In case of renal impairment, all patients must be adequately hydrated prior to procedure • Preparation with oral acetylcysteine and IV sodium bicarbonate may be beneficial in selected patients with renal impairment • Oral hypoglycemic agent (metformin) should be discontinued at least 24 h before and until 24 h after CAS to avoid contrast-induced renal impairment

♦ PT and PTT must be obtained prior to the procedure ♦ Patients must be placed on 325 mg aspirin and 75 mg clopidogrel at least 5–7

days prior to procedure to prevent platelet-induced thromboembolism ♦ In case of emergent CAS procedure, the inhibition of platelets could be

achieved by giving an uncoated 325 mg of aspirin and 300–600 mg of clopidogrel at least 2 h prior to the stenting procedure ■

Intraoperative and postoperative management of CAS ♦ Bradycardia and hypotension are the two most predictable complications of

CAS during pre- and post-balloon angioplasty; these events are not life threatening, as they are predictable and easily managed • Bradycardia ▲ Usually transient and returns to baseline within 5–15 s; most of the

time, no treatment is necessary

▲ If bradycardia with heart rate of £40 beats per min persists for >15 s or

in case of asystole, an IV dose of 0.50–0.75 mg atropine usually returns heart rate to baseline ▲ If baseline heart rate is <60 beats per min, a single dose of 0.5 mg of atropine could be given prior to angioplasty to prevent unsafe drop in heart rate ▲ Adjusted dose of IV glycopyrrolate could be used instead of atropine ▲ Atropine as well as all advanced cardiac life-resuscitation medications must be kept ready prior to CAS procedure • Hypotension ▲ Post-angioplasty hypotension is also transient, lasting from a few min

to 24 h

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▲ Hypotension is well treated with dopamine in addition to volume

expansion

▲ Dopamine drip must be prepared and kept ready for use at 5–8 mg/kg/min

• Seizure ▲ Carotid balloon angioplasty may induce transient seizure and is associ-

ated with sudden ischemia ▲ Is not very common and develops in those patients who do not have

good collaterals ▲ Seizure instantly stops after deflation of balloon and does not require

treatment ▲ If seizure persists, first use IV lorazepam or midazolam

• Ischemic stroke ▲ Thromboembolic events related to carotid angioplasty and stenting pro-

cedure are second most common complication after cardiac ischemia ▲ Incidence of thromboembolic events has reduced after introduction of

distal protection device during CAS ▲ In the event of clinical ischemic event, a complete angiogram of

▲

▲

▲

▲

head and neck must be performed to identify site of blood vessel occlusion If an angiographic occlusion exists, attempt to restore blood flow should be initiated, using either clot retriever device or intra-arterial thrombolysis with thrombolytics Because all patients undergoing CAS are already on aspirin, clopidogrel and therapeutic heparin, caution is advised in excessive use of thrombolytic agents during thrombolysis to prevent unwanted hemorrhagic conversion If angiogram is not consistent with occlusion of blood vessels, an urgent CT scan of the head should be obtained to identify any potential intraoperative hemorrhage If no hemorrhage or ischemic stroke is identified on CT or MRI, IV administration of GPIIbIIIa-receptor antagonist (integrelin) could be initiated to prevent platelet aggregation or breakdown of platelet clots in microvascular circulation

• ICH ▲ ICH is a very rare but life-threatening complication associated with

CAS ▲ Most common cause is perforation of a blood vessel during mechanical

maneuver of devices ▲ Other causes of ICH are associated with anticoagulation during proce-

dure and reperfusion ▲ In case of a hemorrhagic event that is either identified by cerebral angiogra-

phy or brain CT, heparin should be reversed immediately with protamine

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Y.M. Lodi et al. ▲ If a life-saving ventriculostomy is indicated, it must be inserted imme-

diately after the reversal of heparin and must not be held for platelet transfusion ▲ If the craniotomy is indicated, immediate transfusion of platelets before and during craniotomy will reverse platelets for urgent safe surgery ▲ After craniotomy, at least one antiplatelet medication must be started to prevent thrombosis of stent • Cardiac ischemia ▲ Most common complication after CAS procedure, occurring in 1–2%

of patients ▲ Thought to be associated with poor coronary perfusion that occurs with

bradycardia and hypotension, induced during angioplasty ▲ Proper screening of patient prior to the procedure and optimal man-

▲ ▲ ▲

▲

agement of heart rate and blood pressure may prevent unwanted cardiac ischemia Each institution should follow its own protocols for cardiac ischemia Post-stenting hypertension must be avoided to prevent hyperperfusioninduced brain injury There are no guidelines for blood pressure control; SBP >110 mm Hg is adequate after CAS, unless a tandem lesion is present in the same territory or chronic hypertension is present in which a higher blood pressure may be necessary Systolic blood pressure (SBP) of 120–160 mm Hg may be easily tolerated by most patients; SBP >160 mm Hg should be treated

• Groin hematoma and retroperitoneal hemorrhage ▲ Incidence of groin complication is declining due to the use of micro-

puncture femoral access kit and closure devices ▲ Recent studies have revealed that morbidity and mortality associated

with CAS increase significantly in the event of retroperitoneal hemorrhages, which further amplify in the presence of hemodynamic instability ▲ Every effort must be undertaken to prevent groin hematoma; in the event of retroperitoneal hemorrhage, prompt hemodynamic stability must be achieved ▲ An urgent vascular surgery consultation should be initiated for surgical repair of the puncture site to prevent further hemodynamic instability • Instant thrombosis ▲ Instant thrombosis is a rare complication associated with CAS; it

occurs in ~1% of cases

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▲ Stent thrombosis may begin immediately after deployment of a carotid

▲ ▲

▲ ▲ ▲ ▲

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stent and is most commonly seen in the first 24 h; therefore, a post-procedure carotid ultrasound is recommended within 24 h for all CAS patients prior to their discharge home to identify any acute in-stent thromboses Underlying mechanisms are platelet activation by the stent and inadequate inhibition of platelets If stent thrombosis is detected during procedure, IV or intra-arterial administration of GPIIbIIIa-receptor antagonist (integrelin) usually resolves thrombosis and restores blood flow The IV infusion of GPIIbIIIa-receptor antagonist (integrelin) may need to be continued for 24 h A carotid ultrasound is recommended within 24 h for all CAS patients prior to their discharge home to identify acute in-stent thromboses If the follow-up carotid ultrasound demonstrates no stent thrombosis, patient can be discharged home If an in-stent thrombosis is detected within 24 h by ultrasound, IV infusion of GPIIbIIIa-receptor antagonist (integrelin) is recommended for 24 h and patient should be observed in NCCU

Antiplatelet regimen after CAS ♦ Both 325 mg aspirin and 75 mg clopidogrel are recommended to be continued

daily for at least for 4 weeks for the prevention of stent thrombosis ♦ It takes almost 4 weeks for the endothelium to grow over the stent, when the

stent becomes part of the wall of the carotid artery ♦ After 4 weeks, either 325 mg aspirin or 75 mg clopidogrel alone is recom-

mended to continue until contraindicated ■

Follow-up after CAS ♦ In addition to the monitoring of the clinical symptoms, all patients who

undergo a CAS procedure must be periodically evaluated using carotid duplex studies ♦ It is recommended that carotid duplex evaluation of stent patency be conducted at 1, 3, and 6 months and then q 12 months

Acute Ischemic Stroke and Emergent Endovascular Revascularization Rationale for Interventional Treatment for Ischemic Stroke ■

IV recombinant tissue plasminogen activator (rtPA) is the first-line FDAapproved therapy for acute ischemic stroke but must be administered within 3 h and is relatively ineffective for proximal occlusions

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♦ Only 7% are eligible (patients who present <3 h from symptom onset without

contraindication) ♦ Of the eligible patients, only half receive the treatment ♦ 50% of patients who receive rtPA achieve good recovery, but only 8% are in

subgroup of patients with severe stroke ♦ Mechanical and/or intra-arterial thrombolysis can be performed with good results

by using a number of devices for ~50% of patients with proximal occlusions

Indications for Emergent Endovascular Intervention in Acute Stroke ■ ■ ■ ■

Significant neurologic deficit attributable to large vessel occlusion Noncontrast CT showing absence of hemorrhage or well-established infarct Stroke symptom onset known to be within 6 h from assessment Other potential indications ♦ Combined with or in lieu of IV rtPA in patients with

• Severe stroke (NIHSS > 20) • Advanced age (>80 year) • NIHSS >10 with high clot burden or clot in the ▲ ▲ ▲ ▲

Intracranial carotid artery (“T” occlusion) Basilar artery Proximal MCA Extracranial carotid artery

♦ Contraindications to IV rtPA

• • • •

Recent surgery Arterial puncture On anticoagulation Unclear time of onset or stroke upon awakening ▲ Moderate-to-severe stroke (NIHSS > 10) and absence of well-devel-

oped brain parenchymal hypodensity along the artery territory ▲ Large perfusion deficit with >20% mismatch ▲ Failure of recanalization with IV rtPA and persistent or worsening defi-

cit or fluctuating or worsening deficit with radiologic evidence of reduced perfusion and absence of well-organized infarction

Relative Contraindications During Acute Stroke ■ ■ ■

Advance age Poor premorbid functional status Terminal medical condition with life expectancy <6 months

13  Care Following Neurointerventional Procedures ■

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Loss of gray-white differentiation and other subtle changes consistent with infarction on noncontrast CT involving >50% of artery territory <20% perfusion mismatch >24 h from symptom onset for vertebrobasilar territory >6 h from symptom onset for anterior circulation territory Lack of qualified interventionalist or stroke specialist

Types of Emergent Endovascular Procedures in Acute Ischemic Stroke Management ■

Stenotic artery/dissection ♦ Balloon angioplasty ♦ Stent-assisted revascularization ♦ Balloon angioplasty with stenting

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Acute vessel occlusion ♦ Pharmacologic agents

• Thrombolytic agents ▲ Alteplase ▲ Reteplase ▲ Tenecteplase

• Glycoprotein IIb/IIIa inhibitors ▲ Abciximab ▲ Tirofiban ▲ Eptifibatide

• Vasoactive agents ▲ Verapamil ▲ Nicardipine ▲ Nitroprusside

♦ Nonpharmacologic techniques

• Mechanical clot disruption (thromborrhexis) ▲ Microcatheter ▲ Ultrasound-assisted thrombolysis (EKOS catheter)

• Mechanical thrombectomy ▲ ▲ ▲ ▲

MERCI catheter Alligator retriever Penumbra system – aspiration and clot retrieval with a “ring” device Neuronet snare

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Y.M. Lodi et al. ▲ Balloon angioplasty and/or stenting ▲ Suction thrombectomy ▲ Discontinued devices N Angiojet – suction-inducing saline jets N Latis laser device N EPAR (endovascular photo acoustic recanalization) laser system

Efficacy of Endovascular Therapy ■ ■

Clot accessible in 85–95% of cases Recanalization rates based on TIMI (thrombolysis in myocardial infarction) flow

Grade 0, no perfusion; Grade 1, penetration of blood without reperfusion; Grade 2, partial reperfusion; Grade 3, complete reperfusion ♦ TIMI 1 = 11% ♦ TIMI 2 = 24% ♦ TIMI 3 = 44% ■

Recanalization rate for intra-arterial thrombolysis is 66% for proximal MCA occlusion ♦ Recanalization rates improve with combined mechanical thrombectomy/

thromborrhexis

Endovascular Revascularization End Point and Assessment ■

Recanalization of primary arterial occlusive lesion ♦ Refers to opening/resolution of the primary arterial occlusive lesion (AOL) ♦ Assessed using the AOL score (0–3)

• • • • ■

AOL 0 - no recanalization AOL 1 - partial recanalization without distal flow AOL 2 - partial recanalization with some distal flow AOL 3 - complete recanalization

Reperfusion of distal vascular bed ♦ Refers to restoration of flow to the distal vascular bed ♦ Assessed using

• TIMI grading (0–3) ▲ TIMI 0 – No perfusion ▲ TIMI 1 – Perfusion past occlusion with no distal filling

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▲ TIMI 2 – Perfusion past occlusion with slow distal filling ▲ TIMI 3 – Full perfusion

• Qureshi grading (0–5 with 2 sublevels) ▲ Designed for intracranial circulation ▲ Accounts for collateral circulation and location of occlusion ▲ Validated with correlation in 7-day outcome

Qureshi Grading System (Table 13.1) • TICI (thrombolysis in cerebral infarction) grading (0–3 with one sublevel) ▲ TICI 0 – No perfusion ▲ TICI 1 – Penetration of contrast beyond occlusion with minimal

perfusion ▲ TICI 2 – Partial perfusion N 2a – Partial filling <2/3 of vascular territory N 2b – Complete filling but slow ▲ TICI 3 – Complete perfusion without delay

• Collateral angiographic grading system ▲ Grade 0 – No collaterals visible to ischemic site ▲ Grade 1 – Slow collaterals to the periphery of the ischemic site and

partial perfusion ▲ Grade 2 – Rapid collaterals to the periphery of ischemic site and partial

perfusion Table 13.1  Quareshi grading system Grade Description Grade 0 No occlusion Grade 1 MCA occlusion M3 segment Grade 2 Grade 3 3a 3b

MCA occlusion M2 segment

ACA occlusion A2 or distal segment ACA occlusion A1 and A2 segment

1 BA/VA branch occlusion >1 BA/VA branch occlusion

MCA occlusion M1 segment Lenticulostriate arteries spared and/or leptomeningeal collaterals visualized No sparing of lenticulostriate arteries and/or leptomeningeal collaterals not visualized Grade 4 ICA occlusion collaterals BA occlusion collateral present present 4a Collaterals fill MCA Anterograde filling 4b Collaterals fill ACA Retrograde filling Grade 5 Complete occlusion MCA middle cerebral artery, ACA anterior cerebral artery, BA basilar artery, VA vertebral artery

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Y.M. Lodi et al. ▲ Grade 3 – Slow collateral flow but complete reperfusion by the late

venous phase ▲ Grade 4 - Rapid and complete collateral flow to entire ischemic terri-

tory by retrograde perfusion

Predictors of Good Outcome ■ ■ ■ ■ ■ ■ ■

Minimal hypodensity on baseline CT Low baseline NIHSS score Young age Proximal site of occlusion Good collateral flow Lesion location and volume Time from onset to therapy

Preoperative Medical Management ■ ■ ■

Follow emergent evaluation outlined above Maintain SaO2 > 95%; supplement with O2 as necessary Perform elective intubation if: ♦ ♦ ♦ ♦ ♦

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GCS < 9 Worsening neurologic deficit Inability to protect airway Respiratory distress Agitation/restlessness requiring large doses of sedative/anxiolytic that might compromise hemodynamic status

Ensure adequate volume status with nonglucose-containing solutions (0.9% NS IV at 1–2 mL/kg/h) Keep patient NPO except medications; assess swallowing function and insert nasogastric tube in patients who are deemed unsafe for swallowing for drug administration For patient who did not receive systemic thrombolysis, inhibition of platelet may be achieved with giving 325 mg uncoated ASA PO/NG and 300 mg clopidogrel PO/NG prior to procedure Insert Foley catheter for accurate fluid input/output measurements

Perioperative Anesthetic Consideration ■

No patients who are candidates for interventional treatment should receive any antihypertensive therapy unless their MAP is >150 mm Hg (130 mm Hg for patients who received IV rtPA)

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♦ Avoid anesthetic medications that lower blood pressure during intubation ♦ Obtain 12-L EKG to look for active myocardial ischemia; decision to proceed

with emergent interventional management should be determined by the severity of cardiac dysfunction, and emergent cardiology referral may be warranted for concurrent coronary intervention ♦ Confirm endotracheal tube position after intubation prior to starting the procedure

Intraoperative and Postoperative Medical Management ■

General measures ♦ Monitoring

• Admit to NCCU with neuro check q 30 min × 4 h, then q 1 h if stable • Obtain noncontrast CT immediately after procedure to determine extent of infarction; assess for hemorrhagic transformation and development of cerebral edema • Repeat imaging as necessary to assess progression of hemorrhage or edema ♦ Oxygenation

• Keep SaO2 Sat >95%, supplement with O2 as necessary; delay extubation if patient is slow to recover from anesthesia or if with persistent severe neurologic deficit ♦ Blood pressure

• Patients with complete recanalization should be maintained at SBP 120– 180 mm Hg • Those who have poor recanalization despite intervention may be maintained at a higher blood pressure target, but the risk of cerebral edema and hemorrhagic transformation is increased ♦ Fluid status

• Euvolemia is preferred to maximize cerebral perfusion and avoid cerebral autoregulation-mediated rise in ICP due to vasodilation as a response to hypovolemia ♦ Nutrition

• Feed early enterally ♦ Control of hyperglycemia

• Hyperglycemia is common and is independently associated with poor outcome • Aggressive control of hyperglycemia to maintain glucose level between 80 and 140 mg/dL may be achieved using intermittent sliding-scale insulin protocols or insulin infusion

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♦ Fever control

• Hyperthermia from any cause is a poor predictor of outcome; keep temperature below 38°C using acetaminophen, cooling blanket, ice packs • Surface or endovascular cooling for normothermia enables tight and uniform temperature control without over- or under-shooting (thereby preventing additional complications) and may be preferable ♦ Antiplatelet therapy

• Patients who had angioplasty and stenting require adequate antiplatelet therapy to prevent rethrombosis/reocclusion • Both 325 mg ASA and 75 mg clopidogrel are recommended maintenance medications for at least 4 weeks • Antiplatelet therapy is contraindicated in patients who received systemic or intra-arterial thrombolysis • If patient received both thrombolysis and stenting, decision to institute antiplatelet therapy must be weighed against risk of hemorrhagic transformation ♦ DVT prophylaxis

• Sequential compression devices, embolic stockings, and subcutaneous heparin use prevent thromboembolic complications without increasing risk for hemorrhage ♦ Prevention of pneumonia

• Intubated patients benefit from oral care and regular mouthwashing to prevent ventilator-associated pneumonia ♦ GI prophylaxis

• Provide adequate ulcer prophylaxis with proton pump inhibitors ♦ Catheter site care

• After an uncomplicated procedure, patient may assume sitting position after 2-h bed rest • It is important to examine the groin puncture site for development of hematoma, pseudoaneurysm, or worsening tenderness and loss of distal pulses • Incidence of groin hematoma is declining due to the availability and use of micropuncture femoral access kit and closure devices • Despite this, retroperitoneal hemorrhage occurs and may induce hemodynamic instability and cause impaired cerebral perfusion if not addressed fully • Urgent vascular surgery consultation may be needed if hemostasis cannot be achieved

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Complications and Their Management ■

Procedural complications ♦ Hematoma

• Manual compression for at least 20–30 min to achieve hemostasis and prevent further expansion • If bleeding continues, request vascular surgery consultation for surgical repair ♦ Pseudoaneurysm

• Occurs days to weeks post procedure and requires surgical repair • Vessel dissection – balloon angioplasty and stenting may be done • Embolic clot formation – intra-arterial thrombolysis and mechanical clot retrieval ♦ Neurologic complications

• Hyperperfusion syndrome occurs uncommonly and may be prevented with optimal blood pressure management based on amount of recanalization achieved • For space-occupying hemorrhage or brain edema, manage with aggressive intracranial hypertension protocol • Surgical decompression may be considered in patients <60 years old with nondominant hemisphere involvement and/or with some language preservation and impending sign of herniation • Seizure may be controlled with antiepileptic medication • Rarely, acute re-stenosis or occlusion of the blood vessel occurs; if so, adequate imaging must be done to determine any viable tissues that may still be salvageable prior to considering repeat intervention ♦ Cardiac complications

• Cardiac ischemia may occur concomitant with the stroke or after the procedure • Telemetry monitoring and serial cardiac injury panel determination identify most acute cardiac injury in the perioperative period • If hemodynamic instability occurs or if patient develops congestive heart failure, cardiology consultation may be necessary for possible coronary revascularization ♦ Pulmonary complications

• Aspiration • Respiratory failure • Pulmonary embolism

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♦ Other medical complications

• Infection – UTI, pneumonia • Stress ulcer • DVT

Endovascular Treatment of Unruptured and Ruptured Intracranial Aneurysms ■

Unruptured intracranial aneurysms ♦ Epidemiology

• • • • •

~0.4–6% of all persons with an aneurysm 20–30% of patients will have multiple intracranial aneurysms Roughly 1–2% annual rate of rupture Most aneurysms never rupture Location ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲

30% anterior communicating artery (ACom) 25% posterior communicating artery (PCom) 20% middle cerebral artery (MCA), often at bifurcation 8% internal carotid artery 7% basilar tip aneurysm 4% pericallosal artery 3.5% miscellaneous 3% posterior inferior cerebellar artery

♦ Risk factors

• Suspected cause – Hemodynamic stress precipitates aneurysm formation; most pathology found at weakest points in blood vessels (bifurcations), and microscopy of saccular aneurysms demonstrates loss of or decreased tunica media (middle muscular layer) • Screening ▲ Increased risk of morbidity and mortality with increasing age, size, and

location of unruptured aneurysm in excess of benefit for most patients ▲ Screen patients with CT or MR angiography N Hereditary connective tissue disease N Patient with ³2 first-degree family members with aneurysms

• Genetic risk factors ▲ Increased risk of aneurysms in patients with coarctation of aorta and

connective tissue disorders (Ehlers-Danlos, pseudoxanthoma elasticum, familial aldosteronism type I, polycystic disease of the kidneys)

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▲ Age-adjusted prevalence of aneurysm in first-degree relative of patient

with known aneurysm is ~9% • Modifiable risk factors ▲ Cigarettes – relative risk 3 for men and 4.7 for women; if concomitant

hypertension, then 14 ▲ Hypertension ▲ Estrogen deficiency at menopause is associated with decreased colla-

gen content of vessels in precipitation of aneurysms ♦ Symptomology

• Natural History ▲ Unruptured aneurysms <7 mm rupture at ~0.1%/year vs. those >7 mm,

which rupture at 0.5%/year ▲ 5-year rupture rates (Table 13.2)

• Characteristics ▲ Most are asymptomatic ▲ If symptoms, they commonly include headache, CN III palsy, and facial

pain ♦ Pre-procedure care/counseling

• Increased risk of procedural complications with age ³70 years, posterior location of aneurysm, and if >10 mm in size • Benefit of treatment found in patients with aneurysm £7 mm and if prior history of SAH ♦ Decision to treat – risk of rupture is roughly 1%/year; thus, one must evaluate

patient’s life expectancy when considering treatment • Hold treatment in those with aneurysms <7 mm and life expectancy 15–25 years • Selection of patients ▲ ▲ ▲ ▲ ▲ ▲

Any aneurysm ³7 mm Any aneurysm in patient with SAH If intradural and symptomatic Familial aneurysm of ³5 mm Wide-necked ruptured aneurysm Fusiform aneurysm of ³7 mm

Table 13.2  Five-year rupture rates for intracranial aneurysms Size (mm) Cavernous ICA (%) Anterior circulation (%) 7–12 0   2.6 13–24 3 14.9 6.4 40 ³25

Posterior circulation (%) 14.5 18.4 50

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• Selection of patients specific to stent-assisted endovascular coiling ▲ ▲ ▲ ▲ ▲

Wide-necked aneurysm with diameter of ³7 mm Any symptomatic Wide-necked aneurysm ³2 mm Wide-necked familiar aneurysm ³5 mm Wide-necked ruptured aneurysm Fusiform aneurysm of ³7 mm N Wide-necked aneurysms are defined as having dome-to-neck ratios

<2 or a neck >4 mm in diameter N An intracranial aneurysm is defined as fusiform if the aneurysm was

an out-pouching dilatation of the parent blood vessel affecting at least 270° of circumference of the lumen and possessing no discernible neck ♦ Treatment risks (Table 13.3)

• Poor outcome risk increases with age, 6% risk if 40–49 years, and 30% if >70 years • Surgery vs. coiling for unruptured aneurysm • Intraoperative/procedure rupture ♦ Preparation of patients

• Informed consent – the patient must be willing to take both aspirin and clopidogrel (if stent is required) and participation in frequent outpatient visits, including follow-up angiographic studies • All stent-treated patients must be treated with both aspirin (325 mg/day) and clopidogrel (75 mg/day) at least 5 days prior to their treatment; it is possible to administer a loading dose of 300–600 mg of clopidogrel and 325 mg of aspirin urgently in patients with complex wide-necked aneurysms who may require stent-assisted coiling; this loading dose provides platelet inhibition of 55% in 1 h and 80% within 5 h of administration • As stent-assisted treatment of aneurysms requires general anesthesia, all prospective candidates must be evaluated for candidacy of general anesthesia • Preoperative mandatory laboratory testing – CBC, basic metabolic panel, PT, PTT, urine analysis, 12-lead EKG, chest x-ray, and echocardiography • Treat diabetics, elderly (>75 years), and renally impaired patients, with adequate hydration before, during, and immediately following the procedure. Table 13.3  Treatment risks in unruptured intracranial aneurysms Risk of death/poor outcome 30 Days (%) 1 Year (%) Surgery 13.7 12.6 Endovascular coiling   9.3   9.8

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♦ Intra-procedural management

• All patients must be adequately hydrated prior to the procedure to avoid contrast-induced renal impairment; a stable systolic blood pressure (SBP, 110–140 mm Hg) must be maintained for adequate perfusion of brain and prevention of hypertension • All hypertensive events must be treated with appropriate antihypertensive medications such as labetalol, hydralazine, or nicardipine; sodium nitroprusside must be preserved for the refractory cases • Baseline ACT must be obtained, and IV heparin should be administered to obtain a recommended ACT ³250 s prior to implantation of intracranial stent • Stent-induced spasm could be treated with intra-arterial verapamil and/or nitroglycerine • Instant thrombosis is usually treated with intra-arterial IIB/IIIa receptor antagonist and intraoperative thromboembolism is treated with intra-arterial administration of thrombolytic or mechanical retriever of clot ♦ Post-procedure care (Box 13.1)

• A complete neurologic examination must be performed immediately and q 15 min for 1 h, then q 30 min for 2 h, then q 1 h for 6 h, q 2 h for 12 h, and then q 4 h • Groin care – femoral puncture site must be evaluated along with vital signs as follows: q 15 min for 1 h, then q 30 min for 2 h, then q 1 h for 4 h • All stent-assisted coiling must be monitored in a NCCU setting or at least in the medical ICU with nurses trained in caring for neurosurgical patients • Blood pressure – after stent-assisted coiling procedure, liberalized blood pressure is allowed • Adequate hydration and oxygenation must be maintained; adequate pain control must be obtained, preferably with IV short-acting narcotics such as fentanyl • All patients must have orders for appropriate anti-emetics • Diet – if the patient is wake and alert without any neurologic and swallowing impairment, diet could be advanced as tolerated • If any neurologic deterioration occurs, patient requires an urgent CT of head after the stability of airway and hemodynamics; the treating neurointerventionalist and neurosurgeon must be notified immediately for the appropriate management ♦ Follow-up – observe for recanalization and recurrence

• Recanalization risk is increased with increased size and increased neck of aneurysm if >4 mm, and risk is decreased if balloon-assisted coil placement in wide-necked aneurysm

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Box 13.1  Elective aneurysmal coiling post-procedure checklist ♦ Admission – discuss with reporting physician specifics of case, including:

• Any unplanned events (i.e., clots, aberrant wires, perforations, etc.) • Any remaining aneurysms? • Preprocedure ASA, clopidogrel; use of stents; duration of ASA/ clopidogrel • Ease of intubation/extubation; use and reversal of neuromuscular blockade; net volume after case; use of colloid and/or vasopressors • Use of closure device at angiopuncture sight/duration of extremity immobility • Past medical history and medications ♦ Neurologic

• Continue neurologic assessments sequentially following case • Assess if degree of NMB is unreversed • Pain control ♦ Cardiac

• • • • •

Resume any home meds MAP £130 mm Hg ECG and troponin post-procedure Urinary output and follow for evidence of IV contrast nephropathy Serial extremity pulses to assess perfusion, distal to puncture

♦ Pulmonary

• If extubated – tolerance of extubation/maintenance of airway • If intubated ▲ ▲ ▲ ▲ ▲

Wean ventilator to CPAP and minimal PSV/PEEP Cuff leak Assess mental status, bulbar function, secretions ABG and CXR Extubate when safe

♦ GI

• • • •

Advance diet as tolerated if extubated Hold tube feeds if extubation is immediate SSI and blood sugar control Antiemetics (10 mg metoclopramide IV q 6 h or 4–8 mg ondansetron IV q 8 h)

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• Patients with unruptured aneurysm may be discharged to home after 24 h if they are back to their baseline condition • All patients must continue both 325 mg aspirin and 75 mg clopidogrel daily for at least 6 weeks, followed by either 325 mg aspirin or 75 mg clopidogrel daily until further notice • All patients must be evaluated in the clinic in 2 weeks after discharge to home and require a 3-month follow-up cerebral angiography • Headaches – coil headaches are usually transient, last from a few days to a few weeks, and are treated with oral acetaminophen with codeine, gabapentin, or topiramate ■

Ruptured intracranial aneurysms ♦ Epidemiology

• SAH effects 6–16 patients per 100,000 or ~30,000/year in North America • Outcomes ▲ Case fatality, 32–67% ▲ 19% of patients independent at 4 months after SAH have no reduction

in quality of life; 31% at 18 months ▲ ~50% of survivors with significant neurologic deficits

• Ratio of SAH – 1.6–2 female:1 male • 73% rebleed in first 72 h; 2–4% of aneurysmal SAH rerupture within first 24 h; antifibrinolytics decrease reruptures, but no improvement in outcome • Causes of spontaneous SAH ▲ 85% saccular aneurysm at base of brain ▲ 10% perimesencephalic – extravasation of blood confined to cisterns

around the midbrain, centered anterior to midbrain ▲ Arterial dissection (vertebral artery > carotid artery > intracranial);

30–70% will rebleed, and these are often fatal ▲ Arteriovenous malformation (AVM); 10–20% will have associated sac-

cular aneurysm ▲ Dural AV fistula ▲ Cocaine abuse (“crack:” form > alkaloid form)

♦ Risk factors

• Hypertension, heavy EtOH intake, connective tissue diseases, cigarette smoking, and estrogen deficiency • Familial ▲ If SAH, ~4% of first-degree relatives have aneurysm; familial saccular

aneurysms tend to burst at a smaller size and younger age than do sporadic aneurysms

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SAH is 0.8%; if two, then 7.1% ♦ Classification

• Shapes ▲ Saccular (berry) aneurysms N Most often at bifurcation N Wide-necked aneurysms are defined as having dome-to-neck ratios

<2 or a neck >4 mm in diameter ▲ Fusiform – the aneurysm was an out-pouching dilatation of the parent

blood vessel, affecting at least 270° of circumference of the lumen and possessing no discernible neck; often secondary to atherosclerosis ♦ Symptomology

• Characteristics ▲ 97% with acute-to-subacute onset of “worst headache of life,” ± nau-

sea/vomiting, focal neurologic deficits, photophobia, coma ▲ 10–43% of patients with headache report prior headache or “sentinel”

headache ▲ 30% occur at night ▲ LBP and meningismus common later after bleed

♦ Pre-procedural care

• Endovascular therapy carries a lower risk of adverse outcomes and inhospital death, shorter length of stay, and decreased hospital charges • Patients eligible for endovascular treatment must have an aneurysm without thrombus, willing to have repeated angiography, and a favorable fundus-to-neck ratio • Preoperative mandatory laboratory testing - CBC, basic metabolic panel, PT, PTT, urine analysis, 12-lead EKG, chest x-ray, and echocardiography • Periprocedural hydration as mentioned • Preparation ▲ 60 mg nimodipine PO/PT q 4 h × 21 days ▲ Medically stable for intubation and anesthesia ▲ Enquire as to IV contrast or shellfish allergy; if known, then premedi-

cate with 50 mg prednisone PO/PT 13, 7, and 1 h prior to procedure and with 50 mg diphenhydramine PO/IV/PT 1 h before procedure; if patient develops a reaction, treat with 1–2 L normal saline bolus, 50 mg diphenhydramine PO/PT/IV, 50 mg ranitidine IV, 125 mg methylprednisolone IV, and 0.5 mg IM epinephrine q 5 min prn or epinephrine drops @ 2–10 mg/min • NPO

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♦ Intraprocedural management

• All patients must be adequately hydrated prior to the procedure to avoid contrast-induced renal impairment; a stable blood pressure (SBP, 110–140 mm Hg) must be maintained for adequate perfusion of brain and prevention of hypertension; if a ventriculostomy catheter is inserted, adequate cerebral perfusion of 70 mm Hg must be maintained • All hypertensive events must be treated with appropriate antihypertensive medications such as labetalol, hydralazine, or nicardipine; sodium nitroprusside must be preserved for the refractory cases • Once the dome of the aneurysm has been secured, bolus heparin is given (2,000–4,000 units) to achieve a clotting time 2–2.5 times baseline • A baseline ACT must be obtained, and IV heparin should be administered to obtain a recommended ACT ³250 s prior to the implantation of intracranial stent • Stent induced spasm could be treated with intra-arterial verapamil and/or nitroglycerine • In-stent thrombosis is usually treated with intra-arterial IIB/IIIa receptor antagonist, and intraoperative thromboembolism is treated with intra-arterial administration of thrombolytic or mechanical retriever of clot • Coils/Stents/Balloons ▲ Titanium and platinum wire are used to make microcoils and 3D

spheres ▲ Once in proper position, 1 mA current disconnects junction to coil ▲ Matrix (Boston Scientific) and Cerecyte (Micrus) detachable coils have

▲

▲

▲ ▲ ▲

▲ ▲

bioabsorbable copolymer to accelerate connective tissue formation within aneurysm Hydrogel coils (Microvention) are platinum coils covered with an expanding polymer; with exposure to blood, the coil increases volume 3–4 times, with nearly equivalent recanalization rates to those of Matrix coils Balloon-assisted GDC (Guglielmi detachable coil) therapy has been shown to be safe and effective for wide-necked aneurysms with a neckto-body ratio close to 1; balloon assistance forces the coils to assume the shape of the aneurysm without coils abutting the parent artery Balloon use does have the inherent risk of induced vasospasm, thrombus formation, rupture, and ischemia Stent-assisted endovascular coil occlusion of wide-necked saccular aneurysms achieves ³95% occlusion in 73–100% of patients in recent studies Liquid-based embolic polymer, Onyx, is a treatment for AVM and, potentially, aneurysms; on contact with blood, it transforms into a pulpous substance; the major drawback is migration of the substance to the parent artery and distal embolization 5–14.5% of cases cannot be coiled secondary to tortuous anatomy Patient may be on IV heparin drops 24 h after coiling or may have been bolused during the procedure

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♦ Post-procedural management (Box 13.2)

• Good outcomes rely on skilled observation • Post-procedure problems – hydrocephalus, hypothalamic dysfunction, seizures, cardiac abnormalities, contrast reaction, infection, arterial dissection, pseudoaneurysm, parent artery occlusion, groin hematoma, thromboembolism, and rupture associated with coil/stent/balloon (30–40% mortality) • Upon return, a complete neurologic examination must be performed immediately and q 15 min for 1 h, then q 30 min for 2 h, then q 1 h for 6 h, q 2 h for 12 h, then q 4 h

Box 13.2  Ruptured aneurysm coiling post-procedure checklist ♦ Admission – discuss with reporting physician specifics of case,

including: • Day from hemorrhage? ICP? • Any unplanned events (i.e., clots, aberrant wires, perforations, rehemorrhages, etc.) • Any remaining aneurysms? • Any vasospasm noted? Treatments? • Pre-procedure ASA, clopidogrel; use of stents; duration of ASA/ clopidogrel • Ease of intubation/extubation; use and reversal of neuromuscular blockade; net volume after case; use of colloid and/or vasopressors • Use of closure device at angiopuncture sight/duration of extremity immobility • PMH and medications ♦ Neurologic

• Continue neurologic assessments sequentially following case; if sudden change in MS, consider rebleed vs. seizure vs. hydrocephalus vs. ischemia vs. ICH vs. vasospasm • Assess degree of neuromuscular blockade • Pain control • 500 mg levetiracetam PO/PT q 12 h × 3 days; 60 mg nimodipine PO/ PT q 4 h × 21 days • ICP ▲ Any monitor (EVD, lumbar drain, bolt?) ▲ 1.5–0.5 mg/kg mannitol IV prn for ICP ³25 mm Hg for ³5 min

– OR – 23.4% saline 1–0.35 mg/kg IV prn ▲ Cardiac

(continued)

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Box 13.2  (continued) • Hold any home meds; MAP £130 mm Hg ▲ If patient on chronic b blockade, follow for signs of tachycardia and resume at lower dose ▲ First-line – 5–20 mg labetalol IV q 15 min to total of 340 mg/d; second-line – 2.5–10 mg hydralazine IV q 20 min to total of 40 mg/d; third-line – 2.5 mg/h nicardipine IV titrate q 15 min to 15 mg/h • EKG and troponin post-procedure and prn; transthoracic echocardiogram prn • Monitor urinary output and follow for evidence of IV contrast nephropathy; optimize risk reduction with adequate hydration • Serial extremity pulses to assess perfusion distal to puncture • At day 4 from SAH, maintain intake approximately equaling outputs until day 15 • If central axis present, CVP monitor ♦ Pulmonary

• DVT prophylaxis – TED hose, SCD, and heparin 5,000 U SQ q 12 h starting post-procedure day 1; if prolonged time for procedure, consider lower extremity Doppler ultrasound for DVT screening • If extubated – tolerance of extubation/maintenance of airway • If intubated ▲ ▲ ▲ ▲ ▲

Wean ventilator to CPAP and minimal PSV/PEEP Cuff leak Assess mental status, bulbar function, secretions ABG and CXR Extubate when safe

♦ GI

• • • •

PPI or H2 blocker for GI prophylaxis Advance diet as tolerated if extubated Hold tube feeds/ADAT if intubated SSI and blood sugar control

♦ Infectious Disease

• If EVD, then 1 g Ancef IV q 8 h; 600 mg clindamycin IV q 8 h if patient is allergic to allergic (controversial)

• If vasodilators used in the procedure, ICP is often transiently elevated • Groin care – femoral puncture site must be evaluated along with the vital signs as follows: q 15 min for 1 h, then q 30 min for 2 h, then q 1 h for 4 h

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• Blood pressure – once the aneurysm is secured, allow MAP to rise to £130 mm Hg • Adequate hydration and oxygenation must be maintained; adequate pain control must be obtained preferably with IV short-acting narcotics such as fentanyl • All patients must have orders for appropriate anti-emetics and stool softeners • Diet – if patient is wake and alert without any neurologic and swallowing impairment, diet can be advanced as tolerated • If any neurologic deterioration occurs, patient requires urgent head CT after the stability of airway and hemodynamics; the treating neurointerventionalist and neurosurgeon must be notified immediately for the appropriate management ♦ Follow-up

• Acute medical management ▲ Neurologic N Seizure prophylaxis – a number of retrospective series report poorer

outcome associated with phenytoin; thus, in the acute window, suggest agent such as 500 mg levetiracetam PO/PT q12 h × 3 days if no seizures N Vasospasm – window, day 4–21; peaking days, 7–8 ° Risk factors include dehydration, hyperglycemia, high Fisher

grade, and <50 years of age ° 7% of patients die from vasospasm; use of lumbar drainage or

statins may ameliorate this risk ° Keep euvolemic 4–15 days post-SAH; if severe vasospasm

involves the ICA, A1, or M1 segment, angioplasty has been shown to feasible with dependable results producing clinical improvement ° More distal vasospasm can be amenable to IA vasodilators, resulting in improved clinical outcome scores ° Recent work with continuous magnesium infusion demonstrates a reduction in delayed cerebral ischemia ▲ Cardiac – surging of catecholamines may produce changes in the ECG,

troponins, and left ventricle; commonly, these occur in the first week; ECG findings include QT prolongation, inverted T waves, and the presence of U waves ▲ Pulmonary – DVT prophylaxis with 5,000 U heparin SQ q 12 h or 40 U SQ q d Lovenox after first post-procedure day ▲ GI – stool softeners to limit valsalva strain and serum glucose £180 mg/dL

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Table 13.4  One-year outcome – clip versus coil Outcome (mRS) Surgery (%) Endovascular (%) 0–2 69.1 76.5 3–6 30.9 23.5 ▲ If coil loops are present in the parent vessel, the patient should receive

48 h of heparinization and 6 weeks of aspirin and clopidogrel; all other patients should receive aspirin indefinitely after coiling ▲ 6–12-month follow-up typically occurs with an angiogram; thereafter, with MRA or CTA ▲ Improved long-term outcomes associated with coiling N Benefits in ISAT (International Subarachnoid Aneurysm Trial)

reported to 7 years N 1-year outcome – clip vs. coil (Table 13.4) N Absolute risk reduction of death/dependency at 1 year, 6.9%; rela-

tive risk reduction, 22.6%; number needed to treat for one improved outcome, ~13–14

Intracranial AVMs ■ ■ ■ ■

■

■

■

■

AVMs are direct arterial-to-venous shunt without an intervening capillary bed Prevalence of cerebrovascular AVMs is 0.8–1.4% Risk of hemorrhage is ~2%/year for unruptured AVMs Rate of recurrent hemorrhage increases to 18% per year with previous history of AVM rupture Presence of concomitant intracranial aneurysm and AVM increases twofold the chance of hemorrhage in follow-up period Intracranial AVMs are typically diagnosed before the patient has reached the age of 40 year >50% of AVMs present with ICH; next common presentation is seizure, which occurs in 20–25% of cases Other presentations include headaches (15%), focal neurologic deficit (<5%) and pulsatile tinnitus

Current Treatments ■ ■ ■ ■

Surgery Radiosurgery Embolization Combined treatment

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Indication for Endovascular Embolization of AVMs ■ ■ ■ ■

Pre-surgical embolization for better surgical outcome Pre-radiosurgical embolization for better response Palliative embolization to suppress progression and for symptomatic relief Curative embolization in case of one or two feeders

Preoperative Management Care ■

■

■

Preparation – all patients must be on therapeutic antiepileptic drugs (AEDs), especially those who presented with seizures All patients must have preoperative testing, including anesthesia clearance, as described previously Arrangement to have an intensive care bed must be made prior to scheduling an embolization

Operative Management ■

■ ■

■

■

Verification of a therapeutic antiepileptic medication must be made; if patient is not on AED, an optimum IV AED must be instituted prior to the procedure During the procedure, a normal SBP of 110–140 mm Hg must be maintained Any hypertension must be avoided to prevent complications related to the potential “breakthrough luxury perfusion”: high shunt flow through the AVM reduces perfusion pressure in adjacent brain tissue and leads to chronic low-flow state that may not adjust to rapid increase in perfusion post-AVM embolization; leads to risk of ICH, cerebral edema, and seizures To prevent fluctuations of blood pressure, an IV continuous infusion of antihypertensive medication must be used at least for first 24–48 h If the procedure is performed under general anesthesia, intraoperative neuromonitoring may be considered via Somatosensory-evoked potential and continuous EEG

Postoperative Care ■ ■ ■

■

All patients should ideally be monitored in the NCCU or in a medical ICU for 24 h Adequate hydration and oxygenation must be maintained Complete neurologic examination must be performed; if any neurologic deficit occurs, an urgent head CT must be obtained In case of an ICH, patient must be urgently evaluated by Neurosurgeon for the evacuation of blood

13  Care Following Neurointerventional Procedures ■

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If CT scan is normal but patient still has change in mental status, an urgent EEG must be obtained to diagnose nonconvulsive seizures SBP must be maintained at 110–140 mm Hg To prevent fluctuations of blood pressure, an IV continuous infusion of antihypertensive medication must be used for at least the first 24–48 h

Follow-up ■ ■

All patients need follow-up visit in the clinic in 2 weeks All patients need a 3–6-month follow-up angiogram

Key Points ■

■

■

■

Adherence to strict selection criteria from risk stratification is paramount for patients being considered for neurointerventional procedures Pre-, intra- and post-procedural management is critical for enhancing good outcomes in patients undergoing neurointerventional procedures Use of stents, placement of coils, and liquid polymer use must be assessed adequately for need for heparin and clopidogrel and potential for distal embolization In patients with intracranial aneurysms, endovascular coiling, compared to surgery, has improved outcomes and lowered hospital costs; despite this, ~30% of SAH patients are presently coiled

Suggested Reading Barnett HJ, Taylor DW, Eliasziw M et al (1998) Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 339:1415–1425 Brisman JL, Song JK, Newell DW (2006) Cerebral aneurysms. N Engl J Med 355(9):928–939 Molyneux A, Kerr R, Stratton I et al (2002) International Subarachnoid Aneurysm Trial (ISAT) Collaborative Group. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 360:1267–1274 Qureshi AI (2004) Endovascular treatment of cerebrovascular diseases and intracranial neoplasms. Lancet 363:804–813 Ralph LS, Robert A, Greg A et  al (2006) Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the council on cardiovascular radiology and intervention: the American Academy of Neurology affirms the value of this guideline. Stroke 37:577–617 Yahia AM, Gordon V, Whapham J et al (2008) Complication of neuroformstent in endovascular treatment of intracranial aneurysms. Neurocrit Care 8:19–30

Chapter 14

Ethical Issues and Withdrawal of Life-Sustaining Therapies Wendy L. Wright

Introduction ■

■

■

Healthcare providers in the NCCU render care to a population of patients who are at risk for imminent death as well as for life-altering neurologic disability When rendering that care, it is important for providers to maintain respectable standards of ethics and to be compassionate toward critically ill patients and their families In addition to incorporating ethical principles, it is always advisable to follow local laws and hospital policies related to the topics discussed within this chapter

Ethical Issues ■

Basic ethical principles ♦ Beneficence

• A moral obligation to provide benefit to the patient • This principle deems that the healthcare provider relieve pain and suffering, while striving to maintain and improve health • However, what constitutes a “benefit” for the patient is debatable • Furthermore, beneficence can conflict with other goals of care ♦ Nonmaleficence

• A moral principle that dictates that no harm is done to the patient • A stricter requirement than beneficence

W.L. Wright, MD (*) Emory University School of Medicine, 1365B Clifton Rd., NE, Ste. 6200, Atlanta, GA 30322, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_14, © Springer Science+Business Media, LLC 2011

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• It is not justifiable to inflict harm, even in the name of trying to provide benefit ♦ Justice

• Healthcare resources must be distributed fairly and equitably • Includes the concept that applying medically ineffectual treatments is wasteful and will take resources away from someone who could potentially benefit from them ♦ Autonomy

• The right of patients to make their own decisions • In the NCCU, this principle would deem that the patient can choose or refuse diagnostic tests, treatments, and procedures ♦ Paternalism

• The moral authority of the physician to compromise a patient’s autonomy in the patient’s best interest • For example, withholding information about a poor prognosis and only offering the treatment options that the physician thinks are most appropriate • Paternalism directly violates a patient’s right to self-determination and should not be practiced in most societies, especially those that value autonomy ♦ Shared decision making

• Commonly, the patient and healthcare team will share in medical choices, effectively acting as a decision-making dyad • The physician’s role is to provide all relevant information about treatment options, including the risks and benefits of treatments, and to answer the patient’s questions ♦ Family and friends may be involved as the patient desires, or

• If the patient lacks the capacity to make decisions, a surrogate decision maker will act on behalf of the patient in this paradigm

Informed Consent ■

In most cases, a patient in the NCCU will need to provide informed consent for treatment, diagnostic tests, and procedures ♦ Exceptions include if the patient is unable to provide consent, in which case,

consent should be obtained from a surrogate decision maker, or

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♦ If risk of harm is imminent, the physician may proceed with the treatment,

test, or procedure until consent can be obtained from the patient or surrogate decision maker under the principle of implied consent ♦ Even in an emergency, however, it is not permissible for a physician to perform any treatment, test, or procedure that he knows goes expressly against a patient’s wishes ♦ Three criteria are required to make consent valid: capacity, adequate information, and lack of coercion • Capacity ▲ Capacity is the patient’s physical ability to exercise rational decision-

making ▲ Includes the ability to understand the consequences of a decision, which is

often best assessed by having a conversation with the patient to that effect ▲ Difficult to assess in patients who are mechanically ventilated, but if

▲ ▲ ▲ ▲

▲

they can write or use alternative forms of communication, capacity can be assessed Capacity is decided based on a physician’s clinical judgment However, “capacity” is often mistakenly used interchangeably with the word “competence” by clinicians Competence is the legal right to make decisions regarding one’s health Patients will not be able to make decisions if they do not have the capacity to do so because of altered mental status and therefore will be considered incompetent; however, technically, the matter of competency is a legal declaration Many critically ill neurologic patients lack capacity due to impaired neurologic function as a result of their disease process and therefore must rely on surrogate decision makers

• Adequate information ▲ The amount of information that should be provided is the subject of debate ▲ The “reasonable-person standard” is generally accepted ▲ Clinicians should provide what a reasonable person would need to

know to make a healthcare decision ▲ Would include the diagnosis and prognosis and the probable risks and

outcomes of the available treatments, including the risk of receiving no treatment • No coercion should be applied by physicians or others, ensuring that the consent has been given freely ♦ Surrogate decision makers

• If the patient has explicitly expressed any instructions, either verbally or in writing, surrogate decision makers should be instructed to follow these instructions

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• If no such wishes are known, the surrogate should be instructed to follow the standard of substituted judgment, whereby they would apply the patient’s value system and reproduce the decision that the patient would make if capable of deciding • If the surrogate has no knowledge of the patient’s value system, she would then be instructed to act in the best interest of the patient by weighing the benefits and risks of the treatments before deciding the best course of action

Advance Directives ■

Advance directives are written statements that express the healthcare decisions of patients ♦ Should be honored regardless of physician preferences or bias

• When they are not honored, it is generally because the physician is not aware that they exist or because the written statements are ambiguous ♦ Patients can change or cancel advance directives at any time, as long as they

are of sound mind ■

Living wills ♦ Written, legal documents that describe certain life-sustaining or other medical

treatments that a patient would like to have or forego if they become seriously ill ♦ Often address fluid, hydration, and ventilatory support preferences if the patient

were to have a terminal illness or enter into a persistent vegetative state ♦ May be of limited usefulness in the NCCU because many patients are

impaired with new neurologic dysfunction that they may find unacceptable, but may not necessarily have a terminal illness ♦ However, some living wills can be very specific; therefore, each should be read for details, including which therapies (including dialysis, pain medications, etc.) are authorized or refused and under which conditions ■

“Do not resuscitate (DNR)” orders or “Do not attempt resuscitation (DNAR)” orders ♦ Orders to not perform CPR or ACLS protocols in the event of a respiratory or

cardiac arrest ♦ Depending on hospital policy, many versions of these orders may exist, includ-

ing DNAR in the event of cardiac arrest, or do not intubate (DNI) in the event of respiratory arrest. Therefore, it is important to take note of hospital policies ■

Durable power of attorney ♦ Designates a person or persons who would make healthcare decisions for a

patient if the patient becomes incapacitated

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♦ Generally more useful to the healthcare team than a living will because all

scenarios can be addressed with the durable power of attorney

Communicating Prognosis ■

Prognostic information ♦ In many cases, it is difficult to provide accurate prognostic data because out-

come studies are inadequate ♦ However, patients and surrogates have a right to know the same information

that physicians know about prognosis so that they can make as informed a decision as possible ■

Medical futility ♦ A clinician is not required to make any intervention that is not expected,

♦ ♦

♦ ♦

based on the clinician’s judgment, to provide meaningful benefit as defined by the patient’s personal value set, and is therefore medically futile In fact, honoring a request to provide medically futile treatment may violate the principles of nonmaleficence and justice The American Medical Association supports the notion that futility is a valid reason for physicians to write a “do not resuscitate” order, even without a patient’s consent Medical futility can be difficult to establish. As it is based on training and clinical expertise of the treating physicians, there may be room for debate Many hospitals have a policy to establish futility • Often incorporating that no one physician should establish futility unilaterally • Futility cannot be established without explaining to the patient and/or family the risks, benefits, and goals of therapy, and the possible outcomes of the disease state

■

Fallacy of the self-fulfilling prophecy ♦ A phenomenon such that if published outcome data regarding poor prognosis

are applied to critically ill patients and care is withdrawn, all patients will die as a result of a “self-fulfilling prophecy,” thereby making the outcomes seem even worse for particular disease states in future outcome studies; e.g., the family was told that they had a poor prognosis and then death is ensured by terminating life-sustaining measures ♦ Has been shown to invariably lead to patient deaths in the NCCU and to particularly be a problem in patients with large intracerebral hemorrhage ♦ Further hinders the collection of accurate prognostic information ♦ Slows or altogether halts opportunities for therapeutic advances

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W.L. Wright Fig. 14.1  How to deliver “Bad News” In person, whenever possible Ideally in a private room that has seating for everyone; At least in a private, quiet setting Demonstrate compassion and empathy Make eye contact, extending a comforting touch when appropriate Avoid medical jargon

■

Obstacles in communicating prognoses ♦ One of the biggest obstacles is physician anxiety about delivering the news of

a poor prognosis ♦ This anxiety can lead to avoidance of difficult discussions ♦ Physicians fear blame from the patients’ families and emotional outbursts if

they deliver the “bad news” of a poor prognosis. Avoiding such discussions will usually create mistrust of the healthcare team and false expectations if the family does not understand the prognosis (Fig. 14.1) ♦ Accuracy of prognostic information • Accurate information is not always available • May be rapidly changing due to improvement in treatment modalities ♦ Generalizability of prognostic information

• Not always able to generalize prognostic information available in the literature to individual patients ♦ Medical jargon

• Should be avoided when possible; even the most common words used in the medical community may require definition and explanation to the lay community ♦ Innumeracy

• The inability of a person to conceptualize simple mathematical concepts • Becomes an issue when family members cannot comprehend probability concepts put forward by physicians ♦ Bias

• Physicians should not attempt to impose their own value judgments onto a patient or family member; e.g., a physician might assume that what they think would be an appropriate quality of life is also acceptable for their patients and withhold treatment options that will not be consistent with the physician’s desired goals • In actuality, it is important to try to understand and work toward patients’ desired goals

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♦ Framing

• Has to do with how information is presented • Physicians have an ethical responsibility not to frame prognostic information in a biased manner, applying their own values to the context of the discussions; e.g., to say to a family member, “Surely you wouldn’t want us to operate on your poor, demented mother so that she will probably end up in a nursing home,” will strongly influence that decision. Similarly, a statement such as, “There is a 90% chance that this patient will die,” without mentioning the 10% chance that the patient will survive will also influence decisions ♦ Lack of cultural awareness

• Patients in NCCUs may come from cultures different from that of the physician; e.g., in some non-Western cultures, paternalism dominates over autonomy and patients may not be given information about a poor prognosis. Yet, Western culture dictates that the patient would require this information to make an informed decision about treatment and end-of-life care • When possible, it is better to try to practice in a culturally sensitive manner; e.g., in the above conflict, one may wish to proceed by “offering truth,” which would be to ask the patient how much they would like to know about their prognosis and how much they would like their family to make decisions for them ♦ Denial on the part of the family

• Can be very a very powerful defense mechanism as family members must face the inevitable death of a loved one, and they can perceive the healthcare team as coercing them toward particular end points ■

Role for ethics consultation ♦ Ethics consultants can help to resolve conflicts over medical decisions that

often arise due to differences in values ♦ The benefits of ethics consultations often arise from promoting regular com-

munication between the patient’s family and healthcare team ♦ The consultation process can also give the family more time to accept the

information provided because families often need more time to make decisions than do healthcare providers ♦ Ethics consultants can incorporate cultural sensitivity into the discussion, help to address uncertainty regarding value-laden issues, and offer a range of morally acceptable options ♦ When conflicts exist among the healthcare team about whether or not to withdraw care, it is often the case that some of the care providers wish to continue care and some wish to withdraw. Almost always, the family of the patient will wish to continue care

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Withdrawal of Life-Sustaining Therapies ■

Ethical principles ♦ Withdrawing versus withholding care

• The general consensus among medical ethicists is that withdrawing and withholding life-sustaining treatments are morally and ethically equivalent ♦ Difference between “killing” and “letting die”

• Patients die from their disease states or complications thereof • They are not being killed when they are taken off of a ventilator and succumb to a stroke or brain tumor • Administering a lethal dose of medication that has no therapeutic benefit would be killing a patient, even at the patient’s request or in the patient’s “best interest”; this would be considered euthanasia, or an active process of causing death (i.e., killing), which is very different from allowing the natural dying process to occur in a dignified and unimpeded manner, while providing symptom relief for a patient ♦ Principle of double effect

• Pain medication can be provided for the relief of symptoms, recognizing that they may hasten death • Allows for foreseen but not intended consequences • The intended consequences are the relief of pain and suffering; even though the consequences of hastening death are foreseen, these are not the intended consequences ♦ Common reasons that care is withdrawn or withheld

• Patient or surrogate refusing further treatment • Goals of care as expressed by patient or surrogate cannot be achieved • In a shared decision-making model, it is determined that the quality of life is not consistent with what would be acceptable for the patient • Medical futility is established by the treatment team ♦ Improvement in end-of-life care is necessary, as demonstrated and summa-

rized by the SUPPORT Trial: • • • •

Many patients died with moderate or severe pain Most physicians were unaware of patients’ preferences regarding CPR Physicians were reluctant to discuss end-of-life-issues with patients Physicians often misunderstood their patients’ goals for end-of-life care

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Palliative Care ■

■

Palliative care is a branch of medicine that focuses on the relief of physical, emotional, social, and spiritual suffering Palliative care and critical care are not mutually exclusive. Rather, they should coexist because: ♦ All critically ill patients are at risk of dying ♦ In most cases, it is possible for the patient to have a dignified and pain-free

death ■

■

Most critically ill patients can benefit from inclusion of palliative measures into their management Principles of palliative care ♦ ♦ ♦ ♦

■

Symptom relief Treatment of the patient’s pain often becomes the highest priority Improved functional status Amelioration of emotional, psychological, or spiritual concerns

Role for palliative care consultation ♦ Early involvement in communicating poor prognosis to the family ♦ Identifying advance directives or patient preferences regarding end-of-life

care or if a significant change for the worse in functional status occurs ♦ Implementation of palliative care strategies when goals of care are changed

to “comfort measures only” ♦ Acting as a bridge in communication between family and primary team, espe-

cially when medical jargon is part of the communication barrier ♦ Education of the primary team regarding palliative care strategies

Goals of “Comfort Measures” ■

■

■

Changing the goals of care from curative to comfort measures does not mean that care is no longer provided; it only means a change in focus The absence of pain, dyspnea or other symptoms is a primary indicator of highquality end-of-life care Some common goals ♦ Provide adequate pain and symptom management ♦ Avoid prolongation of the dying process ♦ Respect cultural beliefs and meet cultural expectations when possible

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Any intervention that does not advance the patients’ goals should be eliminated ♦ Assure the patients and/or their families that the patients will not be aban-

doned, but the goals of care will be changed to providing comfort and that the patient will continue to be treated with respect and dignity ■

Moving from curative measures to comfort measures will often be accompanied by an abrupt decline in physician presence, and the families may feel that the patient has been abandoned by the care team

How to Withdraw Life-Sustaining Treatment ■

■

■

Standardized order forms for withdrawal of life-sustaining treatments can help to improve the quality of care provided to patients Communicate with the family or decision makers (In the NCCU, communications are less commonly held with the patient, but be certain to include the patient if he/she is conscious.) Topics of discussion ♦ ♦ ♦ ♦

■

■

How interventions will be withdrawn How comfort will be ensured That length of survival can be unpredictable Continuation of care by clinical team

Ensure that patient is in an appropriate setting with unnecessary monitoring removed Document the entire process, including the reasons for increasing sedation or analgesia

Pitfalls in Withdrawal of Life-Sustaining Therapies ■

Goals of the physician should not supersede those of the patient. Yet, studies show that physician biases are influential in withdrawal-of-care practices; some are listed below. ♦ Preferences are to withdraw support for organs that have failed naturally

rather than from iatrogenic causes ♦ Withdraw recently instituted interventions as opposed to long-standing ones ♦ Withdraw or withhold therapies that immediately lead to death, rather than

lead to death in a delayed fashion ♦ Unless there is diagnostic uncertainty, therapies that lead to death in a delayed

fashion tend to be withdrawn first ♦ Withdraw therapies that are thought to be expensive, in short supply, or

artificial

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♦ Specialists tend to prefer to withdraw therapies with which they are most

familiar; e.g., nephrologists withdraw dialysis, pulmonologists withdraw mechanical ventilation, etc. ♦ A fairly predictable pattern is followed in withdrawing therapies: dialysis, further diagnostic evaluations, vasopressors, IV fluids, hemodynamic and electrocardiographic monitoring, blood tests, antibiotics, and finally, artificial tube feeds and mechanical ventilation ♦ Physicians should make all attempts to resist these biases as they do not reflect patient values ■

Goals of the family should not supersede the goals of the patient ♦ However the goals of the family are an important consideration ♦ For the most part, the family should have the opportunity to spend time with

the dying person • Whenever possible, care should be withdrawn after arrival of family members who had to travel in from a distance ♦ Physical barriers such as restraints, bedrails, and supporting lines should be

removed as needed for patient comfort, or if they prevent family members from being physically close to the patient • Even if a chance exists that the case will be referred to the medical examiner for autopsy, it is permissible to remove invasive lines before death if it is done for the benefit of the patient or family, but it is discouraged and sometimes prohibited after death ♦ Not all family members may want to be at the bedside; if this is the case,

they should be reassured that this is an acceptable choice ♦ A private room is preferable to meet the needs of the family ♦ Families should receive clear and consistent communication regarding any

clinically relevant information (Fig. 14.2)

Fig. 14.2  Needs of families of dying patients   1.  To be with the patient   2.  To be helpful to the patient   3.  To be informed of the patient’s changing condition   4.  To understand what is being done to the patient and why   5.  To be assured of the patient’s comfort   6.  To be comforted   7.  To ventilate emotions   8.  To be assured that their decisions were right   9.  To find meaning in the dying of their loved one 10.  To be fed, hydrated and rested Adapted from Truog et al. (2001)

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• Inform them of changes in condition and impending death • Avoid making any firm predictions about the patient’s clinical course, as such predictions are notoriously inaccurate, and when wrong, this may result in a loss of credibility and may also set unrealistic expectations for the family • Warning family members about anticipated symptoms can be helpful as well; e.g., noisy respirations, for example, are likely more upsetting to the family than to the patient

Managing Symptoms (Table 14.1) ■

Pain ♦ Minimize or eliminate iatrogenic sources of pain

• Opioids ▲ Morphine; often given IV in the NCCU, but many oral formulations are

available, including extended release forms, for patients with oral access ▲ Fentanyl N Causes less hypotension than morphine N Much shorter acting than morphine and less likely to cause euphoria

and sedation ▲ Hydromorphone N Less likely to cause sedation and euphoria than is morphine ▲ Meperidine is not commonly used in end-of-life care because it can

cause excitation of the central nervous system N Can potentially lead to anxiety, tremors, and seizures ■

Dyspnea and respiratory distress ♦ Direct treatment

• Supplemental oxygen ▲ May enhance patient comfort by relieving symptoms but may worsen

anxiety or claustrophobia due to face mask or nasal cannula • • • •

Corticosteroids Diuretics Bronchodilators Opioids ▲ Depress respiratory drive and cause pulmonary vascular vasodilation

14  Ethical Issues and Withdrawal of Life-Sustaining Therapies Table 14.1  Common medications used during end-of-life care Symptom Medication Typical starting dose Pain Morphine 2–10 mg IV q 2–4 h or 0.05–0.1 mg/kg/h infusion

Fentanyl

Hydromorphone Dyspnea

Morphine Propofol

Delirium

Albuterol/Ipratropium Haloperidol

Anxiety

Lorazepam Diazepam

Midazolam

Propofol

Fever Nausea

Acetaminophen Ondansetron Phenergan

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Comments • If no IV access, consider oral, rectal, subcutaneous or transdermal dosing • IM dosing is less preferred due to pain at the injection site 25–100 mcg/h IV infusion • Very short-acting, so infusion must be or 50–100 mcg/h maintained judiciously transdermal patch • Patch can not be titrated quickly and has slow onset of action, but can be used as an adjuvant, especially if patient is already wearing a patch when life-sustaining therapy is withdrawn 0.5–1 mg IV q 2–4 h • Less nausea and sedation than morphine As above 0.5–2 mg/kg/h IV • As an anesthetic agent, many infusion hospitals will only allow infusion in a mechanically ventilated patient • Can be painfully when administered via peripheral IV 2–4 puffs q4 h and prn • Titrate up at 30 min 0.5–10 mg IV q 4–6 h intervals as needed to or 3 mg/h IV control patient’s delirium infusion 0.5–2 mg IV or • Used most commonly po q 2–4 h 2.5–5 mg IV or • Can be painful when po q 2–4 h administered via peripheral IV 2–4 mg IV q1–2 h or 2–4 mg/h via continuous IV infusion 0.5–2 mg/kg/h IV infusion • Many hospitals will only allow infusion in a mechanically ventilated patient • Can be painful when administered via peripheral IV 650 mg po/pr q4 h 4 mg IV q 8 h 25–50 mg po/pr q6 h prn or 12.5–25 mg IV q 4–6 h prn

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W.L. Wright N This effect is more pronounced with morphine compared to other

opioids ■

Delirium ♦ The use of physical restraints should be avoided whenever possible ♦ Haloperidol

■

Anxiety ♦ Benzodiazepines reduce anxiety and cause amnesia

• Lorazepam, diazepam, and midazolam are all commonly used ♦ Propofol

• A sedative and anesthetic drug • Many hospitals have a policy against using it in patients who are not mechanically ventilated • As it has no any analgesic properties, pain management must be addressed separately ■

Fever ♦ Antipyretics ♦ External cooling with ice packs or cooling blankets is often more distressing

than the fever itself and should generally be avoided ■

Nausea and vomiting ♦ Antiemetic agents such as ondansetron and promethazine generally provide

symptom relief ■

Hunger and thirst ♦ Most dying patients are neither hungry nor thirsty, and giving them forced

nutrition and hydration can contribute to discomfort ♦ Food and fluid should be provided only if the patient is hungry or thirsty ■

Neuromuscular blocking agents (NMBAs) ♦ Have no analgesic or anxiolytic effect and should not be given as part or end-

of-life care ♦ However, some patients who are having life-sustaining treatment withdrawn

will have been on NMBAs ♦ A strong argument can be made for allowing these medications to wear off

before mechanical ventilation is withdrawn • It will be difficult to assess the patient’s comfort • It is unclear how long the patients will survive off of the ventilator if they are not paralyzed, but when paralyzed, they will not be able to breathe and will certainly die within minutes

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• However, a clinician must weigh the burdens of reversing the paralytics or waiting for them to wear off with the risks of continuing ventilatory support in a situation in which the goals change to comfort measures only

Dosing and Titration of Medications ■

Most patients will have received some opioids and benzodiazipines during their ICU stay ♦ Therefore, they may have developed tolerance to these medications and will

require higher dosages ♦ Dosages should not be based on theoretical maximal dosages but should be

titrated to the desired effects of symptom relief ■

Anticipatory dosing ♦ As opposed to reactive dosing, anticipatory dosing is the use of sedatives and

analgesia during end-of-life care when the clinician can anticipate a sudden increase in pain, anxiety, or dyspnea. For example, one would anticipate a sudden increase in dyspnea with removal of an endotracheal tube; therefore, an anticipatory dose of morphine may be given ♦ The doses of medication that a patient has been receiving hourly will usually have to be doubled or tripled when given as an anticipatory dose before withdrawing mechanical ventilation

Withdrawing Ventilatory Support ■

Terminal wean versus terminal extubation ♦ The debate is ongoing concerning the optimal way to withdraw ventilatory

support with the goal of comfort care ♦ During terminal wean, ventilatory support is gradually reduced, with the

endotracheal tube left in place over several hours or several days and the goal of extubation if it can be tolerated • Invasive respiratory monitoring is not performed, and even noninvasive monitoring is not consistent with the goals of promoting comfort • The main advantage is that patients do not develop signs of upper air obstruction or air hunger; thereby promoting the comfort of the patient and reducing the anxiety of the family and caregivers that results from labored breathing patterns • However, the risks are that this will prolong the dying process and that the weaning process will be perceived by the families as an attempt to have

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the patient survive once separated from the ventilator, even if this is not the expectation or intent of the clinician ♦ During terminal extubation, patient is separated from the ventilator, usually

to room air • Advantages are that this does not prolong the dying process and that the patient is no longer connected to the ventilator, which many people see as an “unnatural” piece of machinery • Disadvantages are that the patient may have stridor or secretions that are uncomfortable and must be adequately managed from a symptomatic standpoint • Even when managed for the patient, certain breathing patterns and noises can be distressing for the family

Specific Situations ■

Brain death ♦ Brain death is not medically, legally, or ethically controversial ♦ The Uniform Determination of Death Act specifies that brain-dead patients

are dead ♦ Families of brain-dead individuals should not be given the impression that they

have a decision to make about withdrawing or withholding life-sustaining therapies, as the person has already died; i.e., they should not be engaged in discussions about whether or not to remove ventilatory support as if they are in a position to make a choice ■

Persistent vegetative state ♦ The American Academy of Neurology maintains a position statement that

artificial nutrition and hydration may be withdrawn if (a) a patient is in a persistent vegetative state and (b) it is clear that the patient would not have wanted further medical treatment ■

Neurologically devastated patient who retains decision-making capacity ♦ Patients with “locked-in” syndrome, amyotrophic lateral sclerosis, or high

cervical spinal cord processes are just three examples of patients who might make the determination to limit or withdraw life-sustaining treatments for themselves while in the NCCU ♦ As tempting as it is to spare them the pain and suffering of being involved in such conversations, it would be ethically reprehensible if they are capable of making such decisions

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♦ When ventilated, it can be difficult to have conversations that convey that

patients understand the repercussions of such decisions; therefore, careful consideration must be given to the details of decision-making capacity ♦ When in doubt, ethics consultation can be useful ♦ Adequate sedation should be provided, with special attention to anticipatory dosing, around the time of ventilator withdrawal ■

Organ donation ♦ Organ donation is addressed in Chap. 34, but donation after cardiac death

deserves special mention • Donation after cardiac death requires strict adherence to many ethical principles • Most notably, to ensure that death is not hastened in the donor in order to retrieve organs • Customary end-of-life practices should be provided with the goal of relieving pain and suffering • Donation after cardiac death should not be done without a prospectively developed institutional protocol • Most hospitals mandate the involvement of the hospital’s ethics committee

Key Points ■

■

■

■ ■

■ ■

■

■

First do no harm! The desire to do good for a patient should be carefully considered against the potential for harm A patients’ right to self-determination dictates that they (or their surrogate decision maker) have access to as much prognostic information as they physician has There is no ethical distinction between withholding and withdrawing care, but there is a distinction between killing and letting die Be certain to ask patients if they have advanced directives…and follow them! Although futility can be difficult to establish, clinicians are not obligated to provide care that is not expected to provide meaningful benefit to a patient Ethics consultation can help to resolve conflicts surrounding end-of-life care Palliative care and critical care are not mutually exclusive: the goals of pain relief, symptom improvement, and relief of psychosocial stress can be applied to most critically ill patients When relieving pain and dyspnea during end-of-life care, it is acceptable to dose to effect with medications, even if the doses are larger than usual, as long as the primary effect is not to bring about the death of the patient Standardized order forms improved end-of-life care

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Suggested Reading Aulisio MP, Chaitin E, Arnold RM (2004) Ethics and palliative care consultation in the intensive care unit. Crit Care Clin 20:505–523 Bernat J (2004) Ethical aspects of determining and communicating prognosis in critical care. Neurocrit Care 1:107–118 Curtis JR (2005) Interventions to improve care during withdrawal of life-sustaining treatments. Palliative Care Med 8S1:S116–S131 Garvin JR (2007) Ethical considerations at the end of life in the intensive care unit. Crit Care Med 35:S85–S94 Schneiderman LJ (2005) Ethics consultation in the intensive care unit. Curr Opin Crit Care 11:600–604 Truog RD, Cist AFM, Brackett SE et  al (2001) Recommendations for end-of-life care in the intensive care unit: the ethics committee of the society of critical care medicine. Crit Care Med 29:2332–2348 Truog RD, Campbell ML, Curtis JR et al (2008) Recommendations for end-of-life in the intensive care unit: a consensus statement by the American academy of critical care medicine. Crit Care Med 36:953–963 Williams MA (2002) The role of neurologists in end-of-life decision making and care. In: Johnson RT, Griffin JW, McArthur JC (eds) Current therapy of neurologic disease, 6th edn. Mosby, St. Louis, pp 9–12 www.lastacts.org Accessed 11/01/08.

Chapter 15

Collaborative Nursing Practice in the Neurosciences Critical Care Unit Filissa M. Caserta

Introduction ■

■

Neurocritcial care is best delivered with a collaborative, organized, and efficient model of care Utilizing a combination of nursing roles offers a unique opportunity to provide the most comprehensive care to this specialized population. These roles include: ♦ ♦ ♦ ♦ ♦

Registered nurse (RN) Clinical nurse mentor (CNM) Nurse manager (NM) Clinical nurse specialist (CNS) Certified registered nurse practitioner (CRNP)

Registered Nurse ■ ■

■

Any dedicated NCCU relies heavily on the expertise of the RN at the bedside RNs new to the NCCU arena require education and training in both critical care and neuroscience Neurospecific training occurs in the NCCU, and administrators must ensure that training includes a good foundation in the following areas: ♦ A basic yet detailed knowledge of neuroanatomy with correlative assessment ♦ Pathophysiology and management of:

F.M. Caserta, MSN, CRNP, CNRN (*) Neurosciences Critical Care Unit, Johns Hopkins University School of Medicine, 600 N. Wolfe Street - Meyer 8-140, Baltimore, MD 21287-7840, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_15, © Springer Science+Business Media, LLC 2011

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• Cerebrovascular insults (ischemic and hemorrhagic stroke, including aneurysmal subarachnoid hemorrhage) • Neuroinfectious diseases • Traumatic brain injury • Acute spinal cord injury • Tumors of the brain and spine • Seizures • Myasthenia gravis • Guillián-Barré syndrome ♦ Skills review of intracranial monitoring devices

• • • • ■

Intraventricular catheter Lycox Jugular venous saturation catheters Microdialysis catheters

Education can also be obtained via neuroscience nursing internship programs ♦ Goal

• To provide registered nurses with in-depth understanding of the theory and practice of neuroscience nursing and to provide a detailed curriculum that covers a variety of neurologic disorders ♦ 6-month course ♦ Includes education in a variety of neuroscience topics via lecture and clinical

experiences ■

■

Maintaining clinical competence can be achieved via annual neuroscience education, which should include a more in-depth review of the topics discussed in the initial orientation, as well as a review of the most current evidence-based practices in neurocritical care Credentialing as a certified neuroscience registered nurse (CNRN) is obtained by successful completion of the CNRN exam ♦ Criterion for testing: 2 years of experience in the field of neuroscience

nursing ♦ Importance: signifies expert knowledge and experience in the care of patients

with neurologic illness and trauma. ♦ Credential maintenance

• Renewed every 5 years • Continued active involvement in the care of the neuroscience patients • Completion of a defined number of continuing education credits in neurosciences or retest

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Clinical Nurse Mentor ■

■

■

■

Retention of the clinical bedside practitioner is an ongoing struggle in all areas of nursing, including neurocritical care; when bedside nurses feel supported in the clinical setting, their stress is decreased, satisfaction is increased, and ultimately, recruitment and retention are improved Implementing the role of CNM can provide a constant, visible clinical presence to the nurses in the NCCU The CNM position should either be a dedicated position or rotated among the experienced staff on the unit The CNM ♦ Facilitates learning experiences via:

• Hands-on education • Ongoing support at the bedside ♦ Should be an expert neurocritical care registered nurse who possesses the

ability to quickly integrate all components of the clinical picture via experience and intuition ♦ Should possess patience, openness, trustworthiness, positive attitude, good communication, and listening skills ♦ Should not have a patient assignment, as that would render the CNM inaccessible to the unit nursing staff ♦ Should not be given administrative responsibilities, as doing so removes the mentor from the clinical setting and makes it difficult to achieve the primary goal of being hands-on bedside mentor

Nurse Manager ■

The NM of the NCCU has many responsibilities ♦ ♦ ♦ ♦ ♦

■

Management of the unit budget Recruitment and retention of staff Management of human resources of all levels Improvement of staff performance Ensuring provision of the highest-quality patient care

Key attributes for an effective NCCU NM ♦ Knowledge of and previous clinical experience with the neurocritical care

population ♦ Personal experience with the intricacies of the assessment and management

of the neurocritical care patient

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F.M. Caserta

Familiarity with the end-of-life issues that arise in this patient Creative thinking Flexibility Resourcefulness

Advanced Practial Registered Nurse (APRN) ■

■

APRNs are RNs who have obtained advanced education and clinical practice training beyond the basic nursing education required for an RN The following are included within the category of APRN ♦ ♦ ♦ ♦

■

Certified registered nurse anesthetist (CRNA) Certified nurse midwife Clinical nurse specialist (CNS) Certified registered nurse practitioners (CRNP)

Education ♦ APRNs possess either masters degrees or doctorates

■

Scope of practice ♦ Varies from state to state and is delineated in each state’s Nurse Practice Act

■

CNS and CRNP roles are the most strongly represented APRNs in the NCCU environment ♦ CNS

• Comprise 24% of all advanced-practice nurses • Role developed in the 1950s to assist nurse managers in preparing staff for clinical performance • Role has expanded beyond clinical practice to include education and consultation; in some states, the CNS has prescriptive authority • Goal of CNS is to improve outcomes of patients via the three “spheres of influence” ▲ The patient/family ▲ Nursing staff ▲ Organizational systems

• The NCCU CNS is an integral part of the neurocritical care team ▲ Provides guidance in developing a holistic plan of care that incorporates

the physical, spiritual, and cultural needs of the patient and family ▲ Offers education both in and out of the classroom ▲ Ensures that nurses in the NCCU are aware of the current, evidence-

based practice for care of neurologically impaired patients ▲ Creates protocols for practice based on the most current guidelines

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▲ Offers “hands-on” education of various neurospecific devices such as

▲ ▲ ▲ ▲ ▲

those indicated for monitoring of intracranial pressure and brain tissue oxygenation, extraventricular drainage, and microdialysis Utilizes the research process to improve outcomes Collaborates with senior investigators and the NCCU interdisciplinary team to conduct research Evaluates the quality of nursing on the team Participates in obtaining initial primary stroke center certification and maintaining ongoing certification Participates in obtaining initial trauma certification and maintaining ongoing certification

♦ CRNP

• A CRNP is an APRN who provides a wide range healthcare services, including prescribing medications, diagnosing and treating illnesses/injuries, and performing procedures • Comprise 51% of all advanced-practice nurses • Developed in the 1960s in response to the growing need for the delivery of primary care to underserved children in rural areas • Currently, CRNPs can be certified in the following specilaties: ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲

Family Pediatrics Geriatrics Women’s health Neonatal Occupational health Adult primary care Acute care

• The certified acute care nurse practitioner (ACNP) is the most appropriate CRNP for the NCCU, as the scope of practice is limited to the specialty area of certification • Family and adult nurse practitioners with prior acute care experience at the RN level can also work in NCCU ♦ ACNP

• Incorporated into the critical care arena in the late 1990s as a direct result of: ▲ Decrease in the number of medical residents ▲ Regulatory restrictions on resident work hours ▲ The requirement of resident training in the ambulatory care setting

• Functions ▲ Direct patient care N Obtains a detailed history and physical, diagnoses patient, creates a

plan of care, writes orders to carry out the plan, and evaluates the plan

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F.M. Caserta N N N N

Interprets lab and radiographic studies Provides ventilator management Interprets hemodynamic measurements Performs procedures; the type and degree of invasive procedural work varies from practice site to practice site, depending on the patient populations and the institutional policies; however, they can include. ° Insertion of central venous, pulmonary artery, arterial and jugular ° ° ° ° ° °

bulb catheters Intubation Bronchoscopy Thoracentesis Lumbar punctures Placement of lumbar drains Placement of intracranial pressure monitoring devices

▲ Nursing support N Assists bedside nurse in understanding many of the complexities of

managing the neurocritical care patient by: ° Utilizing the rounding process to review pathophysiology and

explain rationales for interventions ° Performing the initial neurologic assessment and the daily

assessment with the novice neuroscience nurse to reinforce the intricacies of the neuro exam N Participates in formal educational offerings, that enable the neuro-

science nursing staff to maintain clinical expertise ▲ Research N Identifies potential patients for clinical trials N Educates nurses, patients, and families about such trials and assists

with data collection. N Measures outcomes of the impact of a nurse practitioner service to

help increase ACNP role recognition and acceptance and ensure longevity. ▲ Billing N Passage of the Balanced Budget Act of 1997 allowed CRNPs and

CNS to be directly reimbursed by Medicare for services provided N ACNPs capture possible lost charges due to: ° The chaotic pace often encountered on the unit ° The nonclinical responsibilities of the neurointensivist ° Decreased availability of neurointensivists during “off” hours

• Direct compensation for ACNPs provides: ▲ Justification for their salaries

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Table 15.1  Summary of national patient safety goals for hospitals published by The Joint Commission 2008 Goal numbera Summary  1 Improve accuracy of patient identification  2 Improve the effectiveness of communication among caregivers  3 Improve the safety of using medications  7 Reduce the risk of healthcare-associated infections  8 Accurately and completely reconcile medications across the continuum of care  9 Reduce the risk of patient harm resulting from falls 13 Encourage patients’ active involvement in their own care as a patient safety strategy 15 Identifies safety risks inherent in its patient population 16 Improve recognition and response to changes in a patient’s condition a Noncontiguous numbering indicates that the missing goal is no longer applicable to the program or has been “retired,” typically because the requirements were incorporated into The Joint Commission standards ▲ Increased professional satisfaction ▲ Peer recognition among the nurse practitioner group ■

Outcomes ♦ APRNs impact the management of critically ill patients by providing patient-

centered, health-focused, and holistic care ♦ Benefits of having APRNs in critical care setting include:

• • • • ■

Decreases in costs, lengths of stay, and patient complaints Improvement in clinical outcomes Enhanced communication among team members Increased patient satisfaction

Safety ♦ Ensure adherence to the National Patient Safety Goals for Hospitals of The

Joint Commission (see Table 15.1) by: • Following the standards • Educating others regarding the standards • Offering support to achieve the goals set forth

Key Points ■ ■

Collaboration among all team members is vital to a successful NCCU practice Avoidance of confusion among various nursing roles (Table 15.2) by: ♦ Formally educating the members of the NCCU team about the different roles

and their functions at divisional staff meeting or grand rounds forum

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Table 15.2  Summary of the neurocritical care nursing roles Role Functions Registered nurse • Neuroscience-specialty-trained registered nurse • “First line” clinician • Plans, implements, and evaluates the plan of care • Participates in performance improvement and research Clinical nurse mentor • Registered nurse clinical expert • Provides “hands-on” clinical support to the RN at the bedside • Participates in performance improvement and research Nurse manager • Baccalaureate, masters, or doctoratl preparation • Manages unit budget • Manages personnel • Ensures performance improvement • Recruits staff and ensures retention Clinical nurse specialist • Advanced practice registered nurse with masters or doctoral preparation • Provides clinical and classroom instruction for RNs • Supervises performance improvement • Develops protocols • Conducts and facilitates research • Advanced practice registered nurse with master’s or doctoral Certified registered nurse preparation practitioner • PRIMARY ○ Diagnoses patient, creates plans of care, prescribes medications, and interprets laboratory and radiographic studies ○ Performs procedures • SECONDARY ○ Supervises performance improvement ○ Develops protocols ○ Conducts and facilitates research ○ Provides RN education

♦ Holding regularly scheduled meetings with the CNM, NM, CNS, ACNP, and

senior nursing staff ♦ Ensuring open and continual communication among all team members

References American Association of Neuroscience Nurses. The CNRN Edge, 2008. (Accessed June 24, 2008, at http://www.aann.org/credential/pdf/CNRNBrochure07.pdf). Bell L (2002) Scope of practice and standards of professional performance for the acute and critical care clinical nurse specialist. American Association of Critical Care Nurses, Aliso Viejo, CA Benner P (2001) From novice to expert: excellence and power in clinical nursing practice. Commemorative Ed. Prentice Hall, Upper Saddle River NJ

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Kleinpell RM (2005) Acute care nurse practitioner practice: results of a 5-year longitudinal study. Am J Crit Care 14:211–221 Latham CL, Hogan M, Ringl K (2008) Nurses supporting nurses: creating a mentorship program for staff nurses to improve the workforce environment. Nurs Adm Q 32:27–39 Phillips J (2005) Neurosciences Critical Care: the role of the advanced practice nurse in patient safety. AACN Clin Issues 16:581–592. Price ME, Dilorio C, Becker JK (2000) The neuroscience nurse internship program: the description. J Neurosci Nurs 32:318–323 Russel D, VorderBruegge M, Burns SM (2002) Effect of an outcome-managed approach to the care of neuroscience patients by acute care nurse practitioners. Am J Crit Care 11:353–362 The Joint Commission National Patient Safety Goals for Hospitals (2008) (Accessed May 14, 2008 at http://www.jointcommission.org/PatientSafety/NationalPatientSafetyGoals/08_hap_ npsgs.htm) Villanueva N, Blank-Reid C, Stewart-Amidei C, Cartwright CC, Haymore J, Jones RW (2008) The role of the advanced practice nurse in neuroscience nursing: results of the 2006 AANN membership survey. J Neurosci Nurs 40:119–124

Part II

Specific Problems in Neurocritical Care

Chapter 16

Coma and Disorders of Consciousness Edward M. Manno

Definitions ■

Consciousness can be defined as the state of awareness of self and one’s relationship with the environment ♦ Consciousness consists of two components: wakefulness or arousal and

awareness ♦ Both components have anatomic substrates that, when affected, can lead to

disturbances in consciousness ■

Wakefulness and varying levels of arousal are processed through the reticular activating system (RAS) ♦ The RAS represents a population of defined neuronal groups (that do not

meet biologic criteria for being nuclei) that project from the brainstem through the diencephalon and thalamus to the forebrain ♦ The cholinergic system, originating in the rostral pons and caudal midbrain, provides the main input to the reticular nuclei of the thalamus, which controls sensory input to the cortex ♦ Cortical activity is simultaneously modulated through a series of direct inputs from monoaminergic neurons that originate in the upper brainstem and posterior hypothalamus ♦ Interaction between these complex groups of neurons is believed responsible for the development and maintenance of the sleep-wake cycle ■

Awareness is the sum of our cognitive and affective abilities ♦ This definition implies that awareness is housed diffusely through the

cerebral hemispheres and is modulated through interaction with one’s subcortical structures; i.e., thalamus, diencephalon, limbic system

E.M. Manno, MD (*) Mayo Clinic School of Medicine, 200 First St. SW, Rochester, MN 55905, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_16, © Springer Science+Business Media, LLC 2011

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Disturbance in consciousness, therefore, must involve a process that affects the RAS, the cerebral hemispheres, or both simultaneously A unilateral hemispheric lesion, even when large, rarely causes a disturbance in consciousness ♦ There are few exceptions; e.g., a massive dominant hemisphere stroke can

transiently depress a patient’s level of consciousness through a decrease in sympathetic input to the cortex ♦ However, in general, a change in consciousness mediated through the cerebral cortex must involve a process that affects the cortex diffusely; e.g., a metabolic encephalopathy, head trauma, anesthesia, etc. ♦ Conversely, a small lesion strategically placed in the brainstem or in the thalamus can lead to profound disturbance in consciousness ♦ Disturbances in consciousness must be differentiated from a fluent aphasia caused by a focal lesion; such patients may initially appear confused but are awake and alert

Terminology used to Describe Disturbances in Consciousness ■

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Drowsy refers to a mild depression in consciousness that can be aroused to full wakefulness through voice Stupor refers to a condition of unresponsiveness that requires a greater and repetitive physical stimulus for the patient to become aroused Coma implies a profound disturbance in consciousness that affects both the RAS and the cerebral hemispheres ♦ Patients in coma subsequently have a disturbance in both arousal and aware-

ness; it is manifested by a patient who lies with his/her eyes closed (representing a disturbance in the sleep-wake cycle) and exhibits no meaningful interaction with the environment ■

Vegetative state refers to a previously comatose patient who has regained sleep– wake cycles mediated through the RAS ♦ Patients who are vegetative can develop brainstem-mediated automatisms that

can be misinterpreted as conscious activity (i.e., grimacing, yawning, alerting responses, etc.) ♦ Persistent vegetative state is a legal term that mandates that the above condition must be present for 1 month ♦ Permanent vegetative state similarly mandates that the above condition must exist for a period of 3 months to 1 year, depending upon the etiology of the state and the age of the patient

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Minimally conscious state is a recently defined condition ♦ Refers to a state of severe impairment of consciousness, but with some

discernible evidence that the patient has some level of awareness to self or the environment ♦ Both vegetative and minimally conscious states may be permanent or transitional states ■

Locked-in syndrome is not a disturbance in consciousness but may occur as a permanent condition in transition from coma ♦ Describes a state of complete or near-complete paralysis of the extremities,

usually caused by structural damage to midbrain pontine structures ♦ Communication may only be possible through eye movements or eye blinking ■ ■

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Brain death refers to the irreversible loss of all functions of the entire brain Other terminology, such as apallic state and akinetic mutism, are historical terms that refer to specific conditions that were previously described but less well characterized Terms such as clouding of consciousness, obtundation, and lethargy are more nebulous in their definitions and should be avoided if more discrete terminology can be applied

Etiology ■

Any process that affects the cerebral hemispheres or the subcortical structures can produce a disturbance in consciousness ♦ Causes are multifactorial ♦ Processes that affect the RAS are usually ischemic, hemorrhagic, or degenerative ♦ Potential causes of alterations in consciousness or coma ●

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Degenerative, including the various forms of dementia: late-stage Alzheimer disease, Parkinson disease, multisystem atrophy, frontotemporal dementia, etc. Psychogenic causes may be secondary to catatonia, severe depression, dissociative states, and possibly, malingering Head trauma is a leading cause of an alteration of consciousness ▲ Trauma may mediate a disturbance of consciousness through several

different mechanisms ▲ Diffuse axonal injury can occur due to shearing of the cortical and

subcortical grey matter structures ▲ Secondary hemorrhages (i.e., subdural and epidural hematomas) may

lead to distortion of the brainstem ▲ Ischemic changes can result from large increases in intracranial pres-

sure or abrupt decreases in cerebral perfusion

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Electrolyte disturbances ▲ Most commonly hypo- or hypernatremia can lead to alterations of

consciousness ▲ Hyper- or hypocalcemia in malignancies is often encountered ▲ Less commonly, disturbances in magnesium and phosphate levels can

depress the sensorium ▲ Refeeding hypophosphatemia is a concern in the surgical patient who

has been without nutrition for a period of time ▲ Hypercapnia secondary to neuromuscular diaphragmatic failure or

chronic obstructive pulmonary disease can lead to a progressive or rapid deterioration in consciousness ●

Metabolic and/or infectious encephalopathy is a broad category that includes disturbances in consciousness due to hepatic failure, porphyria, uremia, sepsis, pneumonia, or urinary tract infections ▲ Endocrine abnormalities can also be included in this category, which

would encompass hypo- and hyperthyroidism, diabetic ketoacidosis, hyperosmolar hyperglycemic state, pituitary apoplexy, etc. ●

Nutritional deficiencies can lead to alterations in consciousness ▲ Wernicke encephalopathy, caused by thiamine deficiency, is probably

the most common ▲ Other deficiencies include B12 deficiency and pellagra due to niacin

deficiency

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Drug intoxication and poisoning can lead to an encephalopathy, either through a direct intoxication (arsenic, ethylene glycol) or due to secondary organ failure Neoplasms may depress consciousness, either through direct mechanisms such as brainstem distortion due to brain tumors or through secondary mechanisms such as a paraneoplastic processes that can affect the limbic system (limbic encephalitis) or infiltration of the brain and meninges Ischemia, either global or focal, can lead to alterations in consciousness ▲ Global anoxia after cardiac arrest is a common form of an

encephalopathy ▲ Ischemic stroke that involves the brainstem or diencephalic structures

will depress consciousness ▲ An acute focal hemispheric ischemic stroke can depress consciousness

●

if a lesion previously existed that involved the opposite cerebral hemisphere thus leading to bi-hemispheric damage Intracerebral hemorrhage involving the brainstem or diencephalon will diminish consciousness ▲ Intraventricular hemorrhage similarly depresses consciousness

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Demyelination syndromes, if extensive enough or involving the brainstem, can depress consciousness and include multiple sclerosis, the childhood and adult leukoencephalopathies, central pontine myelinolysis, and MarchiafavaBignami disease Infections of the meninges can directly depress consciousness or lead to a secondary hydrocephalus ▲ Direct encephalitic infections, bacterial, viral, or prion disease, are

causes of deterioration in consciousness ●

Hyperthermia secondary to neuroleptics or anesthesia can depress consciousness ▲ Neuronal transmission is depressed with fever ▲ Higher temperatures can lead to direct neural damage

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Seizures and status epilepticus is a common cause of neurologic deterioration Sleep disturbances, including the parasomnias, somnambulism, and narcolepsy, may lead to chronic fatigue and sleepiness Disturbances in cerebral autoregulation, commonly encountered in eclampsia, malignant hypertension, and the recently described posterior reversible encephalopathy (PRES), can depress consciousness

Assessment of Coma and Stupor ■

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Assessment of the patient with a depressed level of consciousness involves several steps As most patients will not be able to provide a history, interviewing witnesses, emergency personnel, friends, or relatives will be crucial to obtaining details of the history and providing clues of the possible underlying etiology of the deterioration of consciousness Important details to elicit would include any preexisting conditions, the circumstances of the event, and/or the progression of the loss of consciousness Previous deterioration of consciousness and focal signs or symptoms preceding a worsening level of consciousness may provide additional information Medications and a history of substance abuse must be explored Focused general physical exam can provide clues to a source of neurologic deterioration Scalp lacerations, periorbital ecchymosis, or bruising behind the mastoids suggests a skull fracture Tongue biting or incontinence is suggestive of seizure activity Jaundice, meningismus, or new cardiac murmurs are important findings Fever may imply an infectious source, while hypothermia may suggest exposure or hypothyroidism

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Hypertensive encephalopathies can often be determined on the initial assessment Hypotension leading to cerebral hypoperfusion may be cardiac in nature Neurologic evaluation of the comatose patient can be simplified into assessing the patient’s level of consciousness, cranial nerves, and any localizing features Glasgow Coma Scale (GCS) score has been the mainstay of providing a rapid but complete assessment of the patient, based on motor, verbal, and eye-opening responses More recently, the FOUR score (FOund UnResponsive) has been validated among neurologic physicians and staff (Table 16.1) Initial laboratory assessment should include electrolytes, BUN, and creatinine, a complete blood count, an arterial blood gas Liver and thyroid function tests (including an ammonia level), a blood or urine toxicology screen, and possibly, tests evaluating the adrenal axis Table 16.1  Coma scores Glasgow coma score Eye opening Spontaneous To voice To pain None

4 3 2 1

Motor response Follows commands Purposeful Withdrawal to pain Flexion to pain Extension to pain No response

6 5 4 3 2 1

Verbal Response Oriented Confused Inappropriate Incomprehensible None

5 4 3 2 1

Four score Eye opening Open and tracking Open but not tracking To voice To pain None Motor response Follows commands Localizes to pain Flexion to pain Extension to pain No response Respiration Regular Cheyne-Stokes Irregular Above ventilator rate At ventilator rate Brainstem Reflexes Pupil and corneal reflexes Present Unilateral dilated pupil Pupil or corneal reflexes Absent Pupil and corneal reflexes Absent Pupil, corneal, and cough Reflex absent

4 3 2 1 0 4 3 2 1 0

4 3 2 1 0

4 3 2 1 0

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Fig. 16.1  Algorithm for assessment of the unresponsive patient. GCS Glasgow Coma Scale; IV intravenous; BUN blood urea nitrogen; Cr creatinine; CBC complete blood count; LFTs liver function tests; NH3 ammonia; UA urine analysis; CXR chest X-ray; ECG electrocardiogram; HR heart rate; BP blood pressure; PMH personal medical history; FOUR FOund UnResponsive; EEG electroencephalogram; LP lumbar puncture, Neurosurgical

■ ■

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Blood and urine cultures are indicated if a fever is present Neuroimaging, either a head CT or MRI, is typically obtained as part of the evaluation for coma Subsequent evaluations utilizing electroencephalography, spinal fluid, or intracranial pressure monitoring can be tailored according to the presentation of the patient An algorithm for the assessment of the unresponsive patient is provided in Fig. 16.1

Management ■

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Patients with a depressed level of consciousness are at an increased risk for aspiration pneumonia Patients in a coma can often lose the bulbar muscular tone necessary to maintain airway patency and may need to be endotracheally intubated. Thus, the basics of emergency care, including the establishment of an airway, breathing, and circulation, are paramount in the care of the comatose patient

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Subsequent treatment of the unresponsive patient includes the administration of thiamine and glucose Narcan and flumazenil are also typically administered if drug intoxication is suspected However, overall management of the unresponsive patient is based upon the underlying etiology Trauma is managed supportively, with surgical options utilized to treat expanding hematomas or masses Electrolyte, nutritional, and metabolic disturbances should be corrected Subclinical seizures should be evaluated and addressed Alterations in blood pressure must be normalized Underlying infections, neoplasms, or intoxications need to be treated Induced hypothermia after pulseless ventricular fibrillation has been shown to markedly improve outcome after cardiac arrest Application of hypothermia to patients with head trauma has not proven to be effective However, subgroup analysis suggests that young patients who present hypothermic may benefit from prolonged hypothermia Use of psychostimulants and dopamine agonists for the treatment of prolonged coma or vegetative states is anecdotal

Prognosis ■

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Prognosis for coma is generally poor, with mortality ranging between 40 and 50% for traumatic brain injury and 50 and 88% for cardiopulmonary arrest Prognosis depends upon the etiology of the injury and the depth and duration of the coma. Other important findings include the age of the patient, other neurologic findings, and concurrent medical illnesses Prognosis for coma has been best studied for traumatic brain injury and after cardiac arrest. Good outcomes can still occur in young patients who present with severe head injury Markers of poor outcome as measured by the Glasgow Outcome Scale include: ♦ A persistent GCS score £8 after sedation and paralysis have metabolized

(70% positive predictive value). ♦ Morbidity and mortality worsens with declining GCS score; poor motor ♦ ♦ ♦ ♦

responses appear particularly predictive Loss of pupillary light response (70% positive predictive value) Advancing age, with significantly worse outcome after 40 A single episode of either hypoxia or hypotension (SBP <90 mm Hg) CT findings of: ● ● ●

Compression of the basal cisterns Midline shift of brain structures Traumatic subarachnoid, subdural, or epidural hemorrhage

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♦ Bilateral absence of the cortical response of somatosensory-evoked potentials

(SSEPs) ♦ Elevated serum levels of glial fibrillary acidic proteins and S100B ■

■

Several large studies have examined outcome in coma after cardiac arrest; These were reviewed, and practice parameters developed Indicators of poor outcome after cardiopulmonary resuscitation include: ♦ ♦ ♦ ♦ ♦ ♦

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Initial absence of pupillary light responses or corneal reflexes Extensor or no motor response to pain after 3 days Myoclonic status epilepticus Burst suppression or generalized epileptiform discharges on EEG Bilateral absent cortical SSEP responses Serum neuron-specific enolase >33 mg/L

The Multisociety Task Force on Persistent Vegetative State concluded that a patient diagnosed in a vegetative state 1 year after a traumatic brain injury or 3 months after anoxic brain injury was very unlikely to improve

Key Points ■

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Cardiopulmonary stabilization is critical to prevent secondary brain injury in comatose patients; early endotracheal intubation and maintaining cerebral perfusion are crucial The overriding goal is to provide oxygen/ventilation and maintain a euvolemic state Serial examinations should be performed to detect early deterioration Investigate for readily correctable causes (hypoxia, hypoglycemia) and focal signs on examination (mass lesions). Return to the history, when available, to establish a time course

Suggested Reading Brain Trauma Foundation Management and Prognosis of Severe Traumatic Brain Injury. (2001) American Association of Neurological Surgeons McNealy DF, Plum F (1962) Brainstem dysfunction with supratentorial mass lesions. Arch Neurol 7:10–32 Medical aspects of the persistent vegetative state (1). The Multi-Society Task Force on PVS. N Engl J Med 1994;330(21):1499–508 Posner JB, Saper CB, Schiff ND, Plum F (2007) Plum and Posner’s diagnosis of stupor and Coma, 4th edn. Oxford University Press, Oxford Wijdicks EFM (2008) The comatose patient. Oxford University Press, Oxford Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL (2005) Validation of a new coma scale: the four score. Ann Neurol 58:585–593

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Wijdicks EFM, Hidra A, Young GB et  al (2006) Practice Parameter of outcome in comatose ­survivors after cardiopulmonary resuscitation (an evidence based review). Neurology 67:203–210 Young GB, Ropper AH, Bolton CF (1998) Coma and impaired consciousness. A clinical perspective McGraw-Hill, Philadelphia, PA

Chapter 17

Acute Encephalopathy Robert D. Stevens, Aliaksei Pustavoitau, and Tarek Sharshar

Nomenclature and Classification ■

■

Acute encephalopathy is an abrupt and pathologic alteration in cognitive function and/or behavior caused by an underlying functional or structural brain disorder A number of synonymous terms exist in the literature, including organic brain syndrome, acute confusional state, delirium, acute toxic-metabolic encephalo­pathy, cerebral insufficiency, brain failure, ICU syndrome, ICU psychosis. In recent years, efforts have been made to rationalize and simplify this terminology, with a special emphasis on the clinical syndromes of delirium and coma ♦ Delirium is a disturbance of consciousness that is characterized by impaired

attention, cognitive and/or perceptual changes, and a fluctuating course, for which an underlying explanatory condition exists ♦ Coma is the loss of conscious awareness and is identified as the simultaneous loss of arousal (vigilance, wakefulness) and awareness of self and environment ■

Acute encephalopathies are classified using various schemes ♦ Clinical classification, according to the neurobehavioral/neurocognitive pre-

sentation: delirium and coma in the acute setting; vegetative state, minimally conscious state, and cognitive impairment in the subacute and chronic setting

R.D. Stevens, MD (*) Neurosciences Critical Care Division, Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Division of Neurosciences Critical Care, 600 North Wolfe Street - Meyer 8-140, Baltimore, MD 21287, USA e-mail: [email protected] A. Pustavoitau, MD Johns Hopkins University School of Medicine, Baltimore, MD, USA T. Sharshar Hospital Raymond Poincare, University of Versailles, Versailles, France A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_17, © Springer Science+Business Media, LLC 2011

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♦ Anatomic classification: primary brain disorders that result from a direct insult

to cerebral tissues (e.g., traumatic brain injury, stroke, brain tumors); secondary brain disorders that result from an extracerebral disturbance (e.g., anoxicischemic encephalopathy, hepatic encephalopathy, septic encephalopathy) ♦ Etiologic classification (Table 17.1): infectious and postinfectious encephalitis, inflammatory and immune-mediated encephalopathies, anoxic-ischemic encephalopathy, metabolic and toxic encephalopathies, hepatic encephalopathy, uremic encephalopathy, septic encephalopathy ■

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Many hospitalized patients develop an encephalopathy in which, even after an extensive diagnostic workup, the underlying etiologic factor cannot be definitively identified or is presumed to be multifactorial; this is arguably the most common form of encephalopathy encountered in acutely ill patients Some acquired encephalopathies have been described as specific clinicopathologic or clinicoradiologic syndromes but are of undetermined etiology or have been linked with several different etiologies; such is the case with “posterior reversible encephalopathy syndrome” and “acute disseminated encephalomyelitis”

Epidemiology ■

Delirium ♦ Delirium, diagnosed using validated assessment tools (see below), is identified

♦ ♦

♦

♦

in 15–30% of patients on the general medical wards and in 10–60% of surgical patients Selected surgical populations are at particular risk for delirium, such as those who have undergone cardiac surgery or repair of hip fractures Among critically ill patients, the reported prevalence of delirium is 50–90% (variability in reported rates depends on actual population studied and delirium criteria used) Risk factors for delirium in the ICU include age, premorbid cognitive and educational status, exposure to opioids and benzodiazepines, mechanical ventilation, and restraints Delirium has been associated with an increased risk of death, prolonged mechanical ventilation, and longer durations of ICU and hospital stay

Pathophysiology ♦ A large number of illnesses and physiologic perturbations have been linked

to acute encephalopathy (Table 17.1); however, a clear understanding of how these changes directly or indirectly affect cognition and behavior is lacking in many instances

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Table 17.1  Etiologic classification of acquired acute encephalopathies Vascular Ischemic stroke Intracerebral hemorrhage Subarachnoid hemorrhage Cerebral venous thrombosis Vasculitis Posterior reversible encephalopathy syndrome (PRES) Trauma Focal brain lacerations and contusions Extra-axial hematomas Diffuse axonal injury Neoplasm Primary or secondary brain tumors Seizures/status epilepticus Generalized seizures (convulsive, nonconvulsive) Complex partial seizures Organ failure Cardiac arrest (anoxic-ischemic encephalopathy) Respiratory (encephalopathies associated with hypoxia, hypercapnia) Hepatic encephalopathy Uremic encephalopathy Metabolic Severe electrolyte imbalance Hypoglycemia; hyperglycemic states Cofactor deficiency (Wernicke encephalopathy) Endocrine Hypothalamic and pituitary failure Thyroid (myxedema coma, thyrotoxicosis) Adrenal (Addison disease) Pharmacologic/toxic Prescription medications [opioids, benzodiazepines, barbiturates, tricyclics, neuroleptics, aspirin, SSRIs (selective serotonin reuptake inhibitors), acetaminophen, anticonvulsants] Drugs of abuse (opioids, alcohol, methanol, ethylene glycol, amphetamines, cocaine, hallucinogens) Environmental exposures (carbon monoxide, heavy metals) Central nervous system infection Meningitis Encephalitis Systemic infection Septic encephalopathy Inflammatory and immune-mediated encephalitis Postinfectious encephalitis Post-vaccine encephalitis Paraneoplastic encephalitis Lupus encephalitis Neurosarcoidosis Acute disseminated encephalomyelitis (ADEM)

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♦ Conscious awareness is the integration of multiple cognitive domains

s­ ubserved by networks of neuronal populations located primarily in the cerebral cortex, but it is also dependent on neuronal arousal systems that originate in the brainstem, hypothalamus, and thalamus and project directly or indirectly to the cerebral hemispheres; these systems can be disrupted by the physiologic imbalances that occur in severely ill patients ♦ Among the causes of encephalopathy, vascular, anoxic-ischemic, traumatic, neoplastic, and neuroinfectious causes are covered elsewhere in this volume ■

Patterns of injury ♦ In many instances, acute encephalopathy is associated with normal findings

♦

♦

♦ ♦ ♦

■

on postmortem examination of brain tissue or on neuroimaging; however, delirium-like symptoms may also occur with focal lesions involving the frontal and parietal lobes, the corpus callosum, basal ganglia, and thalamus Studies of patients with delirium, using SPECT (single-photon emission CT), indicate decreases in cerebral blood flow to the frontal and parietal lobes, with a recovery of normal flow patterns after resolution of symptoms Lesions of the cerebral hemispheres, diencephalon, midbrain, or rostral pons will result in decreased arousal, ranging from somnolence to lethargy, stupor, and coma Coma-inducing lesions must involve both hemispheres or must be unilateral lesions large enough to displace midline structures Diencephalic and brainstem injuries that result in coma may be relatively small, but only bilateral or paramedian lesions will significantly affect arousal Transtentorial and central herniation syndromes that result from space-­ occupying hemispheric lesions are typically associated with significant damage to the upper brainstem, usually with disruption of arousal pathways

Metabolic alterations ♦ Neuronal activity is dependent on an array of homeostatic physiologic mech-

anisms that regulate cerebral blood flow and oxygen delivery, blood-brain barrier (BBB) function, water and ionic balance, temperature, pH level, neurotransmitter metabolism, and the processing of energetic substrates ♦ Acute brain dysfunction may result from ●

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Impaired oxygen or substrate delivery to the brain, as may be seen in hypotension, hypoxemia, hypoglycemia, and carbon monoxide or cyanide toxicity Impaired cellular energy metabolism, e.g., mitochondrial dysfunction associated with cyanide toxicity or thiamine deficiency Changes in neuronal excitability caused by electrolyte or acid-base imbalances Changes in brain volume due to either cellular (cytotoxic) or extracellular (vasogenic) edema

Neurotransmitter alterations ♦ Disturbances in neurotransmitter synthesis, release, receptor binding, and

uptake may play a significant role in encephalopathy

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Delirium has been associated with altered acetylcholine, monoamines (dopamine, serotonin, norepinephrine), gamma-aminobutyric acid (GABA), glutamate, and histamine activity. Many of these alterations are the result of pharmacologic exposures A higher risk of delirium has been linked to elevated endogenous anticholinergic activity measured in serum and in cerebrospinal fluid; these findings are consistent with data that show that cholinergic antagonists are deliriogenic and that their effects can be reversed with cholinesterase inhibitors such as physostigmine GABA-A receptor agonists such as the benzodiazepines are associated with increased rates of delirium ▲ Hepatic encephalopathy may result in part from an endogenous benzo-

diazepine-like molecule, as indicated by the short-term relief of symptoms obtained with the GABA-A receptor antagonist flumazenil ●

Increased brain dopaminergic activity is a feature in psychotic disorders and has been linked to delirium ▲ Acetylcholine and dopamine activity have reciprocal actions in the

brain, so that conditions associated with reduced acetylcholine activity frequently result in increased CNS dopamine levels ▲ In clinical practice, the rate and severity of delirium is reduced by the administration of antipsychotic agents with dopamine receptor antagonist activity ●

Elevated brain serotoninergic activity may present as “serotonin syndrome,” a life-threatening disorder characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities ▲ This complication is seen following therapeutic drug use, intentional

self-poisoning, or inadvertent interactions between drugs ■

Inflammatory mechanisms ♦ Neuroinflammation is the prevailing mechanism of injury in infectious,

postinfectious, post-vaccine, and paraneoplastic encephalitis syndromes ♦ Systemic inflammatory response syndrome (SIRS), and sepsis in particular,

have been linked to changes in BBB function, leading to entry of circulating inflammatory mediators into the CNS, activation of brain innate and adaptive immune systems, and induction of neuronal and glial dysfunction and death ●

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Expression of toll-like receptors and cytokines within the brain is a key step in relaying and amplifying peripheral inflammatory signals The brain, in turn, is capable of modulating systemic immune function via autonomic and neuroendocrine pathways ▲ Proinflammatory signaling molecules synthesized in the brain can enter

the systemic circulation

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(cholinergic anti-inflammatory pathway) ▲ The sympathetic nervous system has both pro- and anti-inflammatory

actions

Diagnosis ■

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Most encephalopathies are the reflection of a global cerebral disturbance, and clinical symptoms and signs rarely localize to discrete sites in the CNS, nor are they specific to particular etiologies The fundamental clinical finding in encephalopathy is an abrupt change in cognition and/or behavior that may be grouped into two clinical patterns: delirium and coma ♦ Delirium ●

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The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) defines delirium as an acute onset (hours to days) of a disturbance of consciousness and characterized primarily by a reduced ability to focus, sustain, or shift attention This disturbance must be associated with a change in cognitive function (e.g., memory impairment, disorientation, or language disturbance) or a perceptual disturbance (hallucinations, delusions), and a fluctuating course, and the patient must have a presumptive explanatory general medical condition Subsyndromal delirium describes a condition in which patients have one or more symptoms of delirium but never progress to meet  all of the DSM-IV criteria of delirium Additional findings that are frequent in delirium but not necessary for the diagnosis ▲ Alterations in the sleep wake cycle ▲ Tremor (5–10 Hz), asterixis, muscle twitching, and brisk deep-tendon

reflexes ▲ Signs of autonomic hyperactivity: tachycardia, elevated blood pressure,

tachypnea, hyperthermia, sweating, flushed face, and dilated pupils ●

Patients with delirium are classified into three subtypes, depending on the level of psychomotor activity. Studies indicate that mixed and hypoactive delirium may be far more common, yet more often overlooked, than the hyperactive type and that hypoactive delirium may be associated increased morbidity and mortality ▲ Hyperactive delirium describes patients who are agitated, disruptive,

verbalizing loudly, and likely to inflict significant harm on themselves or others ▲ Hypoactive delirium refers to patients who are quiet, apathetic, withdrawn, and have minimal interaction with health providers or family

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Table 17.2  Confusion assessment method for the ICU (CAM-ICU) Feature 1: Acute onset of mental status changes or a fluctuating course Feature 2: Inattention Feature 3: Disorganized thinking Feature 4: Altered level of consciousness Delirium present if patient has features 1 and 2, plus either feature 3 or 4 Data from Ely et al. (2001)

▲ Mixed delirium describes patients in whom both hyperactive and hypo-

active traits are present ●

Several assessment tools and scoring systems have been developed to facilitate the identification of delirium in critically ill patients ▲ The preponderance of published studies use the Confusion Assessment

Method for the ICU (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC) (Tables 17.2 and 17.3) ▲ These tools are reported to be accurate when compared to standards such as the DSM and have good interobserver reliability

Differential Diagnosis ■

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Acute encephalopathy elicits a broad differential of potential mechanisms and etiologies (Table 17.1) Focused but conscientious efforts to correctly identify the cause or causes of encephalopathy can have a profound impact on subsequent therapeutic interventions and outcomes Differential diagnosis of delirium ♦ Many of the clinical findings of delirium are transiently induced by pharma-

cologic agents with sedative/hypnotic properties ♦ Disagreement exists as to whether the reversible neurologic changes induced

by sedation should be classified as delirium ♦ Delirium must be distinguished from dementia, psychosis, manic episode,

and major depressive episode ●

Dementia is generally not associated with an acute disturbance in consciousness; it has an insidious onset and develops inexorably over months to years, generally without the abrupt fluctuations seen in delirium ▲ Although dementia is characterized by many cognitive deficits,

impaired attention is typically not the most prominent finding ▲ Perceptual disturbances are less common in patients with dementia, and

sleep-wake cycles are usually normal ●

Psychosis is characterized by delusions, hallucinations, and grossly disorganized thought and behavior

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Table 17.3  Intensive care delirium screening checklist (ICDSC) 1. Altered level of consciousness A. Exaggerated response to normal stimulation (score 1 point) B. Normal wakefulness C. Response to mild or moderate stimulation (score 1 point) D. Response only to intense and repeated stimulation (e.g., loud voice and pain) – Stop assessment E. No response – Stop assessment 2. Inattention (Score 1 point for any of the following abnormalities) A. Difficulty in following commands, OR B. Easily distracted by external stimuli, OR C. Difficulty in shifting focus 3. Disorientation (Score 1 point for any one obvious abnormality in orientation to time, person, or place) 4. Hallucinations or Delusions (Score 1 point for either of the following) A. Equivocal evidence of hallucinations or a behavior due to hallucinations B. Delusions or gross impairment of reality testing 5. Psychomotor Agitation or Retardation (Score 1 point for either) A. Hyperactivity requiring the use of additional sedative drugs or restraints to control potential danger, OR B. Hypoactive or clinically noticeable psychomotor slowing or retardation 6. Inappropriate Speech or Mood (Score 1 point for either) A. Inappropriate, disorganized, or incoherent speech, OR B. Inappropriate mood related to events or situation 7. Sleep-Wake Cycle Disturbance (Score 1 point) A. Sleeping <4 h at night, OR B. Waking frequently at night, OR C. Sleep ³4 h during day 8. Symptom Fluctuation (Score 1 point for fluctuation of any of the above items (i.e., 1–7) over 24 h TOTAL ICDSC SCORE (Add 1–8; max, 8; min, 0); A total ICSDC Score ³4 has a 99% sensitivity correlation for a psychiatric diagnosis of delirium. Data from Bergeron et al. (2001) ▲ The disturbances in the level of consciousness, abrupt onset, and fluc-

tuating course seen in delirium are not typical in psychosis ▲ Hallucinations in psychotic patients are more commonly auditory than

visual, while the reverse is true in delirium ▲ Psychotic patients often have complex and systematized delusions as

opposed to the simple unstructured delusions of delirious patients ●

Acute mania is characterized by an elevated, expansive, and irritable mood lasting for more than 1 week, often accompanied by inflated self-esteem or grandiosity, decreased need for sleep, loquacity, flight of ideas, distractibility, increase in goal-directed activity, psychomotor agitation, sometimes associated with psychotic features. Patients with mania typically do not have the disturbance of consciousness and the major cognitive impairment and fluctuating course typical of delirium

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Major depressive episodes are notable for markedly diminished interest or pleasure in most activities, alterations in appetite, sleep disturbance, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or guilt, diminished ability to think or concentrate, indecisiveness, and recurrent thoughts of death or suicide ▲ Major depressive episodes can be mistaken for the hypoactive form of

delirium; however, the presence of attention impairment, fluctuating course, and perceptual disturbances suggest delirium

Management of Encephalopathy ■

■

The acute onset of a change in mental status should be regarded as a medical emergency that mandates a swift yet comprehensive and structured diagnostic and therapeutic strategy (Figs. 17.1 and 17.2) Initial approach should invariably include: ♦ An assessment of airway, breathing, and circulatory status; in instances when trauma

cannot be excluded, the cervical spine should be immobilized in a rigid collar ♦ A neurologic examination adapted to the clinical condition of the patient ■

Delirium (Fig. 17.1) ♦ Patients with a change in mental status but who remain arousable and do not

have a focal neurologic deficit should be evaluated for delirium using the DSM criteria or one of the validated assessment tools (ICDSC, CAM-ICU) ♦ Management of delirium is based on the identification of underlying causes, prevention strategies, and pharmacologic therapy ●

The identification and treatment of underlying etiologies and precipitating factors is the cornerstone of delirium treatment ▲ Physiologic, metabolic, and pharmacologic causes should be investi-

gated aggressively and, whenever possible, corrected or eliminated ▲ Commonly diagnosed etiologies/precipitants include primary brain lesions,

exposure to medications that affect the CNS, alcohol and substance withdrawal, seizures, infection, organ failure, and mechanical ventilation ●

Strategies to prevent delirium include promoting patient reorientation and adequate sleep, noise reduction, physical therapy and mobilization, removal of catheters and physical restraints, and provision of eyeglasses and hearing aids ▲ Implementation of such measures in the form of multicomponent care

bundles has been associated with a significantly reduced incidence of delirium ●

Pharmacologic therapy should be considered in patients who remain delirious after elimination of precipitants, when patient safety is a concern

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Acute change in mental status Assess/treat Airway, Breathing, Circulation

Neurologic examination: mental status, cranial nerves, motor and sensory function, reflexes, coordination

Arousable* No focal deficit **

Consider delirium: inattention, fluctuating course cognitive or perceptual change, evidence of an underlying cause

Arousable* Focal deficit **

Unarousable* Abnormal brainstem reflexes Nonlocalizing motor response

Evaluate for CNS lesion

Unconscious patient (see Fig. 2)

Consider alternative diagnosis: dementia, psychosis, depression

Assess with delirium score: ICDSC, CAM-ICU

Treat underlying cause(s): CNS infection, non-CNS infection, organ dysfunction, endocrinopathy, metabolic imbalance, ethanol/substance withdrawal, pharmacological/toxic exposures

*Minimum criteria Localizes (GCS motor score 5 or greater) Is able to verbalize (GCS verbal score 3 or greater) **Focal deficit, suggesting a brain or spinal cord lesion

Consider symptomatic treatment (haloperidol, olanzapine)

Fig. 17.1  Algorithm for management of altered mental status. CNS central nervous system; ICDSC intensive care delirium screening checklist; CAM-ICU confusion assessment methods for the ICU

(e.g., hyperactive delirium), and in cases where precipitating factors are unknown or cannot be removed promptly (e.g., mechanical ventilation) ▲ Antipsychotic agents such as haloperidol or olanzapine have been asso-

ciated with reduced severity and duration of delirium. ▲ Benzodiazepines are indicated when alcohol-withdrawal delirium is

suspected

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Unconscious patient

Assess/treat Airway, Breathing, Circulation

Coma evaluation: LOC, brainstem reflexes, motor responses, breathing pattern

Immediate serum glucose, electrolytes, arterial blood gas, complete blood count, liver and endocrine tests, toxicology screen; pan-cultures

Etiology not immediately identifiable/reversible: Emergent head CT

If herniation syndrome/increased ICP:

1. 2. 3. 4.

Hyperventilation PaCO2 35–30 mmHg Mannitol 0.5–1.0 g/kg Thiopental, 3–5 mg/kg or Propofol, 2–3 mg/kg Neurosurgical consultation

1. If hypoglycemia <60 mg/dL thiamine, 100 mg IV, then glucose 25 g (50 mL D50%) 2. If suspected seizure activity, lorazepam 1–2 mg IV, maximum 0.1 mg/kg 3. If suspected opioid overdose, 4. naloxone 0.4– 2.0 mg IV q 3 min 5. If suspected benzodiazepine overdose, flumazenil 0.2 mg/min, maximum 1 mg IV 6. If drug intoxication suspected, gastric lavage with activated charcoal

Persisting etiologic uncertainty: Consider MRI, EEG, LP

Fig. 17.2  Algorithm for management of coma. LOC level of consciousness; CT computer tomo­ graphy; ICP intracranial pressure; MRI magnetic resonance imaging; EEG electroencephalogram; LP lumbar puncture

Selected Encephalopathy Syndromes ■

Hepatic encephalopathy ♦ HE is a spectrum of neuropsychiatric abnormalities that have been associated

with both chronic and acute liver dysfunction (Table 17.4) ♦ Presence of HE is a defining characteristic of acute and fulminant types of

liver failure

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Table 17.4  Classification and grading of hepatic encephalopathy Classification of hepatic encephalopathya A Encephalopathy associated with acute liver failure B Encephalopathy associated with portal-systemic bypass and no intrinsic hepatocellular disease C Encephalopathy associated with cirrhosis and portal hypertension or portal-systemic shunts Grading of hepatic encephalopathy (West Haven criteria)b Grade 1 Trivial lack of awareness Euphoria or anxiety Shortened attention span Impaired performance of addition Grade 2 Lethargy or apathy Minimal disorientation for time or place Subtle personality change Inappropriate behavior Impaired performance of subtraction Grade 3 Somnolence to semistupor, but responsive to verbal stimuli Confusion Gross disorientation Grade 4 Coma (unresponsive to verbal or noxious stimuli) a Ferenci et al. (2002) b Atterbury et al. (1978)

♦ Pathophysiology of HE is incompletely understood ●

●

●

Liver failure induces a profound metabolic brain disturbance that leads to varying degrees of brain edema Brain edema is found in 80% of patients with acute HE and is the result of both cytotoxic (ammonia-driven astrocyte swelling) and vasogenic (increased BBB) mechanisms Other factors that contribute to HE include neurotoxins (ammonia, shortand medium-chain fatty acids, mercaptans, phenols), changes in neurotransmitter function (GABA, glutamate, neurosteroids, false neurotransmitters, endogenous benzodiazepines), alterations in BBB permeability, decreased cerebral glucose utilization, increased production of reactive oxygen species, increased cerebral blood flow, and the action of inflammatory mediators

♦ The onset of acute HE is commonly linked to precipitating circumstances

such as gastrointestinal bleeding, increased protein intake, hypokalemia, infection, and exposure to benzodiazepines, opioids, or alcohol ♦ Diagnosis of HE is based on clinical findings that range from minor changes in cognition to coma (Table 17.4) ●

Elevated serum ammonia concentration is common but not necessary for the diagnosis of HE

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Work-up should include a head CT, which will help to determine the presence and severity of brain edema and will exclude associated intracranial hemorrhage Brain MRI typically will show T1-hyperintense lesions in the basal ganglia and increased brain water suggested by an increased apparent diffusion coefficient Electroencephalography (EEG) is nonspecific and reveals a diffuse and symmetric reduction in frequency, often with triphasic waves

♦ Therapy of acute (type A) HE should include the identification and treatment

of precipitating factors, correction of physiologic imbalances and coagulopathy, and the management of brain edema and intracranial hypertension ●

■

HE may be completely reversible if liver function is restored; however, untreated HE can lead to herniation and death

Encephalopathy of renal failure ♦ Brain dysfunction is a common problem in patients with renal failure and

includes uremic encephalopathy and dialysis disequilibrium syndrome ●

These entities must be distinguished from alternative or concurrent mechanisms of encephalopathy such as thiamine deficiency, hypertensive encephalopathy, fluid and electrolyte disturbances, and drug toxicity

♦ Uremic encephalopathy may be seen in both chronic and acute renal failure

but tends to be more severe in the latter ●

●

●

●

●

Symptoms include headache, tremor, choreiform movements, seizures, stupor, and coma Pathophysiology has been linked to the accumulation of dialyzable “uremic neurotoxins,” including urea, guanidino compounds, uric acid, hippuric acid, various amino acids, polyamines, phenols and phenol conjugates, phenolic and indolic acids, acetone, glucuronic acid, carnitine, myoinositol, and phosphates Guanidino-succinic acid may contribute to central and peripheral nervous system demyelination by inhibiting transketolase, a thiamine-dependent enzyme of the pentose phosphate pathway of myelin Evidence also links uremia to deficient sodium-potassium-ATPase function, leading to elevation of intracellular sodium and increased neuronal excitability. Renal failure has also been associated with endocrine disturbances, including raised levels of parathyroid hormone; parathyroid ­hormone-induced increases in tissue calcium have been implicated as a pathogenic mechanism Dialysis or kidney transplantation effectively reverses uremic encephalopathy; however, a 24–48 h delay is usually noted before neurologic improvement

♦ Dialysis disequilibrium syndrome (DDS) refers to an acute neurologic com-

plication usually seen at the initiation of renal replacement therapy and is

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believed to reflect the abrupt onset of brain swelling induced by rapid changes in serum osmolality ●

●

Patients with very high pre-dialysis BUN and those with metabolic acidosis are at higher risk of DDS. DDS is typically self-limiting and resolves with slowing or interruption of dialysis Two mechanistic hypotheses have been proposed ▲ According to the “reverse urea hypothesis,” the clearing of urea by

hemodialysis exceeds the rate of urea removal from the brain, resulting in an osmotic gradient that favors influx of water into the brain ▲ Alternatively, it has been proposed that displacement of sodium and potassium by hydrogen ions, as well as augmented production of organic acids (idiogenic osmoles), can increase intracellular osmolality and promote water movement into the brain ■

Encephalopathy associated with endocrine disorders ♦ Both severe hypothyroidism and hyperthyroidism may be associated with

acute encephalopathy ●

Myxedema coma is the most extreme form of hypothyroidism and typically presents as lethargy or coma associated with bradycardia, hypothermia, hyponatremia, and hypercapnic/hypoxemic respiratory failure ▲ Often precipitated by an acute illness such as infection, stroke, or myo-

cardial infarction ▲ Very low serum unbound thyroxine (T4) and triiodothyronine (T3)

levels are diagnostic and may occur in the setting of either high or low (central hypothyroidism) TSH levels ▲ Treatment includes supplementation with IV thyroid hormone therapy and requires adjunctive measures, including corticosteroids, warming, fluids, vasopressors, mechanical ventilation ●

Thyroid storm, a life-threatening syndrome of excessive thyroid hormone activity, is defined on the basis a constellation of neurologic, thermoregulatory, gastrointestinal, and cardiovascular signs ▲ Neurologic manifestations range from restlessness and anxiety to

delirium and coma ▲ Diagnosis depends on the demonstration of elevated serum T4 and T3

levels usually associated with very low TSH ▲ Treatment includes measures to inhibit T4 synthesis (propylthiouracil

methimazole), inhibition of T4 release (potassium iodide), beta-adrenergic blockade, and cooling ●

Hashimoto encephalopathy (also called “corticosteroid-responsive encephalopathy associated with autoimmune thyroiditis”) is a recently described syndrome of presumed autoimmune origin that occurs in association with

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high titers of antithyroid antibodies, clinical Hashimoto thyroiditis, or spontaneous autoimmune thyroid failure ▲ Clinical findings are nonspecific, and neuroimaging is noncontributory ▲ Treatment is with corticosteroids ♦ Absolute adrenal insufficiency (AI), due either to disease of the adrenal

glands (primary AI) or to deficient pituitary or hypothalamic function (secondary AI), is associated with a spectrum of neurologic symptoms that include fatigue, weakness, anorexia, lethargy, and coma, typically associated with circulatory shock and electrolyte imbalances ●

●

Diagnosis rests on the demonstration of low serum cortisol activity and an abnormal rise in cortisol in response to ACTH (primary AI) or in the presence of low serum ACTH (secondary AI) Treatment consists of administration of hydrocortisone and resuscitation with fluids and vasopressors

♦ Diabetes mellitus, when untreated, may lead to potentially fatal hyperglyce-

mic crises, which include diabetic ketoacidosis and the hyperglycemic hyperosmolar state ●

■

Both are associated with neurologic dysfunction, but lethargy or coma is more common in patients with hyperglycemic hyperosmolar state and is proportional to serum osmolality

Encephalopathy associated with nonendocrine disorders ♦ The term septic encephalopathy was originally used to describe a subset of

patients with sepsis who develop an alteration in mental status associated with diffuse slowing on EEG and a normal cerebrospinal fluid profile ♦ This form of encephalopathy has been reported in 9–71% of patients with sepsis and is associated with an increased risk of death. In one study, 16% of patients with sepsis were comatose (i.e., GCS <8), and the level of consciousness of these patients predicted mortality ♦ Pathophysiology of septic encephalopathy is unknown ●

●

Evidence suggests several mechanisms, including disruption of the BBB, the effects of leukocytes and proinflammatory signaling molecules on the brain, cerebral edema, tissue infarction, hemorrhage, vascular thrombosis, microabscesses, and neuronal cell death Cell death morphology is typically necrotic, but apoptosis also may be observed

♦ Clinical presentation spans from mild confusion to coma. EEG may show pre-

dominant theta and delta waves, triphasic waves, and even burst suppression ●

●

CT of the brain is often unremarkable; however, MRI can reveal cerebral infarction and white matter disease Management is nonspecific and consists of treating the underlying infection

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Wernicke encephalopathy ♦ Wernicke encephalopathy is an acute syndrome that results from thiamine

deficiency ●

●

●

Typically encountered in the setting of malnutrition, alcoholism, gastrointestinal diseases, cancer, chemotherapy, magnesium deficiency, or AIDS Neurologic findings classically include ophthalmoplegia, ataxia, and altered mental status Therapy is parenteral thiamine supplementation

♦ Etiology is decreased tissue thiamine availability. Following absorption, thia-

mine is converted into an essential cofactor necessary for the glycolytic ­pathway (ATP synthesis), lipid synthesis (myelin), and neurotransmitter metabolism (glutamic acid, the precursor for GABA synthesis). Thiamine deficiency leads to cell dysfunction or death, with lesions preferentially located in the midbrain periadeductal grey matter, paraventricular thalamus and hypothalamus, mamillary bodies, and midline cerebellum; this damage may be appreciated as a T2- or FLAIR-hyperintense signal on MRI ■

Alcohol withdrawal delirium ♦ Alcohol withdrawal delirium (AWD), often referred to as “delirium tremens,”

♦

♦ ♦ ♦

♦

is a potentially fatal complication that develops in 5% of hospitalized alcoholdependent patients Like other forms of delirium, it is characterized by an acute disturbance of consciousness with a fluctuating course and cognitive and perceptual abnormalities Usually develops within 48–72 h of the last drink, although earlier presentations are possible Psychomotor agitation and autonomic signs (hyperpyrexia, tachycardia, hypertension, and diaphoresis) are prominent Untreated, AWD may evolve to seizures, lethargy, and coma, and may result in aspiration, respiratory failure, metabolic acidosis, tachyarrhythmias, myocardial infarction, and injury to the patient or healthcare providers Benzodiazepines are the cornerstone of management and have been associated with reduced durations of AWD and decreased mortality ●

■

Use of antipsychotic agents is not supported by available evidence and may even be harmful

Posterior reversible encephalopathy syndrome (PRES) ♦ PRES is a clinicoradiologic entity characterized by the acute onset of head-

ache, altered mental status, seizures, and visual abnormalities and is associated with neuroimaging evidence of vasogenic edema involving, most typically, the parietal and occipital lobes bilaterally ♦ The older term “posterior reversible leukoencephalopathy” is misleading because PRES involves both grey and white matter

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♦ Conditions most commonly linked to PRES include hypertensive crisis,

hypertensive disorders of pregnancy, and immunosuppressive therapy; other etiologic factors are bone marrow transplantation, autoimmune disease, renal disease, liver disease, sepsis, and high-dose chemotherapy ♦ Pathophysiology of PRES is unknown; two theories prevail: ●

●

Severe hypertension exhausts cerebral autoregulatory mechanisms, leading to hyperperfusion, endothelial injury, BBB breakdown, and vasogenic edema Severe vasoconstriction and hypoperfusion leads to brain ischemia and subsequent vasogenic edema

♦ Management involves identifying and, when possible, treating or removing

the underlying cause ♦ Clinical and radiologic signs typically resolve within days, typically without

any sequelae ■

Acute disseminated encephalomyelitis (ADEM) ♦ ADEM is a rare immune-mediated disorder of the CNS characterized by exten-

sive demyelination involving the white matter of the brain and spinal cord ●

●

ADEM is usually preceded by a viral infection or by a vaccination, and it preferentially affects children ADEM classically has a monophasic course, distinguishing it from multiple sclerosis; however, cases of recurrent ADEM have been reported

♦ Pathogenesis of ADEM is unclear ●

●

●

●

Histology reveals clusters of T cells and macrophages and myelin damage in the areas surrounding cerebral venules Association of ADEM with recent infections or vaccinations has suggested that exposure to microbial antigens may elicit a cross-reactive anti-myelin response through molecular mimicry Alternatively, ADEM may be caused by a nonspecific inflammatory response involving T-cell clones A third hypothesis postulates that the T-cell response is induced by prior ­neurotropic viral infections, leading to BBB dysfunction, leakage of myelin antigens into the systemic circulation, and activation of a self-reactive immune response

♦ Clinical signs are protean and include headache, fever, altered mental status,

ataxia, cranial nerve deficits, seizures, and coma ●

●

Cerebrospinal fluid profile indicates a lymphocytic pleiocytosis with increased protein Typical MRI findings are large, multifocal, and asymmetric T2-hyperintense lesions that involve the subcortical and central white matter, as well as the gray-white junction of the cerebral hemispheres, cerebellum, brainstem,

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●

and spinal cord; lesions are also often identified in the thalamus, basal ganglia, and periventricular white matter Data from older series indicate that without any treatment, approximately two-thirds of patients make a complete recovery, while the remainder have sequelae that include focal deficits and a wide range of cognitive or behavioral impairments

♦ Treatment is high-dose IV methylprednisolone, followed by a prednisone taper ●

Plasmapheresis, IV immunoglobulin, and cyclophosphamide may be considered in steroid-refractory patients

Key Points ■

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■

■

■

■

■

■

Acute encephalopathy is a pathologic change in cognition and/or behavior secondary to a rapidly developing structural or metabolic brain disorder In hospitalized and critically ill patients, the most common clinical descriptors of encephalopathy are delirium and coma Delirium is a sudden disturbance of consciousness with impaired attention, ­cognitive and/or perceptual changes, a fluctuating course, and an underlying explanatory condition; it is very common in hospitalized and critically ill patients and is associated with an increased short-term risk of death Coma is the loss of arousal and awareness mechanisms and is a universal predictor of increased mortality and morbidity Etiologies of delirium and coma include primary brain disorders such as trauma or stroke, and secondary insults resulting from extracerebral conditions such as cardiac arrest, organ failure, or infection Management of encephalopathy must consider the severity of neurologic impairment Coma is a true emergency, mandating control of the airway, cardiopulmonary stabilization, brain imaging, and selected additional studies to evaluate for underlying mechanisms Delirium should prompt a comprehensive search for underlying etiologies, many of which are treatable

Suggested Reading American Psychiatric Association (2000) Task force on DSM-IV. Diagnostic and statistical ­manual of mental disorders: DSM-IV-TR, 4th ed. American Psychiatric Association, Washington, DC Atterbury CE, Maddrey WC, Conn HO (1978) Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy. A controlled, double-blind clinical trial. Am J Dig Dis 23:398–406

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Bergeron N, Dubois MJ, Dumont M et  al. (2001) Intensive care delirium screening checklist: Evaluation of a new screening tool. Intensive Care Med 27:859–864 Ely EW, Inouye SK, Bernard GR et al. (2001) Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 286:2703–2710 Ferenci P, Lockwood A, Mullen K et al. (2002) Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: Final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 35:716–721 Posner JB, Plum F (2007) Plum and posner’s diagnosis of stupor and coma, 4th edn. Oxford University Press, New York Pustavoitau A, Stevens RD (2008) Mechanisms of neurologic failure in critical illness. Crit Care Clin 24:1–24, vii Siami S, Annane D, Sharshar T (2008) The encephalopathy in sepsis. Crit Care Clin 24(1):67–82, viii Stevens RD, Bhardwaj A (2006) Approach to the comatose patient. Crit Care Med 34:31–41 Wijdicks EF, Bamlet WR, Maramattom BV et  al. (2005) Validation of a new coma scale: the FOUR score. Ann Neurol 58:585–593

Chapter 18

Traumatic Brain Injury Geoffrey S.F. Ling and Scott A. Marshall

Epidemiology of Traumatic Brain Injury ■

Traumatic brain injury (TBI) is a major cause of traumatic death and disability ♦ ♦ ♦ ♦ ♦ ♦

■

In the US, a brain injury occurs every 7 s and results in death every 5 min ~52,000 patients die from TBI each year TBI accounts for nearly one-third of all trauma-related deaths Common mechanisms include falls, motor vehicle accidents, and assaults In the US, most TBIs are related to motor vehicle accidents Estimate for annual financial cost of direct TBI medical care is ~$50 billion

Mortality from TBI ♦ Recent improvement over past two decades ♦ Mortality of severe TBI in 1987 was 39%, compared to 27% in 1996 ♦ Likely multifactorial contributions to this decrease from improved overall

public safety interventions, avoidance of the development of comorbidities such as venous thromboembolism and gastric stress ulceration, as well as improved surgical and intensive care ♦ Centers with neurointensivists and neurosurgical assets deliver care with a full array of treatment options ♦ Evidence suggests that specialized neurosciences critical care centers (NCCUs) with therapy guided by intracranial pressure (ICP) and cerebral perfusion pressure (CPP) improves outcomes in acute TBI

G.S.F. Ling, MD, PhD (*) Critical Care Medicine for Anesthesiology and Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd. Bethesda, MD 20814, USA e-mail: [email protected] S.A. Marshall, MD Uniformed Services University of the Health Science, Bethesda, MD, USA A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_18, © Springer Science+Business Media, LLC 2011

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Long-term burden of TBI ♦ Survivors of moderate or severe TBI will likely require some form of

rehabilitation ♦ Victims are usually young; thus, societal loss includes cost of long-term care of

disease as well as diminished productivity and societal impact of that individual ♦ Nearly 80% of mild-to-moderate TBIs have evidence of residual symptoms

of brain injury 3 months after injury ♦ Brain injury often results in loss of employment and economic hardship ♦ Awareness of TBI has increased recently, perhaps due to the prominence of

this injury in US casualties in Iraq and Afghanistan ♦ Future societal burden resulting from soldiers who were victims of TBI in

conflicts during the US War on Terror is not known

Pathogenesis of TBI ■

Two phases of TBI ♦ Primary injury occurs at the time of the event and is treatable only through

prevention and public safety interventions, including education ♦ Secondary injury occurs over the following minutes to days after TBI ●

●

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Goal of neurocritical care management of TBI is prevention and minimization of (a) secondary injury and (b) development of comorbidities Secondary injury may result in the most significant neurologic sequelae from TBI Multifactorial etiologies for secondary injury include ischemic injury, hypoxia (local or global), excitotoxicity, free radical damage, ionic dysregulation, inflammatory mediators, intracranial hypertension, and hyperthermia Supportive measures are the mainstay of therapeutic interventions and focus mainly on ensuring adequate CPP and tissue oxygenation, minimization of cerebral edema, and normalization of ICP Ideal monitoring devices for ensuring adequate support remain controversial (i.e., Licox brain tissue oxygenation monitors, jugular bulb oximetry, etc.) Contributing factors to secondary injury from TBI ▲ Hypoxia and hypoperfusion are thought to represent the most critical

contributing factors to this phase of injury ▲ Traumatized brain has an increased susceptibility to hypoxic-ischemic

insults secondary to impaired autoregulation of the cerebral vasculature ▲ Diffuse microvascular damage is associated with loss of cerebral vas-

cular autoregulation and loss of blood-brain barrier integrity; it plays a role in development of vasogenic edema seen in TBI ▲ Areas that show the greatest susceptibility to hypoxic-ischemic insult include the hippocampus and the border zone regions of the middle

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cerebral artery and anterior cerebral artery, as well as those of the middle cerebral artery and posterior cerebral artery territories ▲ Single episode of systolic pressure below 90 mmHg is reported to be associated with a diminution of long-term outcome in severe TBI ♦ Mechanisms of injury ●

●

● ●

●

●

High-speed collisions with rapid deceleration result in movement of cranial structures in the direct and opposite direction of motion against the skull’s inner table Often, a rotational component is associated with injury, and structures will torque, with potential for shearing of microneuronal structures Shearing results in diffuse axonal injury (DAI) High-velocity projectiles (i.e., gunshot wounds) will disrupt neuronal and vascular structures and cause tissue cavitation in a field larger than the direct path of the projectile; this is a variable phenomenon that is influenced by caliber, mussel velocity, and other factors Blast TBI occurs without penetrating injury and is a more recently described phenomenon with a presumed mechanism of neuronal injury via transmitted forces from a concussive pressure wave Pathogenesis of blast TBI requires more study and is a less understood subtype of TBI

Taxonomy of TBI ■

Focal and diffuse injury ♦ Focal injuries occur at the site of direct impact to the brain ● ●

●

Deficits can be localized to the damaged area of the brain Common locations are the anterior temporal lobes and orbitofrontal cortex, due to their position relative to the skull base in the most-often-seen anterior– posterior plane of injury Development of delayed hematomas at these sites can occur up to several days after the inciting trauma

♦ Diffuse injuries occur and are most often described in terms of DAI ●

●

●

●

DAI occurs due to shearing of the axons in cerebral white matter, commonly causing focal deficits and encephalopathy Radiographic evidence of DAI may be seen several hours following initial trauma Radiographic appearance of DAI is most often identified as petechial white matter hemorrhages on CT or MRI studies Higher incidences of DAI with lateral impact or direction of force have been reported versus frontal or even oblique orientation of forces

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Table 18.1  Glasgow coma scale Best motor response (M) Best verbal response (V) Follows commands Localizes to pain Withdrawal to pain Flexor posturing Extensor posturing No response ■

6 5 4 2 1

Oriented, alert Confused, appropriate Disoriented, inappropriate Incomprehensible speech No response

Best eye opening (E) 5 4 3 2 1

Opens eyes spontaneously Opens eyes to voice Opens eyes to pain No response

4 3 2 1

Penetrating and blunt TBI ♦ Blunt or closed brain injury usually occurs with exposure to concussive blast

or acceleration-deceleration injuries such as motor vehicle accidents, falls, or blunt assaults ♦ Penetrating TBI seen with projectiles such as shrapnel from a blast or gunshot wound, penetrating stab wounds, or non-blunt weapon assaults ♦ Penetrating TBI involves violation of the cranium with neurologic and infectious considerations ■

Mild, moderate, and severe TBI ♦ Operative definitions centered around Glasgow Coma Scale (GCA) score

(Table 18.1) ♦ Mild TBI is frequently referred to as concussion, with a GCS of >13 ● ●

● ●

80% of all TBI Mild brain injury occurs with brief loss of consciousness, often with presenting complaints of nausea, vomiting, and headache, often with post-traumatic amnesia Typically, mild TBI patients will recover fully within a few hours to days Adequate convalescence and avoidance of subsequent TBI before full recovery are critical; Guidelines for Return to Play of The American Academy of Neurology can be used to determine when a patient may return to full activity (Table 18.2)

♦ Moderate TBI is seen with an admission GCS score of 9–13 ● ●

●

●

10% of all TBI Often associated with prolonged loss of consciousness and/or neurologic deficit Moderate TBI patients will require inpatient hospitalization and may require some degree of neurosurgical intervention This degree of TBI is likely to be concordant with abnormal CT or MRI imaging

♦ Severe TBI presents with a GCS score of £8 ● ●

10% of all TBI Will typically be evidence by CT and MRI findings

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Table 18.2  Return to play guidelines of the American academy of neurology Grade I (mild) Remove from play Examine immediately and at 5-min intervals May return to duty/work if clear within 15 min Grade I (mild) second event Above, and may return to duty/work in 1 week Grade II (moderate) Remove from play for the remainder of the day Examine frequently for signs of CNS deterioration Physician’s neurologic exam as soon as possible (within 24 h) Return to play after 1 full asymptomatic week (after being cleared by physician) Grade II (moderate) second event Above, and may return to play after 2 full asymptomatic weeks (after being cleared by physician) Grade III (severe) with short LOC Evaluation in emergency department Neurologic evaluation, including appropriate neuroimaging Consider hospital admission for observation Return to play after 1 full asymptomatic week (after being cleared by a physician) Grade III (severe) with long LOC Above, and may return to play after 2 full asymptomatic weeks (after being cleared by a physician) Grade III (severe) second event Above, and may return to play after 1 month Grade III (severe) third event Above, and neurologist evaluation indicated LOC loss of consciousness

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ICU care required, with institution of airway control, mechanical ventilation, neurosurgical evaluation or intervention, and ICP monitoring Protocol-driven ICU care for TBI patients in NCCUs has been shown to improve long-term outcomes among surgical TBI and may improve outcomes in non-surgical TBI

Second-impact syndrome (SIS) ♦ Seen after a subsequent head injury during recovery from the initial TBI ♦ May severely worsen clinical outcome by exponential, rather than additive,

additional effects ♦ SIS is seen most often with TBI in children and adolescents ♦ Mechanisms of SIS are incompletely understood but may be related to impaired

cerebral autoregulation, diffuse cerebral edema, and intracranial hypertension ♦ Severe SIS is uncommon but fatal in up to 50% of cases ♦ Guidelines for return to play are based on avoidance of this severe complica-

tion of TBI (Table 18.2) ■

Post-concussive syndrome ♦ Constellation of delayed symptoms, including headache, concentration diffi-

culty, insomnia, mood disturbances, and dizziness ♦ If symptoms persist for >1 year, resolution of postconcussive syndrome is less

likely

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Clinical Management ■

Examination ♦ Advanced Trauma Life Support important considerations ●

Primary survey consists of assessment and stepwise interventions for Airway with cervical spine control, Breathing and ventilation, Circulation with hemorrhage control, Disability and neurologic status, and Exposure of patient for occult injuries (ABCDE approach) ▲ During the initial survey, life-threatening conditions are identified and

treatment is begun simultaneously ▲ Occult cervical spine injury is always assumed in any TBI patient with

altered mental status or blunt injury above the clavicle until ruled out by imaging ▲ Disability or neurologic evaluation focuses on establishing initial GCS with attention to eyes, motor, and verbal response ▲ Pupil size and reactivity, lateralizing signs, and presence of a spinal cord injury are evaluated during primary survey ▲ Important to be aware that altered mental status or obtundation after trauma may be due to impaired ventilation, oxygenation, perfusion, glycemic derangement, or toxin exposure rather than occult head injury ●

Secondary survey begins immediately after primary survey completed ▲ Obtain AMPLE history (Allergies, Medications, Past illnesses/

pregnancy, Last meal, and Environment related to trauma) ▲ Secondary survey includes a more detailed systemic evaluation, includ-

ing a neurologic examination ♦ Focused neurologic exam (Table 18.3) ●

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Exam should commence immediately after correction of any obvious abnormality seen in the primary survey Assessment of neurologic status ideally should occur before paralysis or sedation for intubation or other procedure Ongoing neurologic assessments ▲ Neurologic exams should be performed at frequent intervals by neuro-

trained nurses and staff ▲ Care by dedicated NCCU trained nurses is associated with improved

outcome among patients with severe head injury ■

Monitoring ♦ Imaging ●

Non-contrast enhanced CT scan should be completed as soon as possible upon presentation in the emergency department

18  Traumatic Brain Injury Table 18.3  Focused neurologic exam Neurologic system Components of exam Mental status Orientation, language exam evaluation, and overall level of consciousness Cranial nerve CN I: sense of smell evaluation CN II: vision

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Important considerations May be accessed quickly while attending to other injuries

CN I: not usually assessed unless mild TBI CN II: pupil reactivity and presence of BTT or field cut on confrontational testing CN III, IV, VI: CN III and VI deficits often associated with increased ICP or transtentorial herniation events; may test with oculocephalics if C-spine is cleared

CN III, IV, VI: vertical and horizontal eye movements and identification of specific CN impairment, if any CN V, VII: corneal reflex testing more CN V, VII: corneal reflex sensitive for subtle reactivity with cotton and facial symmetry to wisp than with saline drops painful stimuli (grimace) CN VIII: gross testing and inspection CN VIII: evaluation of indicated; always inspect TM prior to hearing loss and rapid external canal irrigation with cold water assessment of integrity for caloric testing of TM CN IX, X: commonly tested with in-line CN IX, X: gag or cough (if intubated) response suction via the endotracheal tube CN XI: ensure C-spine is cleared prior to CN XI: SCM or trapezius movement SCM testing CN XII: tongue protrusion CN XII: important midline command, which, along with forced eye closure, may be the only command followed during emergence from coma When administering pain for a motor Motor response Evaluation of spontaneous response, give a stimulus in area where movements, movements withdrawal, localization, or flexion to pain, or strength on responses will be distinct movements commanded movements from each other (i.e., the axilla or the in a cooperative patient inner thigh) Pinprick sensation in the neck, arms, trunk, Sensory response Pain sensation and and legs with evaluation of perception via temperature, vibration grimace or localization in the stuporous and position sense in patient cooperative patients Deep tendon DTRs in the arms, legs, DTRs provide an objective exam finding reflexes and Babinski responses that can help to confirm the presence of a lateralizing exam in an uncooperative patient Difficult to evaluate in the uncooperative or Cerebellar exam In the cooperative patient, comatose patient simple dysmetria evaluation of the arms and legs with fingernose-finger and heelshin testing CN cranial nerve, TBI traumatic brain injury, BTT blink to threat, ICP intracranial pressure, TM tympanic membrane, SCM sternocleidomastoid, DTR deep tendon reflex

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Early CT imaging may identify lesions that may benefit from operative neurosurgical intervention Imaging is repeated at any significant change in exam or with changes in ICP Serial imaging may be used to assist with weaning from ventricular drainage device if exam is poor and ICP remains low Clinical role of diffusion tensor imaging in prognosis is currently under study

♦ Fundamental concept of ICP ●

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Contents of the intracranial cavity are enclosed in a fixed and rigid compartment (the Monro-Kellie doctrine) Three components: brain (80%), blood (12%), and cerebrospinal fluid (CSF) (8%) Any increase/decrease in one component leads to a decrease/increase in another First component to decrease is CSF in the intracranial vault, followed by decrease in blood in the dural venous sinuses ICP monitoring ▲ Patients with GCS £8, any acute abnormality on CT, a systolic blood

▲

▲ ▲ ▲ ▲ ▲ ▲

pressure of <90 mmHg, or age >40 year should have an ICP-monitoring device placed External ventricular drain (EVD) or intraventricular catheter with a micro-strain gauge gives the most accurate data and provides a means of treating increased ICP via supratentorial CSF drainage Concerns of hemorrhage or infection due to EVD placement should not deter ICP monitoring, if indicated EVD is best option if hydrocephalus exists to any extent with raised ICP Routine EVD exchange or prophylactic antibiotics are not recommended as a means to reduce infectious complications Fiberoptic transducers used with an EVD offer similar accuracy to EVD with micro-strain gauge but at a greater expense Parenchymal ICP monitors (Codman) are not able to be recalibrated in situ, although they have a negligible drift during use Fluid-coupled or pneumatic subarachnoid, subdural, and epidural devices are felt to be less accurate

♦ Tissue oxygenation and metabolic monitoring ●

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Goal is measurement of oxygen delivery to the brain with jugular venous saturation (SJO2) monitors, brain tissue oxygenation monitors (Licox), and near-infrared spectroscopy Alternatively, the metabolic state of the brain is accessed with microdialysis catheters SJO2 monitoring provides an estimate of oxygen delivery to the brain with goal mean values of 56–74%

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Arteriojugular differences of oxygen content (AJDO2) as an indicator of oxygen extraction of the brain may offer valuable prognostic information, with higher mean values desirable Periods of low brain tissue oxygen tension (PBRO2) may correlate with poor outcome or death Although ideal use of these devices is not clear and requires further study, outcome data obtained with these devices may allow for significant future advances in the treatment of TBI SJO2 < 50 or PBRO2 < 15 is a trigger for treatment if these values are being monitored, based on a level III recommendation from the Brain Trauma Foundation (BTF) Systemic oxygen saturations > 90% and PaO2 > 60 mmHg should be maintained

Treatment ♦ Medical interventions to treat elevated ICP ● ● ●

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Current BTF guidelines support maintaining ICP at <25 mmHg Treatment should be initiated to lower ICP to 20–25 mmHg Noninvasive interventions should be routinely ordered in all patients with head injury and suspected increased ICP Head of bed should be elevated to 30° and the head kept midline so as not to compress either internal jugular vein (which compromises venous drainage from the dural venous sinuses) Central venous access should be obtained in any patient with elevated ICP who does not have a contraindication for a central line Emergent central venous access during a herniation event may be best obtained with a femoral line, as patients with acute increased ICP should not be placed in the Trendelenburg position for subclavian access; internal jugular lines may also elevate ICP by obstruction of internal jugular drainage If ICP is elevated after conservative maneuvers, osmotherapy and other pharmacologic agents should be used ▲ First-line treatment is usually mannitol, which is given at a dose of

0.5–1.0 g/kg over 10 min via a central or peripheral venous line ▲ Mannitol may be used to treat ICP, traditionally up to a serum osmolarity

of ³320, based on effect

▲ Other options for osmotherapy include hypertonic saline in 2 and 3%

boluses or continuous infusions; mixture of 50% sodium chloride and 50% sodium acetate is used to prevent hyperchloremic metabolic acidosis, and the percentages can be adjusted to complement an individual patient’s acid/base status ▲ 3% hypertonic saline must be given via a central venous line and can be given in boluses of 250 mL ▲ A 30 mL vial of 23.4% hypertonic saline offers an emergent, low-volume option for treating ICP on an emergent basis, given via a central venous line. Rapid IV push of 23.4% HS may cause severe hypotension

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Hyperventilation may be used emergently while other measures are being prepared, but avoidance of persistent low PaCO2 states (such as a PaCO2 <25 mmHg) is essential to maintaining cerebral perfusion ▲ Precise PaCO2 that correlates with improved outcomes is not known

●

Propofol can be given in bolus doses of 2 mg/kg and followed by infusions titrated up to 200 mg/kg/min ▲ Propofol has been associated with the development of a propofol-­

infusion syndrome in children and young adults on high-dose infusions, with renal failure, hyperkalemia, myocardial failure, and metabolic acidosis occurring; often, this is fulminate and fatal ●

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Sodium thiopental in IV doses of 1–5 mg/kg can lower brain metabolic demand or cerebral metabolism (CMRO2) with concomitant reductions in CBF and ICP Steroids are not indicated to control ICP in head injury, and evidence exists that they may cause harm, including increases in 2-week mortality Promising animal data show evidence for induced hypothermia in treating ICP, but it remains controversial in clinical use Goal core temperature for induced hypothermia is 32°–34°C, with shivering controlled by warming of skin surface or hands with forced air only Use of induced hypothermia to control ICP in severe TBI currently maintains only a level III recommendation in BTF guidelines, although this may be a tool of last resort to combat refractory ICP Use of hypothermia for more than 48 h may have a mortality benefit in TBI

♦ Surgical interventions for increased ICP ●

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Decompressive craniectomy and/or lobectomy may be considered in refractory cases Decompressive craniectomy permits the swelling brain to avoid compression by the bony structures and provides an additional margin of error for ICP control Decompressive surgery with a generous craniectomy may also reduce the need to employ pharmacologic methods to control ICP If the patient is not stable for surgical interventions and all other means to control ICP have failed, the condition is likely fatal

♦ Hemodynamics ● ● ●

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CPP is guiding principle to maintain brain perfusion. CPP = MAP - ICP Critical threshold for cerebral ischemia lies in CPP range of 50–60 mmHg BTF guidelines suggest maintaining CPP of >60 mmHg, with further finetuning of this value based on the hemodynamics of individual patients Routine maintenance of CPP at >70 mmHg with vasopressors or aggressive volume expansion is not indicated and may be harmful Systolic blood pressure should be maintained at >90 mmHg

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Table 18.4  Posttraumatic epilepsy Brain injuries that predispose patients to increased risk of posttraumatic seizures Penetrating traumatic brain injury Depressed skull fracture Contusional brain injury Epidural or subdural hematoma Seizure activity within 1 day of injury GCS <10 Intracerebral hemorrhage

♦ Prophylaxis with anticonvulsants ●

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Post-traumatic seizures are either early (within 7 days post-injury) or late (after 7 days post-injury) In high-risk patients, incidence of post-traumatic seizures may be greater (Table 18.4) No evidence exists to support the theory that prevention of post-traumatic seizures improves outcome Phenytoin and valproate are effective in reducing incidence of early post-traumatic seizures Routine use of phenytoin may have neurobehavioral implications Valproate may be associated with an increased mortality risk Evidence suggests that IV dosing of levetiracetam may be neuroprotective in animal models of closed-head injury and subarachnoid hemorrhage Prophylaxis with a well-tolerated agent with a limited side-effect profile for 7 days, which is then discontinued, is a common and recommended practice Successful prophylaxis for early post-traumatic seizures does not alter incidence of late post-traumatic seizures In TBI patients with a poor exam and any concern for nonconvulsive seizures, EEG is indicated and should be obtained Current outcome data are limited concerning implications of nonconvulsive seizures in TBI

♦ Nutrition ●

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Severe TBI patients have a mean metabolic expenditure of ~140% of basal rate despite comatose state Significant weight loss in general critical care patients confers an increased risk of mortality Feeding should be introduced as soon as possible after injury If feeds are begun no less than 72 h post-injury, evidence suggests a reduction in overall infection and ICU complication rate By day 7 post-injury, full daily caloric replacement should be achieved Glycemic control is important, and animal data show that hyperglycemia can worsen contusional and hypoxic-ischemic brain injury

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♦ Prophylaxis for deep venous thrombosis ●

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Patients with TBI have an elevated risk for the development of deep venous thrombosis with subsequent venous thromboembolism Sequential compression devices on the lower extremities are minimally invasive, are not associated with worsening intracranial hemorrhage, and should be used in all patients who do not have a contraindication Heparin for DVT prophylaxis should be started as soon as possible after injury, i.e., as soon as hemostasis is assured. Low-molecular-weight heparin is preferred over unfractionated heparin In TBI with intracranial hemorrhage, timing for introduction of lowmolecular-weight heparin or unfractionated heparin is unclear. However, one of these agents should be started as soon as possible after injury (i.e., within 2–3 days post-injury) Routine placement of removable inferior vena cava filters as prophylaxis for venous thromboembolism is controversial but may be appropriate in TBI patients with contraindications to any anticoagulants

♦ Sedation ●

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Agitation in TBI patients may often be due to pain, hypercapnia, hypoxia, delirium, or poorly tolerated mechanical ventilation Agitation may be reduced by avoidance of polypharmacy and other conservative measures, such as limitations of stimuli (television) and unnecessary personnel in the room, covering the mirror, day-night rhythm training, etc. Nonsedating antipsychotic such as haloperidol or an anxiolytic such as lorazepam can be used with caution in the acute period after TBI In extremely difficult cases, infusion of either midazolam or propofol may be needed In the subacute period after TBI, the better-tolerated atypical antipsychotics may be a better choice for controlling any persistent agitation Pain should be treated with a short-acting narcotic analgesic such as fentanyl Longer-acting narcotics such as morphine or hydromorphone should be avoided Reversal of narcotics with naloxone should be used in emergencies only, as this likely causes severe discomfort Bolus dosing of both fentanyl and sufentanyl has been associated with small increases in ICP, a feature that may be reduced by continuous low-dose infusion Infusions of these agents must be paused to facilitate neurologic checks and examinations

♦ Gastrointestinal prophylaxis ● ●

Gastric ulcers are common in patients with head injury Routine gastric stress ulcer prophylaxis with H2 antagonists or proton pump inhibitors should be used in all ICU patients with TBI

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♦ Autonomic dysfunction in TBI ●

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Paroxysmal autonomic instability with dystonia (PAID) is an emerging term for this syndrome of fever, elevated heart rate, diaphoresis, tachypnea, dystonia, and blood pressure abnormalities PAID is common in TBI patients and may be due to hypothalamic injury; when present, infectious etiologies of fever must be aggressively sought and appropriately treated Other treatable causes that must be excluded include thyroid hormone abnormalities, alcohol or other toxin withdrawal, allergic reactions, malignant hyperthermia, serotonin syndrome, extrapryamidal reactions, and neuroleptic malignant syndrome Incidence of PAID is higher in severe TBI with some component of DAI Treatment is varied and includes beta-blocking agents (propranolol), narcotics, dopamine agonists (bromocriptine), alpha2 adrenergic agonists (i.e., clonidine), and anticonvulsants (gabapentin) If syndrome is persistent, energy expenditure should be considered, and thought should be given to nutritional needs

Prognosis ■

Initial findings on exam ♦ Most practical prognostic indicator after TBI is the neurologic exam at

presentation ♦ For patients with severe TBI, the initial GCS score is the most commonly

used prognostic indicator but is not 100% reliable (Table 18.1) ■

Other factors ♦ Recent evidence has associated 6-month outcome in a large number of TBI

♦

♦ ♦

♦

patients from high- and low-income countries with age, GCS score, pupil reactivity, and the presence of CT findings Older age was most associated with poor outcome in high-income countries, and low GCS was most associated with poor outcome in low-to-middle income countries Absent pupillary reactivity was the third strongest predictor of poor outcome in all TBI patients On CT imaging, obliteration of the third ventricle and midline shift was most likely to be associated with 14-day mortality, and nonevacuated hematoma was most likely to be associated with poor 6-month outcome Diffusion-tensor MRI protocols may also prove to be clinically helpful in the future for prognostication in TBI

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Key Points ■

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For patients with TBI, care in an NCCU by physicians and nurses who have been trained in neurocritical care is ideal and offers outcome benefit in patients with severe head injury Frequent neurologic examinations must be done in the acute period after TBI to discover subtle changes and make necessary interventions Clinical management of TBI focuses on attention to ICP, CPP, and avoidance of secondary injury New physiologic monitoring devices may illuminate the best emerging therapies for TBI Routine anticonvulsant use after 7 days in TBI is likely not helpful for preventing development of late post-traumatic seizures or improvement of outcome Nutrition is a vital aspect of TBI care due to the hypermetabolism associated with this condition Over-sedation of patients with TBI must be avoided, as it confounds the ability to note changes in the neurologic exam Routine steroid use is not recommended Autonomic changes are common in TBI but require ruling out other causes in all cases Prognostic data are incomplete, but important clinical factors are age, initial GCS score, pupil reactivity, and CT findings

Suggested Reading Advanced trauma life support, program for doctors, 11th edn. American College of Surgeons, 2004 Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS Carney NA, Ghajar J (2007) Guidelines for the management of traumatic brain injury. J Neurotrauma 24:S1–S106 Evans RW (2006) Neurology and trauma, 2nd edn. Oxford University Press, Oxford Koenig MA, Bryan M, Lewin JL III et al (2008) Reversal of transtentorial herniation with hypertonic saline. Neurology 70:1023–1029 Lu J, Marmarou A, Choi S et al (2005) Mortality from traumatic brain injury. Acta Neurochirurgica 95:281–285 MRC CRASH Trial Collaborators (2008) Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ 336:425–429 Patel HC, Menon DK, Tebbs S et al. (2002) Specialist neurocritical care and outcome from head injury. Intensive Care Med 28:547–553 Pompucci A, Bonis PD, Pettorini B (2007) Decompressive craniectomy for traumatic brain injury: Patient age and outcome. J Neurotrauma ;24:1182 Practice parameter: the management of concussion in sports (summary statement). (1997) Report of the quality standards subcommittee. Neurology 48:581–5 [update in progress 2008]

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Raslan A, Bhardwaj A (2007) Medical management of cerebral edema. Neurosurg Focus 22:1–12 Ropper AH, Gorson KC (2007) Clinical practice: Concussion. New Eng J Med 356:166–172 Rosenfeld JV, Cooper DJ, Kossmann T et  al. (2007) Decompressive craniectomy. J Neurosurg 106:195–196 Wang H, Gao J, Lassiter TF et al. (2006) Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage. Neurocrit Care 5:71–78

Chapter 19

Acute Myelopathy Angela Hays and Julio A. Chalela

Introduction ■

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Acute myelopathy is a broad term used to describe spinal cord dysfunction of sudden, recent onset Diagnostic possibilities are ample, but practicing neurointensivists deal mainly with traumatic and inflammatory myelopathies Main objective in the initial management is to differentiate those patients who could benefit from acute surgical intervention (compressive myelopathies) from those patients who require medical management

Definitions ■

■

The term myelopathy is used to denote symptomatic spinal cord dysfunction, generally typified initially by lower motor neuron signs and/or sensory changes below the level of the lesion, which can result from a variety of etiologies The term transverse myelitis (TM) is used to describe a clinical syndrome that consists of acute-to-subacute onset of spinal cord dysfunction, which may result from a variety of inflammatory causes

A. Hays, MD Medical University of South Carolina, Charleston, SC, USA J.A. Chalela, MD (*) Medical University of South Carolina, PO Box 250606, Charleston, SC 29425, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_19, © Springer Science+Business Media, LLC 2011

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Etiology ■

Traumatic ♦ ♦ ♦ ♦ ♦

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Fractures/dislocations Ligamentous injury Disc herniation Epidural hematoma Cord contusion

Degenerative spine disease ♦ Spondylosis ♦ Disc herniation

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Neoplastic ♦ Primary ♦ Metastatic

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Inflammatory ♦ Transverse myelopathies ♦ Paraneoplastic ♦ Parainfectious

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Myelopathies associated with systemic disease ♦ ♦ ♦ ♦ ♦

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Sarcoidosis Systemic lupus erythematous Behcet disease Sjogren syndrome Polyarteritis nodosa

Bacterial infections ♦ Epidural abscess ♦ Bacterial myelitis ♦ Tuberculosis

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Viral infections ♦ ♦ ♦ ♦ ♦ ♦

Poliovirus Varicella zoster Herpes simplex Cytomegalovirus Human immunodeficiency virus Human T-cell lymphotropic virus-1

19  Acute Myelopathy ■

Other infectious agents ♦ ♦ ♦ ♦

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Syphilis Lyme disease Schistosomiasis Toxoplasma gondii

Vascular ♦ Spinal cord infarction ♦ Arteriovenous malformations ♦ Hemorrhage

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Toxic/Metabolic ♦ ♦ ♦ ♦ ♦

Vitamin B12 deficiency Copper deficiency Radiation Medication related Hepatic myelopathy

Epidemiology ■

Traumatic spinal cord injury (SCI) ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

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Trauma is the most common cause of acute myelopathy in the US Estimates of incidence range from 28 to 50 SCIs per million people per year Prevalence is higher among males and African Americans Average age is 37.6 years, with injuries in older Americans becoming more common in recent years Motor vehicle accidents account for ~50% of SCIs Falls are the most common cause in patients older than 60 and account for 24% of all SCIs Other common causes include sports (9%) and assault (11%) More than half of all SCIs involve the cervical spine, whereas most nontraumatic spinal cord compression affects the thoracic spine

Transverse myelitis ♦ ♦ ♦ ♦ ♦ ♦

Roughly 1,400 new cases per year are diagnosed in the US Affects all ages, with bimodal peaks at 10–19 years and 30–39 years No gender predilection has been described ~50% of patients progress to paraplegia during the course of the illness The majority of cases are monophasic, with no evidence of systemic involvement Bilateral signs and symptoms of sensory, motor, or autonomic dysfunction attributable to the spinal cord with a defined sensory level

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♦ Progression to maximal deficit within 4 h to 21 days ♦ Spinal fluid examination shows pleocytosis and/or elevated immunoglobulin

G (IgG) index ♦ MRI shows gadolinium enhancement ■

Spinal cord infarction ♦ Rare syndrome that may be underdiagnosed, as its clinical presentation and

imaging characteristics are protean ♦ May occur infrequently as a complication of surgical repair of aortic aneu-

rysms and dissections ♦ Other mechanisms include systemic hypotension or cardiac arrest, cardiac

emboli, occlusive vascular disease, and venous occlusion ♦ The thoracic spinal cord is most commonly affected ♦ A predilection for the anterior aspect of the cord, or the central “watershed”

area, has been described

Pathophysiology ■

Spinal cord ischemia ♦ Ischemia is a cardinal element in the development of all forms of acute myel-

opathy but ischemia can be the sole cause of acute myelopathy ♦ Spinal cord is perfused by two paired posterior spinal arteries, which supply

♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

the posterior one-third of the cord, and the single anterior spinal artery, which supplies the anterior two thirds of the cord Segmental arteries arising from the subclavian, aorta, and iliac arteries provide collateral flow Central arteries, arising from the anterior spinal artery, penetrate the spinal cord and perfuse the anterior horn and portions of the lateral funiculus The artery of Adamkiewicz typically arises between T8 and L4 and supplies the lower two-thirds of the cord The middle and lower thoracic cord and the central gray matter of the cord are particularly vulnerable to watershed infarctions As with the cerebral vasculature, autoregulatory mechanisms maintain spinal cord blood flow at a constant level across a broad range of mean arterial pressures In the setting of trauma, many of these autoregulatory mechanisms are impaired Increased intrathecal pressure, resulting in decreased spinal perfusion pressure, may also be a contributing factor Spinal vascular malformations, including arteriovenous malformations and dural arteriovenous fistulas, produce an ischemic myelopathy that is thought to result from venous engorgement

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Traumatic spinal cord injury ♦ Damage to the spine following trauma results from both primary and second-

ary mechanisms ♦ Primary mechanisms occur at the time of injury and may include shear injury,

♦ ♦ ♦ ♦

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compression, distraction, laceration, and/or cord transaction; the latter is typically seen with penetrating trauma Pathologically, traumatic necrosis of the cord is characterized by hematomyelia, contusion, and destruction of the gray and white matter Pathologic changes are most prominent at the level of the injury and one or two segments above and below Secondary mechanisms result from associated injuries or biochemical cascades initiated by the traumatic event and may present therapeutic targets Ischemia may result from direct disruption of vascular structures, deranged autoregulation, vasospasm, systemic hypotension, or increased intrathecal pressure Inflammatory reaction that involves macrophages, microglia, T-cells, neutrophils, and cytokines follows SCI; these processes are involved in neuronal regeneration but also stimulate apoptotic mechanisms. Mitochondrial dysfunction results in free radical formation and depletion of high-energy phosphate compounds Excitotoxicity due to release of excitatory amino acids has also been implicated

Transverse myelitis ♦ The term applies to a group of disorders in which SCI results from inflamma-

tory and immune-mediated mechanisms ♦ Inflammation is the hallmark, with infiltration by monocytes and lympho-

♦ ♦ ♦ ♦ ♦ ♦

cytes noted on pathologic examination, particularly in patients with TM secondary to multiple sclerosis Demyelination and axonal changes are prevalent, but gray matter may also be affected In TM associated with autoimmune conditions, vasculitic lesions and spinal ischemia may be observed Molecular mimicry, resulting in production of autoantibodies, has been postulated as the underlying mechanism in parainfectious myelitis Antibody to aquaporin-4, called NMO-IgG (neuromyelitis optica antibodiesIgG), has been linked to neuromyelitis optica Recurrent TM has been associated with anti-Ro antibodies and with the antiphospholipid antibody syndrome Immunomodulatory therapies, including steroids and plasma exchange, are frequently employed

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Clinical Presentation ■

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Presenting clinical syndrome is determined by the anatomic involvement of the spinal cord Spinothalamic tract lesions ♦ Result in contralateral loss of pain and temperature sensation below the lesion ♦ Located in the anterolateral white matter

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Corticospinal tract ♦ Lateral corticospinal tract, located in the lateral funiculus, carries most of the

descending motor fibers ♦ Lesions result in ipsilateral loss of voluntary motor control below the level of

the lesion ♦ Upper motor neuron findings (spasticity, hyperreflexia, and weakness without

significant atrophy or fasciculations) appear in the subacute-to-chronic phase ♦ Cervical fibers are located more medially, and lumbosacral fibers more

laterally ♦ Ventral corticospinal tract carries 10–20% of the descending motor fibers and

serves the axial musculature ■

Posterior columns ♦ Located near the midline at the posterior aspect of the cord; lesions result in

ipsilateral loss of proprioceptive and vibration modalities ♦ Cuneate fasciculus, carrying information from the upper extremities, is

located laterally; the gracile fasciculus, carrying information from the lower extremities, runs medially ■

Autonomic fibers ♦ Sympathetic preganglionic neuronal cell bodies reside in the lateral horn of

the spinal cord gray matter at T1–L2

♦ Parasympathetic cell bodies reside in the brainstem and in the lateral horns

at S2–S4

♦ Autonomic injury is manifested by impaired sweating, autonomic dysre-

flexia, hypotension, bradycardia, and impaired sphincter function

Specific Spinal Cord Syndromes ■

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Nosologic classification based on the presenting signs and symptoms is useful in determining the location of the lesion and the likely etiology Central cord syndrome ♦ Characterized by motor impairment in the arms greater than in the legs, with

variable sensory involvement

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♦ Occurs with cervical spine injury due to hyperextension but may also be seen

with syringomyelia ■

Anterior cord syndrome ♦ Presents with loss of pain and temperature sensation, sometimes with dyses-

thesia at the level of the lesion; vibration and proprioception are spared; motor involvement may be present ♦ Occurs with anterior spinal artery ischemia, disc herniation, or hyperflexion injuries ■

Posterior cord syndrome ♦ Characterized by loss of proprioception and vibration sense, with or without

motor involvement ♦ Classically seen with B12 deficiency and syphilis ■

Brown-Sequard syndrome ♦ Characteristically results from cord hemisection, usually due to penetrating

trauma ♦ May also be seen with compression of the lateral aspect of the cord ♦ Ipsilateral motor and proprioceptive loss with contralateral loss of pain and

temperature ■

Conus medullaris syndrome ♦ Results from compressive lesions, infection, or inflammation at the level of

the conus ♦ Due to nerve root involvement, upper and lower motor neuron findings will

be present ♦ Presents with sphincter dysfunction, perineal (“saddle”) anesthesia, and spas-

tic paraparesis ■

Cauda equina syndrome ♦ Results from dysfunction of lumbosacral nerve roots, usually due to compres-

sion; may occur with spinal anesthesia ♦ Presents with saddle anesthesia, bowel and bladder dysfunction, and lower

motor neuron findings in the lower extremities ■

Traumatic myelopathy Deficit is maximal at onset Associated injuries are common Traumatic brain injury accompanies SCI in 25–50% of cases Pain, local tenderness, and deformity are common In the presence of altered mental status, intoxication, or pain from associated trauma (“distracting injuries”), spinal precautions must be observed until spinal injury can be ruled out ♦ Care should be taken during the initial evaluation to ensure hemodynamic stability, patent airway, and adequate respiration ♦ ♦ ♦ ♦ ♦

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♦ Cervical spine should be immobilized using a spine board or hard cervical

collar ♦ Log-roll technique should be used when examining/transferring the patient

Physical Examination ■

General approach ♦ Deformity and/or tenderness to palpation over the spinal column may be

appreciated ♦ Physical examination must include an assessment of motor function, sensa-

tion to pin prick and light touch, rectal tone, deep tendon reflexes, and superficial reflexes ♦ The impairment scale of the American Spinal Injury Association (ASIA) is widely used. Assessment involves testing of sensation bilaterally in all dermatomes, as well as motor and reflex assessment at each testable level ♦ Injuries are graded “A” through “E” (Table 19.1) ♦ Spinal shock, characterized by areflexia, flaccid paralysis, and anesthesia, may be present within the first 24 h ■

Transverse myelitis ♦ Onset is acute to subacute, with progression to maximal deficit within 1–10

days in >80% ♦ History of antecedent infection, vaccination, trauma, radiation exposure, or

prior neurologic events should be sought ♦ Signs and symptoms of autoimmune disorders or collagen vascular disease

may be present ♦ Presenting symptoms often include weakness, paresthesias, and hyperre-

flexia; band-like sensation around the chest or abdomen is often described ♦ Paraparesis occurs in ~50%; tetraparesis and hemiparesis may also occur ♦ Sphincter dysfunction is common, with urinary incontinence occurring in

59% and fecal incontinence in 21%

Table 19.1  The American spinal injury association (ASIA) impairment scale A B C D E

Complete lesion - no motor or sensory function below the level of the injury Incomplete sensory loss with absence of motor function below the lesion Incomplete sensory loss, with motor strength of <3/5 in more than half of the tested muscles below the lesion Incomplete sensory loss, with ³ 3/5 motor strength in at least half of the muscles tested below the lesion Normal motor and sensory function

19  Acute Myelopathy ■

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Spinal cord infarction ♦ As in ischemic cerebral strokes, the deficit is maximal at onset when brought

about by arterial occlusion ♦ Anterior spinal artery is most commonly involved ♦ Pain, motor dysfunction, loss of pain and temperature sensation, and sphinc-

ter dysfunction are common ♦ Radicular pain at the level corresponding to the upper border of the lesion

may occur ♦ Spinal cord infarction may rarely be preceded by spinal transient ischemic

attacks ♦ Spinal arteriovenous malformations and dural arteriovenous fistulas result in

an ischemic myelopathy that presents subacutely, with asymmetric weakness, imbalance, and variable sensory loss ♦ Claudication may be present ♦ Lancinating or cramping pain may be the presenting symptom of intramedullary arteriovenous malformations

Differential Diagnosis ■

■

Clinicians must utilize clinical, epidemiologic, laboratory, and imaging elements to discern the cause of an acute myelopathy The following features may help to narrow the vast differential diagnosis of a patient with SCI ♦ Patients with TM tend to be younger (bimodal peak at ages 10–19 and 30–39

years), while patients with degenerative spine disease tend to be older ♦ Prodrome of fever, malaise, and gastrointestinal or respiratory infection

favors TM ♦ History of optic neuritis or multiple sclerosis favors TM ♦ Inflammatory spinal fluid profile with mildly elevated protein favors TM ♦ The presence of a distinct spinal cord level differentiates TM from Guillain-

♦ ♦ ♦ ♦

♦

Barré syndrome; in addition, the presence of albumin-cytologic dissociation and cranial nerve involvement favors Guillain-Barré syndrome Presence of acute symptoms with predominantly anterior cord symptoms suggests spinal cord infarct History of a prothrombotic state (deep venous thrombosis, pulmonary embolism, factor V Leiden mutation, etc.) suggests a venous infarction Stuttering symptoms in patients older than 40 years suggest dural arteriovenous fistula. Postural dependence of symptoms may also be present Fibrocartilaginous emboli are suggested by the presence of back pain and weakness following maneuvers that increase intra-abdominal or intrathoracic pressure History of radiation suggests (albeit, remotely) radiation-induced myelopathy

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♦ History of steroid use raises suspicion for epidural lipomatosis ♦ Presence of skin rash or systemic symptoms suggests myelopathy associated

with systemic disorders (lupus, Sjogren, etc.) ♦ Presence of uveitis, retinitis, or pulmonary involvement favors sarcoidosis ♦ History of systemic malignancy raises suspicion for epidural metastasis ♦ History of IV drug abuse raises suspicion for epidural abscess

Diagnosis ■

■

■

Spine imaging is the top priority in patients with acute myelopathy, as compressive myelopathy always must be ruled out Serologic markers, cerebrospinal fluid analysis, evoked potentials, and nerve conduction studies are used mainly in the evaluation of noncompressive myelopathies Neuroimaging ♦ ♦ ♦ ♦

■

Serum studies ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

■

Plain spine radiographs CT of the spine MRI of the spine Contrasted myelogram Complete blood count Sedimentation rate Coagulation studies Chemistry Viral serologies (herpes simplex 1 and 2; human immunodeficiency virus; human T-cell lymphotropic virus type 1; hepatitis A, B, and C) Mycoplasma titers Parasite serologies Lyme titers Immune markers (antinuclear antibodies, ant-DNA antibodies, complement levels, antiphospholipid antibodies, anti-Ro antibodies) Hematologic markers (protein C, protein S, antithrombin III levels) Vitamin B12 levels

Cerebrospinal fluid examination ♦ ♦ ♦ ♦ ♦ ♦ ♦

Cell count Protein Gram stain India ink Myelin basic protein Oligoclonal bands IgG index

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♦ Neuromyelitis optica antibodies (NMO) ♦ Viral polymerase chain reaction (herpes simplex 1 and 2, human herpes virus 6,

varicella zoster, cytomegalovirus, Epstein-Barr virus, enteroviruses) ♦ Fungal cultures ♦ Lyme titers ♦ Venereal Disease Research Laboratory test ■

Other studies ♦ Nerve conduction studies ♦ Evoked potentials ♦ CT of the chest

Management of Acute Myelopathy in the ICU ■

Respiratory management; as with all medical emergencies, establishing an adequate airway is the top priority ♦ Diaphragm is supplied by C3–C5 segments ♦ Injury at C3–C5 produces immediate ventilatory failure ♦ Injuries below C3–C5 preserve the diaphragm but compromise the intercostals

muscles

♦ Injuries below C3–C5 lead to contraction of the diaphragm without expansion

of the chest, resulting in decreased vital capacity and maximal inspiratory force ♦ Loss of the contribution of the abdominal muscles to expiration leads to decreased expiratory force ♦ Spasticity of the respiratory muscles ensues over time, and increases forced vital capacity and maximum expiratory force ♦ Intubation ● ● ●

●

●

●

●

Rapid shallow breathing compensates only transiently after acute SCI Atelectasis develop as a result of inefficient air movement The decision to intubate is a clinical one, and one-third of patients with cervical injuries will require intubation within 24 h Serial measurements of vital capacity may be useful, with intubation becoming necessary when it falls below 1L Patients with impaired cough mechanism, copious secretions, or decreased level of consciousness need to be intubated immediately, even if oxygenation and ventilation are normal Orotracheal intubation with in-line stabilization is safe in most patients with cervical spine injury Succinylcholine should be avoided in patients who have been weak or paralyzed for >2 days (risk of fatal hyperkalemia; peak 2–7 days)

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♦ Pneumonia ● ● ●

●

●

Leading respiratory complication after SCI Risk of pneumonia is 1–3% per day of intubation Early pneumonia is caused by Streptococcus pneumoniae or Haemophilus influenzae while late infection is caused by Pseudomonas aeruginosa or Staphylococcus aureus Presence of two of the following: temperature >38°C or <36°C, leukocytosis or leucopenia, purulent secretions, or hypoxemia suggests ventilatorassociated pneumonia Antibiotic therapy should be guided by culture identification of an organism, but it is not clear that bronchial alveolar lavages are superior to routine cultures

♦ Atelectasis ●

●

● ●

●

Most common respiratory complication, but pneumonia carries the highest morbidity and mortality Atelectasis is caused by impaired lung expansion, cephalad displacement of the abdominal contents, retained bronchial secretions, and weak cough Reduced surfactant production may contribute to atelectasis Aggressive pulmonary toilet, use of recruitment maneuvers, and adequate patient positioning are the mainstay in the treatment of atelectasis Intermittent positive-pressure breathing, increased positive end-expiratory pressure, manual inflation of the lungs with the use of an ambu bag, and the addition of sighs to the ventilator should be used to treat atelectasis

♦ Increased pulmonary secretions ● ●

●

●

●

●

●

Increased pulmonary secretions are a common problem with acute SCI An imbalance between the unopposed parasympathetic system and an inactive sympathetic system leads to increased secretions Increased secretions are a nuisance to the patient and may lead to mucus plugging Secretions return to normal a few weeks after SCI; during the early aftermath, inhaled or systemic anticholinergic agents may be effective Intrapulmonary percussive ventilation delivers high-frequency pulsations of air at rates of 100–300 cycles per min in the form of a flutter valve and can be used to loosen secretions Use of quad coughing (an assisted cough performed by delivering an abdominal thrust in synchrony with a spontaneous or assisted breath) may assist in clearing secretions Use of kinetic therapy with a rotating bed may assist with secretion management

♦ Bronchospasm ●

Occurs frequently in patients with SCI, even in the absence of any prior airway reactive disease

19  Acute Myelopathy ●

●

●

335

As in the case of increased secretions, the most likely explanation for bronchospasm is an increased unopposed parasympathetic tone Sympathetic supply to the lungs originates from the upper thoracic ganglia, while the parasympathetic arises from the vagal nucleus Inhaled anticholinergics are the mainstay in the treatment of bronchospasm

♦ Pulmonary edema ●

●

●

●

●

Pulmonary edema in SCI is most often due to fluid overload, neurogenic causes, and acute respiratory distress syndrome Aggressive fluid administration used to treat hypotension leads to fluid overload and is the leading cause of pulmonary edema Neurogenic edema occurs likely due to exaggerated pulmonary and systemic vasoconstriction Placement of a pulmonary artery catheter may help to determine the etiology of the pulmonary edema Positive-pressure ventilation, judicious use of diuretics, and inotropic support are the main treatment options

♦ Chest trauma ●

●

●

●

●

Chest trauma is a frequent and often overlooked cause of respiratory dysfunction in patients with acute SCI Pulmonary contusions, cardiac contusion (right ventricle), rib fractures with flail chest, avulsion of a bronchus, diaphragmatic rupture, hemothorax, pneumothorax, and hemopericardium are common complications of thoracic trauma Normal chest x-ray and normal arterial gasimetry do not exclude the possibility of a significant thoracic injury Highest risk of respiratory complications (up to 51%) is seen with injuries to T1–T6 Large pneumothorax or hemothorax requires tube thoracostomy, and a significant hemopericardium requires pericardiocentesis

♦ Pulmonary thromboembolism ● ●

● ●

●

●

●

Deep venous thrombosis occurs in 70–100% of patients with acute SCI Risk of deep venous thrombosis rises after 72 h post-injury and remains elevated for the first 2 weeks Most thromboembolic events in SCI occur in the first 3 months Pulmonary embolism occurs in 5% of patients with SCI and is the third leading cause of death Risk factors for pulmonary embolism include tetraplegia, male gender, and complete motor injury Pharmacologic prophylaxis with low-molecular-weight heparin should commence as soon as possible after SCI Vena cava filters should be used when pharmacologic prophylaxis is contraindicated

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The role of prophylactic retrievable vena cava filters, which can be removed after the high-risk period has resolved, remains to be determined

♦ Timing of tracheostomy ●

●

●

●

●

■

Prolonged intubation results in subglottic stenosis, tracheomalacia, and sinusitis Tracheostomy improves patient comfort, facilitates secretion management, reduces dead-space ventilation, and aids in weaning from the ventilator Tracheostomy should be separated from anterior cervical stabilization surgery by a 1–2-week period Patients with C2–C4 injuries, ASIA A injuries (“complete” cord syndrome), history of smoking, history of pulmonary disease, age > 45 years, pneumonia, and comorbid problems require tracheostomy more often Patients who are not successfully extubated after 2–3 weeks require tracheostomy

Cardiocirculatory management ♦ Acute SCI often results in hemodynamic instability ♦ Interruption of sympathetic fibers that exit the spinal cord, with resulting unop-

posed parasympathetic activity result in cardiac dysrhythmias and hypotension ♦ Most common dysrhythmia is sinus bradycardia, but supraventricular dys-

rhythmias can occur ♦ Hypotension (spinal shock) occurs in the first few days as a result of the loss

of vascular tone ♦ The classic presentation findings are hypotension with inappropriately low

heart rate ♦ Hypotension often requires the use of IV fluids and vasopressors with alpha

and beta action, as the cardiac accelerator fibers are affected ♦ Placement of a central venous line, arterial line, and assessment of cardiac

filling pressures and vascular resistance may be needed to guide fluid replacement and pressor requirements ♦ The ideal spinal cord perfusion pressure has not been determined, but hypotension is known to worsen SCI. As with the brain, perfusion is autoregulated during normal circumstances, which may be lost following injury. Observational studies suggest that a mean arterial pressure of 80–85 mmHg in the first few days may be a reasonable goal ■

Gastrointestinal and nutritional management ♦ Gastroparesis and paralytic ileus are frequent problems in acute SCI ♦ Prokinetic agents may be needed to improve gastric emptying and intestinal

peristalsis ♦ Metoclopramide and erythromycin are useful agents to treat impaired

gastrointestinal motility ♦ Stool softeners and laxatives are necessary to avoid constipation and fecal

impaction

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♦ Oral naloxone may be used to counteract opioid-induced constipation ♦ In the acute phase, patients are hypercatabolic and have increased nutritional

requirements ♦ Indirect calorimetry and/or nitrogen balance should be evaluated to determine

nutritional needs ■

Corticosteroids ♦ Use of steroids in traumatic SCI is highly controversial and cannot be recom-

♦

♦ ♦

♦

■

mended, as more recent data have negated the prominent published results that suggest benefit However, the accepted practice continues to be administration of 30 mg/kg methylprednisolone IV followed by 5.4 mg/kg/h for 23 h in patients who present within 0–3 h of injury It is less common practice to administer 30 mg/kg methylprednisolone IV followed by 5.4 mg/kg/h for 48 h in patients who present within 3–8 h of injury The original clinical studies suggested motor function improvement at 6 months in patients who receive IV steroids; however, these studies have been shown to have had serious methodologic flaws, and the observed recovery data, in fact, were no different from patients who did not receive the prescribed steroid regimen Regardless, use of steroids beyond 24 h is definitively associated with increased incidence of infections and gastrointestinal complications

Autonomic dysreflexia ♦ SCI is often associated with autonomic instability ♦ Lesions above T6 tend to produce autonomic dysreflexia ♦ Common findings include paroxysmal hypertension (can be as high as 300

mmHg systolic), bradycardia, flushing, diaphoresis, and headache ♦ Common precipitants include visceral distention and surgical manipulation ♦ Vasodilators are the main treatment modality

Prognosis ■ ■ ■

Determination of prognosis in traumatic SCI is relatively easy Prognosis determination in nontraumatic myelopathies is very complex Reasonable data are available to help to determine prognosis in TM ♦ Transverse myelitis ●

● ●

●

Neuromyelitis optica antibodies carry a poor prognosis and increase the risk of recurrence Long lesions on MRI tend to have a worse prognosis Female patients and younger patients are more likely to convert to multiple sclerosis Elevated serum glucose is associated with poor outcome

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●

Back pain, cervical sensory level, rapid progression to spinal shock, and rapid progression of symptoms are associated with poor outcome Roughly one-third of patients recover with no sequelae, one-third are left with moderate disability, and one-third are left with severe disability

♦ Complete tetraplegia ●

● ●

●

Complete tetraplegia carries poor prognosis; most recovery occurs during the first 3 months Most patients recover one root level Initial strength of the muscle is a strong predictor of outcome; if the first level of injury has 0/5 strength at 72 h only 30% of patients will recover to 3/5 in that muscle Muscle strength levels of 0/5 at 1 month have only a 10% chance of improvement

♦ Incomplete tetraplegia ●

●

●

Possibility of recovery is two times higher with incomplete tetraplegia (as compared to complete injuries) Patients with incomplete injuries with preserved pinprick sensation have better outcome than do patients with preserved light touch Most motor recovery occurs within the first 6 months after injury

♦ Complete paraplegia ● ●

●

Potential for recovery is significantly higher in patients with SCI below T9 Up to 55% of patients with neurologic injury below T11 will recover function significantly Most movement is regained in the proximal leg musculature, reflecting possible “root escape”

♦ Incomplete paraplegia ● ●

●

■

Best prognosis seen in patients with incomplete paraplegia Up to 80% of patients with incomplete paraplegia will recover antigravity hip flexion and knee extensors at 1 year Recovery in patients with incomplete paraplegia may take up to 1 year

Late recovery ♦ The Model Spinal Cord Injury System data indicate that up to 16% of patients

with complete injury will improve at least 1 classification grade at 1 year ♦ At 1 year, 6% of patients who were initially grade A (“complete”) convert to

grade B (“incomplete” with some sensory return) ♦ Late conversion can occur even years after SCI, usually to grade B or C

(“incomplete” with some motor function return) ■

Other predictors of recovery ♦ Spinal shock is associated with a more rapid progression of injury and a

worse prognosis

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♦ Persistence of the delayed plantar flexor response has high correlation with

complete injury and poor outcome ♦ Presence of cross adductor reflex in the acute stage is associated with good

outcome ♦ Older patients tend to have worse outcome ♦ Normal MRI cord signal is a good prognostic sign ♦ Intramedullary hemorrhage carries poor prognosis

Key Points ■

■

■

■

Myelopathies are commonly encountered in the ICU setting from traumatic SCI, TM and spinal cord infarctions Etiologic diagnosis and recognition of specific syndromes can provide valuable insights into further management and prognosis ICU management of patients with acute myelopathies centers on the cardiopulmonary systems and autonomic dysreflexia Determination of prognosis in traumatic SCI is relatively easy, but it is complex in nontraumatic myelopathies

Suggested Reading Ball PA (2001) Critical care of spinal cord injury. Spine 26:S27–S30 Berly M, Shem K (2007) Respiratory management during the first five days after spinal cord injury. J Spinal Cord Med 30:309–318 Brinar VV, Habek M, Brinar M,et al (2006) The differential diagnosis of acute transverse myelitis. Clin Neurol Neurosurg 108:278–283 de Seze J, Stojkovic T, Breteau G et al (2001) Acute myelopathies: Clinical, laboratory, and outcome profiles in 79 cases. Brain124:1509–1521 Ho CH, Wuermser L, Priebe MM et al (2007) Spinal cord injury medicine. 1. Epidemiology and classification. Arch Phys Med Rehabil 88(3 Suppl 1):S49–S54 Hummers LK, Krishnan C, Casciola-Rosen L et al (2004) Recurrent transverse myelitis associates with anti-Ro (SSA) autoantibodies. Neurology 62(1):147–149 Kaplin AI, Krishnan C, Deshpande DM, et al. (2005) Diagnosis and management of acute myelopathies. Neurologist 11:2–18 Kim JH, Lee SI, Park SI, Yoo WH (2004) Recurrent transverse myelitis in primary antiphospholipid syndrome – case report and literature review. Rheumatol Int 24(4):244–246 Novy J, Carruzzo A, Maeder P, Bogousslavsky J (2006) Spinal cord ischemia: Clinical and imaging patterns, pathogenesis, and outcomes in 27 patients. Arch Neurol 63:113–1120 Nowak DA, Mutzenbach S, Fuchs H-H (2004) Acute myelopathy. Retrospective clinical, laboratory, MRI, and outcome analysis of 49 cases. J Clin Neurosci 11:145–152 Sekhon LHS, Fehlings MG (2001) Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 26:S2–S12 Wuerner L-A, Ho Chiodo AE et al (2007) Spinal cord injury medicine. 2. Acute care management of traumatic and nontraumatic injury. Arch Phys Med Rehabil 88(3 Suppl):55–61

Chapter 20

Ischemic Stroke Neeraj S. Naval and Anish Bhardwaj

Definitions ■

■

Ischemic stroke: Focal neurologic deficit referable to the CNS that corresponds to an arterial territory Transient ischemic attack (TIA) ♦ Stroke symptoms resolve within <24h, typically within <1h ♦ Might be related to transient hypotension in the setting of critical stenosis or

could be secondary to a clot/embolus, with subsequent recanalization of obstructed vessel

Epidemiology ■ ■

■ ■ ■

Account for 80% of all strokes Third highest cause of mortality in the US after heart disease and cancer in patients >40years of age One stroke worldwide every 45s, one death due to stroke every 3min Leading cause of disability worldwide Disability has significant impact on productivity of person and healthcare costs (~$40 billion/year)

N.S. Naval, MD Neuroscience Critical Care Fellowship Program, Oregon Health and Science University, Portland, OR, USA A. Bhardwaj, MD, FAHA, FCCM, FAAN (*) Department of Neurology, Tufts University School of Medicine, Tufts Medical Center, Box 314, 800 Washington Street, Boston, MA 02111, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_20, © Springer Science+Business Media, LLC 2011

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N. Naval and A. Bhardwaj

Ischemic Stroke Subtypes ■

Embolic ♦ Cardioembolic ♦ Artery-to-artery embolus ♦ Paradoxic embolism (deep venous thrombosis → right atrium → patent

­foramen ovale → systemic circulation)

■

Thrombotic ♦ ♦ ♦ ♦ ♦ ♦ ♦

Intracranial atherosclerosis Lipohyalinosis Arterial dissection Arteritis Fibromuscular dysplasia Vasospasm Hypercoaguable states

Risk Factors ■

Modifiable ♦ ♦ ♦ ♦ ♦

■

Diabetes mellitus Hypertension Smoking Hypercholesterolemia Coronary artery disease

Non-modifiable ♦ Age ♦ Male sex ♦ Family history

Specific Stroke Mechanisms by Etiology ■

Atrial fibrillation ♦ Blood clots typically within dilated left atrium or on atrial appendage second-

ary to stasis or turbulence lead to embolic stroke, most commonly to inferior division of the middle cerebral artery ■

Carotid stenosis ♦ Caused by atherosclerosis of the carotid artery distal to the carotid bifurcation

20  Ischemic Stroke

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♦ Leads to either thrombotic stroke due to significant obstruction or critical hemo-

dynamic compromise, or embolic stroke due to stasis and/or turbulence of flow ■

Intracranial atherosclerosis ♦ Focal atherosclerosis of the large intracranial vessels of the circle of Willis ♦ Clues: Perfusion-dependent ischemia, recurrent TIA/stroke in the same vas-

cular territory ■

Vertebral or carotid dissection ♦ Intimal tear of the vertebral or carotid artery ♦ May cause stroke secondary to focal stenosis or, more commonly, embolization

■

Patent foramen ovale (PFO) ♦ Paradoxic embolization of venous thrombi via right to left shunt due to failure

of closure of the foramen ovale ♦ High index of suspicion in patients with a known deep vein thrombosis (DVT) ♦ PFO present in 15% of the normal population; 50% of patients with crypto-

genic stroke ♦ Incidence of stroke higher when PFO is associated with concurrent atrial

septal aneurysm ■

Dilated cardiomyopathy ♦ Stasis and turbulence of blood flow within dilated ventricle causes intralumi-

nal thrombus formation, leading to embolic stroke ♦ Increasing risk for stroke with decreasing ejection fraction, especially

if <30% ■

Watershed infarcts ♦ Ischemic stroke involving the watershed region between two vascular territo-

ries due to reduction in perfusion pressure (e.g., intraoperative or intraprocedural hypotension) ♦ Most commonly occurs between the middle cerebral artery (MCA) and anterior cerebral artery (ACA) territories (man-in-barrel syndrome: bilateral proximal arm/leg and trunk weakness) or deep and superficial branches of MCA ■

Primary CNS vasculitis ♦ Autoimmune ♦ Inflammatory disease of medium- and small-sized cerebral arteries; occurs in

the absence of other systemic vasculitic manifestations ♦ Usually characterized by step-wise neurologic deficits ■

Lacunar strokes ♦ Lipohyalinosis of penetrating arteries secondary to long-standing hyperten-

sion; diabetes with small thrombotic strokes in basal ganglia, thalamus, pons, middle cerebellar peduncle

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N. Naval and A. Bhardwaj

Hypercoaguable states ♦ Could be embolic or thrombotic mechanism ● ●

● ● ● ● ● ●

■

Factor V Leiden mutation Antiphospholipid antibodies (lupus antibodies) Factor C or S deficiency Antithrombin III deficiency Prothrombin Gene (G21201A) mutation Hyperhomocysteinemia Oral contraceptives Malignancy

anticoagulant/anti-cardiolipin

Rare causes of ischemic stroke ♦ Mitochondrial myopathy encephalopathy lactic acidosis and strokes

(MELAS) ♦ Cerebral autosomal dominant arteriopathy subcortical infarcts and leukoen-

cephalopathy (CADASIL) ♦ Fibromuscular dysplasia

Symptoms by Subtype ■

Thrombotic strokes are more likely to have a progressive or stuttering course ♦ May be sensitive to fluctuations in blood pressure with resolution/amelioration

of symptoms with induced hypertension in the setting of perfusion-dependent critical stenosis ■

Embolic strokes are usually maximal at onset ♦ More likely to be multiple in number, either in a single or multiple arterial

distributions, often bilateral ♦ MCA territory most commonly involved ♦ May be associated with seizures at onset ■

Lacunar strokes are more likely to have a stuttering course ♦ May have abnormality restricted to a single aspect of neurologic exam (pure

motor or pure sensory or cerebellar) ■

Watershed strokes, especially from large-vessel insufficiency, usually have a sudden course with sustained hypotension for any significant length of time, but could be characterized by recurrent stereotypical TIAs

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Symptoms by Location ■

Anterior circulation stroke syndromes ♦ MCA stroke syndromes ●

●

●

M1 occlusion: Face/arm/leg weakness, hemisensory loss, homonymous hemianopsia, eye deviation toward the lesion/away from side of weakness, global aphasia (dominant lobe) or anosagnosia/hemineglect (usually, but not exclusively, nondominant lobe) Superior division: Face + arm > leg weakness, expressive aphasia, eye deviation toward the lesion, some hemisensory loss Inferior division: Homonymous hemianopia or quadrantanopia, receptive aphasia (dominant) or neglect (nondominant)

♦ ACA stroke syndromes ●

Contralateral leg weakness, proximal (deltoid) upper-extremity weakness; If bilateral ACAs arise from a single origin, occlusion leads to paraplegia, abulia, and personality changes (psychomotor slowing, depression)

♦ Specific parietal lobe syndromes ●

●

Gerstmann syndrome (finger agnosia, left/right confusion, acalculia, agraphia): Dominant inferior parietal lobule Apraxias ▲ Dominant hemispheric involvement; inability to perform complex,

learned movements with preserved (ideomotor) or impaired (ideational) understanding of the intended movement; clumsiness of skilled acts (limb-kinetic apraxia) ▲ Nondominant hemispheric involvement; dressing apraxia; constructional apraxia ■

Posterior circulation stroke syndromes ♦ Anton syndrome ● ●

Bilateral cortical blindness with denial of blindness Visual hallucinations

♦ Balint syndrome ● ●

● ●

Bilateral occipitoparietal strokes Simultagnosia (inability to synthesize disparate images within the visual field into a coherent whole) Optic ataxia (inability to reach targets under visual guidance) Gaze apraxia (inability to direct gaze at a target)

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N. Naval and A. Bhardwaj

♦ Prosopagnosia ● ● ●

Bilateral occipitotemporal strokes Inability to recognize and identify familiar faces Inability to interpret facial expressions

♦ Alexia without agraphia ●

Dominant occipital lobe and splenium of the corpus callosum due to posterior cerebral artery stroke

♦ Dejerine–Roussy syndrome ● ●

■

Thalamic ventroposterior lateral and/or ventroposterior medial stroke Hemisensory loss followed by painful paresthesias during recovery of sensory function

Common brainstem syndromes ♦ Weber syndrome ●

Midbrain stroke; ipsilateral CN III lesion and contralateral hemiparesis

♦ Claude syndrome ●

Midbrain stroke; ipsilateral CN III lesion and contralateral ataxia/tremor

♦ Benedikt syndrome ●

Midbrain stroke; ipsilateral CN III lesion and contralateral hemiparesis and ataxia/tremor

♦ Peduncular hallucinosis ●

Midbrain stroke; well-formed “cartoonish” visual hallucinations

♦ Wallenberg syndrome ●

● ● ● ● ● ●

■

Lateral medullary stroke due to occlusion of the vertebral or posterior inferior cerebellar artery Ipsilateral CN V, IX, X, XI palsy Ipsilateral Horner syndrome Nausea, vertigo, nystagmus, hiccups Ataxia Contralateral hemianesthesia No motor weakness

Lacunar syndromes ♦ ♦ ♦ ♦

Pure motor hemiplegia; internal capsule or ventral pontine stroke Pure sensory stroke; lateral thalamic stroke Clumsy hand-dysarthria; paramedian pontine stroke Ataxic hemiparesis; pontine stroke

20  Ischemic Stroke

347

Investigations ■

Head CT (noncontrast) ♦ Rules out hemorrhage ♦ Early signs of stroke such as sulcal effacement or loss of grey-white matter

differentiation ♦ Significant hypodensity evolves after 24–48h ♦ Hyperdense vessel (MCA) sign (hyperdensity along an occluded vessel) ♦ MCA dot sign (clot in MCA branches within the sylvian fissure) ■

MRI ♦ MRI is the gold standard ♦ DWI (diffusion-weighted imaging); bright signal with correlating dark signal on

ADC (apparent diffusion coefficient); appears within 30min, lasts for 1week ♦ PWI (perfusion-weighted imaging) shows tissue at risk and distinguishes

ischemic (at-risk) from infarcted tissue ■

4-vessel cerebral angiography/MRA/CTA ♦ Delineates detailed intracranial and extracranial vasculature ♦ 4-vessel digital-subtraction angiography (DSA, gold standard) > 3D CTA > MRA

■

Carotid Doppler ultrasound ♦ Carotid bruit is 60–80% specific for carotid stenosis >50% among patients

with stroke or TIA (symptomatic bruit) ♦ Carotid bruit is only 30–60% sensitive for carotid stenosis >50% among

asymptomatic patients ■

Echocardiography ♦ Transthoracic (TTE) or transesophageal (TEE) ♦ Indicated for evaluation for dilated cardiomyopathy, intracardiac thrombus,

atrial fibrillation, PFO ♦ TTE usually performed first, yield for intracardiac thrombus higher with TEE

(95% sensitivity) compared to TTE (60% sensitivity) ■

Transcranial Doppler ♦ Identifies vessel occlusion/stenosis using blood flow velocities ♦ PFO may be diagnosed by bubble TCD, especially with valsalva maneuver

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Lab testing ♦ ♦ ♦ ♦ ♦

Hypercoaguable work up (select cases) Lipid profile HbA1c ANA, ESR RPR

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Treatment ■

tPA (tissue plasminogen activator) ♦ IV tPA is FDA approved for treatment of acute ischemic stroke within 3h of

onset ♦ 30% more likely to have no or minimal deficit at 90 days than those not

receiving drug ♦ Risk of ICH is 6%, of which 3% are fatal ♦ Contraindicated in patients with rapidly resolving deficits, prior stroke or

head trauma <3months, major surgery <14days, prior ICH, uncontrolled BP (SBP >185, DBP >110mmHg) despite two doses of IV antihypertensives (continuous infusions not permitted), GI or urinary tract hemorrhage <21days, elevated PT/PTT, platelets <100,000, blood glucose <50 or >400 ♦ IA tPA is NOT FDA approved and is an investigational/experimental drug ●

●

■

To be used for similar indications as IV tPA, except time window is 3–6h (anterior circulation) and 3–48h for basilar thrombosis; use only in setting of MRI-proven diffusion-perfusion mismatch and intraluminal thrombus Efficacy better for embolic strokes (red clot) compared to intracranial atherosclerosis (white clot)

Induced hypertension ♦ Acute stroke with MRI evidence of diffusion-perfusion mismatch of >20% ♦ Stroke volume <145mL ♦ Trial of pressors to 10–20% increase in mean arterial pressure; if deficit

resolves/improves, target MAP 10% higher than critical threshold, start midodrine and florinef, hold all home antihypertensives ♦ Supportive evidence is limited ■

Heparin ♦ Bridge to warfarin (cardioembolic source) ♦ No other definite indication for IV or low-molecular-weight heparin

(LMWH) ♦ May be withheld for a week in patients with large stroke ♦ No reduction in early stroke recurrence in all comers with acute ischemic stroke ♦ IV heparin is still used for dissection, stroke-in-evolution, and vertebrobasilar

insufficiency, but not evidence-based ■

Warfarin ♦ ♦ ♦ ♦ ♦ ♦

Atrial fibrillation Dilated cardiomyopathy with ejection fraction <30% Hypercoaguable states ? Carotid/vertebral dissection ? Aortic arch atherosclerosis INR goal 2–3; higher in antiphospholipid antibody syndrome

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Antiplatelet therapy ♦ Aspirin conventionally used; appropriate dose unclear ♦ No benefit of adding aspirin to clopidogrel for secondary prevention ♦ Aspirin/dipyridamole superior to aspirin or clopidogrel alone

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Statins ♦ Used for both primary and secondary prevention of stroke ♦ Most optimal statin; ideal dose unclear

■

Surgical/endovascular options ♦ Carotid endarterectomy (CEA) for symptomatic patients with carotid artery

stenosis >70% and select cases of 50–69% stenosis ♦ CEA for asymptomatic >60% carotid stenosis in select patients ♦ Carotid stenting/angioplasty reasonable alternative in patients with medical

comorbidities (high surgical risk) due to age >80, chronic obstructive pulmonary disease, congestive heart failure, unstable angina ♦ Extracranial-intracranial bypass optional in select cases [Superior temporal artery (STA)-MCA Bypass] ♦ MERCI (mechanical embolus removal in cerebral ischemia) device for acute stroke in patients contraindicated for tPA ♦ Hemicraniectomy for large strokes with intractable intracranial hypertension ■

Other treatments ♦ Peptic ulcer prophylaxis with H2 blocker or 5HT3 blocker ♦ DVT prophylaxis with subcutaneous heparin or, preferably, LMWH

Management of Acute Stroke in ED ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■

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ABCs Establish IV access (two PIVs) History (time of onset) Medication history (Coumadin?) Past medical history Vital signs assessment Quick-look neurologic exam (NIHSS) Baseline labs, including blood sugar, coagulation profile, platelets EKG STAT head CT 0–3h time of onset and meets IV tPA criteria, review history, labs and NIHSS, consent for IV tPA If SBP >185 and not controlled with two IV boluses, DO NOT give IV tPA; use of IV infusions prior to IV tPA not permitted If IV tPA is administered, give 0.1mg/kg bolus over 1min, followed by 0.9mg/kg infusion over 1h

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Maintain SBP during and after IV tPA infusion at SBP goal <180mmHg Frequent neurochecks during and for 24h after administration of tPA If 3–6h time of onset, get MRI brain with DWI/PWI sequences for possible IA tPA If significant mismatch, call neurointerventional radiology for angiogram and possible IA tPA or mechanical thrombolysis (MERCI) If no tPA administered, maintain SBP goal <220mmHg; do not treat unless SBP >220 (unless coexisting significant cardiac disease) Consider induced hypertension in select cases 325mg aspirin if no tPA given Statins/HMG CoA reductase inhibitors Tight glycemic control (80–110mmHg for 24h, <185mmHg subsequently— controversial) Peptic ulcer prophylaxis DVT prophylaxis (LMWH preferred to unfractionated subcutaneous heparin if nonambulatory) Antidepressant medications/counseling in some cases Speech and swallowing therapy consult; assess ability to safely tolerate PO intake Physical therapy/occupational therapy consult Decubitus ulcer watch, frequent turning

Complications ■

Cerebral edema ♦ Maintain sodium goal of 135–145mEq/L if asymptomatic ♦ In setting of worsening neurologic exam/mental status secondary to cerebral

♦ ♦ ♦ ♦ ♦

■

edema, use hypertonic saline (3%), with goal Na 145–155mEq/L (requires central venous access) Intubation for airway protection followed by short-term hyperventilation is also recommended Transfer to NCCU for closer monitoring In setting of clinical herniation, consider 1g/kg mannitol or 23.4% saline 30mL×1 dose For definitive treatment, hemicraniectomy is advisable, especially if age <60years, independent of lateralization of stroke In patients with complete MCA or ICA strokes, early hemicraniectomy (0–48h) may be advisable

Hemorrhagic conversion ♦ Observed with larger strokes, and heparin use, at higher blood pressures ♦ Follow patient clinically; treat as necessary if increased mass effect

20  Ischemic Stroke ■

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Seizures ♦ Incidence, 4–8%, more common with embolic strokes, cortical strokes, and

following hemorrhagic transformation ♦ No data support prophylaxis for seizures ♦ Treat with fosphenytoin or other AED if patient has a seizure

Subsequent Care ■

Secondary prevention of stroke ♦ Anti-platelet agents: aspirin, clopidogrel, ticlopidine; dipyridamole/aspirin

combination possibly superior to other options ♦ Statins/HMG CoA reductase inhibitors ♦ Smoking cessation ♦ Treatment of hypertension (ACE inhibitor in combination with thiazide

diuretic preferred) ♦ Tight glycemic control ■

Stroke rehabilitation ♦ Acute inpatient rehabilitation for some patients; different levels of assistance

with activities of daily living for others ♦ Encourage family participation and involvement in patient rehabilitation ♦ Tracheostomy, and/or percutaneous endoscopic gastrostomy tube placements

for some patients for assistance with airway protection, breathing, and feeding ♦ Speech therapy ♦ Counseling, antidepressant medications for select patients

Key Points ■

■

■

■

Both ischemic stroke and ICH may present with an acute onset of focal neurologic deficit that is readily differentiated with a noncontrast CT of brain Patients with ischemic stroke should be evaluated rapidly and efforts made to administer IV tPA; other acute treatment modalities (IA tPA, stenting, angioplasty, or blood pressure augmentation) should be considered All patients with TIA or stroke should be investigated thoroughly to determine etiology, and modifiable risk factors should be treated Normonatremia, normoglycemia, and normothermia should be maintained in patients with acute stroke; institution of DVT and GI prophylaxis, prevention of decubitus ulcers, investigation and treatment of possible infections and early institution of physical and occupational therapy are paramount for good outcome

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Neurologic worsening in stroke patients should be systematically investigated; threshold should be low for admission to an ICU setting

Suggested Reading Ardelt AA. Bhardwaj A, Mirski MA, Ulatowski JA (eds) (2004) Ischemic stroke in handbook of neurocritical care. Totowa, NJ, Humana Press Caplan LR (2000) Stroke: a clinical approach. Butterworth-Heinemann, Woburn, Massachusetts Osborn AG (1994) Diagnostic neuroradiology. Philadelphia, Mosby

Chapter 21

Intracerebral Hemorrhage Neeraj S. Naval and J. Ricardo Carhuapoma

Epidemiology ■ ■ ■

■ ■

Intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes 67,000 cases of nontraumatic ICH are reported annually in the US Reported 30-day mortality rates range between 35 and 52%, the highest associated with any kind of stroke Only 20% of survivors are functionally independent at 6 months More common in males, persons >55 years of age, and in certain ethnic groups (Blacks, Japanese)

Pathophysiology (Table 21.1) ■ ■

ICH can be divided based on etiology or location Etiology ♦ Primary/Spontaneous (related to hypertension) ♦ Secondary (related to aneurysms, AV malformation, tumors, amyloid angiop-

athy, coagulopathies, or trauma) ■

Location ♦ Supratentorial (lobar, deep thalamus, basal ganglia) ♦ Infratentorial (brainstem, cerebellum), ± intraventricular hemorrhage (IVH),

± subarachnoid hemorrhage (SAH) N.S. Naval, MD Neurosciences Critical Care Fellowship Program, Oregon Health & Science University, Portland, OR, USA J.R. Carhuapoma, MD (*) Neurosciences Critical Care Division, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_21, © Springer Science+Business Media, LLC 2011

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Table 21.1  Causes, means of diagnosis, and characteristics of intracerebral hemorrhage Primary Means Causes of Diagnosis Characteristics a Hypertension Clinical history Rupture of small arterioles related to degenerative changes induced by uncontrolled hypertension; the annual risk of recurrent hemorrhage of 2%5 can be reduced by treatment of hypertension Amyloid angiopathy Clinical historya Rupture of small and medium-sized arteries, with deposition of b-amyloid protein; presents as lobar hemorrhages in persons older than 70 years of age; annual risk of recurrent hemorrhage of 10.5%6 Rupture of abnormal small vessels Arteriovenous Imaging studies such as connecting arteries and veins; the annual malformation magnetic resonance risk of recurrent hemorrhage of 18%7 angiography and conventional can be reduced by surgical excision, angiography embolization, and radiosurgery Rupture of saccular dilatation from a Intracranial Imaging studies such as medium-sized artery that is usually aneurysm magnetic resonance associated with subarachnoid angiography and hemorrhage; risk of recurrent conventional hemorrhage of 50% within the first 6 angiography months, which decreases to 3% per year8; surgical clipping or placement of endovascular coils can significantly reduce the risk of recurrent hemorrhage Rupture of abnormal capillary-like vessels Cavernous angioma Imaging studies such as with intermingled connective tissue; magnetic resonance annual risk of recurrent hemorrhage imaging of 4.5%9 can be reduced by surgical excision or radiosurgery Rupture of abnormal dilatation of venules; Venous angioma Imaging studies very low annual risk of recurrent such as magnetic hemorrhage (0.15%)10 resonance imaging and conventional angiography Result of hemorrhagic venous infarction; Dural venous sinus Imaging studies such as anticoagulation and, in rare cases, thrombosis magnetic resonance trans-venous thrombolytic agents can venography and improve outcome; risk of recurrent conventional dural venous thrombosis of 10% within angiography first 12 months and of less than 1% thereafter11 Results of necrosis and bleeding within Intracranial neoplasm Imaging studies such as hypervascular neoplasms; longmagnetic resonance term outcome determined by the imaging characteristics of the underlying neoplasm (continued)

21  Intracerebral Hemorrhage Table 21.1  (continued) Primary Means Causes of Diagnosis Coagulopathy

355

Characteristics

Clinical historya

Most commonly associated with use of anticoagulants or thrombolytic agents; rapid correction of underlying abnormality important to avert continued bleeding Vasculitis Measurement of serologic Rupture of small or medium-sized arteries with inflammation and degeneration; and cerebrospinal fluid immunosuppressive medications may be markers; brain biopsy indicated Cocaine or alcohol Clinical historya Underlying vascular abnormalities may be use present Hemorrhage in region of cerebral infarction Hemorrhagic Imaging studies as a result of ischemic damage to bloodischemic stroke such as magnetic brain barrier resonance imaging and conventional angiography a Imaging studies such as magnetic resonance imaging and conventional angiography can provide supportive evidence Reproduced from Spontaneous Intracerebral Hemorrhage, Qureshi et  al., NEJM Volume 344: 1450–60

Clinical Presentation ■ ■

Sudden onset headache Focal neurologic signs ♦ Hemiplegia, aphasia, hemi-neglect, visual field cut (location dependent)

■

Global neurologic signs ♦ Altered mental status [possibly related to primary injury or secondary to

complications such as increased intracranial pressure (ICP)] ■

■

■

Seizures (more common in lobar ICH, especially temporal lobe); could present as status epilepticus (nonconvulsive in some patients) Cranial nerve deficits with primary brainstem hemorrhage or secondary to brainstem compression by supratentorial hemorrhage Airway compromise, irregular breathing, hypertensive crisis, Cushings triad (hypertension, bradycardia, respiratory irregularities) in the setting of increased ICP

Diagnosis (Table 21.1) ■

Noncontrast head CT for early diagnosis ♦ Hyperintense lesion with surrounding hypodense rim likely suggestive of

perihematomal edema

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Other features visible on head CT ♦ ♦ ♦ ♦ ♦

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IVH Hydrocephalus Early signs of herniation Midline shift Underlying calcific mass/aneurysm

ABC method for rough estimation of ICH volume, where A is maximum length, B is width perpendicular to A, and C is thickness (slice thickness X number of slices) ♦ ICH volume = ABC/2

■

Expansion of hematoma by >33% in up to 38% patients ♦ Usually appreciated in the first 4 h in 26% ●

■

■

· 4–20 h in remaining 12%

CT angiogram (CTA)/contrast-enhanced CT (CECT) useful in evaluating for ongoing bleeding by visualization of “Spot sign” or contrast extravasation following injection of contrast; also helps in better visualization of underlying mass (CECT) or aneurysm/arteriovenous malformation (CTA) MRI may be used in evaluating for previous ICH (amyloid angiopathy), underlying mass (MRI with gadolinium) ♦ Gradient ECHO (GRE) sequences preferred for visualization of blood prod-

ucts (hemosiderin, etc.) ♦ MRA for vascular malformations ■

Also useful in assessing age of bleed via MRI, based on following pneumonic: ♦ It Be IdDy BiDdy BaBy DooDoo (3–7 rule; Table 21.2)

Indication for Cerebral angiogram/CTA (any of the following) ■ ■

Age <45 No history of hypertension or nonhypertensive on admission

Table 21.2  3–7 rule Phase Hyperacute Acute Early subacute Late subacute Chronic

Age <7 h 7 h–3 days 3 days–7 days 7 days–3 weeks >3 weeks

T1 Isointense Isointense Bright Bright Dark

T2 Bright Dark Dark Bright Dark

21  Intracerebral Hemorrhage ■

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Location not typical for hypertensive bleeds (basal ganglia, thalamus, cerebellum, pons) Yield of angiogram in patient >45 years, known history of hypertension, and location typical for hypertensive bleed virtually nil

Prognosis ■

Factors that suggest worse prognosis ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

Older age GCS on admission <8 ICH volume >30 mL Associated IVH (especially high volume) Hydrocephalus Infratentorial Location ? Coagulopathy/antiplatelet use ? Increased pulse pressure

Management ■

Emergent―ABCs ♦ Airway ● ●

●

GCS <8 or rapidly worsening GCS for airway protection Uncontrolled seizures, particularly in patients with bulbar dysfunction leading to aspiration and for hyperventilation in patients with elevated ICP Consider use of lidocaine to blunt increases in ICP during endotracheal intubation

♦ Breathing ●

●

Goal of PO2 >60 with strict avoidance of hypercabia, given risk of increased ICP Hyperventilation to goal PCO2 of 28–32 in setting of increased ICP and/or clinical signs of herniation

♦ Circulation ●

● ●

CPP goal >70 (higher than goals for traumatic brain injury in patients with prior history of hypertension due to shifting of autoregulatory curve to the right). Pressors if SBP <90, arterial line monitoring preferred Volume status to be assessed, goal of euvolemia

♦ ICP monitoring if GCS <8 ● ●

Intraventricular or intraparenchymal catheters with aseptic precautions Goal ICP <20, CPP >70

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Management of Primary Injury―Hematoma Stabilization (Tables 21.3 and 21.4) ■

■

Unclear if blood pressure control plays a significant role in hematoma stabilization; clinical trials (ATACH, INTERACT) are underway Blood pressure goals as follows (AHA Guidelines, updated 2007)

IV Medications that May be Considered for Control of Elevated Blood Pressure in Patients with ICH ■

■ ■

Safe to reduce admission SBP/MAP (systolic blood pressure/mean arterial pressure) acutely by 15% in moderate to large hemorrhages More aggressive BP reduction could be considered in smaller hemorrhages Routine use of activated factor 7 (VIIA) for hemostasis is not recommended at this time

Table 21.3  Recommended guidelines for treating elevated blood pressure in spontaneous ICH 1. If SBP is >200 mmHg or MAP is >150 mmHg, consider aggressive reduction of BP with continuous IV infusion, monitoring BP every 5 min 2. If SBP is >180 mmHg or MAP is >130 mmHg, with evidence or suspicion of elevated ICP, consider monitoring ICP and reducing BP using intermittent or continuous IV medications to keep CPP >60–80 mmHg 3. If SBP is >180 mmHg or MAP is >130 mmHg, with no evidence or suspicion of elevated ICP, consider modest reduction of BP (e.g., MAP of 110 mmHg or target BP of 160/90 mmHg) using intermittent or continuous IV medications to control BP, and clinically reexamine the patient every 15 min SBP, systolic blood pressure; MAP, mean arterial pressure; BP, blood pressure; ICP, intracranial pressure; CPP, cerebral perfusion pressure.

Table 21.4  IV Medications that may be considered for control of elevated BP in patients with ICH Drug IV Bolus Dose Continuous Infusion Rate Labetalol 5–20 mg q 15 min 2 mg/min (maximum 300 mg/d) Nicardipine NA 5–15 mg/h Esmolol 250 mcg/kg IVP loading dose 25–300 mcg kg-1 min-1 a Enalapril 1.25–5 mg IVP q 6 h NA Hydralazine 5–20 mg IVP q 30 min 1.5–5 mcg kg-1 min-1 Nipride NA 0.1–10 mcg kg-1 min-1b Nitroglycerin NA 20–400 mcg/min IVP, intravenous push; NA, not applicable a  Because of risk of precipitous lowering of blood pressure, the enalapril first test dose should be 0.625 mg b  High risk of metabolic acidosis with prolonged infusions above 2 mcg/kg/min

21  Intracerebral Hemorrhage ■

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■

359

Reverse coagulopathy secondary to warfarin with fresh frozen plasma and IV (or PO) vitamin K Protamine sulfate should be used to reverse heparin-associated ICH, with the dose dependent on the time from cessation of heparin Role of alternative options such as platelet transfusions in ICH patients on aspirin and the use of prothrombin complex concentrates is being studied

Management of Secondary Injury ■ ■

■

■

Head of bed elevation to >30° Titrate sedation to minimize pain and increases in ICP while enabling evaluation of patient’s clinical status Hyperventilation for acute lowering of ICP, with goal PCO2 28–32; chronic hyperventilation not recommended but slow return to normocarbia to prevent rebound increase in ICP Hyperosmolar therapy for increased ICP ♦ Edema amelioration by use of mannitol or hypertonic saline (3% infusion,

23.4% bolus) in setting of clinical deterioration or acute herniation; Na+ goal 145–155 or serum osmolality goal 300–320 mOsm/L ♦ No proven role of prophylactic hyperosmolar therapy ♦ Maintain euvolemia during hyperosmolar therapy ■

■ ■

ICP monitoring with drainage of CSF by intraventricular catheter placement in setting of hydrocephalus/IVH Pharmacologic coma for refractory intracranial hypertension Surgical intervention optional for decompressive hemicraniectoy, especially in younger patients

Surgical Options ■

■

As a general rule, early surgical intervention for clot evacuation via craniotomy has no advantage over medical management Exceptions ♦ Cerebellar hemorrhages >3 cm with fourth ventricular effacement/hydrocephalus ♦ Lobar hemorrhages with worsening neurologic exam secondary to hematoma

expansion ■

■

Minimally invasive surgical options currently under investigation include stereotactic clot evacuation using clot lysis with tPA followed by clot aspiration Decompressive hemicraniectomy ♦ Efficacy demonstrated in ischemic infarction ♦ Possible option in ICH

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Other Management Issues ■ ■

Seizures in 14–28% of lobar hemorrhages, 4% in deep hemorrhages Prophylaxis may be considered for cortically based hemorrhages, especially in patients with poor clinical exam ♦ Short-term prophylaxis of 1–2 weeks recommended

■

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■

Consider continuous EEG monitoring in comatose patients or patients with neurologic deterioration with ICH Persistent hyperglycemia (>140 mg/dL), especially during the first 24 h to be avoided Goals of normothermia ♦ Use of hypothermia may be considered in the setting of refractory intracranial

hypertension ■

DVT prophylaxis to be initiated immediately with TEDS (thromboembolic disease stockings) and/or SCD (sequential compression device), add subcutaneous heparin early (24 h post-ICH is reasonable)

ICH Recurrence Prevention (Figs. 21.1 and 21.2) ■ ■

Control hypertension in the nonacute setting Avoid smoking, heavy alcohol use, and cocaine use

Key Points ■

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■

Rapid neurologic deterioration may occur secondary to hematoma expansion, accompanying edema, or hydrocephalus, leading to elevated ICP Control of BP, anti-edema therapies, and control of ICP are cornerstones of medical management Surgical evacuation can be life saving but is tailored for the individual patient, depending on age, size and location of hematoma, and comorbidities

21  Intracerebral Hemorrhage

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APPROACH TO PATIENT WITH ICH Signs and Symptoms Sudden onset of headache Decreased level of consciousness ± Lateralizing deficits (aphasia, hemiparesis/hemiplegia, field deficits) Hypertension Emergent noncontrast CT scan of brain

ICH ± IVH

Admit to ICU

ICH with IVH

Hydrocephalus

Intraventricular catheter placement with controlled CSF drainage ICP monitoring Medical management

ICH without IVH

No hydrocephalus

Medical Management Control BP to a target CPP >70 mmHg and SBP <160 mmHg; β blocker (labetalol), hydralazine, nicardipine Coagulation profile: correct coagulopathy Cardiopulmonary monitoring Neurologic monitoring q 30 min–1 hr Intubate prophylactically if GCS <8 or with compromised airway protective mechanisms 0.9% NaCl as IVF Serum Na+ goal—normonatremia to 140–145 mEq/L GI and DVT prophylaxis NPO–close monitoring for aspiration Initiate stroke work-up

CT scan QOD until significant resolution of hemorrhage and/or CSF pathway is communicating Consider angiography if location of ICH is atypical and index of suspicion for vascular anomaly is high

Fig. 21.1  Approach to patient with Intracerebral Hemorrhage. From Geocadin RG, Intracerebral Hemorrhage. In: Bhardwaj A, Mirski MA, Ulatowski JA, eds., Handbook of Neurocritical Care. Totowa, NJ: Human Press, 2004

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N.S. Naval and J.R. Carhuapoma APPROACH TO PATIENT WITH CEREBELLAR HEMORRHAGE Signs

Symptoms

Ataxia (appendicular or truncal) Lower cranial neuropathies Rapid deterioration in level of consciousness, e.g., lethargy, coma Dysarthria, nystagmus

Headache occipital and of sudden onset Dizziness, vertigo Inability to stand Double vision, oscillopsia Nausea and vomiting Slurred speech

Emergent non-contrast CT scan of brain

Admit to ICU

≥ 3 cm diameter hematoma in cerebellar hemisphere with rapid decline in level of consciousness or worsening brainstem function

>3 cm hematoma no hydrocephalus

<3 cm hematoma with hydrocephalus

<3 cm diameter hematoma in cerebellar hemisphere with stable neurologic exam

<3 cm hematoma no hydrocephalus or brainstem compression

Medical Management Control BP Labetalol Enalaprilat Hydralazine Maintain serum Na+ ≥140 Check coagulation profile; correct coagulopathy

Surgical evacuation of hematoma and decompression

IVC placement and CSF drainage + medical management

OR for emergent evacuation

>3 cm hematoma with hydrocephalus

IVC placement + surgical evacuation of hematoma and decompression

Fig. 21.2  Approach to patient with cerebellar hemorrhage. From Geocadin RG, Intracerebral Hemorrhage. In: Bhardwaj A, Mirski MA, Ulatowski JA, eds. Handbook of Neurocritical Care. Totowa, NJ: Human Press, 2004

Suggested Reading Broderick J, Connolly S, Feldmann E, et al. (2007) Guidlines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 38:2001–2023 Broderick JP, Brott TG, Duldner JE, et al. (1993) Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 24:987–993

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Broderick JP, Brott T, Tomsick T, et al. (1993) Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage. J Neurosurg 78:188–191 Brott T, Broderick J, Kothari R, et al. (1997) Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 28:1–5 Goldstein JN, Fazen LE, Snider R, et al. (2007) Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage. Neurology 68:889–894 Hemphill JC 3rd, Bonovich DC, Besmertis L, et al. (2001) The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 32(4):891–897 Jauch EC, Lindsell CJ, Adeoye O, et  al. (2006) Lack of evidence for an association between hemodynamic variables and hematoma growth in spontaneous intracerebral hemorrhage. Stroke 37:2061–2065 Mayer SA, Brun NC, Begtrup K, et al (2008) and FAST Trial Investigators. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 358(20):2127–2137 Mendelow AD, Gregson BA, Fernandes HM, et  al (2005) STICH investigators. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 365:387–397 Qureshi AI, Tuhrim S, Broderick JP, et al. (2001) Spontaneous intracerebral hemorrhage. N Engl J Med 344:1450–60 Zhu XL, Chan MS, Poon WS (1997) Spontaneous intracranial hemorrhage: which patients need diagnostic cerebral angiography? A prospective study of 206 cases and review of the literature. Stroke 28:1406–1409

Chapter 22

Intraventricular Hemorrhage Kristi Tucker and J. Ricardo Carhuapoma

Epidemiology ■

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■

■

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Intraventricular hemorrhage (IVH) is defined as bleeding within the ventricular system IVH can occur as a primary event or in association with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), or traumatic brain injury (TBI) “Primary IVH” is a rare occurrence in which hemorrhage is confined only to the ventricular system “Secondary IVH” denotes a hemorrhage that originates from parenchyma or subarachnoid space and extends into the ventricles IVH with ICH ♦ IVH is seen in ~36–45% of patients with ICH ♦ The presence and the volume of IVH have been demonstrated to be indepen-

dent predictors of mortality at 30 days, as are the Glasgow Coma Scale score on admission, pulse pressure, volume of ICH and hydrocephalus ♦ Mortality is even higher in those with IVH associated with warfarin use – 75% mortality ♦ ICH associated with IVH is often located in the caudate nucleus, thalamus, and basal ganglia ■

The conventional treatment of IVH when associated with symptomatic obstructive hydrocephalus includes the use of external ventricular drainage (EVD)

K. Tucker, MD Departments of Neurology and Anesthesiology/Critical Care, Wake Forest University Health Sciences, Winston-Salem, NC, USA J.R. Carhuapoma, MD (*) Neurosciences Critical Care Division, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_22, © Springer Science+Business Media, LLC 2011

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♦ The efficacy of EVD alone in modifying outcomes following IVH has been

challenged recently; however, the current standard of treatment includes CSF diversion ■

Poor prognosis for pan-ventricular hemorrhage ♦ 100% mortality when seen with ICH vs. 75% with IVH only

■

■

In one study, baseline MAP >120 was a predictor for IVH presence and for IVH growth IVH with SAH ♦ Presence of IVH significantly complicates management of intracranial pres-

sure (ICP) ♦ IVH is seen in 45% of SAH patients on first CT

• More common in those with higher Hunt and Hess grades and those with cardiovascular risk factors such as hypertension, diabetes mellitus, history of myocardial infarction; this is particularly true with aneurysms that arise in the posterior circulation ♦ IVH is significantly associated with hydrocephalus, neurologic worsening,

cerebral infarction, clinical vasospasm, need for angioplasty, and triple H therapy ♦ IVH independently predicts worse neurologic outcome as measured by Glasgow Outcome Scale (GOS) at 3 months ■

IVH with TBI ♦ Prevalence of traumatic IVH in prospective study of trauma patients who had

CT was 1.41%

♦ 70% had poor outcome (GOS £3) ♦ Expect better outcomes with isolated traumatic IVH compared to IVH seen

with other brain injuries ♦ Overall neurologic prognosis is determined by associated brain injuries ■

Primary IVH ♦ A rare occurrence, accounting for ~2% of all ICH admissions to large tertiary

referral centers ♦ Patients commonly present with headaches, nausea and vomiting, and decline

in mental status ♦ Source of bleeding can be found using conventional angiography in 56% of

cases ♦ Most common causes per angiography were arteriovenous malformations

(58%) and aneurysms (36%) ♦ 62% of patients develop hydrocephalus, and 34% require EVD ♦ 39% did not survive to hospital discharge (independent predictors of in-hospital

mortality were age and volume of IVH)

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Pathophysiology ■

■

Brain injury induced by intraventricular blood can be due to hydrocephalus, local mass effects within the ventricle, and/or potential inflammatory damage to ependymal and subependymal tissues from blood itself or from its degradation products Alternative pathophysiologic mechanisms include: ♦ Decreased cerebral perfusion/flow induced by the mechanical presence of IVH ♦ Primary mechanical compression exerted by the clot on periventricular areas

and adjacent brain regions ♦ Inflammation and fibrosis of ependymal lining

Clinical Presentation ■

■ ■

■

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Presenting symptoms vary depending on the etiology, but most often, manifestations of increased ICP, including altered mental status and nausea and vomiting are present CT scan is key for the initial diagnostic process The Graeb or LeRoux grading systems (see Table 22.1) was designed to assess the severity of IVH by characterizing the amount and location of blood in ventricles; an alternative scale is the modified Fisher scale If underlying aneurysm is suspected, patient will need four-vessel cerebral angiogram; other diagnostic modalities such as MRA or CTA have an undetermined role in the early diagnosis of aneurysmal location following SAH at this point Patients are often hypertensive on presentation, especially in cases of IVH with ICH or SAH

Table 22.1  Graeb and Le Roux systems for grading severity of IVH Graeb system Lateral ventricles Each lateral ventricle is scored separately. Maximum total score = 12.   Score 1 = trace of blood or mild bleeding 2 = less than half of the ventricle filled with blood 3 = more than half of the ventricle filled with blood 4 = ventricle filled with blood and expanded Third and fourth ventricles   Score 1 = blood present, ventricle size normal 2 = ventricle filled with blood and expanded LE ROUX system Each ventricle is scored separately and a total score calculated. Maximum score = 16. 1 = trace of intraventricular blood   Score 2 = less than half a single ventricle filled with blood 3 = more than half the ventricle filled with blood 4 = entire ventricle filled and expanded with blood

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Management ■

Systemic hypertension should be treated ♦ The ideal blood pressure goal is unclear at this point and may vary within

individual patient populations ♦ When elevated ICP is a concern, ICP monitoring is suggested to tailor blood

pressure management to cerebral perfusion pressure goals ■

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■ ■

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Check PT/PTT/INR and CBC, including platelets; coagulopathy must be rapidly corrected Must perform serial neurologic examinations; watch for hydrocephalus, particularly if a large amount of blood is present within the ventricles Repeat CT scan for any change in neurologic exam Neurosurgeons must be aware of these patients, as placement of an EVD system may become rapidly indicated Use of fibrinolytic agents to accelerate intraventricular clot lysis is the subject of current research, and results are awaited ♦ As with any other experimental therapy, such therapies could be administered

off-label in individual cases after careful discussion with patients or their surrogates regarding involved risks

Key Points ■

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In adults, IVH is associated with primary ICH (40%), SAH (10–28%), or severe TBI Primary IVH is rare, and secondary causes include intraventricular neoplasms (meningiomas, ependymomas, metastatic tumors), cocaine use, pituitary apoplexy, eclampsia, vascular malformations, and rarely, aneurysms Mortality and morbidity are increased if IVH is associated with obstructive hydrocephalus, elevated ICP, deleterious effects of breakdown products of blood clot that lead to communicating hydrocephalus, direct mechanical compression of periventricular structures, and ventriculitis Externalized CSF drainage via placement of an EVD is usually indicated (especially with accompanying obstructive hydrocephalus) Local infusion of thrombolytic agents (rtPA) via EVD until resolution of clot and hydrocephalus is a promising new therapy

Suggested Reading Aztema C, Mower WR, Hoffman JR et al (2006) Prevalence and prognosis of traumatic intraventricular hemorrhage in patients with blunt head trauma. J Trauma 60:1010–1017

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Engelhard HH, Andrews CO, Slavin KV et  al (2003) Current management of intraventricular hemorrhage. Surg Neurol 60:15–22 Flint AC, Roebken A, Singh V (2008) Primary intraventricular hemorrhage: yield of diagnostic angiography and clinical outcome. Neurocrit Care 8:330–336 Hallevi H, Albright KC, Aronowski J et al (2008) Intraventricular hemorrhage: anatomic relationships and clinical implications. Neurology 70:848–852 Longatti PL, Martinuzzi A, Fiorindi A et al (2004) Neuroendoscopic management of intraventricular hemorrhage. Stroke 35:e35–e38 Naff NJ, Carhuapoma JR, Williams MA et  al (2000) Treatment of intraventricular hemorrhage with urokinase: effects on 30-day survival. Stroke 31:841–847 Rosen DS, Macdonald RL, Huo D et al (2007) Intraventricular hemorrhage from ruptured aneurysm: clinical characteristics, complications, and outcomes in a large, prospective, multicenter study population. J Neurosurg 107:261–265 Steiner T, Diringer MN, Schneider D et  al (2006) Dynamics of intraventricular hemorrhage in patients with spontaneous intracerebral hemorrhage: risk factors, clinical impact, and effect of hemostatic therapy with recombinant activated factor VII. Neurosurgery 59:767–774 Tuhrim S, Horowitz DR, Sacher M et al (1999) Volume of ventricular blood is an important determinant of outcome in supratentorial intracerebral hemorrhage. Crit Care Med 27:617–621 Varelas PN, Rickert KL, Cusick J et  al (2005) Intraventricular hemorrhage after aneurysmal subarachnoid hemorrhage: pilot study of treatment with intraventricular tissue plasminogen activator. Neurosurgery 56:205–213

Chapter 23

Subarachnoid Hemorrhage Eric M. Bershad and Jose I. Suarez

Definition Subarachnoid hemorrhage (SAH) refers to the extravasation of blood into the spaces surrounding the (brain and spinal cord that contain cerebrospinal fluid

Epidemiology ■ ■

Trauma is the most common cause of SAH Spontaneous SAH ♦ Aneurysmal (80%) ♦ Perimesencephalic nonaneurysmal hemorrhage (PMNAH) (10–15%) ♦ Other causes of nonaneurysmal SAH (5%) (Table 23.1)

■ ■ ■ ■

Mean age = 55 years Female:Male = 3:2 African American:Caucasian = 2:1 Incidence of SAH ♦ ♦ ♦ ♦

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6–8 per 100,000 per year in United States 10 per 100,000 per year worldwide Up to ~20 per 100,000 per year in Finland and Japan Comprises ~2–5% of strokes

Prevalence of cerebral aneurysms ♦ 1–5% in adult population

E.M. Bershad, MD and J.I. Suarez, MD (*) Department of Neurology, Baylor College of Medicine, One Baylor Plaza, MS NB302, Houston, TX 77030, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_23, © Springer Science+Business Media, LLC 2011

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E.M. Bershad and J.I. Suarez Table 23.1  Rare causes of nonaneurysmal SAH Inflammatory Primary CNS vasculitis Systemic vasculitis Neoplastic Pituitary apoplexy Glioma Schwannomas Meningeal carcinomatosis Angiolipoma Meningioma Spinal hemangioblastoma Vascular Arterial dissection Arteriovenous malformations (brain and spinal cord) Dural arteriovenous fistulae (brain and spinal cord) Spinal artery aneurysm Venous sinus thrombosis Amyloid angiopathy Infectious Mycotic arteritis Lyme disease Drugs Cocaine Amphetamines Other Coagulopathy

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Aneurysm subtypes ♦ ♦ ♦ ♦ ♦

Saccular Most common Usually located at vessel bifurcations of circle of Willis Fusiform Mycotic • Associated with bacterial endocarditis • Usually occur in distal intracranial arterial branches (especially MCA)

■

Distribution of aneurysms ♦ ♦ ♦ ♦ ♦ ♦

Anterior communicating (Acom) – 30% Posterior communicating (Pcom) – 25% Middle cerebral artery (MCA) – 20% Internal carotid artery (ICA) – 7.5% Basilar tip – 7% Others

23  Subarachnoid Hemorrhage

• • • • • • ■ ■

Anterior cerebral artery Pericallosal Vertebral Superior cerebellar artery Posterior cerebral artery Posterior inferior cerebellar artery

Risk factors for aneurysmal SAH (Table 23.2) Outcome after SAH ♦ Mortality rate is high

• 10–15% die before initial medical evaluation • 25% die within 24 h • 45% mortality at 30 days ♦ High risk of long-term disability

• Up to 50% of survivors have long-term cognitive impairment • One-half to two-thirds of survivors can return to work by 1 year • One-third of survivors require lifelong care ■

Predictors of poor outcome ♦ Increasing age ♦ Poor initial neurologic grade Table 23.2  Risk factors for aneurysmal SAH Modifiable Smoking Hypertension Heavy alcohol consumption Drug abuse: cocaine and amphetamines Oral contraceptive use Nonmodifiable Advancing age Female sex Pregnancy Black ethnicity Family history (more than one first-degree relative) Autosomal dominant polycystic kidney disease (5–40% have aneurysms) Sickle cell disease Marfan syndrome Pseudoxanthoma elasticum Ehlers–Danlos syndrome (type IV) Alpha-1-antitrypsin deficiency Neurofibromatosis type I Fibromuscular dysplasia Collagen disorders

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Larger aneurysm size More blood on initial head CT Associated ICH or IVH Elevated BP on admission Comorbid conditions: hypertension, coronary artery disease Persistently elevated temperature Anticonvulsant use Rebleeding (associated with 75% mortality) Symptomatic vasospasm Delayed cerebral infarction (most important factor)

The risk of SAH in patients with unruptured aneurysms depends on several clinical factors (Table 23.3) ♦ Size of aneurysm ♦ History of SAH ♦ Anterior vs. posterior circulation

Clinical Presentation ■

Signs and symptoms ♦ Headache (most common symptom)

• • • • •

Sudden onset of severe headache (70%) Usually “worst ever” Warning headache in 20–50% days to weeks before SAH Headache may be only symptom of SAH in 40% of patients Meningeal irritation ▲ ▲ ▲ ▲

Nausea Vomiting Photophobia or phonophobia Neck pain

Table 23.3  Five-year cumulative risk of rupture for unruptured aneurysms No history of SAH and No history of SAH posterior circulation or History of SAH and and anterior circulation Size of Pcom aneurysm (%) aneurysm (%) aneurysm (mm) additional aneurysm <7 0 2.5 1.5 and 3.5%a 7–12 2.6 14.5 n/a 13–24 14.5 18.4 n/a >25 40 50 n/a a  For anterior or posterior circulation/Pcom, respectively. Pcom posterior communicating artery. Data derived from Wiebers et al. (2003) International Study of Unruptured Aneurysms Study, Lancet

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♦ Syncope (~50%)

• May be due to sudden elevated ICP with low CPP or cardiac dysrhythmias ♦ ♦ ♦ ♦

Decreased level of consciousness (~2/3 patients) Confused state Seizures Focal neurologic signs • • • • •

Third-nerve palsy – Pcom (most common), or PCA or SCA aneurysm Bilateral lower extremity weakness and abulia – Acom aneurysm Hemiparesis, aphasia or neglect – MCA aneurysm Sixth-nerve palsy – nonlocalizing secondary to global elevated ICP Impaired upgaze – related to hydrocephalus with dorsal midbrain dysfunction

♦ Preretinal hemorrhages (Terson syndrome)

• Due to abrupt elevation of ICP ♦ Acute cardiac abnormalities common

• Troponin elevation (20–30%) • ECG changes (25–100%) ▲ Dysrhythmias ▲ T-wave inversions ▲ ST changes

• Left ventricular dysfunction (8–30%) N Usually reversible ■ ■

Mimics of SAH (Table 23.4) SAH grading scales (Table 23.5) ♦ ♦ ♦ ♦

Hunt and Hess Scale Fisher Scale World Federation of Neurological Surgeons Clinical Grading Scale Head CT Grading Scale Table 23.4  Mimics of SAH Benign thunderclap headache (variant of migraine) Intracranial hemorrhage Arteriovenous malformation Head trauma Meningitis Hypertensive encephalopathy Sinus venous thrombosis Pituitary apoplexy Ischemic stroke Drug intoxication

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Table 23.5  SAH grading scales Grade Hunt and Hessa 0 Unruptured aneurysm 1

2

3

4

WFNS scaleb Unruptured aneurysm

Asymptomatic or mild HA

GCS 15 AND no motor deficit Moderate to severe HA, GCS 13–14 AND nuchal rigidity, no motor deficit ±CN deficits

Confusion, lethargy, or mild focal neurologic deficits Stupor and/or hemiparesis

GCS 13–14 AND motor deficit GCS 7–12 ± motor deficit

Fisher scalec n/a

No SAH on head CT Diffuse SAH, <1 mm thickness, no clots Localized clots, or layers of blood >1 mm IVH and ICH without significant SAH

5

Head CT scaled SAH absent AND IVH absent SAH minimal AND IVH absent SAH minimal AND IVH in ventricles bilaterally SAH thicke AND IVH absent SAH thicke AND IVH in ventricles bilaterally n/a

Coma and/or extensor GCS 3–6 ± motor n/a posturing deficit WFNS World Federation of Neurological Surgeons; SAH subarachnoid hemorrhage; IVH intraventricular hemorrhage; HA headache; GCS Glasgow Coma Scale; CN cranial nerve; ICH intracerebral hemorrhage a  Surgical mortality by Hunt and Hess grade: grade 0–1 = 0–5%, grade 2 = 2–10%, grade 3 = 10–15%, grade 4 = 60–70%, grade 5 = 70–100% b  Hospital mortality and WFNS grade: grade 0 = 1%, grade 1 = 5%, grade 2 = 9%, grade 3 = 20%, grade 4 = 33%, grade 5 = 76% (Oshiro et al (1997) Neurosurgery 41(1):140–147) c  Fisher scale grade 3 carries the highest risk of symptomatic vasospasm of the Fisher grades d  Head CT grading and risk of delayed cerebral ischemia: grade 0 = 0%, grade 1 = 12%, grade 2 = 21%, grade 3 = 19%, and grade 4 = 40%. (Classen et al (2001) Stroke 32:2012–2020) e  Thick denotes complete hemorrhagic filling of one or more of the following cisterns or fissures: frontal interhemispheric fissure, quadrigeminal cistern, suprasellar cisterns, ambient cisterns, basal, or lateral Sylvian fissures

Diagnosis ■

Head CT ♦ Mandatory initial study ♦ Acute bleeding appears hyperdense in CSF spaces ♦ Sensitivity decreases over time

• 100% within 12 h (with modern CT scanning and expert read) • 93% within 24 h • 50% at 7 days

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♦ CT bleeding patterns and findings

• Aneurysmal SAH ▲ ▲ ▲ ▲ ▲ ▲ ▲

Basal cisterns Sylvian fissures (MCA aneurysm) Anterior interhemispheric fissure (Acom aneurysm) Intraparenchymal hematoma Intraventricular hemorrhage Hydrocephalus – communicating or noncommunicating Subdural hematoma (rarely)

• Perimesencephalic nonaneurysmal hemorrhage ▲ Bleeding confined to cisterns anterior to pons and midbrain ▲ Bleeding may be seen posteriorly in the quadrigeminal cistern ▲ Should not extend laterally to Sylvian fissures or anteriorly to the ante-

rior interhemispheric fissure ▲ Hydrocephalus may occur

• Traumatic SAH ▲ Often associated with other signs of traumatic brain injury such as subdural

and epidural hematoma, ICH, contusions, or diffuse cerebral edema ▲ Bleeding more often located more superficially around cortical convexities ■

Lumbar puncture ♦ Mandatory if head CT is negative but suspicion for SAH remains ♦ CSF findings in SAH

• Xanthochromia ▲ Related to breakdown of RBCs N Oxyhemoglobin N Bilirubin ▲ ▲ ▲ ▲

Presence confirms SAH False negatives can occur if lumbar puncture (LP) done too early (<12 h) Xanthochromia best detected by spectrophotometry Visual inspection should be performed by filling an empty tube with water and comparing this tube with a tube containing CSF against a white background

• A declining number of RBCs from first to last tube is NOT accurate enough to differentiate SAH from a traumatic LP ■

■

Failure to confirm diagnosis of SAH by not performing LP may result in potentially hazardous treatment of incidental aneurysms in a patient without SAH Failure to exclude SAH by LP may result in aneurysmal rebleeding, which is associated with high mortality

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Angiography is not indicated if both head CT and CSF exam are negative for SAH as incidentally found aneurysms do not confirm SAH and may lead to inappropriate and potentially hazardous treatment Angiography ♦ Standard contrast angiography

• The “gold standard” test for detecting cerebral aneurysms • Newer technology allows for three-dimensional (3D) reconstruction • Must evaluate circulation of the four major vessels (carotids and vertebrals) • Initial angiography fails to show aneurysm in ~10–20% of SAH cases • Repeat angiography usually indicated after ~1 week if initial exam is negative • CT angiography has been reported in rare cases to detect an aneurysm, despite a negative contrast angiography study • Intraoperative angiography may be useful to ensure adequate clip placement, perforator vessel status, and presence of vasospasm • Potential complications of angiography ▲ Contrast nephropathy N Normal saline infusion may be helpful to attenuate risk N Consider alkalinization of IV fluids for at-risk patients; more effica-

cious than N-acetylcysteine (mucomyst) ▲ Allergic reaction N Consider pretreatment with benadryl and steroids ▲ ▲ ▲ ▲

Groin hematoma Arterial dissection at the access site Femoral neuropathy Neurologic complications (1–2.5%) N N N N

0.1–0.5% risk of permanent neurologic impairment Aneurysmal rebleeding Stroke Arterial dissection

♦ CT Angiography

• • • •

Considered appropriate first-line diagnostic test to evaluate for aneurysms Comparable sensitivity and specificity to standard angiography Noninvasive Provides useful 3D anatomical views

♦ Magnetic resonance angiography

• Inappropriate for diagnosis of aneurysms in patients with suspected SAH

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• May be useful for screening asymptomatic patients for aneurysms • Poor sensitivity for detecting small aneurysms ♦ MRI

• • • •

May be as sensitive as head CT for detecting SAH FLAIR and T2* (gradient echo) essential May be useful for detecting alternative diagnoses Spinal MRI may be indicated if brain imaging is unrevealing

♦ Diagnostic algorithm (Fig. 23.1)

Clinical presentation suggests SAH

Noncontrast head CT

Subarachnoid hemorrhage

No subarachnoid hemorrhage

Angiography OR CT angiography

Lumbar puncturea

Aneurysm(s)

No aneurysm

Plan for prompt treatment

Repeat angiography in 1–2 weeks

Xanthochromia OR Equivocalb

No xanthochromia

SAH ruled out

No aneurysm Consider alternative etiology c

Fig. 23.1  Diagnostic algorithm for SAH. aLumbar puncture should not be performed until >6–12 h after onset of symptoms of SAH to ensure adequate time for breakdown of red blood cells to occur, with resulting xanthochromia. bEquivocol means elevated red blood cells without xanthochromia in an early LP (<6–12 h after onset of SAH). cSee Table 23.1 for rare causes of SAH

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Management ■

Preoperative management ♦ ♦ ♦ ♦

Assess airway, breathing, and circulation Establish peripheral IV access Place arterial line Assess need for intubation • Indications for endotracheal intubation ▲ ▲ ▲ ▲ ▲ ▲ ▲

GCS £8 Poor airway protection Elevated ICP Hemodynamically unstable Poor oxygenation Hypoventilation Need for heavy sedation or paralysis

• Use rapid-sequence intubation ▲ 100 mg lidocaine IV N Blunts cough and gag response and subsequent rise in ICP ▲ 10–40 mg etomidate IV N Minimal hemodynamic effects N Suppresses adrenal-pituitary axis ▲ Propofol (may be used for induction and/or maintenance sedation) N 1–2 mg/kg bolus; and then, 2–10 mg/kg/h ▲ Neuromuscular blockade: 0.1 mg/kg vecuronium or 0.6 mg/kg rocuro-

nium; may double-dose for faster onset N Short acting N Nondepolarizing N Ensure that patient bags easily before paralyzing

♦ Place central line

• • • •

Use strict sterile precautions Wash hands Hat, mask, sterile gloves, gown, and drape Use topical chlorhexidine prep (more effective antibacterial agent than iodine) • Subclavian (SC), internal jugular (IJ) or femoral site may be used ▲ SC and IJ offer Ability to monitor central venous pressures (CVP) ▲ No difference in risk of line sepsis between sites

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▲ Risk of pneumothorax with SC > IJ ▲ SC and IJ require verification by chest X-ray ▲ SC and IJ lines can be changed over wire-to-introducer sheath/

Swan–Ganz if needed ♦ Blood pressure (BP) control (before aneurysm secured)

• Avoid hypotension ▲ Impaired cerebral autoregulation and elevated ICP may lead to cerebral

ischemia if blood pressure is aggressively lowered ▲ Lower BP only if MAP >110 mmHg or end-organ damage N 5 mg nicardipine IV bolus; then, 5–15 mg/h IV N 10 mg labetalol IV q 10–20 min; can double dose each time up to

cumulative of 150 mg N 10 mg hydralazine IV q 10–20 min; can double dose each time up

to cumulative of 150 mg N 0.625 mg enalaprilat 0.625 mg–1.25 mg IV q 6 h ▲ Avoid nitroprusside if possible N May elevate ICP

♦ Hydration

• Normal saline 1–2 mL/kg/h • Avoid hypotonic fluids (may increase cerebral edema) ♦ At risk for rebleeding (7%)

• Mortality ~75% in patients with rebleeding • 4% rebleeding on day 1; then, 1.5% per day for next 14 days • Use of antifibrinolytic therapy with aminocaproic acid (Amicar) is controversial ▲ Reduces risk of early rebleeding ▲ Increases risk of thromboembolic complications, such as stroke, myo-

cardial infarction, and venous thromboembolism; not routinely prescribed in neuro ICUs ▲ Use should be limited to first 24–48 h ▲ Amicar dosing: 5 g IV bolus; then, 1.5 g/h for 24–48 h ♦ At risk for hydrocephalus (20%)

• Options include external ventricular drain (EVD) vs. lumbar drain (LD) ▲ LD contraindicated if signs of obstructive hydrocephalus (ineffective)

or focal mass lesion (herniation risk) ▲ Indications of CSF drainage via external ventricular drain (EVD) are

controversial ▲ Some advocate “watch and wait” strategy, while others recommend

early CSF drainage via EVD

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• Place EVD if suspect elevated ICP and/or decreased level of consciousness • Empiric EVD may be indicated if patient presents with poor neurologic grade and signs of hydrocephalus, as dramatic improvement occasionally seen after ventricular drainage • IF EVD is placed, pressure-release setting (“pop-off”) is typically set at 15–20 cmH2O to avoid precipitating rupture if aneurysm unsecured • Potential complications of CSF drainage ▲ ▲ ▲ ▲ ▲ ▲ ▲

Intracranial hemorrhage (EVD) Ventriculitis (EVD) Meningitis (EVD and LD) Seizures (EVD) Rebleeding (EVD and LD) Epidural hematoma (LD) Subdural hematoma (excessive overdraining) (EVD and LD)

♦ Neuroprotection

• 60 mg nimodipine PO q 4 h for 21 days ▲ Randomized controlled trials show improvement in long-term neuro-

logic outcome ♦ Treat hyperglycemia

• Preferably with IV insulin • Optimal glucose range is not well established • Keep glucose at least less than 150 mg/dL ♦ Temperature <37.5°C

• 650 mg acetaminophen PO/PR q 4–6 h • Active external cooling if temperature refractory to acetaminophen ♦ Replete electrolyte deficiency

• Particular attention to magnesium and potassium ♦ Sedation and analgesia

• Avoid excessive visitors • Quiet environment • Pharmacologic agents include: ▲ 15–60 mg codeine IV/IM q 4–6 h ▲ 2–4 mg morphine IV q 2–3 h ▲ 25–50 mg fentanyl IV q 1 h

♦ Seizure prophylaxis

• 20 mg/kg phenytoin IV load; then, 100 mg IV q 8 h or 300 mg PO daily • Maximum infusion rate, 50 mg/min • Adverse effects

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Hypotension Bradycardia Arterioventricular block Rash

• Alternatives – the following are becoming increasingly popular ▲ 20 mg/kg fosphenytoin IV/IM, phenytoin equivalents ▲ 1,500 mg levetiracetam IV or PO load; then, 500–1,000 mg IV/PO q 12 h ▲ 20–30 mg valproic acid IV load; then, 15–45 mg/kg/day IV/PO

• Discontinue after 1 week if patient is seizure free • Will not alter long-term risk of epilepsy, but may interfere with neurologic recovery ♦ Venous thromboembolism prophylaxis

• Sequential compression devices and elastic hose • Avoid low-dose heparin until at least 24 h postoperatively ♦ Gastrointestinal ulcer prophylaxis

• H2 antagonists • 50 mg ranitidine IV q 8 h, or 150 mg PO b.i.d. • Alternatively ▲ Proton-pump inhibitor (i.e. omeprazole, pantoprazole, lansoprazole) ▲ 1 g sucralfate PO q 6 h

♦ Steroids

• Not supported by randomized controlled data • Indicated for adrenal insufficiency in patients with refractory hypotension ■

Operative management ♦ Early (<48–72 h) definitive treatment of the aneurysm is preferred to avoid

risk of rebleeding and allow for subsequent aggressive hydration and hypertensive therapy, if indicated ♦ Operative management includes either endovascular treatment or surgical clipping ♦ Optimal approach requires multidisciplinary evaluation by neurosurgeons, neurointerventionalists, and neurointensivists that takes into account the following: • • • • • • •

Aneurysm characteristic Size Location Neck Anatomy Parent vessels Perforator status

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♦ Patient characteristics

• • • •

Ability to tolerate respective procedures Neurologic status Patient or patient–advocate preferences Prognosis

♦ In the randomized controlled International Subarachnoid Hemorrhage Trial

(ISAT), SAH patients with aneurysms that were amenable to either endovascular or surgical treatment, had a lower risk of death or dependency at 1 year with endovascular coiling compared to clipping (23.5% vs. 30.9%, P < 0.001). However, patients who underwent coiling had a higher risk of rebleeding ■

Postoperative management ♦ Neurologic complications

• Vasospasm ▲ Angiographic vasospasm (66%) ▲ Symptomatic vasospasm [delayed ischemic neurologic deficit (DIND)]

(33–46%) Usually occurs between days 4 and 12 Lasts up to 21 days Best predictor is amount of blood on initial head CT Symptomatic vasospasm may present with focal neurologic deficits or global symptoms, such as decreased level of consciousness or encephalopathy ▲ Symptomatic vasospasm may lead to ischemic stroke (delayed cerebral ischemia), the most important factor in determining long-term disability ▲ No intervention is known to prevent vasospasm ▲ Avoid hypotension and maintain euvolemia (CVP, 5–8 mmHg) ▲ ▲ ▲ ▲

N Normal saline IV bolus 250 mL N Consider alternating with 25–50 g human albumin (25%) IV N Clinical trial currently underway (ALISAH) to determine if human

albumin is neuroprotective in SAH ▲ Monitoring of vasospasm with daily bedside transcranial Doppler

(TCD) advised; however, no randomized data show improved long-term outcome using this approach. TCD-determined vasospasm categories N N N N N

90–120 cm/s (mean) = elevated velocity 120–160 cm/s = mild vasospasm 160–200 cm/s = moderate vasospasm >200 cm/s = severe vasospasm For posterior circulation, a lower threshold of mean blood flow velocities (MCBFV) is considered abnormal compared to anterior circulation

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N TCD findings of severe vasospasm accurately predict severe

N N N N

angiographic vasospasm but correlate less well with symptomatic vasospasm or delayed cerebral ischemia Increase in MCBFV > 50 cm/s/24 h may better predict symptomatic vasospasm compared to MCBFV alone Lindegaard ratio (MCBFV of MCA:extracranial ICA) controls for global increased cerebral blood flow velocity MCBFV > 120 cm/s and Lindegaard ratio >3:1 = vasospasm MCBFV > 120 cm/s and Lindegaard ratio <3:1 = global hyperemia

▲ CT perfusion was recently reported to be superior to TCD in predicting

symptomatic vasospasm ▲ Other emerging modalities that may be useful in detecting symptomatic

vasospasm include positron-emission tomography and single-photo emission CT scanning, MR perfusion, microdialysis, and EEG • Symptomatic vasospasm ▲ Institute hypertensive, hypervolemic, hemodilution (triple H therapy) N Reported to improve short-term neurologic status in 75% with

symptomatic vasospasm N Hypertension induced with vasopressors such as phenylephrine

or norepinephrine; increase SBP up to 200+ mmHg, mean BP, 110–140 mmHg N Hypervolemia with normal saline/albumin [(CVP 8–12 mmHg or pulmonary capillary wedge pressure (PCWP) 16–24 mmHg)] N Hemodilution refers to decreased blood viscosity achieved by normal saline infusion N In patients with refractory symptomatic vasospasm, augmentation of cardiac output with dobutamine may be considered ▲ Role of endovascular treatment of refractory symptomatic vasospasm

has yet to be determined ▲ Endovascular treatment of vasospasm may include intra-arterial infu-

sion of calcium-channel blockers such as verapamil or nicardipine, or transluminal balloon angioplasty. Infusion of papaverine has fallen out of favor due to reported neurotoxic effects. The only prospective randomized transluminal balloon angioplasty trial for vasospasm was negative for improvement in outcome • Delayed cerebral ischemia ▲ May be related to symptomatic vasospasm, decreased CPP, or throm-

boembolic phenomena ▲ Most important factor in long-term neurologic outcome ▲ Oral nimodipine is the only evidence-based treatment proven to

improve long-term neurologic outcome; however, it does not reduce risk of vasospasm

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• Subacute hydrocephalus ▲ Usually nonobstructive ▲ Late hydrocephalus usually requires long-term shunt

• Seizures ▲ Prophylaxis recommended only for first week ▲ Long-term risk of epilepsy after SAH not influenced by seizure prophylaxis

• Ventriculitis/Meningitis ▲ Associated with prolonged EVD/lumbar drain placement ▲ Routine change of EVD tubing not indicated

• Cerebral salt wasting ▲ ▲ ▲ ▲

Presents with hyponatremia and evidence of volume depletion (low CVP) Untreated, may increase risk of delayed cerebral ischemia Treatment involves aggressive fluid repletion Possible role for fludrocortisone or hydrocortisone to enhance intravascular volume expansion

• Encephalopathy ▲ Etiology should be aggressively sought ▲ May indicate symptomatic vasospasm, nonconvulsive seizures, electro-

lyte disturbance, ventriculitis/meningitis, rebleeding, hydrocephalus ♦ Medical complications

• Cardiac ▲ Left ventricular dysfunction/myocardial stunning can be problematic in

face of concurrent cerebral vasospasm. Greater need for ionotropes; anecdotal support for assist devices (IABP) ▲ Myocardial infarction N Evaluate with echocardiography, troponins N Must weigh risk/benefit ratio regarding antiplatelets/­anticoagulation

use in postoperative period N 12.5–100 mg metoprolol b.i.d. ▲ Dysrhythmias ▲ Correct underlying electrolyte disturbances (magnesium, potassium,

calcium) ▲ 12.5–100 mg metoprolol b.i.d.

• Pulmonary ▲ Pneumonia

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▲ Use standard ventilator precautions to avoid risk of ventilator associated

pneumonia N N N N N

Hand washing Head of bed at 30–45° Avoid frequent circuit changes Continuous subglottic suctioning Chlorhexadine oral rinse (0.12 or 0.2%) 15 mL b.i.d.

▲ Acute respiratory distress syndrome ▲ Use low-tidal volume ventilation 6 mL/kg/ideal body weight and keep

plateau pressure <30 mmHg to avoid barotrauma ▲ 5 cmH2O positive end-expiratory pressure (PEEP) may help to prevent

derecruitment

• Venous thromboembolism (DVT and PE) ▲ Institute low-dose heparin >24 h postoperatively ▲ 5,000 units heparin SC t.i.d. ▲ Alternatively or adjunctively, use sequential compression devices and

elastic hose • Acute pulmonary edema (20%) ▲ Evaluate etiology: acute respiratory distress syndrome vs. cardiogenic ▲ Use diuretics sparingly and carefully monitor CVP to avoid hypoten-

sion and intravascular volume depletion ▲ Increase PEEP if patient is on mechanical ventilation ▲ Reduce intensity of triple H therapy if possible ▲ Evaluate cardiac function with transthoracic echocardiography

• Gastrointestinal ▲ Gastric stress ulcers (see preoperative management) ▲ Ileus N Replete potassium ▲ Early feeding N Enteral route preferred

• Endocrinologic ▲ ▲ ▲ ▲ ▲

Hyperglycemia Sliding scale with IV short-acting insulin Institute insulin drip if persistent hyperglycemia Adrenal insufficiency Check corticotropin stimulation test, if indicated, and consider steroids if abnormal and refractory hypotension

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• Hyponatremia ▲ Distinguish between SIADH and cerebral salt wasting by assessing

fluid balance ▲ If treatment is necessary, options include: N Increase normal saline infusion, or institute hypertonic saline (3%) N Consider fludrocortisone 0.1–0.4 mg daily and oral salt tablets

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SAH carries a high risk of mortality and long-term disability Aneurysmal rupture is the most common (80%) cause of nontraumatic SAH The initial diagnostic test in patients with suspected SAH is a noncontrasted head CT, followed by an LP if the CT is negative Early definitive treatment of the aneurysm by surgical clipping or endovascular coiling is considered the standard of care to both prevent rebleeding and allow for aggressive supportive management to help attenuate the devastating effects of vasospasm Postoperative care requires a multimodality approach that anticipates and treats the neurologic and medical complications of SAH to optimize the patient’s longterm outcome

Suggested Reading Al-Shahi R, White PM, Davenport RJ, Lindsay KW (2006) Subarachnoid hemorrhage. BMJ 333:235–240 Brisman JL, Song JK, Newell DW (2006) Cerebral aneurysms. N Engl J Med 355(9):928–939 Broderick JP, Viscoli CM, Brott T et al (2003) Major risk factors for aneurysmal subarachnoid hemorrhage in the young are modifiable. Stroke 34:1375–1381 Claassen J, Bernardini GL, Kreiter K et al (2001) Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited. Stroke 32:2012–2020 Edlow JA, Caplan LR (2000) Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage. N Engl J Med 342:29–36 Lee M, Hartman J, Rudisill N et al (2008) Effect of prophylactic transluminal balloon angioplasty on cerebral vasospasm and outcome in patients with Fisher grade III subarachnoid hemorrhage: results of a phase II multicenter, randomized, clinical trial. Stroke 39:1759–1765 Molyneux AJ, Kerr RS, Yu LM et al (2005) International Subarachnoid Hemorrhage Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 366:809–817 Naval NS, Stevens RD, Mirski MA, Bhardwaj A (2006) Controversies in the management of aneurysmal subarachnoid hemorrhage. Crit Care Med 34:511–524 Smith M (2007) Intensive care management of patients with subarachnoid hemorrhage. Curr Opin Anasthesiol 20:400–407 Suarez JI, Tarr RW, Selman WR (2006) Aneurysmal subarachnoid hemorrhage. N Engl J Med 354:387–396 Van Gijn J, Kerr RS, Rinkel JE (2007) Subarachnoid hemorrhage. Lancet 369:306–318

Chapter 24

Brain Injury Following Cardiac Arrest Romergryko G. Geocadin

Introduction ■

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Neurologic injury resulting from global cerebral ischemia secondary to cardiac arrest (CA) continues to be a major clinical problem that requires urgent neurocritical care intervention Estimates of the yearly incidence of sudden CA in the US varies widely from 250,000 to 460,000 ♦ 36% of incidences of sudden CA were in-hospital CA and 64% were out-of-

hospital arrests ♦ Survival to discharge for in-hospital CA is ~18%, and for out-of-hospital CA,

it is 2–9% ♦ Overall, CA survivors have poor functional outcome, with only 3–7% able to

return to previous functioning levels ♦ The very high prevalence of coma, persistent vegetative state, and severe

functional impairment among survivors presents an enormous burden on patients, their families, the healthcare system, and society in general

Neuronal Injury After Cardiac Arrest ■ ■

A variety of terms has been used to refer to brain injury after CA As the injury is not limited to brain or any particular organ, no single term adequately captures the spectrum of injury

R.G. Geocadin, MD (*) Division of Neuroscience Critical Care, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_24, © Springer Science+Business Media, LLC 2011

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Recent recognition of special needs of patients following CA has let to characterization of “post-cardiac arrest syndrome”; the term encompasses the global injury – that of brain and heart as well as that of all organ systems injured by circulatory failure Neuronal injury starts rapidly and continues for hours to days after the initial insult Typical neuronal injury cascade includes: ♦ Total circulatory arrest ♦ Loss of ATP production and dysfunction of membrane ATP-dependent ♦ ♦ ♦ ♦ ♦

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Na+–K+ pumps Loss of cellular integrity, which triggers release of neurotransmitters that mediate excitotoxic injury such as glutamate, aspartate, and glycine Reduction of inhibitory neurotransmitters such as g-aminobutyric acid (GABA) Influx of calcium into the intracellular space, with activation of second messengers Reperfusion injury and oxygen free radical formation Lipid peroxidation, protein oxidation, and DNA fragmentation

Although circulatory failure from CA affects the whole brain, specific areas are affected more than others ♦ Most vulnerable areas of the brain are: CA-1 area of the hippocampus, cere-

bral cortex, and cerebellar Purkinje cells ♦ Subcortical areas, such as the brainstem, thalamus, and hypothalamus, are

injured to a lesser degree due to relatively high tolerance to ischemia ■

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Clinical manifestations of injuries are based on the areas involved and may be divided into acute and chronic From the acute and intensive care management perspective, the most common problem is reduction in consciousness level ♦ May range from confusion, caused by very brief cardiac dysfunction, to

comatose state, which is seen with longer duration of CA ♦ Areas that require urgent focus are the bilateral cortical regions and ascending

arousal systems, which involved the subcortex, thalamus, and rostral brainstem ♦ Hippocampal injury and its effect on memory and learning, while highly emphasized in the literature, have little impact on acute presentation and emergent care ■

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Relative tolerance of brainstem to ischemic injury is manifested by the preservation of cranial nerve and sensory motor reflexes Over the course of recovery, comatose survivors may transition to vegetative state, where some aspects of arousal are regained but without the means to interact meaningfully to the environment The vulnerability of the cortex leads to high occurrence of seizures in survivors

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Survivors with cortical hemispheric injury present with cognitive and neuropsychiatric disorders ♦ Wide range, including myoclonic disorders, dyscoordination, and movement

disorders, account for most of the functional impairments in long-term survivors ■

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Numerous drugs believed to have neuroprotective actions (i.e., thiopental, corticosteroids, nimodipine, lidoflazine, magnesium, diazepam, etc.) have failed to show treatment benefit in clinical trials Recently, therapeutic hypothermia showed benefits in survival and functional outcome; the precise mechanism of the neuroprotective effect of hypothermia is not known, but its multiple actions on the injury cascade (especially with the reduction of excitotoxic injury and inflammatory response) appear to contribute significantly to its success as a therapy

Approach to Brain Injury After Cardiac Arrest ■

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Extent of neurologic injury is a major determinant in functional recovery of patients resuscitated from CA Neurologic injury is a major focus in resuscitation efforts as well as in postresuscitation care; considering that most CA survivors are admitted to the cardiac or medical ICU, neurocritical care input in the care of these patients is critical Neurologic care must involve a detailed clinical evaluation and stratification of injury, direct involvement with acute neuroprotective care and strategies, management of acute neurologic problems and complications, prognostication of poor outcome in those severely injured, and the declaration of death by neurologic criteria, withdrawal of life-sustaining therapies, and family counseling in appropriate cases

Brain Injury and the Immediate Post-resuscitative Period ■

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Success of therapeutic hypothermia illustrates that brain injury after CA can be ameliorated; this has changed the focus from care that is totally supportive and focused only on prognostication to care that involves active intervention to attain the best possible neurologic outcome It is important to determine the likely etiology of CA Noncardiac etiology of CA is generally associated with poorer outcome While it is uncommon for neurologic conditions to precipitate a CA, recognizing them early will be important for post-arrest management and prognostication ♦ These conditions include aneurysmal subarachnoid hemorrhage, intracerebral

hemorrhage, and seizures with sudden cardiac death ♦ If any of above conditions are suspected, diagnostic evaluation such as a head

CT scan or EEG may be needed as soon medical stability is attained

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During the post-resuscitation period, it is important to ascertain the pre-cardiacarrest function and neurologic condition of the patients It will also be helpful to know the duration of CA (duration of pulselessness) and CPR [(time of initiation of CPR to return of spontaneous circulation (ROSC))] Every effort must be made to perform a complete neurologic examination after successful resuscitation, thereby establishing baseline post-CPR function; this is crucial to determine neurologic progression ♦ The examiner must take into consideration the multiple factors that may

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obscure the neurologic examination, such as paralytic and sedative medications, illicit drug use before arrest, ongoing cerebral hypoperfusion, seizures or postictal encephalopathy, electrolyte abnormalities, and metabolic derangements Neurologic evaluation should assess mental status by documenting the patient’s ability to arouse and interact meaningfully with the examiner Evaluation of brainstem function includes the testing of cranial nerve function and reflexes, most importantly the pupillary light reflex, corneal reflex, grimacing to noxious stimulation, oculocephalic reflexes, cough and gag reflexes, and the presence of spontaneous respirations In the unresponsive patient, the motor and sensory examination relies on the evaluation of the patient’s response to a noxious stimulus, which may be purposeful (warding off the stimulus), reflexive (extensor or flexor posturing), or absent It is also helpful to note the autonomic responses, such as respiratory pattern, labile core temperature, and extreme swings of heart rate and blood pressure It is common to use the Glasgow Coma Scale (GCS) to track the progression of the patient, but lack of cranial nerve functional assessment limits the utility of the GCS Missing evaluation of cranial nerve functions becomes problematic as prognostication is sought The recently developed Full Outline of UnResponsiveness (FOUR) score, which accounts for eye response, motor response, brainstem response, and respirations, is a potential tool, but its utility in this population requires validation In patients who are able to arouse and interact meaningfully with the examiner post-CPR, it is important to establish the extent of neurologic recovery, considering that neurologic complications are fairly common in the post-CA course; this group of patients is more likely to have good recovery, and careful neurologic evaluation, detection of potential neurologic complication, and its prompt treatment are necessary to attain the best outcome possible

First 24 h: Therapeutic Hypothermia and Other Neuroprotective Strategies ■

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Focus of neurologic treatment is on patients who remain unresponsive or comatose after successful CPR Unfortunately no specific interventions have been studied in responsive or noncomatose patients after CPR

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For this specific patient population, the 2005 Guidelines for CPR and Emergency Cardiovascular Care of the American Heart Association provide that: ♦ Unconscious adult patients resuscitated after out-of-hospital CA should be

cooled to 32–34°C (89.6–93.2°F) for 12–24 h when the initial rhythm was ventricular fibrillation (Class IIa) ♦ Similar therapy may be beneficial for patients with in-hospital CA or out-ofhospital arrest associated with an initial rhythm other than ventricular fibrillation (Class IIb) ■

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The basis for these recommendations on comatose survivors of out-of-hospital CA with ventricular fibrillation is provided below More recent post-trial studies show beneficial effect of hypothermia in those with asystole and pulseless electrical activity Controlled clinical trials with therapeutic hypothermia on patients with in-hospital CA are still necessary The recommendation for in-hospital CA took into account the reported overall poor outcome and weighed the potential benefits against the expected adverse effects of therapeutic hypothermia; therefore, every effort must be made to salvage neurologic functions post-CA It is important to note that withdrawal of life-sustaining therapies is discouraged at this time, especially considering that no prognostic indicator or poor outcome has been definitely established in the first 6–12 h Some conditions that are likely to worsen expected adverse effects or limit the expected benefits may influence against the initiation of hypothermia; these include associated bleeding, coagulopathies, significant traumatic injuries, overwhelming infections, and preexisting terminal condition Guidelines are based on two landmark studies, one by the Hypothermia after Cardiac Arrest (HACA) group in Europe, and the other by Bernard and colleagues in Australia ♦ The multicentered European study randomized comatose survivors after CA

with ventricular tachycardia/fibrillation into a hypothermia arm (137) and a normothermia arm (138). The hypothermia arm targeted the temperature of 32–34°C for 24 h • Hypothermia was achieved by cooling mattress and blanket that deliver cold air over the body; core temperature was monitored with a bladder thermometer • Patients were rewarmed passively over a period of 8 h • Sedation with midazolam and paralysis with vecuronium were used to prevent shivering • Seventy-five of the 136 patients (55%) in the hypothermia group had a favorable neurologic outcome (moderate disability but able to perform daily activity or better) at 6 months, compared with 54 of 137 (39%) in the normothermia group [Relative Risk (RR), 1.40; 95% Confidence Interval (CI), 1.08–1.81] • At 6 months, 56 of the 137 (41%) in the hypothermia group died vs. 76 of the 138 patients (55%) in the normothermia group (RR, 0.74; 95% CI, 0.58–0.95)

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♦ The Australian study enrolled comatose survivors of CA with an initial car-

diac rhythm of ventricular fibrillation, with 43 patient in the hypothermia treatment group and 34 patients in the normothermia group • Hypothermia was initiated in the field with cold packs to the patient’s head and torso and continued in the hospital for 12 h, targeting a core temperature to 33°C • Patients were sedated with midazolam and paralyzed with vecuronium as needed to prevent shivering; rewarming was undertaken with a heated-air blanket beginning at 18 h after arrival; similar sedation and paralysis protocols were provided to patients assigned to the normothermic group, targeting a temperature of 37°C • Passive rewarming was used in these patients if they had mild spontaneous hypothermia on arrival • The primary outcome measure was location of discharge: home, rehabilitation facility, or long-term nursing facility • Discharge to home or to a rehabilitation facility was regarded as a good outcome, whereas in-hospital mortality or discharge to a long-term nursing facility was regarded as a poor outcome • The study found that 21 of 43 patients (49%) who were treated with hypothermia had good outcomes compared with 9 of 34 patients (26%) in the normothermia group (RR of good outcome, 1.85; 95% CI, 0.97–3.49) • Mortality at discharge was 51% (22 of 43) in the hypothermia group and 68% (23 of 34) in the normothermia group (RR, 0.76; 95% CI, 0.52–1.10)

Clinical Impact and Post-trial Experience of Therapeutic Hypothermia ■

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Since the publication of the two landmark trials discussed above, results of several other studies have been published, demonstrating that the therapeutic impact of hypothermia is robust Systematic review (meta-analysis) of the literature shows that to attain the beneficial effect of therapeutic hypothermia after controlling for several variables (e.g., age, gender, arrest duration, CPR time, and CPR technique), the number needed to treat to have one subject benefit in terms of survival and improve outcome is ~5–7 These reviews did not find evidence of treatment-limiting side effects

Delivery of Therapeutic Hypothermia ■

In preclinical studies, the neuroprotective benefits of therapeutic hypothermia were most pronounced when treatment was started soon after ROSC, and conversely, the benefits waned as treatment was delayed

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In humans, the HACA study showed that time from resuscitation to attain target temperature was ~8 h, and in the study by Bernard and colleagues, it was ~2 h The European study rewarmed patients passively over 8 h after 24 h of hypothermia, whereas the Australian study reported active rewarming for 6 h with a heated-air blanket, beginning 18 h after ROSC The delivery of therapeutic hypothermia can be divided into three phases: induction, maintenance, and rewarming The means by which therapeutic hypothermia may be achieved: (a) externally with direct application of ice or cold air, or via specialized pads or helmets or (b) internally by IV infusion of iced saline solution, cold saline gastric lavage, or endovascular catheters. No studies have established therapeutic superiority of any method of cooling Before therapeutic hypothermia is initiated, important readings such as baseline core temperature (preferable from cardiac or bladder sensor), hemodynamic function, coagulation profile, and basic laboratory tests must be obtained (see Table 24.1 for the hypothermia checklist) Therapeutic hypothermia commences with the induction phase to rapidly achieve the target temperature of 32–34°C safely ♦ This can be achieved with rapid IV infusion of cold solutions (i.e., 30 mL of

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normal saline or Ringer lactate); studies showed no hemodynamic, pulmonary, renal, or acid–base complications This intervention was safe and effective in decreasing body temperature rapidly from normothermia to therapeutic range in 30 min to 1 h The induction phase may be also achieved with the use of ice packs, lavages, and by more advanced systems that use specialized pads or endovascular catheter systems A major challenge during the induction phase is the occurrence of shivering, which produces heat and prevents or slows cooling to target temperature; management of shivering is discussed below Once the target temperature (32–34°C) is achieved, the maintenance phase follows The goal of the maintenance phase is to prevent temperature fluctuation beyond the therapeutic range • This goal is best achieved by a treatment protocol that may utilize a wide range of methods, including ice packs, and by more advanced systems that employ specialized pads or endovascular catheter systems

♦ At the termination of the therapeutic hypothermia, the rewarming process

must be conducted in a controlled and cautious manner ♦ While the optimal rewarming rate is not known, current consensus provides a

rewarming rate of ~0.25–0.5°C/h ♦ Because of the increased risk of worsening neurologic injury, rapid rewarm-

ing should be avoided ■

In the absence of studies that compare the numerous methods of delivering therapeutic hypothermia, some factors to consider are those associated with the

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Table 24.1  Checklist for therapeutic hypothermia after cardiac arrest Initial patient assessment prior to beginning cooling □ Assess medical therapy (vasopressor and vasodilators may affect heat transfer, increase potential for skin injury, and contribute to adverse hemodynamic response) □ Obtain core temperature – rectal or bladder temperature □ Obtain vitals and hemodynamic values □ Monitor cardiac rhythm □ Assess baseline electrolytes, glucose, ABG, coagulation labs, lactate, CPK with MB fractions □ Assess baseline neurological examination □ Assess ventilatory function □ Assess bowel sounds, abdomen and GI function □ Assess skin integrity (external cooling devices may exacerbate skin injury, especially if patient has preexisting conditions such as diabetes and/or the patient is on vasopressors) Ongoing assessment □ Full assessment q 4 h □ Temperature check q 1 h □ Vitals q 15 min × 4; then q 1 h □ Hemodynamics evaluation by Pulmonary Artery Catheter protocol □ Assess for signs of shivering □ Cardiac rhythm q 4 h □ If shivering occurs and no pulse oximetry is available, draw ABGs q 1 h until shivering ceases □ Maintain normal blood glucose; use insulin as necessary Interventions (cooling process) □ Initiate ICU Sedation/Tranquilization Protocol (midazolam infusion is agent of choice) □ Vecuronium 5–10 mg/h IV prn for signs of shivering □ Adjust cooling/warming based on established clinical target and based on method and device used for cooling/warming Interventions (rewarming process) □ Once patient is maintained at target temperature for 24 h, remove cooling blanket; may add warm blankets, and remove wet/damp clothing or bed linens □ Passive rewarming to normal temperature over 8 h (not faster than 0.5°C/h) Documentation □ Vitals signs with temperature q 1 h □ Hemodynamic parameters per protocol □ Assessment q 4 h □ Skin integrity q 1–2 h □ Cardiac rhythm q 4 h □ Intake and output q 1 h □ Continuous sedation drips, boluses of paralytic agents prn □ The following protocols initiated: ○ ICU sedation/tranquilization ○ Heparin protocol, bleeding precautions (if ordered) ○ Neuromuscular blocking agent (if utilized) ○ Electrolyte protocol, especially potassium, ○ Insulin therapy □ Ventilator settings Modified from CCU Nursing Protocol of the Johns Hopkins Hospital

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location where hypothermia is initiated (in the field, emergency department, or ICU), the capacity of first responders to initiate hypothermia, the rapidity of induction and stability of temperature during treatment, the ability to control rewarming, the portability of the device, specific adverse effects, whether the device hampers provision of care in the critical care environment, and cost

Management of Shivering ■

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Shivering in response to hypothermia leads to generation of heat that is associated with increase in oxygen consumption and worse neurologic outcome; in generating heat, shivering delays attainment of therapeutic temperature All of these are likely to lessen the benefits of hypothermia; shivering may be pronounced during the induction of hypothermia At this time, the use of sedatives and paralytics during this period may be more than during other periods; in clinical trials, vecuronium was used as a paralytic agent, and IV midazolam was used as a sedative agent Some changes have been institute in practice, from continuous sedation and pharmacologic paralysis to noncontinuous and as-needed pharmacologic paralysis, with sedation based on presence of shivering Considering that only unresponsive or comatose survivors of CA who are already intubated on mechanical ventilatory support undergo therapeutic hypothermia, the management of shivering in this patient population is less challenging than in awake patients with unprotected airway with other forms of neurologic injuries Of note, hypothermia impedes the rate of metabolism and clearance of paralytic and sedating agents leading to longer duration of action; this delay must be considered in the clinical evaluation and prognostication Other drugs, such as IV magnesium, meperidine, buspirone, and dexmedetomidine, may control shivering Nonpharmacologic strategies such as counter-warming of face and extremities may be tried

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Potential complications of therapeutic hypothermia include renal insufficiency, bleeding, sepsis, and pancreatitis In clinical trials, the incidence of these conditions was similar in both hypothermia and normothermia groups Some notable potential complications include a trend toward increased bleeding and sepsis in the hypothermia group in the HACA study and a trend toward lower cardiac index, higher systemic vascular resistance, and more hyperglycemia in the study by Bernard and colleagues

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Other possible complications include hypokalemia, metabolic acidosis, and cardiac dysrhythmia (bradycardia is most common) To manage these complications effectively, a well-developed protocol that addresses hypothermia induction, maintenance, and weaning must include close monitoring and prompt recognition, with prevention or correction of complications From a neurologic perspective, acute complications such as seizures have been noted in patients treated with normothermia and hypothermia It is advisable to have a low threshold to perform EEG on patients who are suspected to have seizures, especially those who are paralyzed or heavily sedated, as these conditions can mask the clinical manifestation

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In patients who are not treated with therapeutic hypothermia or those that have completed 12–24 h of therapeutic hypothermia, the neurologic care must focus on ongoing injury and interventions to prevent further neurologic injury Cerebral perfusion and oxygenation ♦ Early hemodynamic optimization is an important goal post-CPR ♦ Systemic hypotension and hypoxemia worsen cerebral ischemia, and they

should be avoided ♦ Optimal mean arterial pressure (MAP) for post-CA patients is not known ♦ Microvascular dysfunction and autoregulatory failure contribute significantly

to impairment of cerebral perfusion • Conceptually, cerebral perfusion is highly dependent on higher MAP to ensure adequate cerebral blood flow • However, definitive studies are necessary to fully understand the role of augmented cerebral perfusion • A MAP of 80–100 mmHg has been suggested to be beneficial, at least for the first 24 h after arrest; systemic hypotension is detrimental and should be avoided • A clinical study showed that hypertension (MAP >100 mmHg) during the first 5 min after ROSC did not improve neurologic outcome; however, MAP during the first 2 h post-ROSC correlated with neurologic outcome • Attempts to augment MAP must be made with caution, considering the cardiovascular injury that is primarily associated with CA • Oxygenation with 100% oxygen may be harmful, and the recommendation is to keep arterial oxygen saturation at 94–96% ■

Temperature management ♦ Temperature elevation must be avoided in patients not treated with therapeutic

hypothermia or in those who have completed treatment ♦ Risk of poor neurologic outcome increases for each degree of body tempera-

ture higher than 37°C

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♦ The reported worse outcome includes severe disability, coma, or persistent

vegetative state; in managing temperature elevation, etiology must be worked up aggressively ♦ Associated infection should be treated with appropriate antibiotics ♦ Temperature elevation, especially associated with noninfectious conditions, requires interventions that may range from conservative measures such as use of antipyretics and surface cooling (ice pack, alcohol wipes, etc.) to aggressive measures with the use of temperature-modulating devises and infusion of iced saline solution to achieve normothermia ■

Seizure and myoclonus ♦ Common and occur in 5–15% of patients post-CPR ♦ More noticeable in 10–40% of comatose patients ♦ Seizures are detrimental to recovering brain because of the increased neuronal

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injury, increased cerebral metabolic demand, and elevated intracranial pressure (ICP) Seizures may also delay return of consciousness after resuscitation Benefits of prophylactic use of anticonvulsants have not been established; therefore, it is not recommended at this time If a patient develops a seizure, it should be worked up as a new-onset seizure and treated with standard anticonvulsant medications Myoclonus may occur independently or in association with seizures; the treatment of myoclonus may be difficult, and agents that have been used successfully include clonazepam, sodium valproate and levetiracetam EEG should be performed on any patient who is suspected of having seizures or in those with myoclonus to rule out associated seizures Incidence of seizures associated with hypothermia or seizures masked by paralysis with hypothermia has been increasing Except for case reports, no studies have documented any increase in seizure post-hypothermia; in the HACA study, no statistical difference was reported in the occurrence of seizure between the groups treated with and without hypothermia In cases where nonconvulsive seizures are suspected, continuous EEG monitoring is necessary to establish the diagnosis Presence of myoclonic status epilepticus as well as intractable status epilepticus has been highly associated with poor outcome; impact of the two conditions on prognostication is discussed below

Cerebral edema and elevated ICP ♦ ICP has not been widely studied in the post-CA period ♦ A few reports indicate that ICP is not commonly elevated after CA, but cere-

bral edema may be observed ♦ If it occurs, ICP elevation can compromise cerebral blood flow, and cerebral

edema may lead to cerebral herniation syndromes, leading to severe impairment or death

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♦ In comatose patients with evidence of elevated ICP, such as clinical signs of

herniation or cerebral edema on CT scan, ICP monitoring may be helpful to guide therapies for optimization of ICP and cerebral perfusion pressure ♦ Hypoxia, hypotension, and hypercapnia can worsen brain damage and they should be avoided; in the absence of ongoing ICP elevation, prophylactic and long-standing hyperventilation worsens brain injury ♦ In general care in the post-CA period, the goal of mechanical ventilation is to achieve normocapnia ♦ In cases in which worsening cerebral edema and mass effect are noted, standard brain edema management may also be undertaken (see Chap.) ■

Glucose management ♦ Hyperglycemia after ischemic brain injury has been associated with worse

outcome ♦ Hyperglycemia is common after CA ♦ Recent studies have shown that tight glucose control in some populations of

critically ill patients can lead to better outcome ♦ A recent study of unconscious patients after CPR showed that blood glucose

levels at 12 h post-ROSC were associated with neurologic recovery over 6 months • Favorable neurologic outcome was noted in patients with tight glucose control (range of 67–115 mg/dL) as well as in those with moderate blood glucose control (range 116–143 mg/dL) • More episodes of hypoglycemia were noted in patients subjected to tight glucose control (67–115 mg/dL) • No difference in morality was noted between the two groups studied

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Despite the advances in resuscitation medicine, most CA survivors continue to have poor outcomes Prognostication after CA resuscitation was once the main reason that neurologic consultation was sought in these patients With success of therapeutic hypothermia, prognostication in CA survivors should be refocused Process of prognostication is based on the determination of the extent and the irreversibility of neurologic injury and its impact on the functional outcome of survivors Factors used to predict outcome after CPR are divided into pre-CA parameters, intra-CA parameters, and post-CA factors With an evidence-based review, the American Academy of Neurology (AAN) published practice parameters on the prediction of poor outcome in comatose

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survivors of CA; the following several important points should be considered in prognosticating based on these recommendations: ♦ The AAN prognostication guidelines were based on studies on patients who

were not treated with hypothermia ♦ The AAN prognostication guidelines provide the prediction of poor outcome

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in comatose survivors of CA only; therefore, the opposite observation does not necessarily predict favorable outcome No definitive studies have been undertaken to predict functional recovery in noncomatose survivors The clinical parameters used in prognostication may be affected by physiologic perturbations (hypotension, hypothermia, electrolyte abnormality, etc.) and drugs (paralytics and sedatives) Factors that may impede neurologic function at the time of prognostication, possibly leading to erroneous assessment have to be corrected Pre-CA factors • Numerous studies have investigated patients’ pre-CA characteristics, but no pre-arrest characteristic has been established as a reliable predictor of outcome • Some of the patient characteristics studied are age, race, activity level, and preexisting health conditions such as diabetes, cancer, and renal failure • The pre-arrest Acute Physiologic Chronic Health Evaluation (APACHE) II and III scores are not reliable predictors of outcome

♦ Intra-CA factors

• Several factors closely associated with CA and resuscitation have been associated with poor outcome; however, none of these prove to be reliable predictors of outcome • Most notable of these factors are prolonged duration of pulselesness (CA time), prolonged CPR duration, lack of adherence to CPR guidelines, noncardiac cause for the arrest, initial cardiac rhythms other than ventricular tachycardia or fibrillation (e.g., asystole and pulseless electrical activity) and hyperthermia at time of CA ♦ Post-CA factors

• Currently, clinical factors derived in the post-CA period remain the most reliable predictors of outcome • These factors may be divided into the bedside neurologic evaluation and the diagnostic tests undertaken, such as EEG, evoked potential, serologic markers (S100B, NSE and CPK BB), and neuroimaging • Numerous studies on the use of these factors have been undertaken and have served as a basis for the practice parameters for the prediction of poor outcome in comatose survivors of CA issued by the AAN

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• Strength of the predictive parameters is based on the false positive rate (FPR); FPR was chosen because the AAN committee wanted the clinicians to be informed about the ability of the clinical exam and the laboratory test to predict poor outcome with a high level of certainty (low FPR) • A decision algorithm from the AAN practice parameters is found in Fig. 24.1 • Neurologic evaluation: The bedside neurologic examination continues to be the most reliable and widely validated predictor of functional outcome after CA

Fig. 24.1  Reproduced from the 2006 AAN practice parameters and shows an algorithmic approach to the prognostication in comatose survivors of cardiac arrest. Detailed discussion, especially on the limitations, such as the lack of standardization with NSE and the occasional difficulty in discerning myoclonic status epilepticus on day 1 is provided in the text. Major confounders need to be excluded before prognostication can be undertaken. The diamond contains the prognostic parameters indicating the outcome in the square. The triangle contains the false positive rates (FRP) and the numbers in parenthesis are % confidence intervals. The asterisks indicate that these test may not be obtained in a timely fashion

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▲ Sudden interruption of blood flow to the brain and brainstem leads to

widespread neurologic failure ▲ Absence of neurologic function immediately after ROSC is not a reli-

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able predictor of poor outcome; however, the retention of any neurologic function during or immediately after CPR portends a good neurologic outcome; in the era of effective intervention with therapeutic hypothermia, prognosticating poor outcome, thereby possibly leading to withdrawal of life support on day 1, is not advised Reliability and validity of neurologic examination as a predictor of poor outcome depends on the presence of neurologic deficits at specific time points after ROSC Findings of prognostic value include persisting coma state, the absence of some brainstem reflexes and lack of motor response to pain; of these, the absence pupillary light response, corneal reflex, or motor response to painful stimuli at day 3 provides the most reliable predictor of poor outcome (vegetative state or death) AAN practice parameters provide that absent brainstem reflexes or a GCS motor score of £2 at 72 h provide a 0% FPR (95% CI, 0–3%) Absence of pupillary or corneal reflexes at 72 h had a 0% FPR (95% CI, 0–9%), whereas absent motor response at 72 h had a 5% FPR (95% CI, 2–9%) for poor outcome Another important bedside observation is the occurrence of seizures and myoclonus, which if prolonged and repetitive, may carry their own grave prognosis Although myoclonic status epilepticus has been regarded as a reliable predictor of poor outcome (FPR 0%; 95% CI, 0–8.8%), it is imperative to consider myoclonus or seizures as separate entities, as good outcome has been observed in these cases Because of recent reports showing favorable outcome in cases with myoclonus or seizures post arrest, the enthusiasm on the use of these parameters in prognostication has decreased substantially

• Neurophysiologic tests: The time point from which neurophysiologic tests were studied varies widely, but the period from 1 day to 1 week has been deemed reliable ▲ Somatosensory-evoked potential (SSEP) appears to be the best and

most reliable prognostic test because it is influenced less by common drugs and metabolic derangements ▲ The N20 component (representing the primary cortical response) of the SSEP with median nerve stimulation is the best studied evoked-potential waveform in prognostication ▲ In a comatose survivor, the absence of the bilateral N20 component of the SSEP with median nerve stimulation from 24 h to 1 week after ROSC very reliably predicts poor outcome (FPR = 0.7%; 95% CI, 0.1–3.7); however, the presence of the N20 waveform in comatose survivors did not reliably predict a good outcome

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• Electroencephalography has been extensively studied as a tool for evaluating the depth of coma and extent of damage after CA; many malignant EEG patterns have been associated with poor functional outcome, such as generalized suppression to <20 mV, burst suppression pattern with generalized epileptiform activity, and generalized periodic complexes on a flat background ▲ A meta-analysis of studies reporting malignant EEG patterns within the

first 3 days after ROSC calculated an FPR of 3% (95% CI, 0.9–11%) ▲ While electroencephalography is noninvasive and easy to record even

in unstable patients, its widespread application is hampered by the lack of a unified classification system, lack of consistent study design, the need for EEG expertise, and its susceptibility to numerous drugs and metabolic disorders ▲ Considering all of these, EEG is insufficient to reliably prognosticate futility • Biochemical markers derived from cerebrospinal fluid (creatine phosphokinase CPK-BB) or blood [neuron-specific enolase (NSE) and S100b] have been used to prognosticate functional outcome after CA ▲ Ease of obtaining samples has favored blood-based over cerebrospinal

fluid-based biochemical markers ▲ Of these, the most reliable, per the AAN practice parameters, is NSE,

▲

▲

▲ ▲

a cytoplasmic glycolytic enzyme found in neurons, cells, and tumors of neuroendocrine origin Serum NSE concentrations >33 mg/L drawn between 24 and 72 h after ROSC predicted poor outcome after 1 month, with an FPR of 0% (95% CI, 0–3%) Caution must be taken with the use of NSE, considering that the lack of standardization in study design and patient treatment, the wide variability of threshold values to predict poor outcome, and differing measurement techniques The other biochemical marker, S100b, a calcium-binding protein from astroglial and Schwann cells, is less favored An S100b cutoff of >1.2 mg/L drawn between 24 and 48 h after ROSC was required to achieve an FPR of 0% (95% CI, 0–14%), with a sensitivity of 45%; other less robust studies show similar high specificity with low sensitivity

• Neuroimaging and monitoring modalities: Neuroimaging is commonly performed to define structural lesions related to brain injury after CA ▲ At the present time, no well-designed study using neuroimaging has been

undertaken to allow its use in reliable outcome prediction after CA ▲ Several studies using CT scans of the brain showed that widespread

injury and changes in edema characteristics are associated with poor outcome

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▲ Certain MRI sequences, such as diffusion weighted imaging (DWI)

or fluid-attenuated inversion recovery (FLAIR) may show cortical abnormalities that are associated with poor outcome; functional neuroimaging such as MR spectroscopy or positron-emission tomography (PET) may show cellular dysfunction that is associated with poor outcome ▲ At this time, the practical utility of neuroimaging, especially CT scanning, is limited to excluding intracranial pathologies such as hemorrhage or stroke ▲ The detection of structural and functional abnormality may be used to help support the other clinical findings

Neurologic Prognostication After Therapeutic Hypothermia ■

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The recent practice parameters issued by the AAN focused only on predictors of poor outcome in patients who were not treated with hypothermia As a therapy, hypothermia has the ability to alter both survival and functional outcome Furthermore, hypothermia is known to alter some physiologic processes, e.g., clearing of paralytic agents and causing some delay in the return of motor function It has not been established which prognostic modality and at what time point is best for patients treated with hypothermia; therefore, the application of the AAN practice parameters should be modified to account for these additional confounders At this time, a delay in prognostication is strongly advised; for example, 3–5 days of normothermia from the end of therapeutic hypothermia to allow for the evolution of neurologic recovery, if any, to be observed For patients treated with hypothermia, two substudies of the HACA trial provide some limited insight into the use of evoked potentials and biochemical markers as prognosticators A substudy of the HACA trial examined the prognostic accuracy of SSEPs in 57 patients 24–28 h after CA Thirty patients were treated with hypothermia, and the N20 latency was prolonged in all of them Eleven patients had absent N20 responses (three hypothermic and eight normothermic patients) and none of them regained consciousness; this small study suggests that SSEP performed 24–28 h after CA seems to retain its specificity for poor outcomes, even in hypothermic patients Another HACA substudy compared NSE and S100b in 34 hypothermic and 32 normothermic patients after CA found that the serum NSE was lower in the hypothermia-treated patients, but no difference in S100b levels was observed between the hypothermia- and normothermia-treated patients Survival, recovery of consciousness, and good outcome seemed to correlate with decreasing levels of NSE between 24 and 48 h

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Although the investigators identified cut-off values for NSE concentrations that were predictive of poor outcomes, these values differed between the hypothermia and normothermia groups

Key Points ■

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Brain injury continues to be the leading cause of disability after CA, despite significant advances in resuscitation and critical care over several decades Care of these patients can be challenging, and it requires a great deal of medical resources and expenditures Therapeutic hypothermia, in demonstrating benefit in survival and functional outcome measures, has renewed the enthusiasm for the amelioration of brain injury in post-CA patients Implementation of the recommendations of the American Heart Association to initiate hypothermia as soon as possible after resuscitation from out-of-hospital ventricular fibrillation arrest has been slow, even at academic medical centers As the specialists whose primary focus it is to enhance recovery from neurology injuries, neurointensivists should take a lead in the implementation of this therapy Several challenges and uncertainties persist about therapeutic hypothermia, including basic understanding of the mechanisms of benefit, the optimal depth of hypothermia, timing of initiation of therapy, treatment duration, the best mechanism for achieving hypothermia (internal or external cooling), and the availability of a bedside indicator of brain response to hypothermia Once the best efforts have been undertaken to provide the appropriate interventions to protect the brain from further injury post-CA, the focus of neurologic care shifts to prognostication, especially in those survivors who remain comatose Outcome prediction based on neurologic function has been shown to influence decisions by physicians and families regarding withdrawal of life support in patients with poor outcome after resuscitation from CA Several questions remain, especially in those treated with hypothermia and in patients who recover consciousness but have long-term neurologic impairment

Suggested Reading Arrich J(2007), European Resuscitation Council Hypothermia After Cardiac Arrest Registry Study Group Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med 35(4):1041–1047 Bernard SA, Gray TW, Buist MD et al (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346(8):557–563 Geocadin RG, Koenig MA, Jia X et al (2008) Management of brain injury after resuscitation from cardiac arrest. Neurol Clin26(2):487–506

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Hypothermia after Cardiac Arrest Study Group (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346(8):549–556 Neumar RW, Nolan JP, Adrie C et  al (2008) Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication: a consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, Inter American Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council). Circulation118(23):2452–2483 Nolan JP, Morley PT, Vanden Hoek TL et al (2003) Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. Circulation 108(1):118–121 Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S; Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Jul 25; 67(2):203–10.

Chapter 25

Meningitis and Encephalitis Barnett R. Nathan

Meningitis Definitions and Epidemiology ■

Meningitis specifically means presence of inflammation of the meninges ♦ Practically, this means that inflammatory cells and inflammatory markers are

in the subarachnoid space ♦ Inflammation may be infectious (bacterial, viral, fungal), chemical (blood,

anesthetics), or idiopathic ■

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Viral meningitis (also referred to as aseptic meningitis) is the most common cause of this syndrome (75,000 cases/year in the US) but will not be considered in this chapter, as it rarely requires acute hospitalization Fungal meningitis is uncommon in the immunocompetent patient ♦ In the immunosuppressed patient, the species Cryptococcus and Coccidiodes

may cause devastating disease and are the most common fungal pathogens to cause meningitis ■

Bacterial meningitis is relatively uncommon in the US (about 15,000 cases/ year), though worldwide, particularly in Africa, it may be up to ten times more common (>100,0000 cases/year) ♦ In the US, the epidemiology of bacterial meningitis has changed substantially

since the early to mid-1990s due to the introduction of the Haemophilus influenzae type b (Hib) vaccine

B.R. Nathan, MD (*) Department of Neurology and Internal Medicine, University of Virginia School of Medicine, PO Box 800394, Charlottesville, VA 22908, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_25, © Springer Science+Business Media, LLC 2011

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• The number of cases of Hib meningitis has decreased by 94% • Though not as dramatic, the incidences of Streptococcus pneumoniae and Neisseria meningitidis meningitis have also decreased • Adults are now more likely than are children to develop meningitis (S. pneumoniae) ♦ The incidence of meningitis or ventriculitis associated with ­post-neurosurgical

or brain device/catheter complications ranges between 1 and 10%, depending on the case series and the definition of the syndrome

Etiology ■

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Predominant causative pathogens in community-acquired adult bacterial meningitis are S. pneumoniae (pneumococcus) and N. meningitidis (meningococcus), which are responsible for ~80% of all cases; Listeria monocytogenes is the third most common cause of bacterial meningitis and commonly occurs in elderly patients and patients with defective cell-mediated immunity In neonates, gram-negative bacilli and streptococci are most common. In older children, with the reduction of H. influenzae, pneumococcus and meningococcus are now the most common Most common organisms following neurosurgical procedures are gram-negative bacilli and staphylococci (including Pseudomonas and methicillin-resistant Staphylococcus aureus)

Clinical Presentation ■

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The presentations of 352 consecutive cases of community-acquired bacterial meningitis are described in Table 25.1; only 59% presented with the classic triad of fever, neck stiffness, and altered mental status Classic signs of acute community-acquired meningitis: fever, altered mental status, and meningismus need not all be present in each patient, although 95% of all patients have at least two of these features Most sensitive sign (85–95%) is fever; the next most sensitive sign (70%) is neck stiffness, and altered mental status is least sensitive (67%) Brudzinski and Kernig signs are typically positive in only 50% of patients and therefore may be of no diagnostic benefit Fungal meningitis may present with nonspecific symptoms (malaise, weight loss), but it may also present with signs and symptoms similar to those of bacterial meningitis; while bacterial meningitis is typically a fulminant disease, fungal meningitis may present subacutely or as a chronic presentation

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Table 25.1  Symptoms and signs on presentation from 352 consecutive cases of communityacquired bacterial meningitis Symptoms and signs on presentation Seizures 24/326 (7%) Headache 256/305 (84%) Neck stiffness 280/344 (81%) Heart rate >120 beats/min 84/331 (25%) Body temperature ³38°C 291/345 (84%) Diastolic blood pressure <60 mmHg 18/342 (5%) Glasgow Coma Scale score <14 (indicating altered mental status) 298/351 (85%) <8 (indicating coma) 68/351 (19%) Papilledema 8/175 (5%) Triad of fever, neck stiffness, and change in mental status 206 (59%) Focal neurologic abnormalities 141 (40%) Aphasia 79/234 (34%) Hemiparesis 39/344 (11%) Cranial nerve palsies (excluding hearing loss) 43 (12%) Hearing loss 23/243 (9%) Data from Weisfelt M, van de Beek D, Spanjaard L, Reitsma JB, de Gans J (2006) Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series. Lancet Neurol 5(2):123–129

Diagnosis ■

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In patients with acute meningitis, CT is used mainly to assess the safety of lumbar puncture (LP), rather than to make a diagnosis A variety of pediatric and adult series show that the risk of cerebral herniation proximal (within several hours) to the LP is 1–1.8%; in these series, a “normal” CT scan did not always predict safety, nor did an “abnormal” CT with subsequent LP predict herniation According to the Practice Guidelines for the Management of Bacterial Meningitis, a CT scan should be performed prior to an LP if the patient has: ♦ ♦ ♦ ♦ ♦ ♦

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An immunocompromised state A history of CNS disease Altered level of consciousness A new-onset seizure Papilledema A focal neurologic deficit

Blood cultures should be drawn prior to the initiation of antibiotic therapy ♦ Blood cultures identify the etiologic agent in bacterial meningitis in ~50% of

all cases, though this depends on the bacterium

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♦ Blood cultures are likely to be helpful in the following (descending order):

H. influenzae, S. pneumoniae, N. meningitides, beta-hemolytic streptococci, and S. aureus ♦ Analysis of CSF is the gold standard for diagnosing bacterial meningitis ♦ Typical ranges of CSF parameters in bacterial meningitis • • • • • • ■

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Opening pressure: >15 cmH2O CSF WBC: 1,000–10,000 cells/mm3; predominantly neutrophils CSF Glucose: <40 mg/dL CSF:Serum Glucose ratio: <0.33 CSF Protein: >50 mg/dL Lactate: >3.5 mmol/L

99% certainty that CSF represents bacterial meningitis (rather than viral) if glucose is <34 mg/dL, CSF:serum glucose is <0.23, protein is >220 mg/dL, WBC is >2,000 mm3 or >1,180 PMN/mm3 In fungal meningitis, the CSF typically demonstrates lymphocyte predominance ♦ Number of WBC in the CSF is at least partially determined by the immuno-

logic status of the patient ♦ Severely immunosuppressed patients may have a minimal number of WBC in

the CSF, whereas those with normal immune systems typically have 100s–1,000s of cells/mm3 ■ ■ ■

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Glucose is typically slightly low to normal CSF protein may be very high owing to a CSF obstruction (Froin syndrome) Patients can also develop communicating hydrocephalus (particularly in Cryptococcal meningitis); therefore, opening pressures may be quite high Gram stain has 92% sensitivity and >99% specificity in diagnosing bacterial or fungal meningitis in those who have received no treatment Diagnosing post-neurosurgical infections can be problematic ♦ Most of these patients have received perioperative or postoperative antibiotics

at some time in their hospital course, which may make the recovery of organisms (gram stain or culture) difficult ♦ The gold standard for diagnosing these infections remains CSF culture and gram stain; however, many case series use an acute change in other CSF parameters (CSF WBC, protein, glucose, and lactate) with clinical changes (fever, altered mental status), even in the face of negative gram stain and culture, as evidence for infection

Management (Fig. 25.1) ■

Treatment, particularly antibiotics in bacterial meningitis, should never be delayed once the diagnosis is suspected

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Fig. 25.1  Diagnosis and treatment algorithm for suspected community-acquired bacterial meningitis. From Tunkel AR, Hartman BJ, Kaplan SL et al (2004) Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39(9):1267–1284

♦ Most patients should still have positive CSF cultures after 1–2 h subsequent

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to parenteral antibiotic treatment. Therefore in most cases, antibiotics can be administered prior to the CT and LP The literature does not support a consistent relationship between time to presentation and morbidity/mortality; it is clear, however, that meningitis and other CNS infections can be rapidly progressive entities for which urgent antibiotic administration is necessary Because delay should be minimal in administering antibiotics, appropriate choice of antibiotics is dependent first on the likely etiologic agent (based on age, immunocompetency, comorbidities, evidence of epidemics) Once the organism is cultured and antibiotic sensitivities are obtained, the antibiotic treatment can be more focused Recommendations for empiric therapy are summarized in Table 25.2, and those for specific etiologic agent are summarized in Table 25.3 Duration of treatment is dependant on the organism identified. Meningococcus can typically be treated for 7 days, pneumococcus for 14 days, and gramnegative bacteria require at least 21 days of treatment

Fungal meningitis is more complicated to treat and should be done with the help of an infectious diseases specialist; however, the cornerstone of treatment for many of the fungal pathogens remains amphotericin B Adjunctive treatment (Fig. 25.1) ♦ Five randomized, controlled studies have evaluated the use of adjunctive ste-

roids in the treatment of community-acquired bacterial meningitis

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Table 25.2  Recommendations for empiric treatment regimens for community-acquired bacterial meningitis Predisposing factor Common bacterial pathogens Antimicrobial therapy Age Ampicillin plus cefotaxime <1 month Streptococcus agalactiae, Escherichia or ampicillin plus an coli, Listeria monocytogenes, aminoglycoside Klebsiella species Vancomycin plus a third1–23 months Streptococcus pneumoniae, Neisseria generation cephalosporina,b meningitides, S. agalactiae, Haemophilus influenzae, E. coli 2–50 years N. meningitidis, S. pneumoniae Vancomycin plus a thirdgeneration cephalosporina,b >50 years S. pneumoniae, N. meningitidis, Vancomycin plus ampicillin L. monocytogenes plus a third-generation cephalosporinab Head trauma Basilar S. pneumoniae, H. influenzae, group Vancomycin plus a thirdskull fracture A b-hemolytic Streptococci generation cephalosporina Vancomycin plus cefepime, Penetrating trauma Staphylococcus aureus, coagulasevancomycin plus negative staphylococci (especially ceftazidime, or vancomycin Staphylococcus epidermidis), aerobic plus meropenem gram-negative bacilli (including Pseudomonas aeruginosa) Postneurosurgery Aerobic gram-negative bacilli (including Vancomycin plus cefepime, vancomycin plus P. aeruginosa), S. aureus, coagulaseceftazidime, or vancomycin negative staphylococci (especially plus meropenem S. epidermidis) CSF shunt Vancomycin plus cefepimec, vancomycin plus ceftazidimec, or vancomycin plus meropenemc From Tunkel AR, Hartman BJ, Kaplan SL et al (2004) Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39(9):1267–1284 a  Ceftriaxone or cefotaxime b  Some experts would add rifampin if dexamethasone is also given c  In infants and children, vancomycin alone is reasonable unless Gram stains reveal the presence of gram-negative bacilli

• Significant survival and sequela improvement was demonstrated in adults when dexamethasone was administered prior to the administration of antibiotics • Improvement was most dominant in S. pneumoniae meningitis • Dosing of dexamethasone prior to antibiotics reduces the subsequent intrathecal inflammatory response that occurs with the bacterial lysis • Dexamethasone should be dosed at 10 mg (IV) q 6 h for 4 days

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Table 25.3  Recommendations for specific treatment regimens for community-acquired bacterial meningitis Microorganism Recommended therapy Alternative therapies Vancomycin plus a thirdMeropenem, fluoroquinolone Streptococcus generation cephalosporina,b pneumoniae Penicillin G, ampicillin, Neisseria meningitidis Third-generation chloramphenicol, cephalosporina fluoroquinolone, aztreonam Listeria monocytogenes Ampicillind or penicillin Gd Trimethoprim-sulfamethoxazole, meropenem Streptococcus agalactiae Ampicillind or penicillin Gd Third-generation cephalosporina Haemophilus influenzae Third-generation cephalosporina Chloramphenicol, cefepime, meropenem, fluoroquinolonec a Third-generation cephalosporin Cefepime, meropenem, Escherichia coli aztreonam, fluoroquinolonec, trimethoprim-sulfamethoxazole Note. In children, ampicillin is added to the standard therapeutic regimen of cefotaxime or ceftriaxone plus vancomycin when L. monocytogenes is considered and to an aminoglycoside if a gram-negative enteric pathogen is of concern From: Tunkel AR, Hartman BJ, Kaplan SL et al (2004) Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39(9):1267–1284 a  Ceftriaxone or cefotaxime b  Some experts would add rifampin if dexamethasone is also given c  Gatifloxaxin or moxifloxacin d  Addition of an aminoglycoside should be considered

Acute Viral Encephalitis Definitions and Epidemiology ■

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Encephalitis implies direct inflammation of the brain; most infectious encephalitides affect the cortical structures, though many also cause inflammation of the deeper structures Variety of different organisms, such as herpes simplex, arbovirus, and rabies, can cause encephalitis Most common cause of sporadic fatal encephalitis in the US are the herpes simplex viruses (HSVs) ♦ ♦ ♦ ♦ ♦ ♦

HSVs are distributed worldwide Humans are the sole reservoir Estimated to occur in 1/250,000–1/500,000 in US; 250–500 cases/year in US 30% of those afflicted are <20 years of age; 50% are older than 50 No sex, seasonal, or racial variation 70–95% of humans are seropositive for HSV by adulthood

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Pathophysiology of herpes simplex encephalitis (HSE) Either primary or recurrent infection Primary infection more common in younger patients Patients with HSE and cutaneous lesions may have two different strains of HSV Triggering factors not identified Immunosuppression does not predispose to HSE, though there may be a worse prognosis ♦ HSV spreads from cell to cell, infecting both neurons and glia ♦ ♦ ♦ ♦ ♦

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West Nile Virus (WNV) has been epidemic in the US since 2002 ♦ ssRNA virus: Flavivirus ♦ Family of viruses includes Japanese encephalitis, Saint Louis encephalitis,

Kunjin virus ♦ Serologic cross-reactions with these viruses ♦ Thought to have originated in Uganda, though genetic lineage of US WNV

comes from Middle East ♦ Only US and Israeli WNV have caused death in humans and birds ♦ Recent history

• 1999 – 62 cases of severe disease, 59 cases of encephalitis, and 7 deaths occurred in the New York area • 2003 – 9,862 cases, 2,866 encephalitis cases, 264 deaths • 2007 – 3,630 cases, 1,217 meningo-encephalitis cases, 124 deaths • 1999 – 2007 – WNV current total case count ▲ Total number of cases – 27,264 ▲ Total encephalitis cases – 10,050, ~36% of total ▲ Deaths – 1,023, ~4% mortality

♦ 10% mortality with encephalitis ♦ Most cases are transmitted via mosquitoes, though it can be spread via blood

transfusions (all blood is screened now), organ transplant, vertical transmission in third trimester, and via breast milk

Clinical Presentation ■

Herpes encephalitis ♦ ♦ ♦ ♦ ♦ ♦

Change in personality, altered mental status, and decreasing level of consciousness Fever Focal neurologic findings Dysphasia, cranial nerve paresis, hemiparesis Headache, papilledema, vomiting Seizures (focal and generalized) in two-thirds of cases

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WNV encephalitis ♦ “Flu-like” syndrome (fever, malaise, myalgias, etc.) during the summer in

nonencephalitic patients ♦ Encephalitis

• Fever, fatigue, headache, altered mental status, weakness, movement disorders/parkinsonism • Risk increases after 50 years of age ▲ Ten times higher risk of meningitis or encephalitis at 50–59 years

(vs. 0–19 years) ▲ 43 times higher at >80 years

• Mortality 11–14% with encephalitis • 50% with weakness ▲ Motor neurons affected by virus ▲ Electrodiagnostic studies showed reduced motor responses, preserved

sensory responses, scattered denervation, and neurogenic recruitment, without evidence of myopathy or polyneuropathy • Bladder dysfunction

Diagnosis ■

HSE ♦ LP/CSF analysis

• WBC range – 10–100s, with values up to 1,000–2,000 • Usually 75–100% lymphocytes, but 10–15% of early-phase specimens can have up to 40% PMNs • RBC <10 in half of HSE specimens, and range of 10–1,000s in the other half • RBCs and xanthochromia help to distinguish HSE from other viral encephalitis • Protein – 50–90 mg/dL (50%), >90 mg/dL (25%), and normal (25%) • Glucose moderately reduced in a small percentage • Opening pressure can be elevated in approximately one-third of patients ♦ EEG

• Relatively sensitive noninvasive procedure, but specificity is poor ▲ Sensitivity – 84% ▲ Specificity – 32.5% ▲ Characteristic EEG – spike and slow-wave activity and PLEDS (peri-

odic lateralized epileptiform discharges), which arise from temporal lobe; attenuation of background

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♦ Imaging

• CT scan ▲ Can demonstrate low density areas with mass effect in the temporal

lobe, which can progress to hemorrhagic lesions; however, CT scan is rarely helpful • MRI ▲ Hyperintensity on T2 in one or both temporal lobes, which may extend

into insular cortex ▲ Gadolinium enhancement around the periphery of the infection ▲ No study conducted yet to determine the sensitivity and specificity, but

both are most likely high ▲ Abnormality never extends deeper than cortical structures

♦ Polymerase chain reaction (PCR)

• High sensitivity (96%) and specificity (99%) • May be negative on first day and may become negative after several days of treatment • Dependent on proper sample handling (must remain frozen in transit) ■

West Nile Virus ♦ Antibodies

• IgM in serum or CSF • IgM does not cross blood–brain barrier; therefore, presence in CSF strongly suggests CNS infection • Cross-reaction with yellow fever (vaccine), Japanese encephalitis (vaccine), St. Louis encephalitis, or Dengue fever • IgM antibody-capture immunoassay is test of choice, but IgM antibody may remain detectable for up to 500 days after infection ♦ Serum

• WBC mostly normal or elevated • Occasional lymphopenia • Hyptonatremia in encephalitis ♦ CSF

• Pleocytosis (0–2,000 WBC), predominantly lymphocytes (PMNs early) • Elevated protein, normal glucose ♦ CT scan; typically normal ♦ MRI

• One-third have enhancement of meninges or periventricular areas • Lesions are seen in the cortex, basal ganglia, cerebellum, brainstem, and spinal cord

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• T2 and gadolinium enhancing ♦ Culture: low yield ♦ PCR-CSF

• Not routinely available • Less sensitive because of short duration of human viremia

Management ■

HSE ♦ Acyclovir – 10 mg/kg q 8 h (total, 30 mg/kg/day) for 21 days

• Adequate hydration • Renal function should be monitored; if creatinine begins to rise, may need to temporarily discontinue drug, although renal dysfunction is almost always reversible • Even with acyclovir, ~30% mortality occurs • Neurologic sequelae are common • Supportive care and rehabilitation is important ■

West Nile Virus No approved treatment No evidence that antivirals are effective Supportive care is very important High proportion of patients with spinal cord (motor neuron) involvement will need mechanical ventilation ♦ 4% mortality (overall), with 10% mortality in patients with encephalitis ♦ At least 50% of survivors of encephalitis will have neurologic sequelae ♦ ♦ ♦ ♦

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Given the risk of mortality in adults with meningitis, the clinician must be aware of the most common presenting signs to begin potential life-saving treatments In suspected bacterial meningitis, empiric antibiotics should be chosen based on the patient’s risk factors and should be started immediately; choices for antibiotic coverage should be refined based on culture and sensitivity results In those patients who present with focal neurologic deficits or a decreased level of consciousness, a CT scan of the head should be performed prior to LP; antibiotics should not be held for the sake of these procedures Depending on the resistance patterns of the institution, S. pneumoniae may be resistant to penicillins and cephalosporins

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Corticosteroids should be used in the treatment of bacterial meningitis Dosage for acyclovir treatment in HSE is 10 mg/kg q 8 h WNV should be suspected if the patient develops encephalitis in the spring and fall, and particularly if presentation includes moderate to severe muscle weakness

Suggested Reading de Gans J, van de Beek D (2002) Dexamethasone in adults with bacterial meningitis. N Engl J Med 347:1549–1556 Jeha LE, Sila CA et al (2003) West Nile virus infection: a new acute paralytic illness. Neurology 61:55–59 Leis AA, Stokic DS (2002) A poliomyelitis-like syndrome from West Nile virus infection. N Engl J Med 347:1279–1280 Lozier AP, Sciacca RR et  al (2002) Ventriculostomy-related infections: a critical review of the literature. Neurosurgery 51:170–181; discussion 181–182 Poon WS, Ng S et al (1998) CSF antibiotic prophylaxis for neurosurgical patients with ventriculostomy: a randomised study. Acta Neurochir Suppl 71:146–148 Tunkel AR, Hartman BJ et al (2004) Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39:1267–1284 van de Beek D, Gans J de et al (2004) Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 351:1849–1859 Whitley RJ (2006) Herpes simplex encephalitis: adolescents and adults. Antiviral Res 71:141–148 Whitley RJ, Alford CA et  al (1986) Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med 314:144–149

Chapter 26

Cerebral Venous Sinus Thrombosis Agnieszka A. Ardelt

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Cerebral venous sinus thrombosis (CVST) constitutes ~1% of all stroke presentations Occurs at any age, but incidence peaks in the neonatal period and in the third decade Estimated annual incidence: adults, three to four cases per million; children or neonates, seven cases per million Female-to-male ratio: 1.5–5 to 1

Etiology ■

Risk factors, i.e., specific conditions associated with, although not necessarily proven to be causative in, CVST ♦ Adults

• • • •

Multiple risk factors – 44% of cases No risk factor identified – 13% of cases Hormonal contraceptives – 54% of cases of CVST in women <50 years old Genetic hypercoagulablilities – 22% of patients with CVST ▲ Includes Factor V Leiden mutation, prothrombin gene mutation, pro-

tein C deficiency, protein S deficiency, anti-thrombin III deficiency

A.A. Ardelt, MD, PhD (*) University of Chicago, Departments of Neurology and Surgery (Neurosurgery), Division of Neurocritical Care, 5841 South Maryland Ave MC2030, Chicago, IL 60637, USA e-mail: [email protected]

A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_26, © Springer Science+Business Media, LLC 2011

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• Pregnancy/puerperium – 20% of cases of CVST in women <50 years old ▲ CVST is more likely during puerperium, especially within 3 weeks of

delivery ▲ Associated with caesarian delivery, hyperemesis, concomitant infec-

tion, hypertension, increasing maternal age • Inflammatory, hematologic, endocrine, systemic disorders – 19% of cases ▲ Includes inflammatory bowel disease (particularly ulcerative colitis),

systemic vasculitis, collagen vascular diseases (e.g., systemic lupus erythematosus, Behcet disease, Sjogren syndrome), sarcoidosis, anemia, post-surgical status, dehydration • Other thrombophilic conditions – 16% of cases ▲ Includes anti-phospholipid antibody syndrome, hyperhomocysteine-

mia, nephrotic syndrome • Infections – 12% of cases ▲ Intracranial, head, orbit, and neck infections, e.g., meningitis, meningo-

encephalitis, mastoiditis, otitis ▲ Systemic infections

• Malignancy – 7% of cases ▲ CNS

tumors, solid tumors outside the CNS, hematologic malignancies

• Mechanical trauma – 5% of cases ▲ Includes traumatic brain injury, jugular bulb catheterization, cranial or

spinal surgery, lumbar puncture • Hormone replacement therapy – 4% of cases • Vascular CNS disorders, e.g., dural fistulae – 2% of cases ♦ Children

• Infection – 47–74% of cases • Dehydration – 21% of cases • Risk factor not identified – <5% of cases ♦ Neonates

• Perinatal complications – 50% of cases • Dehydration – 30% of cases • Maternal gestational complications – 26% of cases

26  Cerebral Venous Sinus Thrombosis

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Anatomy ■

Normal anatomy ♦ Cerebral venous system

• Components – dural sinuses, superficial cortical veins, deep cerebral veins, posterior fossa veins • Anatomy is much more variable than the cerebral arterial system • Many veins are not named ♦ Dural sinuses

• Superior sagittal sinus ▲ Arises near the crista galli and continues posteriorly ▲ Receives blood from superficial cortical veins ▲ With the straight, transverse (lateral), and occipital sinuses, forms the

confluence of sinuses (torcular herophili or confluens sinuum) • Inferior sagittal sinus ▲ Contained within the inferior margin of the falx cerebri ▲ Unites with the vein of Galen to continue as the straight sinus

• Transverse (lateral) sinuses ▲ Paired structures ▲ Arise (along with the occipital sinus) as divisions of the torcular herophili ▲ Continue first as the sigmoid sinuses, then as jugular veins

• Tentorial sinuses ▲ Multiple ▲ Receive blood from the cerebellar hemispheres and drain into dural

sinuses near the torcular herophili • Cavernous sinuses ▲ Paired, septated extradural venous spaces ▲ Receive blood from ophthalmic veins

♦ Veins

• Superficial cortical veins ▲ Superficial middle cerebral vein, vein of Trolard, vein of Labbe; others

are not named • Deep cerebral veins ▲ Medullary veins, subependymal veins (including the internal cerebral

vein), basal veins of Rosenthal, vein of Galen

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A.A. Ardelt

• Posterior fossa veins ▲ Include the anterior pontomesencephalic vein, precentral cerebella

vein, superior and inferior vermian veins, cerebellar hemispheric veins ■

Anatomic variations ♦ Hypoplasia

• Anterior portion of the superior sagittal sinus – 6–7% of people • Transverse (lateral) sinuses – 20–30% of sinuses have segmental narrowing or frank atresia ♦ Asymmetry of paired structures

• Transverse (lateral) sinuses – 50–80% of people ▲ Right transverse sinus dominant 75% of the time ▲ Congenital absence of one transverse sinus – 1–5% of people ■

Frequency of occlusion of specific sinuses and veins (Table 26.1)

Pathophysiology ■

Predisposition to thrombus formation ♦ Hypercoagulability ♦ Stasis of blood ♦ Mural injury (inflammatory or mechanical)

■

Consequences of thrombus formation ♦ Obstruction of cerebral vascular drainage, resulting in

Table 26.1  Frequency of occlusion of specific sinuses and veins Frequency, percent of casesa Adult Pediatric n = 624 n = 160 Sinus/vein Superior sagittal sinus 50 55 Lateral sinus 45 (left), 41 (right) 51 Straight sinus 18 24 Superficial cortical veins 17  6 Jugular veins 12  9 Deep cerebral veins 11 19 Cavernous sinus 1.3 Cerebellar veins 0.4 a  Multiple sinuses and veins are involved in ~30% of adult patients and 50% of pediatric patients

26  Cerebral Venous Sinus Thrombosis

• • • • • ■

425

Flow diversion Cerebral edema Ischemia (venous infarct) Intraparenchymal hemorrhage Intracranial hypertension

Natural history of thrombosis in CVST ♦ Recanalization in most patients

• Occurs within the first 4 months • Up to 40% have incomplete or no recanalization

Clinical Presentation ■

Adults ♦ Extremely wide spectrum of presentation, from isolated headache to coma,

depending on location of thrombus, presence of alternative venous drainage (venous collaterals), volume of thrombus, and rate of extension of thrombus ♦ Timing of presentation of CVST • Acute – 37% of cases • Subacute – 56% of cases • Chronic – 7% of cases ♦ Spectrum of presentation of CVST (symptoms and signs may fluctuate or

progress) • Headache – 75–95% of cases ▲ Usually chronic and lingering ▲ Thunderclap headache in up to 15% of cases ▲ The combination of headache, seizure, and focal neurologic deficit is

highly suggestive of CVST ▲ The combination of headache, visual disturbance, lethargy, nausea,

and papilledema on funduscopic exam may suggest the diagnosis of idiopathic intracranial hypertension, but up to 30% of patients with this presentation may harbor CVST • Papilledema – 30–45% of cases • Focal neurologic deficit – 30–60% of cases ▲ Due to cerebral edema and/or ischemia, intraparenchymal hemorrhage,

seizure and/or Todd’s paralysis • Seizures – 10–50% of cases • Encephalopathy – 30% of cases

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• • • • ■

Isolated intracranial hypertension – 23–29% of cases Isolated cranial nerve palsies – 10% of cases Isolated visual complaints – 9% of cases Coma – 5–13% of cases

Children and neonates ♦ Timing of presentation – 83% acute ♦ Spectrum of presentation

• Seizures – 58% of cases • Diffuse neurologic signs – 76% of cases • Focal neurologic signs – 42% of cases

Clinical Differential Diagnosis ■

Acute presentation ♦ ♦ ♦ ♦

■

Ischemic stroke Intracranial hemorrhage, including subarachnoid hemorrhage Seizure/post-ictal Metabolic disturbance

Subacute presentation ♦ ♦ ♦ ♦

Encephalitis or meningo-encephalitis Brain tumor or other mass CNS vasculitis Idiopathic intracranial hypertension

Diagnostic Tests ■

CT of the head ♦ Diagnostic value of CT

• Normal in 25–30% of patients with CVST • Aids in ruling out other pathology including tumor or abscess • Helical CT venography ▲ Improves diagnostic yield ▲ Reveals filling defects and abnormal venous drainage patterns

• Multi-slice CT angiography ▲ Aids in ruling out arterial occlusion as a cause of presentation

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♦ Specific signs of CVST

• Noncontrast CT ▲ Dense triangle (cord) sign – hyperdense signal in sinuses or veins due

to thrombus, observed in up to 25% of CVST cases • CT with iodinated contrast ▲ Empty triangle (delta) sign – non-opacification of the sinus due to pres-

ence of thrombus, observed in 16–46% of CVST cases ♦ Nonspecific signs of CVST

• Hypodensity and mass effect suggestive of cerebral edema and/or venous infarction – 40–70% of CVST cases • Hyperdensity due to intraparenchymal hemorrhage – 30% of CVST cases ▲ May be in a speckled, multifocal, petechial pattern within a hypodense

area ▲ May appear as a consolidated area of hemorrhage, suggestive of a pri-

mary cerebral hemorrhage ♦ Overall assessment of head CT in evaluation for CVST

• Pros ▲ ▲ ▲ ▲

Almost universal 24–7 availability Rapid acquisition of images (may be useful in uncooperative patients) No specific contraindications to noncontrast CT Contrasted venography has good sensitivity for CVST diagnosis

• Cons ▲ Radiation exposure ▲ Low sensitivity for signs specific to CVST, unless iodinated contrast is

used ▲ Contrast nephropathy and/or anaphylaxis ■

MRI of the brain ♦ Diagnostic value of MRI

• Considered by some to be the best tool for CVST diagnosis and follow-up • Gadolinium-enhanced magnetic resonance venography (MRV) increases specificity and sensitivity for CVST diagnosis ♦ Signs of CVST on MRI (Table 26.2)

• Absence of intravascular signal on gadolinium enhanced T1 sequences suggests thrombus • Loss of intravascular signal on time-of-flight angiography suggests thrombus but may be artifactual or reflective of congenital hypoplasia or stenosis • Appearance of thrombus on MRI

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A.A. Ardelt

Table 26.2  Signs of CVST on MRI MRI sequence Age of thrombus (time from onset) T1-weighted

T2-weighted

Comments

Acute (days)

Isointense

Hypointense

Subacute (weeks to a month) Chronic (>1 month)

Hyperintense

Hyperintense

Isointense

Hyperintense

Deoxyhemoglobin in intact red blood cells Methemoglobin in lysed red blood cells Varies depending on recanalization

♦ Overall assessment of MRI in evaluation for CVST

• Pros ▲ High sensitivity for parenchymal and vascular lesions

• Cons ▲ May not be available 24–7 ▲ Longer acquisition times problematic for unstable or combative patients

or those with claustrophobia ▲ Contraindicated in some patients, i.e., those with pacemakers ▲ Some sequences are prone to false-positive artifact; e.g., flow gaps on

MRV due to hypoplasia may mimic thrombus in 30% of normal cases ▲ Possibility of gadolinium-related systemic sclerosis in patients with

renal impairment ■

Conventional cerebral angiography (CCA) ♦ Diagnostic value of CCA

• Considered the gold standard for cerebral vascular imaging • Currently not routinely used, as the diagnosis can be made with MR- or CT-based imaging in most patients ♦ Signs of CVST on CCA

• Direct ▲ Filling defect in a sinus or vein

• Indirect ▲ ▲ ▲ ▲ ▲

Collateral drainage Dilated cortical veins with corkscrew morphology Delayed sinovenous drainage Flow reversal (away from thrombosed sinus or vein) Dural fistulae

♦ Overall assessment of CCA in evaluation for CVST

• Pros

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▲ High sensitivity and specificity ▲ Real-time view of drainage patterns

• Cons ▲ Radiation exposure ▲ Iodinated contrast with risk of contrast nephropathy or anaphylaxis ▲ Invasive, with risk of ischemic stroke, groin hematoma, arterial injury ■

Lumbar puncture (performed in selected patients after brain imaging with CT or MRI to rule out intracerebral lesions with mass effect) ♦ Diagnostic value of lumbar puncture

• Aids in ruling out septic thrombosis, bacterial meningitis, encephalitis • Enables measurement of cerebrospinal fluid pressure ♦ Cerebrospinal fluid findings in CVST

• • • • ■

Opening pressure >180 mm H2O – 84% of cases Mild pleocytosis or lymphocytosis – 47% of cases Increased protein content – 34% May be normal

Electroencephalography ♦ Not specifically useful in diagnosis of CVST ♦ May reveal epileptogenic foci, generalized slowing, or no abnormalities

Management of CVST ■

Monitoring ♦ Patients with poor neurologic exam; hemorrhage, edema, or infarct; frequent

seizures or status epilepticus; or concurrent systemic illnesses warrant admission to the ICU for: • • • • • ■

Serial neurologic examination Invasive ICP monitoring and ICP treatment Seizure monitoring and treatment Hemodynamic and/or ventilatory monitoring and support Prevention and management of neurologic and systemic complications

Systemic anticoagulation ♦ ♦ ♦ ♦

Absolute risk reduction in mortality – 14% Absolute risk reduction in death or dependency – 15% Presence of intraparenchymal hemorrhage is not a contraindication Specific goals of therapy

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A.A. Ardelt

• Prevention of thrombus extension • Prevention of thrombus formation elsewhere • Provision of environment favorable to clot dissolution ♦ Drugs of choice

• Unfractionated heparin is favored acutely, especially in critically ill patients, due to ease of reversal • Low-molecular-weight heparin can be used, but efficacy/safety compared to unfractionated heparin in CVST is unknown • Warfarin is favored after the acute period ♦ Suggested approach

• Initial anticoagulation with dose-adjusted unfractionated heparin ▲ Weight-based titration to partial thromboplastin time (PTT) goal 71–100 s

• Conversion to warfarin (INR goal, 2.0–3.0) once the patient is stable ▲ Warfarin is teratogenic and should not be used in pregnant patients

• Optimal duration of therapy is unknown ▲ 3–6 months is typical, especially if CVST was due to a transient risk factor ▲ Longer courses may be needed in selected patients ■

Thrombolysis ♦ Systemic pharmacologic thrombolysis

• Variable results and insufficient data to allow recommendations ♦ Local pharmacologic and mechanical thrombolysis

• No controlled randomized trials have been conducted, although many case series have been published • Risk-benefit compared, or as an adjunct, to systemic anticoagulation cannot be calculated due to paucity of trial data • Decision to offer thrombolysis is made on a case-by-case basis ▲ Coma or deterioration despite systemic anticoagulation is criterion

sometimes used • Standardization of the procedure is lacking ▲ Typically, a microcatheter is threaded retrograde to the site of the

obstruction, and a thrombolytic agent (usually recombinant tissueplasminogen activator) is injected into the thrombus, along with mechanical disruption using the guidewire • Potential complications ▲ Intracranial hemorrhage, ischemic stroke, groin hematoma, systemic

hemorrhage, re-thrombosis despite anticoagulation

26  Cerebral Venous Sinus Thrombosis ■

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Therapy in septic CVST ♦ Appropriate systemic antibiotics ♦ Systemic anticoagulation ♦ Surgical resection of infected tissue may be necessary

■

■

■

Discontinuation of oral contraceptives, hormone replacement, and other prothrombotic drugs Treatment of underlying associated conditions, if appropriate (e.g., systemic lupus erythematosus) General supportive care ♦ ♦ ♦ ♦ ♦ ♦

Hydration Treatment of fever Treatment of hyperglycemia Prophylaxis for deep venous thrombosis if not anticoagulated Nutritional support Physical, occupational, speech therapy

Complications and Their Management ■

Intracranial hypertension ♦ Cerebral edema – 50% of cases

• Usually no specific therapy other than anticoagulation is required ♦ Isolated intracranial hypertension (headache, papilledema)

• Therapeutic lumbar puncture(s) ▲ Anticoagulation should be withheld before and after procedure

• Acetazolamide or diuretics ▲ No controlled data on efficacy

• In cases of progressive vision deterioration despite above therapy ▲ Shunt, e.g., ventriculoperitoneal, lumboperitoneal ▲ Optic nerve fenestration ▲ Investigational interventional (stenting) approaches

♦ Elevated intracranial pressure and/or herniation – 20% of cases

• Management according to general neurocritical care principles ▲ Head-of-bed elevation, neck midline ▲ Hyperventilation, osmolar therapy (dehydration should be avoided),

metabolic suppression ▲ Decompressive surgery in selected intractable cases ▲ Steroids are not beneficial and should be avoided

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A.A. Ardelt

Seizures and epilepsy ♦ Incidence

• Early seizures – up to 50% • Late seizures – 10% • Epilepsy – 5% ♦ Risk factors for post-CVST epilepsy

• Intracerebral hemorrhage • Early seizure • Paresis ♦ Treatment of seizures

• Appropriate anti-epileptic medications • Optimal duration of therapy unknown, but at least 1 year is typically recommended ♦ Seizure prophylaxis

• Controversial • Reasonable option in some patients, e.g., those with a supratentorial intracerebral hemorrhage or other risk factors ■

Persistent headache ♦ 53–55% reported on follow-up

• 10–14% severe ♦ Management is the same as for other chronic headache patients (after other

causes of headache are ruled out) ■ ■

Severe visual loss – 1–5% Dural and pial arteriovenous fistulae ♦ Frequency unknown but relatively low ♦ Management according to neurosurgical principles

Outcome ■

Adults ♦ Complete recovery – 79%

• ~50% in those ³65 years old ♦ Dependency – 5% ♦ Death – 8%

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• • • •

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Rate varies between 5 and 30% in case series Increased frequency in septic CVST, varies from 50 to 80% 50% of deaths occur acutely 44% of deaths that occur in the subacute period are due to underlying conditions, e.g., malignancy – not due to CVST

♦ Independent predictors of death

• Coma • Deep cerebral venous thrombosis • Posterior fossa involvement ♦ Neuropsychologic and functional outcome

• Return to previous occupation – 47% • Change to part-time work – 33% • Cessation of work – 20% ♦ Risk of CVST recurrence – 2% of cases

• 42% recurred while on anticoagulation • No increased risk of recurrence is associated with subsequent pregnancy in cases of puerperal CVST ♦ Risk of recurrence of any thrombosis – 7% ■

Pediatric patients ♦ Complete recovery – 54% ♦ Persistent neurologic deficits – 38%

• • • • • •

Motor deficit – 80% Cognitive deficits – 10% Developmental delay – 9% Speech impairment – 6% Visual impairment – 6% Other – 26%

♦ Mortality – 8%

Key Points ■ ■

■ ■ ■

CVST is a rare cause of stroke presentation Thrombophilia (especially genetic or related to oral contraceptives or puerperium) is the most common risk factor in adults Headache is the most common feature of CVST presentation in adults A subacute course is the most common presentation of CVST in adults MR- or CT-based imaging or conventional angiography of the cerebral venous system is used for diagnosis

434 ■

■

■

■

■

A.A. Ardelt

Systemic anticoagulation for 3–6 months is the typical treatment, but a longer course may be necessary in selected patients Randomized controlled trials of thrombolysis for CVST are lacking, thus risks/ benefits cannot be determined at this time Outcomes of CVST are generally favorable, especially in younger adult patients – 79% of patients make a complete recovery; mortality is 8% Coma, presence of deep venous thrombosis, and posterior fossa involvement are predictors of mortality in adults Rate of CVST recurrence is low in adults, even in cases of pregnancy/puerperium-related CVST

Suggested Reading Agnelli G, Verso M (2008) Epidemiology of cerebral vein and sinus thrombosis. Front Neurol Neurosci 23:16–22 de Freitas GR, Bogousslavsky J (2008) Risk factors of cerebral vein and sinus thrombosis. Front Neurol Neurosci 23:23–54 deVeber G, Andrew M, Adams C et al (2001) Cerebral sinovenous thrombosis in children. N Engl J Med 345:417–423 Ferro JM, Canhao P (2008) Complications of cerebral vein and sinus thrombosis. Front Neurol Neurosci 23:161–171 Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F, ISCVT Investigators (2004) Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke35(3):664–670 Masuhr F, Einhaupl K (2008) Treatment of cerebral venous and sinus thrombosis. Front Neurol Neurosci23:132–143 Masuhr F, Mehraein S, Einhaupl K (2004) Cerebral venous and sinus thrombosis. J Neurol251:11–23 Osborn A (1994) Diagnostic neuroradiology. Mosby, Inc., St. Louis, MO Paciaroni M, Palmerini F, Bogousslavsky J (2008) Clinical presentations of cerebral vein and sinus thrombosis. Front Neurol Neurosci 23:77–88 Renowden S (2004) Cerebral venous sinus thrombosis. Eur Radiol 14:215–226

Chapter 27

Neuroleptic Malignant Syndrome, Malignant Hyperthermia, and Serotonin Syndrome Panayiotis N. Varelas and Tamer Abdelhak

Neuroleptic Malignant Syndrome ■

Epidemiology ♦ Neuroleptic malignant syndrome (NMS) is rare, diagnosed annually in 2,000

hospitalized patients in the US ♦ Recent studies suggest an incidence of 0.01–0.02% in patients treated with

antipsychotic medications ♦ Risk factors

• Prior physical exhaustion and dehydration • Previous episode of NMS (10–20% of cases) • Exposure to antipsychotic drugs ▲ High-potency, conventional antipsychotics convey a greater risk for

NMS than do clozapine, olanzapine, or risperidone ▲ Risk with quetiapine, apiprazole, or ziprasidone may be even lower ▲ Low potency D2-receptor antagonists, such as metoclopramide or

tricyclic antidepressants, have also been implicated ▲ An association may exist between parenteral administration, higher

titration rates, and total amount given, but even therapeutic doses can provoke the syndrome ♦ Associated with a 10% mortality ■

Clinical presentation ♦ Symptoms and signs required by DSM-IV-TR criteria require

• Both elevated temperature and severe extrapyramidal muscle rigidity (“lead-pipe”), occurring after administration of an antipsychotic drug, PLUS

P.N. Varelas, MD, PhD (*) and T. Abdelhak, MD Departments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, MI, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_27, © Springer Science+Business Media, LLC 2011

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• Two associated signs or symptoms (mental status change, tremors, dysautonomia with tachycardia or bradycardia and labile blood pressure, tachypnea or hypoxia, diaphoresis, incontinence or sialorrhea), OR • Laboratory abnormalities (rhabdomyolysis, metabolic acidosis, leukocytosis, generalized EEG slowing) ♦ Symptoms and signs develop within 24 h after administration of antipsychotic

drugs in 16%, within 1 week in 66%, and in all cases within 1 month ♦ After the antipsychotic is discontinued, symptoms and signs regress within

1 week in 63% of patients; persistent signs of extrapyramidal rigidity or catatonia may last for weeks in a few patients ♦ Differential diagnosis • Malignant hyperthermia (similar symptoms develop intraoperatively after exposure to anesthetic agents, and usually patient has familial history of disease) • Serotonin syndrome (withdrawal or introduction of serotoninergic agents) • Intoxication with anticholinergic agents, MDMA (methylenedioxymethamphetamine, “ecstasy”), amphetamines, or phenylcyclidine • Withdrawal syndrome (alcohol, sedatives, amantadine, l-dopa, baclofen) • Neuroleptic hypersensitivity syndrome in dementia with Lewy bodies • Nervous system infections (meningitis, encephalitis, abscess, tetanus) or sepsis • Nonconvulsive status epilepticus • Heat stroke • Thyrotoxicosis or pheochromocytoma • Diencephalic storms (in severe head trauma or intraventricular hemorrhage) • Akinetic mutism or malignant catatonia ■

Management ♦ High level of suspicion, early recognition ♦ Immediate cessation of antidopaminergic agent ♦ Admission to an ICU for monitoring and supportive treatment; NMS is self-

limited, and these measures may be adequate ♦ Monitor for signs of disseminated intravascular coagulation (DIC), follow

electrolytes, creatine phosphokinase, and renal function closely ♦ Volume resuscitation (if rhabdomyolysis present, at least 150–200 mL/h IV

fluids), with central venous pressure goal of 6–10 mmHg ♦ Systemic cooling (ice packs, fans, cold IV fluids, surface or invasive cooling

systems) ♦ Benzodiazepines (e.g., lorazepam 1–2 mg IV q 6–8 h) ♦ Dopaminergic agents (amantadine 200–400 mg/day orally or bromocriptine

2.5 mg q 8 h orally, up to 45 mg/day) ♦ Dandrolene (initial dose of 1–2.5 mg/kg IV, followed by 1 mg/kg q 6 h, up to

10 mg/kg/day until symptoms resolve; oral dandrolene up to 50–200 mg/day

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in divided doses is an alternative); monitor for excessive muscle weakness or hepatotoxicity ♦ Electroconvulsive therapy (6–10 bilateral electrode treatments) ♦ Avoid antipsychotics for at least 2 weeks after recovery from NMS and restart gradually, at lower doses (test dose) and with different or newer agents after informed consent; risk for recurrence of NMS after re-challenge with these drugs is estimated at 30%

Malignant Hyperthermia ■

Epidemiology ♦ The incidence of malignant hyperthermia (MH) is between 1:5,000 and

1:50,000 anesthesias ♦ Although it can occur with the first exposure, patients may require three anes-

thesias on the average to develop symptoms ♦ More common in males than in females (2:1) and more common in young

patients (mean age 18.3 years) ♦ MH is an inherited condition (autosomal dominant); prevalence of the genetic

abnormality is between 1:3,000 and 1:8,500 individuals ♦ Triggering factors

• Halogenated inhalational anesthetics • Succinylcholine. Non-depolarizing paralytics, propofol or ketamine have not been implicated • Extreme stress, vigorous exercise, and exposure to heat may rarely trigger MH ♦ Genetic abnormality in MH has been found in most cases to be in a sacroplas-

mic reticulum calcium channel named ryanodine receptor (RYR), isoform 1 • >100 mutations have been described within the RYR gene; this mutation leads to increased intracellular calcium release in response to ­triggering factors, activation of muscle contraction, increased oxygen consumption, and eventually, anaerobic metabolism and generation of CO2 and heat • However, at least six other genetic loci unrelated to the RYR, including dihydropyridine receptor mutations, account for some MH cases ♦ A range of rare myopathies has been associated with MH, including:

• Central core disease (an autosomal-dominant or, less commonly, autosomal-recessive disease with a mutation in the RYR1 implicated in most cases) • Multiminicore disease • Some sodium-channel forms of myotonia

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• Hypokalemic periodic paralysis • King Denborough syndrome (very rare) ♦ Mortality from MH is <5% with modern anesthesia techniques ■

Clinical presentation ♦ MH occurs during anesthesia or immediately after; symptoms and signs

include: • Unexpected increase in end-tidal CO2 > 55 mmHg or PaCO2 > 60 mmHg, which is usually the first sign and is followed within minutes to a few hours by: ▲ Markedly increased minute ventilation during spontaneous breathing ▲ Unexplained sinus tachycardia, ventricular tachycardia or fibrillation,

labile blood pressure, congestive heart failure ▲ Metabolic acidosis (base deficit >8 mEq/L, pH < 7.25) with elevated

lactate ▲ Altered mental status at the end of anesthesia (from delirium to coma) ▲ Generalized muscle rigidity, severe masseter rigidity (despite neuromus-

▲ ▲ ▲ ▲

cular blockade), rhabdomyolysis (with creatine kinase >20,000 U/L, myoglobinuria, and dark urine) with compartment leg syndrome Acute renal failure Hyperkalemia Hyperthermia (in dramatic cases, up to 1–2°C q 5 min, sometimes up to 44°C), usually a later sign DIC, especially with temperature >41°C

♦ Two laboratory tests have been found to be useful in the evaluation of indi-

viduals or families for MH • The in  vitro contracture test (IVCT) is based on contracture of muscle fibers biopsied from the suspected individual and exposed to halothane or caffeine • Genetic DNA testing for RYR mutations ▲ Because of the heterogeneity and metabolic complexity of the disease,

the predictive value of the test is only 50–80%, and a negative DNA test is not a proof for absence of MH susceptibility; therefore, the IVCT should be used first and, if positive, genetic analysis should be performed to identify the mutation ♦ Differential diagnoses

• • • •

Sepsis (usually responds to antipyretics) or tetanus Thyrotoxicosis or pheochromocytoma Iatrogenic overheating Rebreathing of CO2 from faulty anesthesia equipment

27  Neuroleptic Malignant Syndrome, Malignant Hyperthermia, and Serotonin Syndrome

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• Intrathecal injection of high-ionic, water-soluble contrast – myoclonic jerks start from the lower body and progress rostrally, ending in seizures and hyperthermia • NMS or serotonin syndrome • Hyperkalemic cardiac arrest in young children with asymptomatic or undiagnosed Duchenne or Becker muscular dystrophy (X-linked inheritance) ▲ These children develop rhabdomyolysis and hyperkalemia-induced

cardiac arrest, but no hyperthermia or muscle rigidity, after succinylcholine administration ■

Management Immediate cessation of all inhalation agents or succinylcholine Admission to an ICU for monitoring and supportive treatment Increased minute ventilation to normalize PaCO2 Body cooling – nasogastric lavage with icy solutions, fans, ice packs in groins, axillae or neck, surface or invasive cooling systems; goal is temperature of 38.5°C ♦ Dandrolene (directly antagonizes RYR1-mediated Ca2+ release) – 2.5 mg/kg IV bolus and repeat q 15 min up to 10 mg/kg/day if tachycardia or hypercarbia are not controlled; continue at 1 mg/kg IV or 2 mg/kg orally q 4–8 h for 3 days; monitor for excessive muscle weakness or hepatotoxicity ♦ Hyperkalemia ♦ ♦ ♦ ♦

• • • • • •

Hyperventilation Albuterol (10 mg via nebulizer) Kayxalate 30–60 g orally or rectally) Glucose (1 amp of DW 50%) + insulin (10 units regular IV) Calcium gluconate (10 mL of 10% IV over 2–5 min, lasts for 30 min) Bicarbonate (1 mEq/kg IV over 3–5 min, avoid after calcium administration)

♦ Rhabdomyolysis

• IV fluids at 200 mL/h, assure urine output of 2 mL/kg/h, can use mannitol or furosemide as diuretics • Monitor for signs of DIC, follow the electrolytes, creatine phosphokinase, and renal function closely in the ICU ♦ Monitor for recrudescence – 25% of patients may develop return of signs and

symptoms at, on the average, 13 h from initial reaction ♦ Factors associated with recrudescence

• • • •

Muscular body type MH grading score >35 Temperature increase Period between induction to adverse reaction >150 min

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P.N. Varelas and T. Abdelhak

♦ Preventive measures for future anesthesia on the index patient or family

members, including genetic counseling • No volatile agents or succinylcholine should be used in MH-susceptible patients, but regional anesthesia with local agents or generalized anesthesia with barbiturates, propofol, etomidate, benzodiazepines, ketamine, and nondepolarizing neuromuscular blocking agents can be used • Such patients should also avoid exposure to vigorous exercise in heated conditions

Serotonin Syndrome ■

Epidemiology ♦ From post-marketing surveillance studies, serotonin syndrome (SS) was

found to affect 0.4 cases per 1,000 patient months in patients taking the antidepressant drug nefazodone ♦ Affects 14–16% of patients overdosing on SSRIs (selective serotonin reuptake inhibitors) ♦ SS is believed to result from overstimulation of the 5-HT1A or 5-HT2A receptors from various medications, including: • Excess of serotonin or serotonin agonists – buspirone, LSD, Lithium, sumatriptan, l-tryptophan, trazodone • Increased serotonin release – amphetamines, MDMA, cocaine, fenfluramine, reserpine • Decreased serotonin breakdown – MAO (monoamine oxidase) inhibitors, linezolid (a weak MAO inhibitor), ritonavir • Decreased serotonin reuptake – SSRIs, tricyclics, trazodone, venlafaxine, meperidine, dextromethorphan, fentanyl, tramadol ■

Clinical presentation ♦ Patient probably has had a recent addition of a serotoninergic agent (or an

increase in dosage) ♦ Symptoms and signs begin abruptly within 6 h after ingestion ♦ Based on the revised criteria developed by Radomski et al. (Table 27.1), SS

can be subdivided into: • Mild form – tachycardia, shivering, diaphoresis, mydriasis, hypereflexia • Moderate form (or full-blown SS) – tachycardia, hypertension, hyperthermia (up to 40°C), diaphoresis, mydriasis, hyperactive bowel, hypereflexia and clonus (characteristically seen in lower extremities and seen much less in upper extremities), horizontal ocular clonus, agitation/ hypervigilance, and rotatory head turning movements

27  Neuroleptic Malignant Syndrome, Malignant Hyperthermia, and Serotonin Syndrome

441

Table 27.1  Revised diagnostic criteria for SS A serotoninergic agent should be added to the regimen (or the dose increased), and four major symptoms should be manifested (or three major plus two minor) These symptoms must not be explainable by a psychiatric disorder, a recent introduction or change in dosage of a neuroleptic agent, or an infectious, metabolic, or other toxic cause Major Mental symptoms: confusion, elevated mood, coma Autonomic symptoms: fever, diaphoresis Neurologic symptoms: myoclonus, tremors, hypereflexia, chills, muscle rigidity Minor Mental symptoms: agitation, nervousness, insomnia Autonomic symptoms: tachycardia, tachypnea, diarrhea, low or high blood pressure Neurologic symptoms: impaired coordination, akathisia, mydriasis

• Severe form – hypertension or shock, agitated delirium, muscle rigidity and clonus (more in the lower extremities), hyperthermia (>41.1°C) with rhabdomyolysis, metabolic acidosis, renal failure, DIC ♦ Differential diagnoses (Table 27.2)

• • • • • •

NMS MH Anticholinegic drug intoxication Thyrotoxicosis or pheochromocytoma, hypoglycemia Delirium tremens Infection, including meningoencephalitis, sepsis, or tetanus

♦ Laboratory evaluation

• Urine toxicology screen for cocaine, amphetamines, and myoglobin • Blood toxicology screen for tricyclics, thyroid function tests, glucose, electrolytes, blood cultures, CK, DIC panel, lithium level ■

Management ♦ Immediate cessation of all serotoninergic drugs; this single measure resolves

SS within 24 h in most patients ♦ Admission to an ICU for monitoring and supportive treatment ♦ Benzodiazepines for sedation (e.g., lorazepam 1–2 mg IV q 6–8 h) ♦ Increased IV fluid rate or boluses to account for the increased fluid loss and

to maintain a MAP of >65 mmHg ♦ If hypotension is related to MAO inhibitors, only direct-acting sympathomi-

metic drugs (norepinephrine, phenylephrine, epinephrine) should be used and indirect-acting (e.g., dopamine) should be avoided, to support MAP ♦ In severe hypertension, short-acting IV agents such as nitroprusside or esmolol should be used; if intracranial pressure is elevated, nicardipine infusion may be an alternative

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P.N. Varelas and T. Abdelhak

Table 27.2  Differential diagnosis of SS, MH, NMS and anticholinergic intoxication SS NMS MH Anticholinergics Anticholinergic Drug Serotoninergic Dopamine Succinylcholine, agent agent antagonist inhalational anesthetics Lag time 6–12 h 1–7 days 30 min to few 6–12 h hours Vitals ↑ HR, ↑ BP, ↑ RR ↑ HR, ↑ BP, ↑ HR, ↑ BP, ↑ HR, ↑ or ↔ ↑ RR ↑ RR BP, ↑ RR Fever £40°C in moderate, >41.1°C Up to 46°C £38.5°C >41°C in severe Pupils ↑↑ ↔ ↔ ↑↑ Mucosa Sialorrhea Sialorrhea Normal Dry Mottled, Hot and dry Skin Diaphoresis Pallor, diaphoresis diaphoresis Bowel ↑sounds, diarrhea Normal or ↓ ↓ sounds ↓ sounds sounds ↑in LE ↑↑ Lead-pipe ↑↑, Masseter Normal Muscle tone Bradyreflexia ↓ Normal Reflexes ↑↑, Clonus in LE, ocular clonus Mental Agitation, coma Stupor, akinetic Agitation Agitated status mutism, coma delirium HR heart rate; BP blood pressure; RR respiratory rate; LE lower extremities. Adapted from Boyer EW, Shannon M (2005) The serotonin syndrome. N Engl J Med 352:1112–1120

♦ For moderate cases, 5-HT2A antagonists:

• Cyproheptadine, initially 12 mg orally; then, 2 mg q 2 h until symptoms abate or a dose of 32 mg/day is reached; continue with 8 mg q 6 h; may cause sedation • Olanzapine 10 mg sublingually • Chlorpromazine 50–100 mg IM ♦ For hyperthermic or severe cases

• • • •

Benzodiazepines (lorazepam or midazolam drip) Intubation and mechanical ventilation Paralysis with nondepolarizing agents such as vecuronium Temperature control with fans; ice packs in groin, axillae, or neck; surface or invasive cooling systems; no role for antipyretics, as hyperthermia is due to increased muscular activity

Key Points ■ ■

Rare, but potentially lethal syndromes Immediate onset after anesthesia for MH, within a few hours for SS, slower (up to a week) for NMS

27  Neuroleptic Malignant Syndrome, Malignant Hyperthermia, and Serotonin Syndrome ■ ■ ■ ■

443

Cessation of offending agents is the most important first step Dandrolene is useful in MH and NMS Dopaminergic agents are useful in NMS Temperature control and rhabdomyolysis management are imperative

Suggested Reading Birmes P, Coppin D, Schmitt L, Lauque D (2003) Serotonin syndrome: a brief review. CMAJ 168:1439–1442 Boyer EW, Shannon M (2005) The serotonin syndrome. N Engl J Med 352:1112–1120 Burkman JM, Posner KL, Domino KB (2007) Analysis of the clinical variables associated with recrudescence after malignant hyperthermia reactions. Anesthesiology 106:901–906; quiz 1077–1078 Caroff SN, Campbell EC, Sullivan KA (2007) Neuroleptic malignant syndrome in elderly patients. Expert Rev Neurother 7:423–431 Jones D, Story DA (2005) Serotonin syndrome and the anaesthetist. Anaesth Intensive Care 33:181–187 Larach MG, Localio AR, Allen GC et  al (1994) A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology 80:771–779 Litman RS, Rosenberg H (2005) Malignant hyperthermia: update on susceptibility testing. JAMA 293:2918–2924 Reulbach U, Dutsch C, Biermann T et al (2007) Managing an effective treatment for neuroleptic malignant syndrome. Crit Care 11:R4 Rosenberg H, Davis M, James D et al (2007) Malignant hyperthermia. Orphanet J Rare Dis 2:21 Strawn JR, Keck PE Jr, Caroff SN (2007) Neuroleptic malignant syndrome. Am J Psychiatry 164:870–876

Chapter 28

Brain Tumors Sherry Hsiang-Yi Chou

Epidemiology ■

■ ■ ■

■ ■

■ ■

Brain tumor is the most common cause of death from intracranial disease, second to stroke ~18,500 new diagnoses of brain tumor per year in the US in 2005 ~12,760 deaths from brain tumor per year in the US in 2005 Metastatic brain tumors are twice as prevalent as primary brain tumors in the adult population Overall 5-year survival of all brain tumors is estimated to be 33% The only well-validated risk factor for developing primary brain tumor is ionizing radiation exposure, typically from prior treatment of cancer Gliomas account for ~33% of all primary brain tumors 67% of all gliomas are high grade gliomas

Etiology ■

Solid malignancies in the nervous system ♦ Primary tumors of the nervous system, according to classification by the

World Health Organization, are summarized in Table 28.1 ♦ Certain inherited syndromes are associated with tumors that involve the ner-

vous system; these are summarized in Table 28.2

S.H.-Y. Chou, MD.CM, MMSc. (*) Division of Critical Care Neurology and Cerebrovascular Diseases, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_28, © Springer Science+Business Media, LLC 2011

445

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S.H.-Y. Chou

♦ Metastatic brain tumors are the most common brain neoplasms in the adult

population ♦ The most common metastatic brain tumors, in order of prevalence

• • • • • • •

Lung (18–64%) Breast (2–21%) Melanoma (4–16%) Colorectal tumors (2–12%) Renal cell carcinoma (1–8%) Lymphoma (<10%) Brain tumor of unknown origin (1–18%)

♦ 26% of all brain tumors are metastatic

• 80% of all metastatic tumors are supratentorial, and 15% occur in the cerebellum ■

Carcinomatous meningitis ♦ Presence of tumor cells in the leptomeninges ♦ Typically presents with multifocal neurologic symptoms and signs

• • • • • • • •

Cranial nerve palsies Radiculopathy Myelopathy Cauda equina syndrome Headache Hydrocephalus Nausea/vomiting Meningismus

♦ Typically occurs as a late complication of cancer in the setting of active sys-

temic disease; most common sources include: • • • • • • • •

Small cell lung cancer (15%) Leukemia (5–15%) Lymphoma (6%) Breast (5%) Melanoma (5%) Non-small-cell lung cancer (1%) Gastrointestinal tumors (1%) Head and neck tumors (1%)

♦ Primary brain tumors known to spread to leptomeninges

• • • •

Primary CNS lymphoma Neuroblastoma Medulloblastoma Malignant glioma

28  Brain Tumors

447

Table 28.1  Primary brain tumors (2007 WHO Classification) WHO Prognosis Tumor grade Epidemiology Tumors of neuroepithelial tissue Astrocytic Tumors Pilocytic astrocytoma

I

More common in children Common locations: cerebellum, hypothalamus, and optic nerve Onset in infancy (median age of onset is 10 months) Occur in hypothalamus or optic chasm More common in children Associated with tuberous sclerosis Rare Average age of onset is 10 years

Pilomyxoid astrocytoma

II

Subependymal giant cell astrocytoma

I

Pleomorphic xanthoastrocytoma

II

Diffuse astrocytoma (fibrillary astrocytoma; gemistocytic astrocytoma; protoplastic astrocytoma) Anaplastic astrocytoma

II

Age of onset is 30–40 years Mostly supratentorial in location Can occur in spinal cord and brainstem

III

Mean age of onset is 41 years Male predominance

Glioblastoma (giant cell glioblastoma; gliosarcoma)

IV

Gliomatosis cerebri

IV

Peak age of onset is 40–60 years Arise either as primary tumor or transformation from anaplastic astrocytoma Diffusely infiltrating glioma involving more than two lobes of the brain May extend into posterior fossa and spinal cord

Usually slow growing, and prognosis is typically better than that of astrocytoma Outcome depends on surgical accessibility of tumor Prognosis worse than that of pilocytic astrocytoma

Benign

Postoperative survival ranges from 2 to 17 years Slow growing but may undergo malignant transformation Survival is 6–8 years after surgical resection Gross total resection associated with better prognosis

5-Year survival rate is 30% Presence of oligodendroglial component improves survival Gross total resection is associated with better prognosis Median survival on treatment is 12 months 5-Year survival rate is 3.3%

Very poor prognosis Median survival is 12 months

(continued)

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S.H.-Y. Chou

Table 28.1  (continued) Tumor

WHO grade

Epidemiology

Prognosis

Slow growing Often calcified Mean age of onset is 42.6 years Account for <5% of all brain tumors Mean age of onset is 48.7 years

Median survival is 11.6 years Lack of contrast enhancement on imaging is associated with better survival

Recurrence post resection is common Younger age and lower grade at initial diagnosis are associated with better prognosis Prognosis depends on histologic grade

Oligodendroglial Tumors Oligodendroglioma

II

Anaplastic oligodendroglioma

III

Median survival is 3.5 years Chromosome 1p and 19q deletion is associated with better prognosis

Oligoastrocytic Tumors Oligoastrocytoma

II

2.3% of all brain tumors Largely located supratentorially Occur in adults

Anaplastic oligoastrocytoma

III–IV

Rare

Subependymoma

I

Myxopapillary ependymoma

I

Ependymoma (cellular; papillary, clear cell, tanycytic)

II

90% occur in adults Associated with tuberous sclerosis Male:Female = 2.2:1 Almost exclusively located in cauda equina More common in adults than in children Comprise 4% of all brain tumors Third most common CNS tumor in children 90% are in brain, and 10% in spinal cord

Anaplastic ependymoma

III

Rare

I

Comprise 0.5% of intracranial tumors Males affected more often than females Onset usually in first decade of life May cause hydrocephalus due to excess CSF production

Ependymal Tumors Often asymptomatic and found incidentally on autopsy Survival >10 years

10-Year survival is 45% in adults Total resection associated with better prognosis Seeding of CSF space is associated with poor prognosis Prognosis worse with higher grade

Choroid Plexus Tumors Choroid plexus papilloma

Benign; surgery is curative

(continued)

28  Brain Tumors

449

Table 28.1  (continued) Tumor

WHO grade

Atypical choroid plexus papilloma

II

Choroid plexus carcinoma

III

Epidemiology

Prognosis

Choroid plexus papilloma with increased mitotic activity Tends to arise in the lateral ventricle and invade adjacent brain Systemic metastases may occur Diagnosis is made only after exclusion of metastatic lung adenocarcinoma in adults

Surgery can be curative Recurrence rate higher than that of choroid plexus papilloma 5-Year survival rate is 26–50%

Other Neuroepithelial Tumors Astroblastoma

I

Rare glial neoplasm of uncertain histogenesis Mostly occurs in young adults but have been reported in children II Occurs exclusively within Chordoid glioma the rostral third of the third ventricle ventricle Angiocentric glioma I Occur mainly in children and young adults Leading symptom is refractory epilepsy Neuronal and Mixed Neuronal-Glial Tumors Dysplastic gangliocytoma of cerebellum (Lhermitte–Duclos) Desmoplastic Infantile astrocytoma/ ganglioglioma Dysembryoplastic neuroepithelial tumor

Gangliocytoma

I

I

I

I

Unknown

Surgical excision is treatment of choice Benign; Surgery is curative

Rare syndrome CNS manifestation of Cowden disease Variant of ganglioglioma; occur up to age 2 years Mean age of onset is 9 years Temporal lobe is the most common location Associated with cortical dysplasia Occurs mostly in children and young adults 0.4% of all brain tumors Temporal lobe is the most common site

Variable

Surgery can be curative

Associated with intractable childhood epilepsy Favorable outcome after surgical resection

5-Year survival is 80% Associated with seizures

(continued)

450

S.H.-Y. Chou

Table 28.1  (continued) Tumor

WHO grade

Ganglioglioma

Epidemiology

Prognosis

II–III

Most occur before age 21 4–8% of all pediatric brain tumors Temporal lobe is the most common site

Anaplastic ganglioglioma

IV

Central neurocytoma

II

Extraventricular neurocytoma

II

Cerebellar liponeurocytoma Papillary glioneuronal tumor

II

Rosette-forming glioneuronal tumor of the fourth ventricle

I

Paraganglioma

I

Rare malignant transformation of ganglioglioma Usually located in lateral or third ventricle near foramen of Monro, frequently within septum pellucidum Onset in second or third decade Similar to central neurocytoma but located outside of ventricular system Arise in cerebellum of adults Wide age range; mean age of onset is 27 years Temporal lobe is the preferential location Rare Primarily in young adults (mean age of onset is 33) Analogous to pheochromocytoma Most often located in filum terminale Rarely produces catechola-mines

Excellent prognosis after complete resection Brainstem location is associated with worse prognosis Associated with seizures Poor

I

Excellent prognosis after surgical resection

Favorable outcome with maximal resection

Favorable outcome following surgery Benign

Benign; surgery is curative

Variable

Tumors of the Pineal Region Pineocytoma

I

Slow growing, usually favorable prognosis

II, III

<1% of all brain tumors Occur in middle-aged or older adults Rare

Pineal parenchymal tumor of intermediate differentiation Pineoblastoma

IV

<1% of all brain tumors

Poor prognosis

5-Year event-free survival is ~60–69%

Metastasize via CSF pathways (continued)

28  Brain Tumors

451

Table 28.1  (continued) WHO grade

Epidemiology

Prognosis

II, III

Rare Affect children and young adults (mean age of onset is 32 years)

5-Year event-free survival is 27–73% Recurrences are common

Medulloblastoma (desmoplastic/nodular medulloblastoma; medulloblastoma with extensive nodularity, anaplastic medulloblastoma; large cell medulloblastoma)

IV

Recurrence is common, and most recurrences occur within 2 years of initial resection 5-Year progression-free survival is 60–80%

CNS primitive neuroectodermal tumor (PNET) (CNS neuroblastoma; CNS ganglioneuroblastoma; medulloepithelioma, ependymoblastoma) Atypical teratoid/rhabdoid tumor

IV

Over 50% occur in children younger than 10 years of age Second peak occurs in ages 18–25 Originate in the cerebellum, usually in the midline Can metastasize to extracranial sites such as bone and lymph nodes Occurs mostly in children and young adults Metastases to lungs and other systemic organs can occur Childhood disease >60% occurs in the posterior fossa

Survival rate in children under 3 years old is <10% 2-Year survival is <20%

Tumor Papillary tumor of the pineal region

Embryonal Tumors

IV

Death occurs within 8–24 months of diagnosis

Tumors of cranial and paraspinal nerves Schwannoma (cellular, plexiform, melanotic)

I

Neurofibroma

I

Perineurioma (perineurioma, I–III NOS; malignant perineurioma)

8% of all intracranial and 29% of all spinal tumors Female:Male = 2:1 Peak incidence in the fourth and fifth decades Most common site is the vestibular nerve Arises from nerve terminal in the dermis and large nerve trunks Associated with neurofibromatosis (NF) I Rare

Prognosis is excellent post resection Malignant transformation is exceedingly rare

Prognosis depends on the prognosis of NF1

Variable

(continued)

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S.H.-Y. Chou

Table 28.1  (continued) WHO grade

Epidemiology

Prognosis

>50% occur in patients with NF1

5-Year survival is 34%; 10-year survival is 23%

I–III

Majority are benign Female:Male = 3:2 Common sites: cerebral convexities, falx cerebri, olfactory groove, tentorium cerebelli, sphenoid ridge, and parasellar region

More aggressive subtypes include atypical, clear cell, choroid, rhabdoid, papillary, and anaplastic

Lipoma

n/a

Benign

Angiolipoma

n/a

Hibernoma

n/a

Liposarcoma Solitary fibrous tumor

n/a n/a

Fibrosarcoma

n/a

Malignant fibrous histiocytoma

n/a

Leiomyoma Leiomyosarcoma

n/a n/a

Rhabdomyoma

n/a

Favors midline locations Lumbosacral lipomas are associated with spinal dysraphism Rare Contains adipose tissue and blood vessels Derived from brown fat Very rare Very rare Rare Occurs in adults Mimics meningioma Rare, <1% of all intracranial tumors Tumor containing pleomorphic atypical histiocyte and fibroblast-like cells Very rare Rare Rare Tumor cells express EBV in AIDS patients Rare

Tumor

II–IV Malignant peripheral nerve sheath tumor (MPNST) (epithelioid MPNST; MPNST with mesenchymal differentiation, melanotic MPNST; MPNST with glandular differentiation) Tumors of the meninges Tumors of Meningothelial Cells Meningioma (meningothelial; fibrous; transitional, psammomatous; angiomatous, microcystic; secretory, lymphoplastmacyte-rich; metaplastic, chordoid, clear cell, atypical, papillary, rhabdoid, anaplastic) Mesenchymal Tumors

Benign Invasion of surrounding tissue is rare Benign Variable Benign

May invade neural parenchyma Variable

Benign Variable

Variable (continued)

28  Brain Tumors

453

Table 28.1  (continued) Tumor

WHO grade

Rhabdomyosarcoma

n/a

Chondroma

n/a

Chondrosarcoma

n/a

Osteoma

n/a

Osteosarcoma Osteochondroma

n/a n/a

Hemangioma Epithelioid hemangioendothelioma Hemangiopericytoma

Epidemiology

Prognosis Variable

n/a

Rare Resembles neuroepithelial neoplasm Commonly arises from skull base or spine Preferentially located in petrosal, occipital, or sphenoid bones Commonly arises from skull base or spine May occur in Paget disease Commonly arises from skull base or spine Vascular malformations

n/a

Very rare

II

Most CNS hemangiopericytomas occur in the meninges Occurs in all ages; peak in fourth to sixth decade

Benign Variable

Benign Variable Benign Benign unless they hemorrhage Variable Recurrence post surgery is 80% 20% have systemic metastases 5-Year survival rate is slightly less than 50% Variable

Anaplastic hemangiopericytoma Angiosarcoma Kaposi sarcoma

III

Very rare

n/a n/a

Very rare Very rare Associated with AIDS

Variable Variable

Ewing Sarcoma – PNET

n/a Rare From leptomeningeal melanocytes Rare Rare Must exclude metastatic disease from cutaneous melanoma Rare

Variable

Primary Melanocytic Lesions Diffuse melanocytosis

n/a

Melanocytoma Malignant melanocytoma

n/a n/a

Meningeal melanocytosis

n/a

Benign Malignant tumor Total resection appears to improve prognosis Variable

Other Neoplasms Related to the Meninges Hemangioblastoma

I

1–2.5% of all intracranial tumors Frequently occurs in young and middle-aged persons Commonly occurs in the cerebellum Associated with von Hippel–Lindau disease

Prognosis worse with post-operative recurrence or multiple hemangioblastoma

(continued)

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S.H.-Y. Chou

Table 28.1  (continued) Tumor

WHO grade

Epidemiology

Lymphomas and haemopoietic neoplasms Malignant lymphoma n/a Account for <1% of primary CNS tumor; lesions may be multiple in immunocompromised patients

Plasmacytoma

n/a

Granulocytic sarcoma

n/a

98% are B-cell lymphomas EBV virus is present in 95% of tumors in immunocompromised patients 10% of AIDS patients develop CNS lymphoma Majority evolve into systemic multiple myeloma Exceedingly rare Tumors of malignant white blood cells

Prognosis Median survival is 17–45 months in immunocompetent patients and 2–6 months in immunocompromised patients Solitary mass is associated with better prognosis

Not known

Not known

Germ cell tumors Germinoma

n/a

Embryonal carcinoma

n/a

Yolk sac tumor

n/a

Choriocarcinoma

n/a

Teratoma

n/a

CNS is second most common site for germinomas Accounts for 60% of pineal region tumors 2–5% of all CNS malignancies Male:Female = 2.5:1 Occurs primarily in children and adolescents Most undifferentiated germ cell tumor a-Fetoprotein is elevated in CSF Malignant Rare Malignant Presents with CNS hemorrhages Malignant Rare

Mixed germ cell tumors

n/a

Rare

5- and 10-year survival rates are 75–95% 10–15% have spinal cord metastases

Poor prognosis 3-Year survival is 27.3%

Poor prognosis 3-Year survival is 27.3% Poor prognosis 3-Year survival is 27.3% 10-Year survival is 70–92% Variable, depends on the components of the mixed cell lines (continued)

28  Brain Tumors

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Table 28.1  (continued) Tumor Tumors of the sellar region Craniopharyngioma (adamantinomatous; papillary) Granular cell tumor Pituicytoma

Spindle cell oncocytoma of the adenohypophysis

WHO grade I

I I

I

Epidemiology

Prognosis

Second most common neoplasm of sellar region Most are asymptomatic Rare Glial neoplasms that originate in the neurohypophysis or infundibulum Oncocytic, nonendocrine neoplasm of the anterior pituitary Affects adults (mean age of onset is 56 years)

Recurrence is common 10-Year survival rate is 68% Benign Unknown

Benign

Table 28.2  Genetic syndromes with associated brain tumors Syndrome Gene Clinical manifestation Neurofibromatosis I NF1 = Schwannomas, neurofibromin astrocytomas, optic nerve gliomas, meningiomas, neurofibromas, neurofibrosarcomas Neurofibromatosis II NF2 = merlin Bilateral vestibular schwannomas, astrocytomas, multiple meningiomas, ependymomas Von Hippel–Lindau VHL/VHL tumor Hemangioblastomas, suppressor pancreatic cysts, retinal angiomas, renal cell carcinomas, pheochromocytomas Li-Fraumeni TP53/p53 Gliomas, sarcomas, breast cancer, leukemia Turcot syndrome APC/adenomatous Gliomas, medulloblastomas, polyposis coli adenomatous colon polyps, adenocarcinoma PTCH/patched Basal cell carcinomas, Basal cell nevus medulloblastomas (Gorlin) syndrome

Chromosome location 17

22

3

17 5

9

(continued)

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S.H.-Y. Chou

Table 28.2  (continued) Syndrome Gene Tuberous sclerosis

TSC1; TSC2

Clinical manifestation

Chromosome location

9q34; 16p13.3 Cortical tuber, subependymal giant cell astrocytoma, subependymal nodules, lymphangiomyomatosis, adenomata sebaceum (angiokeratomas), retinal hamartomas, ungula or periungual fibromas, cardiac rhabdomyoma, renal angiomyolipoma, cysts of kidney, bone, and lung, gingival fibromas, hamartomatous rectal polyps

Clinical Presentation (Symptoms and Signs) ■

Headache ♦ Brain tumor can cause headaches secondary to:

• • • •

Elevated intracranial pressure Focal irritation of the meninges Hydrocephalus Venous sinus compression and thrombosis

♦ Headaches may be associated with nausea and vomiting ♦ Headaches in patients with brain tumors are indistinguishable from tension

headaches ♦ Characteristics of headaches that should raise concern include:

• • • • • ■

New-onset headaches in older patients A change in headache character Worsening of headache over time Headache associated with progressive neurologic dysfunction Headache that worsens with valsalva maneuvers, coughing, and laying down

Seizure ♦ Seizures are the presenting symptom in ~33% of brain tumor patients ♦ Seizure incidences vary with tumor type

• Low-grade gliomas are associated with seizure rates as high as 80% • Primary CNS lymphoma causes seizures in ~20% of cases

28  Brain Tumors

■

457

• Seizures are particularly common in patients with metastatic melanoma, which tends to produce multiple cortical lesions • ~10–20% of adults with new-onset seizures have brain tumors • Empiric use of anticonvulsants has not been effective in primary prophylaxis of seizures, and should only be given to patients with brain tumors who have had a known seizure Progressive focal neurologic deficits ♦ The location of the tumor determines the neurologic symptoms manifested as

a result of direct tumor invasion and swelling of surrounding brain tissue ♦ Tumors occurring in or near the cerebral hemispheres may cause progressive

focal symptoms • • • • •

Motor weakness Spasticity Hyper-reflexia Sensory deficits Psychomotor slowing

♦ Tumors in the occipital region may cause visual field defects or problems

with visual processing ♦ Tumors in the posterior fossa (brainstem and cerebellum) may cause:

• Ataxia and dysmetria • Generalized symptoms such as headache, nausea, anorexia, vomiting, and gait disturbances ♦ Midline tumors such as pituitary adenomas or metastatic tumors to this region

may cause vision loss from direct compression of the optic nerves and chiasm as well as endocrine dysfunction ♦ Tumors that occur in the cerebellopontine angle can compress cranial nerves V, VII, and VIII; associated symptoms may include: • • • • • •

Sensorineural hearing loss Tinnitus Dysequillibrium Facial palsy (similar to Bell’s palsy) Facial numbness Large tumors at this location may also cause brainstem compression and lead to: ▲ ▲ ▲ ▲ ▲ ▲

Ataxia Diplopia Headache Vertigo Dysarthria Nausea and vomiting

458 ■

S.H.-Y. Chou

Altered mental status ♦ Patients with brain tumor may present with progressive altered mental status

due to pressure effect from the tumor and surrounding edema; neurologic findings may include: • • • • • • •

Excessive somnolence Confusion Speech and language difficulties Personality changes Memory and concentration impairment Slowing in processing speed Neglect

♦ Tumors may also lead to progressive confusion, somnolence, ataxia, and uri-

nary incontinence by inducing secondary hydrocephalus ♦ Brain tumors may cause acute mental status alteration by inducing seizure

with postictal state or from sudden expansion due to hemorrhage into the tumor ■

Intracerebral hemorrhage ♦ Brain tumors may become symptomatic when they become hemorrhagic ♦ The most common intracerebral hemorrhagic tumors are lung metastases ♦ Certain tumors have a particularly high predilection for hemorrhage:

• • • • ■

Choriocarcinoma Melanoma Papillary thyroid carcinoma Renal cell carcinoma

Intracranial pressure (ICP) elevation ♦ Tumors may lead to focal ICP elevation due to mass effect or global ICP

elevation by causing hydrocephalus ♦ Unilateral or bilateral papilloedema are signs of ICP elevation ♦ Unilateral or bilateral abducens (VI) nerve palsy may represent global ICP

elevation and hydrocephalus ♦ Focal ICP elevation may lead to cerebral uncal herniation, which may present

with: • Ipsilateral oculomotor (III) nerve palsy (ptosis, dilated pupil) • Weakness • Altered mental status ♦ Upper motor neuron dysfunction such as spasticity, hyper-reflexia, and exten-

sor plantar response may be associated with direct tumor effect or compression of motor fibers due to elevated ICP from tumor

28  Brain Tumors

459

Diagnosis and Differential Diagnosis ■

Physical examination and systemic workup ♦ All patients suspected to have brain tumor should undergo a thorough physi-

cal examination; areas of examination should include breast, testicular, prostate, and skin, when appropriate. ♦ Metastases are the most common intracranial neoplasm in the adult population • A complete search for systemic malignancy should typically precede a brain biopsy and should be performed using contrast-enhanced CT scan of the chest, abdomen, and pelvis. • Bone scan and positron emission tomography (PET) have been used to search for the primary tumor, but their sensitivities and specificities are unknown. • The role of tumor markers is unknown in patients who present with brain neoplasms ■

Imaging ♦ ~90% of brain tumors are detected on contrast-enhanced CT scan of head;

low-grade tumors, tumors close to bone, and brainstem tumors may be missed on CT ♦ CT may be superior for detecting tumors that involve bone or tumors that can calcify, such as meningiomas and oligodendrogliomas ♦ MRI with gadolinium is considered the optimal modality for imaging brain tumors. ♦ MR spectroscopy (MRS) is used at some centers for diagnosing brain tumor • Loss of N-acetylaspartate (NAA) and increased choline levels are typical findings in brain tumors on MRS • Decreased NAA signal is attributed to neuronal loss due to infiltrating mass, and elevated choline signal is attributed to increased turnover of cell membrane • PET scan is used at many centers as a brain tumor diagnostic, particularly in distinguishing between tumor progression and radiation necrosis ♦ Functional MRI has been used for preoperative planning and mapping of

eloquent cortex in patients with brain tumor ■

Cerebrospinal Fluid (CSF) studies ♦ Positive CSF cytology is the gold standard in diagnosing carcinomatous

meningitis ♦ CSF studies may also show elevated protein, decreased glucose, and increased

opening pressure at lumbar puncture in carcinomatous meningitis

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S.H.-Y. Chou

Diseases that mimic brain tumors ♦ Tumorfactive multiple sclerosis: mimics brain tumors on MRI/CT imaging ♦ Progressive multifocal leukoencephalopathy (PML), a disease that arises

from re-activation of JC Virus infection and is associated with immunocompromised host; characterized by: • Progressive stepwise neurological deficits associated with multifocal white matter lesions on imaging ♦ Infections such as cysticercosis ♦ Radiation necrosis

Management ■

Tumor-related complications ♦ The most important factor in managing brain tumor patients is the recognition

and timely treatment of life-threatening signs and symptoms ♦ Though brain tumors typically cause slow progressive increase in intracranial

pressure and/or cerebral edema, sudden acute ICP spikes and cerebral herniation can occur ♦ Symptoms that should raise concern for rapid deterioration include those of acute ICP elevation, such as altered mental status, nausea and vomiting, papilloedema, and cranial nerve palsies ♦ In particular, tumors in the posterior fossa can cause acute life-threatening deterioration from acute hydrocephalus ♦ In addition to first presentation of brain tumors, patients undergoing radiation therapy for brain tumor can also develop acute life-threatening neurologic deterioration from cerebral edema and increased ICP from the treatment ■

Cerebral edema ♦ Brain tumors may be associated with both cytotoxic and vasogenic cerebral

edema ♦ To prevent worsening of chronic cerebral edema from brain tumor, patients

should maintain normal serum tonicity (Na 135–145 mEq/dL) and avoid excessive hypotonic fluid intake ♦ Corticosteroids, particularly dexamethasone, are preferentially used to treat cytotoxic edema associated with brain tumors • Typical dosage is 4–10 mg IV or PO bolus, followed by 4–40 mg daily dose divided over 6, 8, or 12 hr intervals • Corticosteroids may produce rapid tumor shrinkage and false-negative brain biopsy results in primary CNS lymphoma and should therefore be used with caution in patients who are suspected to have this condition prior to biopsy

28  Brain Tumors

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♦ Osmotic therapy such as mannitol and hypertonic saline solutions can be used

as rescue therapy for refractory mass effect and impending cerebral herniation ♦ Surgery is recommended as acute management of patients with life-threatening

elevation of intracranial pressure from brain tumor ■

Seizure treatment and prophylaxis ♦ Patients with brain tumors are at increased risk of developing new-onset seizures ♦ Empiric use of antiepileptic drugs (AED) for primary seizure prevention in patients

with known brain tumors but no prior history of seizure is not recommended ♦ Long-term AED are appropriate for patients with brain tumor who have suf-

fered an unprovoked seizure ♦ Many traditional AEDs such as phenytoin, carbamazepine, and phenobarbital

have significant interaction with chemotherapeutic agents ♦ Non-enzyme-inducing AEDs such as levetiracetam and valproic acid are

preferred in patients with brain tumor who are undergoing or expected to start chemotherapy ♦ Acute-onset seizures in patients with brain tumor may be treated with IV loading of AEDs. ♦ Common anticonvulsant choices, their dosages, and their side effects are listed in Table 28.3 ■

Hydrocephalus ♦ Acute hydrocephalus may be treated with placement of external ventricular

drainage (EVD) catheter for CSF drainage ♦ Chronic hydrocephalus may be treated with various mechanisms of perma-

nent CSF shunting, typically with ventriculoperitoneal, ventriculopleural, or ventriculo-atrial shunts ♦ Permanent CSF shunting in brain tumors may be complicated by seeding of tumor to the peritoneum or other connections to the CSF space, as well as shunt occlusion by tumor or poor CSF flow through shunt due to high CSF protein. ■

Pituitary insufficiency ♦ Pituitary insufficiency may occur in patients with pituitary or other midline

tumors that cause mass effect on the pituitary gland or stalk ♦ Multiple different hormonal deficiencies may occur with pituitary insufficiency

• Diagnostic studies include serum thyroid hormone (TSH, free T4), Adrenocorticotropic hormone (ACTH), cortisol, and prolactin levels ♦ Central diabetes insipidus (DI) may occur following pituitary surgery

• These patients should be monitored with hourly urine output check • If urine output exceeds 200 mL/h, patients should be evaluated regularly for urine specific gravity, urine osmolality, and serum sodium and osmolality • Central DI can be treated with ddAVP administered intranasally, PO, SC, or IV. It is important to match urine output in patients with DI to prevent hypovolemia

15–20 phenytoin-equivalent units/kg IV

1,000–2,000 mg IV × 1 15–20 mg/kg IV or 500 mg PO × 2–3 doses

15–20 mg/kg IV

Fos-phenytoin

Levetiracetam Valproic acid

Phenobarbital

Table 28.3  Common anticonvulsants Medication Loading dose Phenytoin 15–20 mg/kg IV or 500 mg PO × 2–3 doses

50–100 mg PO bid or tid

500–1,500 mg bid 250–1,000 mg PO/IV bid/tid

n/a

Chronic dose 100 mg tid; then adjust according to serum level

25–40 mg/mL

Not defined 50–100 mg/mL

10–20 mg/mL (corrected for albumin and renal function)

Therapeutic level 10–20 mg/mL (corrected for albumin and renal function)

Major side effects Rash, Stevens–Johnson syndrome Cardiac dysrhythmias Interacts with many drugs Hypotension, especially during bolus Epidermal necrosis if IV infiltrates Myelosuppression Ophthalmoplegia Ataxia Rash, Stevens–Johnson syndrome Myelosuppression Ophthalmoplegia Ataxia Agitation Hyperammonemia Platelet dysfunction Encephalopathy Tremor Pancreatitis Lowest risk for rash Thrombocytopenia Sedation Enzyme induction Hepatitis Hypotension Respiratory depression

462 S.H.-Y. Chou

None

No load

No load

No load

No load

No load

Gabapentin

Pregabalin

Trileptal

Zonisamide

Lacosamide

Cannot load this drug! Lamotrigine (not appropriate for acute use; must titrate upward slowly over 6 weeks) Topiramate none

Carbamazepine

Start 50 mg po or IV bid, titrate up to 100–200 mg bid

Start 100 mg q d; may titrate upward to 300 mg q d

Start 300 mg bid; may titrate upward to 900 mg bid

First degree A-V block – need to monitor PR interval on EKG; Atrial fibrillation.

Not defined

Not defined

Not defined

Angioedema Sedation Myoclonus Weak enzyme inducer May disqualify patients from some chemotherapeutic trials Hyponatremia Acidosis Encephalopathy Stevens–Johnson syndrome

Myelosuppression Rash Hyponatremia Enzyme inducer Ataxia SIADH/hyponatremia Risk of rash is higher in patients with brain tumor, particularly after weaning off of steroids post-radiation. Interacts with valproic acid, which inhibits lamotrigine Weak enzyme inducer Kidney stones Acidosis Encephalopathy Sedation Myoclonus

Not defined

Not defined

Not defined

Start 50 mg bid; titrate up to 400 mg bid

Start 300 mg tid; titrate up to 1,500 mg– 2,400 mg divided tid Start 75–300 mg bid; may titrate upward

Not defined

8–12 mg/mL

Depends on other concomitant medications

Start 200 mg bid; may titrate up to 600 mg bid

28  Brain Tumors 463

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S.H.-Y. Chou

♦ Syndrome of inappropriate ADH secretion (SIADH) is a common delayed

complication of pituitary surgery • Treatment is free-water restriction and sodium supplementation ■

Venous thromboembolism (VTE) prevention, diagnosis, and treatment ♦ VTE is a prevalent and life-threatening complication in patients with brain

tumors; more than half of patients with primary CNS lymphoma develop VTE, and 7% of these are fatal ♦ Malignant glioma is associated with 30% risk of VTE within 2 years of diagnosis; factors associated with increased VTE risk in glioma patients include • • • • • •

Recent surgery Leg weakness Age >60 years Large tumor Treatment with chemotherapy Histologic diagnosis of glioblastoma multiforme

♦ Recommended preventative measures for VTE include early mobilization,

♦

♦ ♦

♦

♦

intermittent pneumatic compression boots, graded compression stockings, and early use of subcutaneous low-molecular-weight heparin (LMWH) injection Diagnostics for VTE include compression duplex ultrasonography for deep venous thrombosis, pulmonary VQ scan, and high-resolution chest CT angiography for pulmonary emboli Most patients with brain tumor with VTE can be treated with long-term systemic anticoagulation therapy Low molecular weight heparin (LMWH) is twice as effective as warfarin in preventing recurrent VTE in brain tumor patients without any difference in hemorrhagic risk Contraindications to systemic anticoagulation may include recent neurosurgery, chemotherapy-induced thrombocytopenia, hemorrhagic brain tumor, and other systemic or intra-cerebral hemorrhagic conditions Placement of inferior vena cava filters is largely reserved for patients with VTE and strong contraindication to anticoagulation

Treatment of Brain Tumors ■

Surgery ♦ Surgery may be performed with goal of biopsy or maximal tumor resection;

some retrospective data suggest survival benefit in patients who underwent maximal resection ♦ Decision regarding maximal resection vs. biopsy depends on tumor location, size, type, and patient’s medical condition

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♦ For metastatic brain tumors

• Surgical resection should be considered for patients with single metastasis in an acceptable location who have a reasonable life expectancy • Role of surgery in patients with multiple brain metastases is usually limited to palliative resection of large symptomatic lesions or biopsy for tissue diagnosis ■

Chemotherapy and complications ♦ Chemotherapy may cause associated myelosuppression, immunosuppresion,

and a range of neurotoxicity, including seizures, encephalopathy, peripheral neuropathy, and stroke-like syndromes ♦ Temozolomide is a common chemotherapeutic agent in glioma patients; it causes mild myelosuppression and gastrointestinal distress ♦ Some common chemotherapeutic agents used in CNS malignancies are listed in Table 28.4 ■

Radiation therapy (XRT) and complications ♦ Limited-field XRT has become the standard of care for focal brain tumors;

typical dose is 60 Gy administered in five-time weekly fractions over 6 weeks ♦ Whole brain XRT (WBRT) produces symptomatic improvement in 75–80% of patients with brain metastases • Typical dosage is 30 Gy in ten fractions over 2 weeks • WBRT following surgical resection in metastatic brain tumors is associated with a reduction of recurrence rate (from 70 to 18%) and death due to neurologic causes (44–14%) • WBRT is not associated with overall survival benefit • WBRT may be associated with memory impairment, poor concentration, and depression ♦ Acute radiation toxicity includes alopecia, scalp irritation, nausea, headache,

and fatigue ♦ Peritumor cerebral edema may worsen during and following XRT ♦ Incidence of radiation necrosis is 3–5% and increases with patient survival

after XRT ♦ Long-term complications from XRT include neurocognitive decline, urinary

incontinence, gait ataxia, neuro-endocrine dysfunction, and hydrocephalus ■

Other treatment options for brain tumors ♦ ♦ ♦ ♦

External beam XRT Stereotactic radiosurgery such as gamma knife or proton-beam therapy Brachytherapy Intrathecal chemotherapy is used for treatment of carcinomatous meningitis

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S.H.-Y. Chou

Table 28.4  Chemotherapeutic agents and common side effects Agent Treatment Side effects Subacute or chronic Primary brain tumors, Nitrosoureas: carmustine encephalopathy multiple myeloma, (BCNU); lomustine lymphoma (CCNU) Seizure Lethargy Leukoencephalopathy Retinopathy and blindness Worsening focal neurological deficits MAO inhibitor; CNS depression Procarbazine Primary brain tumors, and acute hypertension may Hodgkin disease, occur with tyramine-rich systemic lymphoma foods Lethargy, depression, confusion, hallucinations, agitation, and psychosis Peripheral neuropathy (20%) Thiotepa Leptomeningeal disease Encephalopathy and cognitive impairment Myelopathy (rare) Nephrotoxicity Cisplatin CNS tumors, testicular, lung, ovarian, head Peripheral sensory and neck, and many neuropathy other tumors Autonomic neuropathy Dorsal root ganglionopathy Encephalopathy Retrobulbar neuritis and retinopathy Seizures Transient cortical blindness Ototoxicity Stroke Myasthenic syndrome Carboplatinum Similar to cisplatin Least neurotoxic Rare ototoxicity and blindness Sensory neuropathy Confusion Cyclophosphamide Lymphoma; leukemia, breast, ovarian, lung, SIADH and bladder cancers, Hemorrhagic cystitis and others Cytarabine liposome injection Lymphomatous Arachnoiditis meningitis Confusion Temozolomide Recurrent glioma; Seizures melanoma Encephalopathy Myelosuppression (continued)

28  Brain Tumors Table 28.4  (continued) Agent Thalidomide

Vincristine

467

Treatment

Side effects

Peripheral neuropathy Primary brain tumors, breast cancer, Kaposi Encephalopathy and somnolence sarcoma, renal carcinoma, melanoma, multiple myeloma, and others Primary brain tumors, leukemia, lymphoma, Kaposi sarcoma

Key Points ■

■

■

■ ■

Clinical presentation of brain tumors depends on tumor location, presence of ICP elevation from tumor bulk, associated cerebral edema and/or hydrocephalus, endocrine dysfunction, cranial nerve palsies, and seizures Main treatment modalities for brain tumors include surgical resection, steroids, chemotherapy, and XRT Treatment is individualized, taking into account the location, type, and histologic grade of tumor, as well as general patient characteristics Prognosis for primary brain tumors depends largely on pathologic tumor grade Postoperative management focuses on judicious monitoring of the neurologic exam, maintenance of a normal metabolic milieu, maintenance of therapeutic antiepileptic drug levels, and monitoring for complications

Suggested Reading Louis DN et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109 Miller AE (2005) Neuro-oncology. CONTINUUM Lifelong Learn Neurol 11(5):13–160 Norden AD, Kesari S (2006) Cancer neurology: primary and metastatic brain tumors. In: Atri A, Millgan TA (eds) Hospital Physician, Neurology Board Review Manual 10(3):1–16 Smith TW, Poirier J, Louis DN (2004) Tumors of the nervous system. In: Gray MF, De Girolami U, Poirier J (eds) Manual of basic neuropathology. Butterworth-Heinemann, Philadelphia, pp 21–57 Wen PY (2003) Neuro-oncology. In: Samuels MA, Feske SK (eds) Office practice of neurology. Churchill Livingstone, Philadelphia, pp 1006–1181

Chapter 29

Hydrocephalus Michel T. Torbey

Introduction ■

■

■

Derived from the Greek words hydro, meaning “water,” and cephalus, meaning “head” First described by Hippocrates, but it remained an intractable condition until the twentieth century, when shunts and other neurosurgical treatment modalities were developed Defined as dilation of cerebral ventricles

Epidemiology ■

■ ■

Hydrocephalus affects one in every 500 live births, making it one of the most common birth defects Is the leading cause of brain surgery for children in the US In the US, the healthcare cost for hydrocephalus has exceeded $1 billion per year

Classification ■

Hydrocephalus can be caused by impaired cerebrospinal fluid (CSF) flow, reabsorption, or excessive CSF production ♦ Most common cause of hydrocephalus is obstruction of CSF flow, which

hinders the free passage of CSF through the ventricular system and

M.T. Torbey, MD, MPH, FAHA, FCCM (*) Department of Neurological Surgery and Neurology, Medical College of Wisconsin, Department of Neurology, 9200 W. Wisconsin Avenue, Milwaukee, WI 53226, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_29, © Springer Science+Business Media, LLC 2011

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M.T. Torbey

s­ ubarachnoid space (e.g., stenosis of the cerebral aqueduct or obstruction of the ­intraventricular foramina – foramina of Monro – secondary to tumors, hemorrhages, infections, or congenital malformations) ♦ Hydrocephalus can also be caused by overproduction of CSF (relative obstruction) (e.g., papilloma of choroid plexus) ♦ Based on its underlying mechanisms, hydrocephalus can be classified into communicating and noncommunicating (obstructive); Both forms can be either congenital or acquired ■

Communicating hydrocephalus ♦ Also known as nonobstructive hydrocephalus ♦ Caused by impaired resorption of CSF fluid in the absence of any obstruction

of CSF flow • Theorized that this is due to functional impairment of the arachnoid granulations, which are located along the superior sagittal sinus and allow CSF resorption into the venous system ♦ Various neurologic conditions may result in communicating hydrocephalus,

including: • • • • • ■

Subarachnoid/intraventricular hemorrhage Meningitis Chiari malformation Normal-pressure hydrocephalus Hydrocephalus ex vacuo

Normal-pressure hydrocephalus (NPH) ♦ A particular form of communicating hydrocephalus ♦ Characterized by enlarged cerebral ventricles, with only intermittently elevated

CSF pressure ♦ Diagnosis of NPH can be established with the help of continuous intracranial

pressure (ICP) recordings through a lumbar drain, as more often than not, instant measurements yield normal pressure values ♦ Dynamic compliance studies may also be helpful ■

Noncommunicating hydrocephalus ♦ Also known as obstructive hydrocephalus ♦ Caused by obstruction to CSF flow (either due to external compression or

intraventricular mass lesions) • Obstruction of the foramen of Monro may lead to dilation of one or, if large enough (e.g., in colloid cyst), both lateral ventricles • Aqueduct of Sylvius may be obstructed by a number of genetic or acquired lesions and lead to dilatation of both lateral ventricles, as well as the third ventricle • Fourth ventricle obstruction will lead to dilatation of the aqueduct, as well as the lateral and third ventricles

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471

• Subarachnoid space surrounding the brainstem may also be obstructed due to inflammatory or hemorrhagic fibrosing meningitis, leading to widespread dilatation, including the fourth ventricle ♦ Cerebrospinal fluid

• CSF is formed at a rate of 0.3 mL/min (or 20 mL/h, or 500 mL/24 h) • Total CSF volume is ~150 mL with 75 mL in the cranial vault • CSF is under ICP, which is normally ~10 mmHg ■

Diagnosis ♦ Symptoms of increased ICP may include:

• • • • • •

Headaches Nausea Vomiting Papilledema Altered mental status Coma

♦ The Hakim triad of gait instability, urinary incontinence, and dementia is a

relatively typical manifestation of NPH ♦ Focal neurologic deficits may also occur

• Abducens nerve palsy and vertical gaze palsy (Parinaud syndrome due to compression of the quadrigeminal plate) ♦ Diagnostic studies

• Neuroimaging ▲ Noncontrast head CT ▲ MRI with T1 and T2 imaging ▲ CT findings N N N N

Dilated cerebral ventricles Bowing of third ventricle if under pressure Fourth ventricle is dilated in communicating hydrocephalus Absence of fourth ventricular dilation is suggestive of noncommunicating hydrocephalus

▲ MRI findings N Dilated ventricles N Increased T2-weighted signal in periventricular area, signifying

transependymal CSF flow • Radioisotope cisternography ▲ Injection of radioisotope into the lumbar thecal sac ▲ If there is reflux, isotope will appear in the ventricles ▲ Normally, isotope distributes over cerebral convexities

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M.T. Torbey

• Lumbar puncture ▲ Cerebrospinal fluid: normal ▲ Opening pressure: may be increased ▲ Lumbar puncture should be avoided when noncommunicating hydro-

cephalus is present ■

Treatment ♦ If communicating hydrocephalus is present and patient is symptomatic

consider: • Serial lumbar punctures • Trial of large volume (40–60 mL) CSF drainage • Trial of lumbar drain ♦ If communicating hydrocephalus and symptoms are suggestive of NPH, con-

sider protocol in Fig. 29.1 ♦ If noncommunicating hydrocephalus:

• An intraventricular catheter (IVC) should be placed ▲ Initially place IVC drain pop-off at 0 mmHg, unless the patient just

had an aneurysmal subarachnoid hemorrhage. In this case, it is CSF pressure monitoring Drainage trial 10 mL/hr

B-waves, plateau waves Near plateau waves

Yes

No Responded to CSF drainage trial

Yes

No

Shunt surgery

Continue medical Rx Consider repeat monitoring in few months

No surgery

Fig. 29.1  Algorithm for shunt placement in suspected NPH patients. CSF cerebrospinal fluid; Rx prescription

29  Hydrocephalus

473

advised to keep pop-off at 15–20 mmHg and only drain if ICP is elevated ▲ As the patient clinically improves, the pop-off may be increased ▲ Initially, it should be 5 or 10 mmHg ▲ Once patient has been shown to tolerate a pop-off of 20 mmHg, a trial of monitoring only (i.e., no CSF drainage) should be attempted prior to IVC removal (Fig. 29.2) ♦ CSF diversion (shunts)

• If a patient cannot tolerate increasing pop-off, placement of an indwelling shunt system should be considered • Systems are generally either ventricle to peritoneal (VP) or lumbar to peritoneal (LP) • Others that are less common are ventricle to jugular (VJ) or VA ventricle to cardiac atrium (VA)

Fig. 29.2  Medical College of Wisconsin Algorithm for discontinuation of external ventricular drain

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M.T. Torbey

Key Points ■ ■

■

■

Hydrocephalus is a common accompaniment of acute brain injury Communicating vs. noncommunicating hydrocephalus must be distinguished by neuroimaging techniques In noncommunicating hydrocephalus, an external ventricular drain, rather than a lumbar drain, should be placed It is important that patients with NPH are monitored and given a drainage trial prior to shunt placement

Suggested Reading Ariada N, Sotelo J (2002) Review: treatment of hydrocephalus in adults. Surg Neurol 58:377–384 Brady WG (2001) Diagnostic tools in hydrocephalus. Neurosurg Clin N Am 12:661–684 Maramarou A, Bergsneider M, Klinge P et al (2005) The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal pressure hydrocephalus. Neurosurgery 57:S17–S28 McAllister JP (2000) Hydrocephalus enters the new millennium: an overview. Neuro Res 22:2–3 Pattisapu J (2001) Etiology and clinical course of hydrocephalus. Neurosurg Clin N Am 12:651–659 Relkin N, Marmarou A, Klinge P et al (2005) Diagnosing idiopathic normal pressure hydrocephalus. Neurosurgery 57:S4–S16 Suarez-Rivera O (1998) Acute hydrocephalus after subarachnoid hemorrhage. Surg Neurol 49:563–565

Chapter 30

Neuromuscular Disorders Jeremy D. Fields and Anish Bhardwaj

General Considerations ■

Neuromuscular diseases may require ICU care for three primary disease-associated reasons ♦ Respiratory muscle weakness ♦ Bulbar muscle weakness, leading to failure to protect airway ♦ Autonomic dysfunction/instability, leading to hemodynamic compromise

from swings in blood pressure, heart rate, or dysrhythmia ■

Choice of ventilation mode/intubation sequence ♦ Noninvasive positive-pressure ventilation generally not useful because of

high risk of aspiration with bulbar dysfunction; patients with chronic neuromuscular weakness may benefit ♦ Avoid succinylcholine for relaxation for intubation (risk – hyperkalemia) in patients with select neuromuscular disease (central core myopathy, Duchenne, King–Denborough) ♦ In patients with neuromuscular disease associated with autonomic features [Guillain–Barré Syndrome (GBS), Lambert–Eaton, botulism], be prepared for excessive heart rate and blood pressure response to induction agents ♦ Consider early tracheostomy in patients with prolonged expected recovery (GBS, tetanus, botulism)

J.D. Fields, MD Department of Neurology, Oregon Health & Science University, Portland, OR, USA A. Bhardwaj, MD, FAHA, FCCM, FAAN (*) Department of Neurology, Tufts University School of Medicine, Tufts Medical Center, Box 314, 800 Washington Street, Boston, MA 02111, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_30, © Springer Science+Business Media, LLC 2011

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Diagnostic studies that may be helpful ♦ Blood work – basic chemistries, CK, lactate, auto-antibodies associated with

muscle disease, myasthenia gravis, or paraneoplastic syndromes ♦ Lumbar puncture ♦ Electromyogram (EMG)/nerve conduction studies; specialized testing may

include nerve conduction studies of the phrenic nerve and EMG of the diaphragm, repetitive nerve stimulation ♦ Muscle biopsy or nerve biopsy ■

Comprehensive ICU care ♦ ♦ ♦ ♦

Prophylaxis for deep vein thrombosis (DVT) Bowel prophylaxis (antacids, H2 antagonists) Control of hyperglycemia Adequate fluid balance (insensible losses increased in diseases with autonomic involvement)

Bedside Assessment ■

Respiratory evaluation ♦ Check forced vital capacity (FVC), negative inspiratory force (NIF), and

maximum expiratory force (MEF) frequently (q 2–4 h while awake; q 4–6 h when asleep) ♦ 20, 30, 40 rule for possible intubation: FVC <20 mL/kg; NIF <30 cmH2O; MEF <40 cmH2O • >25% decrease in FVC when supine suggests significant diaphragmatic weakness ♦ Count as high as possible on one breath

• >25 predicts FVC >2 L • >10 predicts FVC >1 L ♦ Signs/symptoms of distress – brow sweating, tachycardia, dypsnea, use of

accessory muscles, paradoxical breathing, rapid shallow breathing, staccato speech, orthopnea ■

Bulbar function ♦ Facial weakness, palatal elevation, cough, gag ♦ Warning signs: dysphagia, cough after swallowing, severe dysarthria

30  Neuromuscular Disorders ■

477

Assessment of autonomic function ♦ Systemic/cutaneous – absent sweating or lacrimation, unreactive pupils, con-

stipation, urinary retention ♦ Hemodynamic – orthostatic hypotension, blood pressure lability, heart rate

either labile or abnormally constant, dysrhythmia

Differential Diagnosis ■ ■

Before considering neuromuscular cause, a CNS etiology should be excluded Differential diagnosis of neuromuscular etiologies can be approached based on pattern of weakness: ♦ ♦ ♦ ♦

Generalized weakness (Table 30.1) Primary involvement of respiratory muscles (Table 30.2) Primary involvement of bulbar muscles (Table 30.3) Primary involvement of the autonomic nervous system (Table 30.4)

GBS: Acute Inflammatory Demyelinating Polyneuropathy ■

Epidemiology ♦ 2/100,000 annual incidence ♦ 25–50% require mechanical ventilation; median duration, 18–29 days

■

Typical features ♦ Preceding illness with flu-like symptoms or diarrhea 1–3 weeks prior in 2/3

of cases ♦ Symmetric quadriparesis, classically beginning in legs, affecting both proxi♦ ♦ ♦ ♦ ■

mal and distal muscles Correlation with Campylobacter Paresthesias and back pain Areflexia or hyporeflexia CSF protein >45 mg/dL

Variants account for ~10% of cases in North America ♦ Acute motor axonal neuropathy (AMAN)

• Axonal motor variant without demyelination • Severe weakness/prolonged recovery • Associated with GM1, GM1b, GD1a, or GalNAc-GD1a

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Table 30.1  Neuromuscular causes of acute generalized weakness Localization Disease CNS Diseases with bilateral hemispheric injury Diseases of the brainstem Diseases of the spinal cord Motor neuron Motor neuron disease West Nile virus infection Poliomyelitis Other enteroviruses Neuromuscular junction Myasthenia gravis Lambert–Eaton myasthenic syndrome Organophosphate poisoning Botulism Tick paralysis Hypermagnesemia Snake/insect/marine toxins Neuropathies Guillain–Barré syndrome Critical illness polyneuropathy Chronic idiopathic demyelinating polyneuropathy Toxic neuropathies Vasculitic neuropathy Porphyric neuropathy Diphtheria Lymphoma Carcinomatous meningitis Acute uremic polyneuropathy Eosinophilia-myalgia syndrome Myopathies Critical illness myopathy Dermatomyositis Polymyositis Periodic paralysis/hypokalemic myopathy Myotonic dystrophy Acid maltase deficiency Muscular dystrophies Mitochondrial myopathies Corticosteroid-induced myopathy

Table 30.2  Neuromuscular causes of acute respiratory muscle weakness Localization Disease CNS Motor neuron Neuromuscular junction Neuropathies

Myopathies

Diseases of high cervical cord or medulla Motor neuron disease Myasthenia gravis Lambert–Eaton myasthenic syndrome Idiopathic bilateral phrenic nerve paresis Guillain–Barré syndrome (rare) Neuralgic amyotrophy Large artery vasculitis Multifocal motor neuropathy Acid maltase deficiency

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479

Table 30.3  Causes of acute predominantly bulbar weakness Localization Disease CNS Brainstem diseases Bilateral white matter diseases Syrinx Motor neuron Amyotrophic lateral sclerosis Kennedy disease Neuromuscular junction Myasthenia gravis Lambert–Eaton myasthenic syndrome Botulism Neuropathies Guillain–Barré syndrome (rare) Carcinomatous meningitis Skull base tumor or metastases Miller–Fisher disease Sarcoidosis Basilar meningitis Myopathies Dermatomyositis Polymyositis Oculopharyngeal muscular dystrophy Myotonic dystrophy Distal myopathy with vocal cord paralysis Table 30.4  Causes of acute failure of the autonomic nervous system Localization Disease CNS Diseases affecting the hypothalamus, brainstem/medulla/high cervical cord R insular stroke Neuromuscular junction Lambert–Eaton myasthenic syndrome Botulism Neuropathies Diabetic autonomic neuropathy Amyloid neuropathy Guillain–Barré with predominant dysautonomia Paraneoplastic dysautonomia Associated with connective tissue disorders Sjogrens SLE Infectious Chagas HIV Leprosy Diphtheria

♦ Acute motor and sensory axonal neuropathy (AMSAN)

• Associated with GM1, GM1b, or GD1a ♦ Miller–Fisher syndrome

• Triad of acute external ophthalmoplegia, ataxia, and areflexia without significant motor or sensory deficit in the limbs • Accurate anatomic lesion sites and pathogenesis are still unknown • Associated with GQ1b or GT1a

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J.D. Fields and A. Bhardwaj

Electrophysiology ♦ Early – F waves are normal very early; then, prolonged ♦ Later – prolonged distal motor latencies and increased duration/polyphasia of

distal compound muscle action potentials ♦ In AMAN, axonal injury predominates without sensory involvement,

although conduction block and absent F waves may still be present; in AMSAN, an axonal pattern combined with reduced sensory nerve action potentials is present ■

Indications for admission to NCCU ♦ Respiratory weakness

• PFTs – FVC <40 mL/kg; NIF <40 cmH2O; decline in FVC or NIF >30% in 24 h • Clinical signs of fatigue or dyspnea • Significant neck flexor weakness or poor cough (predict respiratory muscle weakness) • Chest X-ray – infiltrates, atelectasis, or pleural effusion ♦ Dysphagia/inability to protect airway

• Bulbar dysfunction/bilateral facial weakness • Failed swallow evaluation (increased risk of aspiration) ♦ Autonomic instability

• Dysrhythmia (R-R interval prolongation may predict fatal dysrhythmia) • Blood pressure lability • Profound sensitivity to sedatives ♦ Others

• Plasma exchange planned • Requires check of vital signs q 2 h or intensive nursing care • Time from onset of symptoms to admission <7 days ■

Indications for intubation (early intubation may be associated with decreased pulmonary complications) ♦ Respiratory weakness

• PFTs – FVC <20 mL/kg; NIF <30 cmH2O; PaO2 <70; decrease >50% in 24 h • Hypoventilation (PaCO2 >45 or significantly increasing) or hypoxia (PaO2 <70 on room air) ♦ Dysphagia

• Aspiration • Severe bulbar dysfunction/bilateral facial weakness

30  Neuromuscular Disorders ■

481

ICU management ♦ Treatment most effective within 14 days of symptom onset

• IVIG, 0.4 mg/kg q 1 day × 5 days, OR • Plasma exchange, 1 volume q 1–2 days for five exchanges; use albumin as replacement fluid unless coagulopathy develops ♦ Autonomic failure

• Often labile, with transient increases and decreases about normal mean pressure; short-acting agents thus preferred • Hypotension – treat with fluids before considering pressors; phenylephrine is pressor of choice, as primary problem is peripheral vasodilation • Hypertension – treat only extremes of blood pressure; consider nicardipine or sodium nitroprusside (peripheral vasodilators) • Maintain positive fluid balance, as insensible losses are often markedly increased • Monitor for dysrhythmia (predicted by prolonged R-R interval) ♦ Chest physiotherapy

• Chest PT, cough stimulation, etc., particularly if not intubated • Recruitment maneuvers ♦ Aggressive prophylaxis for DVT and ulcer (very high risk for DVT and mod-

erate risk for ulcer) ♦ Weaning criteria

• Strength improving on confrontation testing • FVC >10 mL/kg or NIF >–20 cmH2O ♦ Extubation criteria

• Tolerate pressure support ventilation 5/5 for >2 h (prolonged SBT); some evidence suggests T-piece or PSV 0/5 may better predict successful extubation • Secretions manageable

Myasthenia Gravis ■

Epidemiology ♦ Prevalence 5/100,000; peak in young women and older men ♦ Myasthenic crisis (rapid and severe decline in respiratory muscle function)

occurs in 15–20% of patients with myasthenia gravis (MG) ♦ May be unmasked by drugs that inhibit neuromuscular junction transmission

(Table 30.5)

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J.D. Fields and A. Bhardwaj Table 30.5  Drugs that inhibit transmission across neuromuscular junction Localization Disease Antibiotics Aminoglycosides Trimethoprim/sulfamethoxazole Tetracyclines Clindamycin Carbapenems Neomycin/colistin Cardiovascular Quinidine Procainamide Diltiazem Verapamil b Blockers CNS Phenytoin Carbamazepine Diazepam Morphine Other d-Penicillamine Interferon a Neuromuscular blockers Corticosteroids Magnesium Lithium

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Key features ♦ Fatigable weakness of extraocular muscles, bulbar musculature, neck, and

limbs (proximal pattern of weakness) ♦ Antibodies to acetylcholine receptor or muscle-specific kinase (MUSK) anti-

bodies (present in 90–95% of patients) ♦ Electrical decrement on repetitive nerve stimulation at 2–3 Hz >20% ♦ Objective response to edrophonium test (short-acting acetylcholinesterase

inhibitor) or ice pack may be supportive of diagnosis ♦ Suggestions for edrophonium test

• Use placebo control and choose an objective measure (e.g., quantify degree of ptosis) • Monitor blood pressure and pulse • Have atropine available for bradycardia • Give 10 mg total ▲ 2 mg as test dose; watch for side effects ▲ If side effects tolerable after 30 s, give remaining 8 mg

• Observe for duration of effect of edrophonium (2–20 min) ♦ Associated with thymoma; therefore, all patients should be screened with

chest CT with contrast ■

Myasthenic crisis ♦ Characterized by severe impairment of respiratory function (often defined as

FVC <1 L)

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♦ Precipitating factors – infection (especially lower and upper respiratory tract

infection), change in medication for myasthenia, medication interfering with neuromuscular junction, aspiration, pregnancy, surgery ■

Cholinergic crisis ♦ Increased weakness due to overdose of anti-acetylcholinesterase medications ♦ Symptoms of excess cholinergic activity – miosis, diarrhea, increased saliva-

tion, bradycardia ♦ If difficult to distinguish from myasthenic crisis, consider tensilon test ■

Indications for intubation (overall approach similar to GBS) ♦ FVC <15–20 mL/kg; NIF <20–30 cmH2O; rapid decline in PFTs ♦ Hypoventilation (pCO2 >45 or significantly increasing) or hypoxia (pO2 <70

on room air)

♦ Severe bulbar dysfunction or aspiration ■

Treatment ♦ Anticholinesterase medications (e.g., pyridostigmine, 30–60 mg × 5 per day

orally; IV dose 1/30 oral dose) may be used in patients without severe disease; in patients either intubated or at risk for intubation, these medications increase secretions, have variable oral absorption, increase weakness in overdose, and are therefore usually withheld in myasthenic crisis ♦ Corticosteroids (e.g., prednisone, 60–80 mg/day) are often initiated for milder exacerbations but may cause transiently increased weakness an average of 5 days after initiation of therapy ♦ Plasma exchange (five 1-volume exchanges q day or qod) is equivalent to IVIG (0.4 mg/kg q day × 5 days) but may work faster ♦ Obtain chest CT to rule out thymoma ■

Weaning criteria ♦ FVC >10 mL/kg or NIF >–20 cmH2O

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Extubation criteria ♦ Tolerate pressure support ventilation 5/5 for >2 h ♦ Secretions manageable ♦ Watch for fluctuations in disease

Critical Illness Neuropathy/Myopathy ■

Epidemiology and risk factors ♦ Reported incidence of up to 25–50% of patients on mechanical ventilation >7

days and 50–100% with sepsis and multiorgan failure ♦ Critical illness neuropathy and myopathy frequently overlap; therefore, the

term ICU-acquired weakness is sometimes used

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♦ Risk factors

• Vastly increased risk of critical illness myopathy with combination of corticosteroids (usually high dose and prolonged) and neuromuscular blockers • Increased risk of critical illness myopathy and neuropathy in sepsis/systemic inflammatory response syndrome, trauma, and multiorgan failure • Hyperglycemia • Immobility ■

Presentation ♦ Difficulty weaning from ventilator (most common) ♦ Generalized weakness, often unrecognized due to delirium or depressed sen-

sorium, until after recovery of other organ systems ■

Clinical features of critical illness polyneuropathy ♦ Distal limb weakness with hyporeflexia (only 1/3 retain reflexes) ♦ EMG features

• Axonal, with decreased compound motor action potentials and/or sensory nerve action potentials (up to 40% pure motor) • Preserved conduction velocities • Evidence of active denervation (early) or poor recruitment (later) ♦ Nerve biopsy shows axonal loss without inflammation, and muscle biopsy

generally reveals neurogenic atrophy or critical illness myopathy ♦ Recovery may be prolonged and incomplete ■

Clinical features of critical illness myopathy ♦ Persistent moderate or severe generalized weakness, with decreased tone and

eventual atrophy ♦ Proximal and distal symmetric pattern of weakness (occasionally distal pre-

dominates and is occasionally asymmetric) ♦ CK normal in 15%, generally ~3× normal ♦ EMG shows low amplitude, short duration, polyphasic CMAPs and variable

amounts of fibrillations in weak muscles but preserved SNAPs and distal motor latencies ♦ Muscle biopsy is myopathic, with findings of muscle fiber atrophy (predominantly type II), occasional fiber necrosis, and decreased myofibrillar adenosine triphosphatase staining (corresponding to loss of myosin filaments) with a relative absence of inflammatory cells ♦ Recovery generally over 4–12 weeks ■

Treatment and prognosis ♦ Treatment is primarily supportive, including physical and occupational ther-

apy, early limb mobilization, braces to prevent contractures, sedation holidays, and optimal nutrition

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♦ Intensive glucose control may decrease the incidence of these diseases; there-

fore, aggressive glucose control is likely warranted in affected patients ♦ Associated with prolonged ventilation time ♦ Complete recovery in ~2/3 of patients

Prolonged Neuromuscular Blockade ■

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Defined as prolonged neuromuscular blockade after administration of neuromuscular blocking agents; may be prolonged for hours to as much as 40 days Primarily seen in patients with renal, hepatic, or multiorgan failure Diagnosis most certain if a decrement to repetitive nerve stimulation is present

Tetanus ■

Pathophysiology and clinical features ♦ Risk factors

• • • •

Wounds or lacerations IV drug use Diabetes Lack of immunization

♦ Four patterns

• Generalized – most common • Local ▲ Muscle contractions limited to one limb or body region ▲ Often precedes generalization

• Cephalic ▲ Seen in patients with injury to head or neck ▲ Initially involves only cranial nerves

• Neonatal ♦ Clostridium tetani enters damaged human tissue, releases the toxin tetanos-

pasmin, which travels via retrograde axonal transport to CNS ♦ Incubation period typically ~1 week ♦ Physical exam

• Trismus (lockjaw) is initial symptom in 50–75% • Risus sardonicus (facial muscle contraction) common

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• Nuchal rigidity, board-like abdomen, periods of apnea and dysphagia • As disease spreads, generalized muscle spasms occur either spontaneously or triggered by sensory stimuli • Cranial nerve palsies only in cephalic tetanus: VII >> VI > III > IV > XII • Hyperadrenergic state with sweating, tachycardia, and hypertension are common • Spatula test (94% sensitivity, 100% specificity) ▲ Insert spatula into oropharynx ▲ Patient gags/tries to expel spatula → normal ▲ Patient bites spatula (due to reflex masseter spasm) → positive for

tetanus

♦ Diagnosis is clinical ■

Treatment ♦ Wound irrigation/debridement ♦ Antibiotics

• Metronidazole or penicillin G × 3–7 days • Consider second- or third-generation cephalosporin if mixed wound infection suspected ♦ Antitoxin and immunization

• Human tetanus immune globulin 3,000–6,000 U given as soon as disease suspected • Tetanus diphtheria toxoid administered q 2 weeks for three total doses ♦ Muscle spasms

• Sedatives – benzodiazepines (midazolam, lorazepam, diazepam) often effective • Baclofen may be helpful • Neuromuscular blockade – vecuronium in refractory cases ♦ Autonomic dysfunction

• Can be severe (11–28% fatality rate) • Cardiac dysrhythmias and MI most common fatal events • Manage with b blockade, antihypertensives (labetalol); may also respond to opiates (fentanyl or morphine) ♦ Respiratory management

• Endotracheal intubation for patients with respiratory distress, severe dysautonomia, inability to protect airway • Early tracheostomy decreases laryngospasm compared with endotracheal tube

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Botulism ■

Pathophysiology and clinical features ♦ Caused by neurotoxin of Clostridium botulinum, which blocks presynaptic

release of acetylcholine at the neuromuscular junction ♦ Stereotypical clinical presentation

• Ocular and bulbar muscle weakness, typically with symmetric cranial nerve palsies (III, IV, VI, VII, IX) ▲ Always initial presentation ▲ Presence of cranial nerve palsies with other symptoms listed below

effectively rules in disease • • • •

Descending flaccid paralysis (neck, then shoulders, then arms, then legs) Weakness usually bilateral but may be asymmetric Sensory system spared, and mentation usually spared Autonomic dysfunction common ▲ Constipation, dry eyes, dry mouth almost universal ▲ Hypotension may occur

♦ Botulism syndromes

• Food-borne botulism (only ~20 cases/year in US) – most commonly from improperly canned foods • Wound botulism – most common in heroin users who “skin pop”; also present in dusty areas such as construction sites • Infant botulism – results from colonization of intestines ♦ Laboratory features

• Assay for toxin in serum, vomitus, stool, or wound ▲ Overall sensitivity, 33–44% ▲ <30% sensitive after ³2 days after symptom onset

• Stool culture positive in 1/3 • EMG/nerve conduction studies ▲ ▲ ▲ ▲

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Normal sensory studies and motor conduction velocities Decremental response to repetitive nerve stimulation Post-tetanic facilitation Increased brief polyphasic motor unit action potentials and spontaneous denervation potentials

Treatment ♦ Primarily supportive

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♦ Antitoxin sometimes used if disease is detected early

• Administer test dose subcutaneously • Decreased anaphylaxis (<1%) in patients given only one vial

Key Points ■

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Neuromuscular diseases frequently present with respiratory failure requiring cardiopulmonary support Diagnosis is made following careful elicitation of history of illness, pattern of weakness, physical examination and ancillary laboratory diagnostic tests Dysautonomia is a common accompaniment of neuromuscular disorders Treatment in ICU involves immunomodulatory therapies, cardiopulmonary support, and prevention of systemic infection Early rehabilitation should be instituted to prevent contractures and compression neuropathies

Suggested Reading Green DM (2005) Weakness in the ICU: Guillain–Barré syndrome, myasthenia gravis, and critical illness polyneuropathy/myopathy. Neurologist 11:338–347 Maramattom BV, Wijdicks EFM (2006) Acute neuromuscular weakness in the intensive care unit. Crit Care Med 34:2835–2841 Schweickert WD, Hall J (2007) ICU-acquired weakness. Chest 131;1541–1549 Sobel J (2005) Botulism. Clin Inf Dis 41:1167–1173

Chapter 31

Status Epilepticus Marek A. Mirski

Definition ■

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A seizure that persists for a sufficient length of time or is repeated frequently enough to produce a fixed and enduring epileptic condition Distinct seizure phenomenon – not simply a prolonged seizure; status epilepticus (SE) represents a reconfiguration of excitatory and inhibitory networks within the brain Historically, experts in the field arbitrarily defined SE as unremitting seizures for a specific duration of 30 min Subsequently, shorter seizure epochs have been defined as SE Based on typical seizure duration of 1–2 min, SE should likely be considered in seizure events that are 5–10 min in duration; this definition of SE with a shortened epoch of onset is supported by the American Academy of Neurology, the American Epilepsy Society, and the International League Against Epilepsy (ILAE)

Epidemiology ■ ■

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100,000–150,000 patients/year estimated in US, with mortality 20–25% Data likely underestimate true incidence of SE, as many cases of SE are of nonconvulsive type, which are only diagnosed by concurrent EEG SE represents only 0.2% of ICU admission diagnoses; most hospital cases occur post-admission In an ICU setting, nonconvulsive SE (NCSE) may occur in as many as 8–34% of neurologically ill patients who are in coma of unclear etiology

M.A. Mirski, MD, PhD (*) Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street Meyer 8 – 140, Baltimore, MD 21287, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_31, © Springer Science+Business Media, LLC 2011

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Subtypes of SE: Three Major Categories ■

Generalized convulsive SE (GCSE) ♦ Classic motor SE ♦ May be overt or have subtle motor manifestations, especially if SE is

prolonged ♦ By far, most commonly reported SE type ♦ Clearly associated with neuronal injury, with prolonged duration of activity ■

Focal motor SE or epilepsy partialis continuans ♦ Single limb or side of face is most common phenotype ♦ Less clear if neuronal injury occurs following prolonged duration

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NCSE ♦ Current umbrella term for wide spectrum of continuous non-motor seizures,

from primary generalized SE, such as absence SE having stereotypic EEG, to secondary generalized with variable EEG features ♦ Other terms within NCSE: complex-partial SE, subtle SE, non–tonic-clonic SE, subclinical SE ♦ Hallmark is diminishment of neurologic exam secondary to seizure, but patient may present anywhere along the spectrum of awake and ambulatory to coma; true incidence of this subtype of SE is unknown and likely underrecognized ♦ Recent trend is to assign label of NCSE to severe anoxic/ischemic encephalopathy when EEG spikes are present

Anatomy of SE ■

Partial or focal SE ♦ Single focus with local spread; often occur in brain regions with previous

injury ♦ EEG usually capable of identifying focus, unless in deep or medial cortical

area (e.g., deep hippocampus) ♦ Bi-hemispheric or “generalized”

• Commonly focal cortical nidus with rapid spread (may be too rapid for EEG to detect) – termed “secondary” generalization • Such seizures spread via cortical networks or cortical–subcortical circuits • “Primary” generalized seizures (e.g., absence) probably utilize brainstem/ subcortical structures in mediation and propagation

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Etiologies of Seizures and SE ■

Neurologic (cortical) injury ♦ Possible causes of seizures include primary pathology in the patient or iatro-

genic causes ♦ Regarding etiology of SE on admission to hospital, anticonvulsant non-

compliance, alcohol withdrawal, and other drug toxicity are most common precipitants per data obtained during the 1980s and more recently (Table 31.1) ♦ Primary neurologic disorders that have cortical involvement carry an appreciable risk of seizures and SE; overall incidence of seizures is 3 to >30–40% following cortical injury (Table 31.2) ■

Traumatic brain injury (TBI) ♦ Incidence of TBI in the civilian population is 3–12%; in the military follow-

ing blast and penetrating wound injuries, risk of seizures is up to >50% Table 31.1  Common etiologies of status epilepticus Neurologic pathology Neurovascular Stroke Arteriovenous malformations Hemorrhage Tumor Primary Metastatic CNS infection Abscess Meningitis Encephalitis Inflammatory disease Vasculitis Acute disseminated encephalomyelitis Traumatic head injury Contusion Hemorrhage Primary epilepsy Primary CNS metabolic disturbance (inherited)

Non-primary pathology Hypoxia/ischemia Drug/substance toxicity Antibiotics Antidepressants Antipsychotics Bronchodilators Local anesthetics Immunosuppressives Cocaine Amphetamines Phencyclidine Drug/substance withdrawal Barbiturates Benzodiazepines Opioids Alcohol Infection fever (febrile seizures) Metabolic abnormalities Hyponatremia Hypophosphatemia Hypoglycemia Renal/hepatic dysfunction Surgical injury (craniotomy) Adapted from Mirski MA, Varelas PN (2008) Seizures and status epilepticus in the critically ill. Crit Care Clin 24(1):115–47, ix

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M.A. Mirski Table 31.2  Risk of seizures from specific neuropathologies Pathology Risk Conditions that exacerbate risk Stroke 6–12% Hemorrhagic Large cortical involvement Acute confusional state Intracranial tumor >25% Cortical – primary Cortical – metastatic Cerebral contusion Traumatic head injury ³4% Acute SDH Depressed skull fracture Penetrating missile injury Evacuation/chronic SDH Adapted from Mirski MA, Varelas PN (2008) Seizures and status epilepticus in the critically ill. Crit Care Clin 24(1):115–47, ix SDH subdural hematoma

♦ Such incidence likely under-reports true risk; with EEG monitoring, true

incidence of NCSE may be doubled ♦ Highest reported incidence of seizures/SE following TBI is associated with

depressed skull fracture, intracerebral hematoma, or subdural hematoma ♦ Poorer outcome is associated with early seizures (first week following TBI),

but these are less a factor than are other variables, such as severity of TBI or age ♦ Following initial post-TBI seizure, recurrence risk is high, especially if seizure is late onset (>1 week), approaching 90% or higher without prophylaxis ■

Stroke ♦ Following a stroke, incidence of seizures is ~3–14%; stroke most common

cause of seizures in patients >60 years of age Early seizures (first 3–4 weeks) are result of disinhibition in “penumbral” region Late seizures (>4 weeks) are result of gliosis and meningocerebral scarring Patients with late-onset seizures are at 2–3 times the risk for subsequent stroke SE occurs in 15–25% of post-stroke patients as initial seizure; interestingly, not associated with subsequent risk of seizures if effectively treated ♦ Overall risk of seizures post-stroke is 2–3 times higher following intracerebral hemorrhage (ICH) than following ischemic stroke; some reports suggest >25% risk of EEG-detected seizures after ICH ♦ As expected, cortical (lobar) localization of ICH is associated with much higher seizure risk than is hemorrhage in basal ganglia or thalamic or posterior fossa ♦ ♦ ♦ ♦

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Aneurysmal subarachnoid hemorrhage (aSAH) ♦ Early (<1 week) and late (>1 week) seizures occur with similar frequency: up

to ~15%; prophylaxis is routine to reduce possible seizure-induced aneurysmal re-rupture – efficacy unproven

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♦ Commonly, re-rupture of the aneurysm may manifest by an early post-SAH

seizure ♦ Coiling vs. clipping of an aneurysm that is responsible for an aSAH roughly

halves risk of subsequent seizures ■

Cerebrovenous sinus thrombosis ♦ Very common, high risk; seizure incidence, 30–50%; often presenting

manifestation ♦ Recurrent seizures or SE may occur due to continued cortical irritation and

regional ischemia ■

Cerebral neoplasms ♦ Seizures are common sequelae (~25–30% risk) but are pathology and location

(cortical, supratentorial: high risk) dependent ♦ Slower growing, lower grade neoplasms (astrocytomas, meningiomas) have

higher reported risk (50–70%); 90% reported for oligodendrogliomas in patient series ♦ High-grade, rapidly growing tumors (glioblastoma) are associated with 25–35% risk ■

Non-neurologic injury (Table 31.1) ♦ Seizures in the ICU are particularly prone to be as a consequence of drug

toxicity or rapid changes in electrolyte and metabolic condition ♦ Particular to an ICU setting and critical illness, non-neurologic injuries such

as metabolic abnormalities, sepsis, and drug toxicity comprise >30–35% of all seizures, of which SE can be complicating sequelae

In-Hospital-Based Seizures and SE ■

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Metabolic abnormalities – uremia, hyponatremia, hypocalcemia, hypoglycemia – most common causes; incidence, 30–35% Hypo-osmolarity, not hyponatremia itself, leads to the high incidence of seizures in patients with low serum sodium Up to 15% of hospital-based seizures are linked to alcohol or medication toxicity, and such seizures can commonly transition to SE Incidence of hospital-based seizures increases to 45% if one includes acute withdrawal from prescribed medications such as benzodiazepines or opiates; the withdrawal syndrome imposes rebound excitation, upregulating the glutamatergic system Alcohol-withdrawal seizures are typically generalized tonic-clonic convulsions, often leading to SE; they occur within first 48 h, preceding development of delirium tremens

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Seizures from drug toxicity, although rare as event of routine pharmaceutical administration (0.08–0.1%; Boston Collaborative Surveillance Program Data), must be considered as precipitants of ED and hospital-based SE Antibiotics are most common group associated with seizures, especially the penicillins and cephalosporins, due to b-lactam group (1–6% overall risk, highest for imipenam) Proconvulsants – aztreonam, fluoroquinolones, isoniazid, metronidazole – all antagonize the action of GABA Next highest risk for seizures – psychotropic group, especially the antidepressants (0.1–4%) Serotonin selective re-uptake inhibitors have lowest incidence, as do trazodone, doxepin, and monoamine oxidase inhibitors Medium-risk agents include the tricyclics and buproprion High-risk agents include maprotiline and amoxapine Phenothiazines also lower seizure threshold; chlorpromazine most commonly prescribed (3–5% risk) Theophylline (with serum levels >20 mg/mL) and lidocaine (>8–10 mg/kg) can also precipitate SE

Morbidity from SE ■

GCSE ♦ Clear evidence exists of association with systemic complications and

direct  neuronal injury as a consequence of unremitting seizure activity (Table 31.3) ♦ Seizures that last >1 h represent an independent predictor of poor outcome (mortality odds ratio of 10) ♦ Certain regions of brain are particularly vulnerable to the effects of SE, and these regions typically have high excitatory amino acid–receptor activity • Brain regions most vulnerable to SE Hippocampal complex Pyramidal cells of cerebellum Amygdala Middle cortical lamina Thalamus Local, cortical inhibitory circuits that normally assist in limiting seizure duration become ineffective during SE; seizures themselves augment this disinhibition As a consequence, the longer the duration of SE, the more difficult it is to terminate ▲ ▲ ▲ ▲ ▲

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495 Table 31.3  Associated complications of GCSE Systemic Acidosis Hyperthermia Rhabdomyolysis Renal failure Dysrhythmias Trauma Impaired V/Q matching Pneumonia Neurologic Direct excitotoxic injury Epileptogenic foci Synaptic reorganization Impaired protein synthesis

Ncse ♦ An equally strong consensus exists for not aggressively treating absence SE ♦ Apart from the altered cognition during the seizure that may be disabling, no

♦ ♦

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evidence suggests that permanent morbidity has been attributed to this form of SE Thus, therapy should be directed toward chronic prevention of attacks In other subtypes of NCSE, the data are less clear; in the classic form of ambulatory NCSE, again, little evidence exists to support permanent injury from SE, although days or weeks of memory disturbance have been reported In hospitalized patients – certainly in the ICU – the diagnosis of NCSE is usually associated with moderate to severe cerebral injury, similar to following an anoxic-ischemic event or trauma Associating the effects of NCSE with direct neuronal injury is difficult in this setting, although most epileptologists agree that in such scenarios, the presence of continuous paroxysmal activity may accentuate injury incurred by the primary insult Therefore, it is prudent to attempt therapy as rapidly as is feasible

Monitoring ■

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EEG is critical in correctly diagnosing SE and in monitoring therapeutic response; EEG seizures often persist following effective termination of convulsive SE (>14%) (Fig. 31.1) In light of emphasis to treat NCSE in a hospital setting, EEG criteria for NCSE are required (Fig. 31.2) The common EEG features of GCSE and NCSE are listed in Tables 31.4 and 31.5

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Fig. 31.1  Example of complex-partial SE (CPSE) over left hemisphere, predominantly temporalparietal region, with large amplitude, rhythmic discharges. (From Kaplan PW. The EEG of Status Epilepticus, with permission)

Typical EEG Presentation of GCSE and NCSE (Table 31.4) ■

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Some notable associated EEG waveforms are controversial as to whether they represent ictal activity; in particular, the periodic lateralizing epileptic discharges (PLEDs if unilateral, BiPLEDs if bilateral/independent, and PEDs if focal or bilateral/uniform) and triphasic waves (TW) (Fig. 31.3) Many epileptologists regard PLEDs in this context as being an interictal event, while others disagree and consider them as continuation of the seizure Such a perspective would necessitate treating PLEDs, even if not coincident with recognizable classic EEG ictal periods Regardless, the presence of PLEDs suggests severe underlying neuronal injury, with BiPLEDs suggesting even worse injury (mortality of 29% in the former group compared to 61% in the latter) Obtaining an EEG early when SE is suspected is helpful in establishing the diagnosis of seizures, evaluating for a possible epileptic focus, and evaluating for residual, nonclinical epileptiform activity ♦ This is true even for convulsive seizures that are treated rapidly, after which

the patient returns to his/her baseline level of wakefulness and cognition

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Fig. 31.2  Example of NCSE, displaying generalized rhythmic sharp-wave discharges; the patterns of NCSE are often continuous (Fig. 31.1) but may also occur in bursts or in a waxing and waning pattern (From Kaplan PW. The EEG of Status Epilepticus, with permission)

Table 31.4  Typical EEG presentation of GCSE and NCSE Classic GCSE Generalized spike or sharp wave pattern begins from a normal background rhythm; SE is characterized by an unremitting spike activity or, more commonly, a crescendo-decrescendo pattern of major motor ictal periods interspersed with lower-voltage paroxysmal activity; no abrupt termination or “post-ictal depression” is observed, as it is in following simple seizures NCSE EEG is variable, with a number of EEG patterns being recognized (see Table 31.5); generally, seizures such as complex-partial seizures resemble their non-SE counterparts

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It is not uncommon for patients to present to the ED with motor manifestations that are convincing of SE but are proven to be pseudoseizures once EEG monitoring is enabled Similarly, residual epileptiform activity may be evidence for NCSE For ongoing SE, EEG (preferably continuous) is mandatory to ensure effective treatment

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Table 31.5  EEG criteria for NCSE Primary 1. Repetitive generalized or focal spikes, sharp waves, spike-and-wave, or sharp-and-slow complexes at >3/s 2. As above, but <3/s, and meeting criterion #4 under secondary criteria 3. Sequential rhythmic waves along with secondary criteria 1, 2, 3, ±4 Secondary 1. Incrementing onset: increase in voltage and/or increase/decrease in frequency 2. Decrementing offset: decrease in voltage or frequency 3. Post-discharge slowing or voltage attenuation 4. Significant improvement in clinical state or EEG with anticonvulsant therapy From Brenner RP (2002) Is it status? Epilepsia 43(Suppl 3):103–113

Fig. 31.3  Example of BiPLEDs, with the lateralized periodic discharges seen independently over both hemispheres; BiPLEDs, vs. PLEDS alone, often represent severe cortical injury given the generalized nature of dysfunction (From Kaplan PW. The EEG of Status Epilepticus, with permission)

♦ Commonly, convulsive SE is incompletely treated and is associated with residual

subtle convulsive SE or NCSE, despite cessation of motor ictal activity ♦ Some clinical reports suggest residual electrographic seizures in almost 50%

of patients with GCSE and a 10–20% incidence of NCSE in those patients treated for GCSE with cessation of motor seizure activity

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For the most common SE, i.e., GCSE, a variety of algorithms and agents have been used during the past 20 years, and new drugs are being continuously investigated Nevertheless, some standards for therapy appear well supported by clinical data First-line therapy for SE (Table 31.6) ♦ Overwhelming evidence exists to support benzodiazepines (BDZ) being

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♦ ♦ ■

the rational first-line agent for the treatment of seizures that can be classified as SE Although one well-conducted study supports the drug lorazepam as most efficacious, the three commonly used BDZ – lorazepam, midazolam, diazepam – all are effective in appropriate doses Advantage of lorazepam is its long clinical duration of plasma concentration and action (t½, 15 h) secondary to its high water solubility and slow elimination Diazepam is highly lipophilic and rapidly redistributes out of the plasma compartment; thus, its duration of action from a single bolus is quite brief (5–20 min) The elimination half-life (t½, 20 h) of diazepam is the longest of the three, possibly contributing to prolonged sedation if large doses or infusions are administered Midazolam is also lipophilic, very brief in action, yet rapidly metabolized, yielding more consistent correlation between dosage and clearance Hence, if a continuous infusion of BDZ is desired, this latter drug offers the best pharmacokinetic profile

Second-line therapy for SE (Table 31.7) ♦ First-line BDZ treatment for SE is effective ~65% of the time in stopping SE ♦ For SE events that terminate using BDZ, the need for continued prophylaxis

against seizures usually exists ♦ IV agents are used for rapid effect and when a fully awake patient is not

required; BDZ are not appropriate agents for chronic use as single agents due to tachyphylaxis Table 31.6  First-line therapy for SE Benzodiazepine Lorazepam Midazolam Diazepam

Elimination time (t½, h) 15 2–4 20

Recommended dosage range (mg/kg) 0.05–0.1 0.05–0.2 0.1–0.4

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M.A. Mirski Table 31.7  Second-line therapy for SE Anticonvulsant Dosage Phenytoin 15–20 mg/kg Fosphenytoin 15–20 mg/kg PE Valproate 15–20 mg/kg

Target serum level (mg/mL) 15–20 15–20 50–100

♦ Phenytoin (PHT), fosphenytoin (fPHT), and sodium valproate (VPA) are

common selections ♦ Although similar in parent compound, fPHT is a phosphate ester pro-drug

of PHT ♦ fPHT is soluble in water and does not require an ethylene glycol vehicle, as

does PHT; consequently, it may be administered IV or IM; because fPHT is metabolized to PHT in a few minutes, the drug is dosed as PHT equivalents (PE); fPHT can be administered three times faster than PHT (150 mg/min vs. 50 mg/min) – no hypotension occurs from the ethylene glycol, but the required serum enzymatic conversion translates to similar kinetics of loading to target free serum PHT levels as the native compound ♦ When SE persists despite adequate trial of BDZ, the IV agents PHT/fPHT, and VPA are added to high therapeutic target levels

Medical and Pharmacologic Treatment of SE (Table 31.8) ■

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As new anticonvulsants become available, their utility in treating refractory seizures and possibly SE is evaluated, if only superficially Levetiracetam (Keppra), available as IV formulation, is often administered as adjunctive anticonvulsant; anecdotal evidence of efficacy (no large, controlled series) but has advantage of not having drug interactions or hemodynamic effects, which are major advantages in critical care management Due to the lack of IV formulations, new drugs are assessed only as add-on agents Some success has been reported with drugs listed in Table 31.9 in the treatment of refractory seizures; they may be used for SE in appropriate circumstances as patients are weaned from pharmacologic EEG seizure suppression Because functional enteral absorption is required, deep pharmacologically induced coma likely precludes such interventions

Drug Toxicity-Induced SE: Need for Nonconventional Therapy ■

■

In certain circumstances of drug toxicity, specific therapies may be indicated; most antibiotics that may cause seizures act via GABA antagonism Hence, BDZ remain the first-line therapy, and PHT and other agents may offer little added benefit

31  Status Epilepticus

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Table 31.8  Medical and pharmacologic treatment of SE Initial management Preserve airway and oxygenation by intubation; order EEG to be available during therapy Measure finger-stick blood glucose and administer IV glucose if <40–60 mg/100 dL Immediate benzodiazepines: 5–10 mg lorazepam IV, 20–40 mg diazepam, or 5–20 mg midazolam over 5 min PHT loading dose 20 mg/kg at 50 mg/min or 20 mg/kg fPHT PE (PHT equivalents) at 150 mg/min; goal serum level, 15–20 mg/dL Continuous EEG if available If seizures continue, PHT or fPHT (additional 5–10 mg/kg or 5–10 mg/kg PE); goal serum level, 20–25 mg/dL Option: 1,500–2,000 mg levetiracetam (Keppra) IV; anecdotal evidence of efficacy For Refractory SE – several options Rapid pharmacologic burst suppression/coma with hemodynamic support – propofol, 2 mg/kg and 150–200 mg/kg/min infusion, or thiopental, 4 mg/kg and 0.3–0.4 mg/kg/min Blood pressure support may be necessary – consider 20–100 mg/min phenylephrine or 5–20 mg ephedrine IV 0.2 mg/kg midazolam, followed by 0.1–0.2 mg/kg/h may be used as alternative to propofol or thiopental 60–70 mg/kg VPA may be tried 5–10 mg/kg pentobarbital, followed by 1–10 mg/kg/h is common recipe for long-term burstsuppression requirement Recommend propofol infusion for initial burst-suppression agent; higher clearance may permit weaning within 1 h; pentobarbital coma requires 2–4 days of weaning and EEG/neurologic recovery Weaning from EEG seizure suppression Using continuous EEG, maintain in SE-suppressed state (possibly true burst-suppression not required) for 12–48 h before attempting to withdraw pharmacologic coma Ensure adequate anticonvulsant levels of selected agents for chronic seizure control; aim for high levels of fewest number of anticonvulsant agents; most common: PHT and VPA Wean infusion, follow EEG as background rhythm begins or increases; if breakthrough seizures recur, rebolus using 30–70%, as necessary, of original bolus amount required of infusion drug Re-adjust anticonvulsant serum level or add additional agents before another wean attempt Not uncommon for more than one adjustment to be made before successful wean

Table 31.9  Indications for newer anticonvulsants as adjunctive therapy for refractory seizures Primary generalized Partial Lamotrigine Yes Yes Gabapentin Yes Felbamatea Yes Yes Topiramate Yes Tiagabine Yes Vigabatrinb Yes Yes Levetiracetam Yes Yes  Restricted use due to aplastic anemia  Not available in US

a

b

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In refractory cases or in other drug overdose states, hemodialysis is a viable therapeutic option Several more common drug offenders and potential treatment strategies are listed in Table 31.10

Drug Interactions ■

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■

■ ■

■ ■

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Anticonvulsant drug interactions may complicate therapy for refractory SE when no single agent is able to control the seizures and poly-pharmacy is required Usually this occurs when weaning from EEG-suppressive therapy (barbiturates, propofol, etc.) is undertaken The goal is to wean with maximal serum level of a single selected anticonvulsant (i.e., PHT or VPA) Despite attaining high levels, breakthrough seizures persist It is important to recognize that anticonvulsants may stimulate hepatic enzyme systems or alter serum protein binding, thereby disturbing the kinetics of other agents The common known cross-effects of anticonvulsants are listed in Table 31.11 Similarly, anticonvulsants may interact with common drugs used in the ICU setting, where patients treated for SE are commonly managed The alterations in efficacy of several commonly used medications are listed in Table 31.12 Table 31.10  Therapies for specific drug-induced SE Drug Treatment options Benzodiazepines, Antibiotics – penicillins, b-lactams, hemodialysis fluoroquinolones Theophylline Midazolam, hemodialysis Isoniazid IV Pyridoxine Table 31.11  Alterations in drug plasma levels with combination anticonvulsants Effect on plasma levels of primary agents Added drug % Bound PHT PB CBZ VPA BDZ PHT 90 ~ ↓ ↓ PB 45 ↑, then ↓ ~ ↓ ↓ CBZ 75 ~ ~ ↓ ↓ ↓ VPA 90 ↓a ↑ ~ or ↑ b ↑ BDZ ↓ ~ ~ Keppra ~ ~ ~ ~ ~ ~ % bound = percentage serum protein bound, PHT phenytoin; PB Phenobarbital; CBZ carbamazepine; VPA valproate; BDZ benzodiazepines; Keppra, levetiracetam; ↓, decrease; ↑, increase; ~, variable a ↑ Free DPH level b Epoxide

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Table 31.12  Effects of anticonvulsants on commonly used medications Effect on plasma levels or clinical effectiveness of primary agents Added drug Warfarin Theophylline Steroids Haloperidol Lithium PHT ↓ ↓ ↓ PB ↓ ↓ ↓ ↓ ↑ CBZ ↓ ↓ ↓ ↓ PHT phenytoin; PB phenobarbital; CBZ carbamazepine; ↓ decrease; ↑ increase

Key Points ■

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■ ■

■ ■

GCSE is rapidly assessed and treated to prevent further primary and secondary brain injury, systemic manifestations of muscle convulsive activity, and risk of cardiopulmonary complications Intubation is suggested, as nearly all AEDs have sedative effects, compounding coma from SE Treatable causes of SE should be identified early An algorithm should be followed with sequential drug administration for persistent SE NCSE may not need to be treated as aggressively as GCSE EEG is required to determine resolution of SE or presence of nonclinical SE

Suggested Reading Bleck TP (2005) Refractory status epilepticus. Curr Opin Crit Care 11:117–120 Bleck TP (2007) Intensive care unit management of patients with status epilepticus. Epilepsia 48(Suppl 8):59–60 Brenner RP (2002) Is it status? Epilepsia 43(S3):S103–S113 Brenner RP (2004) EEG in convulsive and non-convulsive status epilepticus. J Clin Neurophysiol 21:319–331 Coulter DA, DeLorenzo RJ (1999) Basic mechanisms of status epilepticus. Adv Neurol 79:725–733 Kaplan PW (1999) Assessing the outcomes in patients with non-convulsive status epilepticus: non-convulsive status epilepticus is under diagnosed, potentially over treated, and confounded by morbidity. J Clin Neurophysiol 16:341–352 Kaplan PW (2006) The EEG of status epilepticus. J Clin Neurophysiol 23:221–229 Lowenstein DH (2006) The management of refractory status epilepticus: an update. Epilepsia 47(Suppl 1):35–40 Nuwer M (2007) ICU EEG monitoring: non-convulsive seizures, nomenclature, and pathophysiology. Clin Neurophysiol 118:1653–1654 Treiman DM et  al (1998) A comparison of four treatments for generalized convulsive status epilepticus. NEJM 339:792–798 Varelas PN, Mirski MA (2004) Management of seizures in critically ill patients. Curr Neurol Neurosci Rep 4:489–496 Varelas PN, Mirski MA (2007) Treatment of seizures in the neurologic intensive care unit. Curr Treat Options Neurol 9:136–145 Wasterlain CG, Fujikawa DG, Penix L, Sankar R (1993) Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia 34 (S1):S37–S53

Chapter 32

Deep Venous Thrombosis and Pulmonary Embolism Wendy C. Ziai

Epidemiology of Venous Thromboembolism ■ ■ ■

10% of hospital deaths are attributed to pulmonary embolism (PE) In-hospital case-fatality rate of venous thromboembolism (VTE) is ~12% Pulmonary embolism (PE) ♦ 79% of patients who present with PE have evidence of DVT in lower ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

■

extremities Overall 3-month mortality is ~15% Most common cause of early death is right ventricular failure Mortality after 30 days is usually caused by underlying disease 18% of patients with PE and right ventricular (RV) failure or pulmonary hypertension present in cardiac arrest Mortality of untreated PE is ~30% Mortality can be reduced to 2–8% with anticoagulant therapy Independent comorbid predictors of 3-month mortality: age, congestive heart failure, cancer, chronic lung disease Rate of recurrent VTE on anticoagulation is <5% (30% after 10 years) PE occurs in ~15% of patients with central venous catheter-related upperextremity deep venous thrombosis (DVT) Intracranial VTE can be a cause of new-onset seizure activity

DVT ♦ Risk of DVT in at-risk medical patients without anticoagulant prophylaxis is

10–15% ♦ 10–20% of calf thrombi extend to the proximal veins ♦ PE occurs in up to 50% of patients with DVT

W.C. Ziai, MD (*) Department of Neurology and Neurological Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street – Meyer 8-140, Baltimore, MD 21287, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_32, © Springer Science+Business Media, LLC 2011

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♦ Central venous catheter-associated thrombosis risk is ~5% ♦ Despite a relatively low incidence of VTE in medical patients, most deaths

due to PE occur in medical patients ■

VTE in specific neurologic conditions (Fig. 32.1) ♦ Spinal cord injury – highest in-hospital prevalence of VTE (60–80%) ♦ Traumatic brain injury (isolated) – DVT incidence of 25% using venous

color-flow Doppler imaging despite use of pneumatic compression devices ♦ Ischemic stroke – in-hospital prevalence of VTE of 20–50%

• Risk of asymptomatic DVT with Doppler ultrasonography is 5–30% • Absolute risk of fatal PE in first month after acute ischemic stroke (AIS) is 1–2% • PE accounts for up to 17% of early deaths • Fatal PE unusual in first week; most common between 2 and 4 weeks • VTE prevalence – 2–3% of AIS patients on aspirin with or without elastic stockings within 10–14 days of onset • Most important risk factor is low Barthel Index score • Antiplatelet drugs decrease incidence of PE but do not affect risk of DVT

Prevalence of VTE in Hospitalized Patients (%) Medical Patients General Surgery Urologic/Gyne Surgery Neurosurgery Stroke Hip/Knee Surgery Major Trauma Spinal Cord Injury Critical Care Patients 0

10

20

30

40

50

60

70

80

Prevalence (%)

Fig. 32.1  Prevalence of VTE in hospitalized patients (%). From Geerts WH, Pineo GF, Heit JA et al (2004) Prevention of venous thromboembolism. Chest 126:338S–400S

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♦ Intracerebral hemorrhage (ICH) – Untreated clinical DVT after primary ICH

associated with estimated >10–20% risk of fatal PE and 10–20% risk of nonfatal clinical PE ♦ Malignant glioma – cancer with highest association with VTE • 2-Year cumulative incidence is ~7.5% • 55% of cases occur within 2 months of surgery • Occurrence of VTE is associated with 30% increase in risk of death within 2 years ♦ DVT risk without prophylaxis for combined cranial/spinal procedures is

29–43% ♦ Elective spine surgery – risk of DVT without prophylaxis is 7–14% ■

Risk Factors for VTE Venous valvular insufficiency Right-sided heart failure Postoperative period Prolonged bed rest/immobilization/travel Trauma to extremities Advanced malignancy and cancer therapy Pregnancy and postpartum state Estrogen-containing birth control pills or hormone replacement therapy (HRT) ♦ Traumatic spinal cord injury and paralysis of lower extremities ♦ History of VTE ♦ Hypercoagulable states ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

• Deficiency of antithrombin III, protein C, protein S not clinically important risk factors for recurrent VTE • Antiphospholipid antibody • Factor V Leiden mutation ▲ ▲ ▲ ▲

Causes protein C resistance Homozygosity is most common hypercoagulable state May have higher risk of recurrent VTE Hyperhomocysteinemia: associated with recurrent VTE

♦ Increasing age/obesity/smoking ♦ ICU-related factors: neuromuscular paralysis/prolonged mechanical ventila-

tion, severe sepsis, central venous catheterization, consumptive coagulopathy, heparin-induced thrombocytopenia ■

Risk factors for VTE in patients with malignant glioma ♦ Older age (>45 years) ♦ Male sex ♦ One or more comorbid conditions

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♦ Histologic subtype – Glioblastoma Multiforme ♦ Major neurosurgical procedure

Clinical Presentation of DVT ■ ■ ■ ■ ■

Tenderness along deep venous system Entire leg swollen Calf swelling >3 cm vs. other side Pitting edema of symptomatic leg Collateral superficial veins

Clinical Presentation of PE ■ ■ ■ ■ ■ ■ ■ ■

Tachypnea Pleuritic chest pain Dyspnea Cough Hemoptysis Hypoxemia Tachycardia Unexplained fever present in 14%; usually low grade ♦ Often associated with clinical evidence of DVT ♦ Not necessarily associated with pulmonary hemorrhage or infarction

Differential Diagnosis for PE (Acute Respiratory Distress) ■ ■ ■ ■ ■ ■ ■

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Acute main bronchus obstruction Bronchospasm Pneumothorax Pulmonary edema Atelectasis Auto-PEEP (positive end-expiratory pressure) Malfunction of mechanical ventilation ♦ Inappropriate ventilator setting ♦ Endotrachial tube or tracheostomy tube malposition/dislodgement ♦ Machine dysfunction Abdominal distension

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Diagnostic Tests ■

D-dimer ♦ Degradation products of cross-linked fibrin ♦ D-dimer assays rely on monoclonal antibodies to bind to this specific protein

fragment ♦ Quantitative rapid ELISA most clinically useful assay ♦ Sensitivity – 95%; negative likelihood ratio 0.1 for excluding DVT and PE ♦ Unidirectional finding: negative result used in diagnostic pathway to exclude

DVT or PE (negative predictive value: 92%) ♦ Causes of false-positive D-dimer: Liver disease, high rheumatoid factor,

inflammation, malignancy, trauma, pregnancy, recent surgery, advanced age ♦ Causes of false-negative D-dimer: sample too early, delayed sample, anticoagulation ♦ May guide decision about duration of therapy

• Persistent elevation associated with increased recurrence rate ■

Venous Doppler ultrasound (US) ♦ Highly accurate ♦ Positive-predictive value (PPV) – 97% with finding of noncompressible

common femoral vein or popliteal vein ♦ Negative-predictive value (NPV) – 98% in a symptomatic patient with full

compressibility of both sites Less sensitive for DVT limited to calf (33–70%) US positive in 10–20% of asymptomatic high-risk patients US positive in ~50% of patients with proven embolism Therefore, negative US cannot exclude diagnosis of PE When ventilation-perfusion (V/Q) scan is nondiagnostic for PE, US abnormal in ~5% of cases ♦ Normal US may be used to reduce probability of PE when V/Q scan or spiral CT non diagnostic because subsequent risk for symptomatic VTE is <2% in 6-month follow-up ♦ ♦ ♦ ♦ ♦

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Contrast venography ♦ ♦ ♦ ♦ ♦ ♦ ♦

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Definitive test – high sensitivity Limited availability, rarely performed Questionable clinical relevance of small or distal thrombi Incomplete or nondiagnostic rates of at least 20–40% Moderate interobserver variability in interpretation Patient discomfort and risks related to use of a contrast agent High cost

V/Q scan ♦ Theory – mismatched patterns of perfusion and ventilation

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Typical classification – high, intermediate, low probability, normal Better classification – high probability, nondiagnostic, normal Up to 75% of tests inconclusive High probability – probability of PE is ~90% Normal V/Q scan – excludes clinically important PE Low probability: cannot exclude PE; may be sufficient to stop further workup if negative duplex US of lower extremities ♦ Intermediate probability or indeterminate: no value ♦ Clinically useful to use perfusion scanning alone ♦ ♦ ♦ ♦ ♦ ♦

• Differentiate abnormal scans with wedge-shaped deficit (PE+) vs. without wedge-shaped deficit (PE–) ♦ Current indications

• Contraindication to spiral CT (24%) ▲ Impaired renal function ▲ Contrast allergy

♦ In ICU, presence of lung disease produces abnormal scan in 90% of cases ■

CT pulmonary angiography (helical and multidetector row CT) ♦ First-line PE imaging test ♦ Greater accuracy for emboli in main or lobar pulmonary arteries (93% sensi-

tivity; 97% specificity) ♦ Lower accuracy for emboli in segmental or subsegmental arteries (71–84%

sensitivity) ♦ Questionable importance of small subsegmental emboli ♦ Withholding anticoagulant therapy based on negative CT does not adversely

affect clinical outcomes ♦ Negative likelihood ratio of a VTE after a negative chest CT for PE = 0.07;

NPV = 99.1% ♦ NPV of mortality due to PE is ~99.4% ♦ Addition of CT venography (CTV) of lower extremities, but not pelvis,

increases sensitivity slightly but may not be worth the added radiation ♦ Measures of right-heart function, pulmonary artery pressures, and clot burden

must be standardized and validated ■

MRI venography ♦ ♦ ♦ ♦ ♦ ♦ ♦

Allows visualization of proximal DVT with satisfactory accuracy Sensitivity – 94–96% Specificity – 90–92% (in symptomatic outpatients) Distal DVT sensitivity – 83–92% Diagnoses thrombotic extension into iliac veins and vena cava Method of choice for diagnosis of suspected pelvic thrombosis Unsatisfactory diagnostic accuracy for asymptomatic high-risk subjects

32  Deep Venous Thrombosis and Pulmonary Embolism ■

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Pulmonary angiography ♦ Gold standard for the diagnosis of PE ♦ Complication rates from PIOPED (Prospective Investigation of Pulmonary

Embolism Diagnosis) trial: • Mortality – 0.5% • Major nonfatal complications – 0.8% (respiratory failure, renal failure, or hematoma necessitating transfusion) ♦ Limited interobserver agreement for subsegmental pulmonary emboli

(45–66%)

Diagnostic Approach ■

■

Use validated clinical prediction rules to estimate probability of VTE and for basis of interpretation of subsequent tests Wells prediction rule – Determine clinical probability of DVT/PE (Table 32.1) ♦ Performs best in younger patients without comorbidities or a history of VTE

than in older patients with comorbidities ♦ Wells Prediction Rule for Diagnosing DVT (Table 32.2) ♦ Wells Prediction Rule for Diagnosing PE (Table 32.3) ■ ■

■

Use Clinical Probability Score to determine which diagnostic tests to use Low pretest probability of DVT/PE → high-sensitivity D-dimer reasonable option Low pretest probability for PE (<15–20%) → normal D-dimer rapid ELISA result ♦ No further testing required ♦ Post-test probability of PE – 0.7–2%

■ ■

Abnormal D-dimer requires further testing Intermediate to high pretest probability of DVT in lower extremities ♦ Venous Doppler US

■

Intermediate to high pretest probability of PE ♦ Diagnostic imaging study Table 32.1  Wells prediction rule to determine clinical probability of DVT/PE Wells score for Wells score for PE Clinical probability DVT diagnosis diagnosis Low 0–1 £0 Intermediate 1–2 2–6 High ³3 ³7

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W.C. Ziai Table 32.2  Wells prediction rule for diagnosing DVT Clinical feature Score Active cancer 1 Paralysis, paresis, recent immobilization 1 Immobilized >3 days or surgery in past 4 weeks 1 Tenderness along deep venous system 1 Entire leg swollen 1 Calf swelling >3 cm vs. other side 1 Pitting edema of symptomatic leg 1 Collateral superficial veins 1 Alternative diagnosis as likely as DVT –2 Wells PS, Anderson DR, Bormanis J et  al (1997) Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 350:1795–1798 Table 32.3  Wells prediction rule for diagnosing PE Clinical feature Score Signs, symptoms of DVT 3.0 HR >100/min 1.5 Immobilized ³3 days or surgery in past 4 weeks 1.5 Prior PE or DVT 1.5 Hemoptysis 1.0 Cancer (6 months) 1.0 PE likely or more likely than other diagnoses 3.0 Chagnon I, Bounameaux H, Aujesky D et  al (2002) Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism. Am J Med 113:269–275

• Multidetector helical CT scan, OR • V/Q scan, OR • Pulmonary angiography

Management Algorithms for PE ■

Low clinical probability of PE algorithm ♦ Positive D-dimer Rapid ELISA → CTA

• If CTA is negative (NPV 96%) → No treatment • If CTA is positive (PPV 58%) ▲ Main or lobar PE (PPV 97%) → Treat ▲ Segmental PE (PPV 68%) or Subsegmental PE (PPV 25%) → Proceed

to other options

N Repeat CTA if poor quality N Doppler US (or MRI venography), serial US

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N V/Q scan N Pulmonary angiogram ■

Intermediate clinical probability of PE algorithm ♦ Positive D-dimer Rapid ELISA → CTA

• If CTA is negative (NPV 89%) → No treatment ▲ Consider Doppler US or MRI venography

• If CTA is positive (PPV 92%) → Treat ■

High clinical probability of PE algorithm ♦ CTA

• If CTA is positive (PPV 96%) → Treat • If CTA is negative (NPV 60%) ▲ Proceed to other options N N N N

Repeat CTA if poor quality Doppler US (or MRI venography), serial US V/Q scan Pulmonary angiogram

Management ■

VTE prevention in traumatic brain injury ♦ Guidelines of the Brain Trauma Foundation recommend graduated compres-

sion stockings or intermittent pneumatic compression stockings until patient is ambulatory ♦ Low-molecular-weight heparin (LMWH) or low-dose unfractionated heparin (UFH) should be used in combination with mechanical prophylaxis ♦ LMWH prophylaxis initiated 12–24 h after injury (following repeat head CT) showed no evidence of active or increased ICH in a small subset of patients with traumatic brain injury (n = 174) ■

VTE prevention after elective neurosurgery ♦ LMWH started within 24 h after surgery + elastic stockings, vs. elastic stock-

ings alone, is more effective for prevention of VTE ■

VTE prevention in AIS ♦ Low-dose LMWH (compared to high-dose LMWH or standard unfractionated

heparin) appears to have best benefit/risk ratio in patients with AIS; a dosedependent bleeding risk exists ♦ UFH – (£6,000 IU/day or weight-adjusted £86 IU/kg/day)

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• Reduced incidence of both DVT (OR 0.34; 95% CI, 0.19–0.59) and PE (OR, 0.36; 95% CI, 0.15–0.87) • No increased risk of ICH or extracranial hemorrhage • NNT (number needed to treat to prevent one case) = 7 (DVT), 38 (PE) ♦ PREVAIL study of enoxaparin (40 mg qd) vs. low-dose UFH started within

48 h of stroke found lower incidence of VTE (but not symptomatic VTE) in LMWH group, but also higher rate of major extracranial bleeding ♦ After confirmed DVT (in patients with contraindication to anticoagulation), LMWH recommended as prophylaxis to prevent PE (in addition to consideration for IVC filter) ■

VTE prevention in acute ICH ♦ Intermittent pneumatic compression, compared to elastic stockings alone, sig-

nificantly decreased occurrence of asymptomatic DVT for patients with ICH ♦ Prophylaxis with low-dose UFH, if started early (day 2), does not increase

risk of rebleeding but significantly decreases incidence of PE ■

LMWH prophylaxis regimens ♦ Enoxaparin (Lovenox)

• 40 mg SC qd (moderate risk) • 30 mg SC bid (high risk) • 40 mg SC qd (renal failure, high risk) ♦ Dalteparin (Fragmin)

• 2,500 units SC qd (moderate risk) • 5,000 units SC. qd (high risk) • No dose adjustment for renal failure ♦ Fondaparinux is an effective prophylactic agent ■

VTE treatment ♦ IV heparin – Standard treatment for both DVT and PE is UFH by continuous

IV infusion using weight-based dosing ♦ Randomized trials support use of LMWH or fondaparinux for symptomatic

PE and for DVT ♦ In patients with cardioembolic transient ischemic attack, ischemic stroke,

anticoagulants increase risk of major ICH, especially in first 2 weeks ♦ Decision to start anticoagulant treatment should be determined on an

individual basis in patients with intracranial vascular pathology ♦ Subsegmental PE demonstrated on CT angiography is generally treated ♦ Guidelines were developed for patients who weigh <130 kg

• Loading dose (80 IU/kg) IV bolus for PE usually not given to patients with risk of hemorrhage in CNS • IV heparin infusion – 18 IU/kg/h

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• aPTT 6 h after heparin bolus/start of infusion • Adjust heparin infusion based on protocol; PTT goal – 1.5–2 × control • Failure to achieve adequate heparinization in first 24 h increases risk of recurrent emboli • Less heparin required to maintain adequate anticoagulation after first 48 h ♦ Bleeding complications correlate with:

• • • •

Concurrent illness (renal disease) Heavy ETOH Aspirin Peptic ulcer disease

♦ Bleeding complications do not correlate with supratherapeutic PTT ♦ LMWH

• Reduces mortality during 3–6 months of follow-up for treatment of DVT, vs. UFH (Level 1) • Once (tinzaparin) or twice (enoxaparin) daily subcutaneous injection • No need to monitor anticoagulantion • Fewer episodes of major bleeding • At least as effective as UFH heparin for PE • Cost saving or at least cost effective, vs. UFH • Problematic in critically ill patients due to longer half-life • Consider monitoring anti-factor Xa activity in patients >150 kg, <40 kg, pregnant, or with change in renal function ♦ Fondaparinux

• Pentasaccharide antithrombotic agent with anti-factor Xa activity • Like LMWH, longer half-life than heparin and better bioavailability after subcutaneous injection • Once-daily subcutaneous dosing without anticoagulation monitoring • Potentially lower risk of heparin-induced thrombocytopenia than with LMWH • More cost effective than LMWH • Avoid in patients with severe renal insufficiency (creatinine clearance <30 mL/min) ♦ Warfarin

• With a reversible cause of VTE and no planned procedures, warfarin can be started on the first day of heparin therapy • Heparin, LMWH, or fondaparinux should be administered for at least 5 days and until INR is therapeutic (2.0–3.0) for at least 2 days ♦ LMWH vs. vitamin K antagonist for treatment of VTE

• Ten randomized, controlled trials (RCTs) from 1994 to 2005 with active surveillance

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• In only one study (cancer patients with normal Cr), LMWH group had lower recurrence rate of DVT than did those in warfarin group; other studies showed no difference • Bleeding rates in all LMWH groups were similar or below rates in oral anticoagulant group • LMWH may be useful for patients in whom INR control is difficult and may be more efficacious in patients with cancer • Full anticoagulation appears acceptably safe in patients with intracranial malignancy ♦ Optimal duration of vitamin K antagonist treatment for VTE

• Rates of recurrence depend on setting of DVT – idiopathic, transient risk factor, permanent risk factor • Recurrent DVT risk decreases stepwise as duration of anticoagulation increases from 3 to >12 months with INR 2–3 • Incidence of major bleeding increases from 0.4 events/100 patient years (<3 months) to 1.5 events (>12 months) • Unprovoked VTE or second episode of VTE – extended duration (6–12 month) treatment may be optimal (Level 1) • Provoked first VTE – 3-month anticoagulation recommended (Level 2) ♦ Heparin-induced thrombocytopenia with VTE

• Treat with direct thrombin inhibitor – argatroban (hepatic metabolism) or lepirudin (renal excretion) • Do not start warfarin until disease is controlled and platelets return to normal • Warfarin can precipitate thrombotic complications ▲ Venous limb gangrene ▲ Warfarin-induced skin necrosis

♦ Catheter-directed thrombolysis of DVT may be efficacious in well-chosen

patients with higher patency rates and lower prevalence of venous reflux ■

Inferior vena cava (IVC) filters – three types ♦ Permanent

• • • • • •

Long-term complications Thrombotic occlusion of the IVC – 6–30% Filter migration – 3–69% IVC perforation – 9–24% Post-thrombotic syndrome – 5–70% Post-insertion PE – 5%

♦ Temporary

• Frequent complications (thrombosis, infection, migration)

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♦ Retrievable

• Most not retrieved (only 22% retrieved in a series of trauma patients) ■

Appropriate indications for IVC filter ♦ Contraindication or complication of anticoagulant therapy in an individual

with a proximal DVT or PE ♦ Recommended by American Stroke Association in patients with ICH and DVT ♦ Many potential indications

• • • •

Prophylaxis in high-risk trauma, orthopedic, gynecologic, and bariatric surgery Thrombolysis of DVT Pregnancy Hemodynamic instability in patients who will not be given thrombolytic therapy • Massive PE (where additional emboli may be fatal) ♦ No randomized trials demonstrate clear benefit of IVC insertion in trauma

patients ♦ IVC filters only modestly reduce recurrent PE and do not affect mortality

(Level 2) ♦ Recurrent DVT significantly higher among patients with proximal DVT ± PE

treated with IVC filter vs. without at 2 years (20.8% vs. 11.6%)

Risk Stratification After PE and Treatment of Massive PE ■ ■

Categories of PE (Table 32.4) Risk stratification tools ♦ Clinical evaluation

• Look for Signs of acute RV dysfunction: tachycardia, low SBP, distended neck veins, increased pulmonic component of S2, TR murmur • SBP at time of PE diagnosis is most powerful predictor of early death ▲ SBP <90 mmHg – 52% 90-day mortality ▲ SBP >90 mmHg – 15% 90-day mortality

♦ EKG

• 25% of patients with acute PE have normal EKG • Signs of RV strain Table 32.4  Categories of PE Massive PE Arterial hypotension (SBP <90 mmHg) + cardiogenic shock Submassive PE Hemodynamically stable patient with right ventricular dysfunction Nonmassive PE Hemodynamically stable patient with normal right ventricular function

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Sinus tachycardia Right bundle-branch block SI QIII TIII T-wave inversion in V2, V3 Qr in V1 (pseudoinfarction pattern) ST depression, ST elevation Shift of QRS transition Low limb lead voltage

• RV strain associated with elevated cardiac biomarker levels • Both T-wave inversion and pseudoinfarction pattern in precordial leads predict adverse clinical outcomes, including death, CPR, mechanical ventilation, use of pressors and thrombolysis ♦ ABG

• Low PaO2 (<80 Torr) • Respiratory alkalosis (tachypnea); acidosis (dead space) • Higher median alveolar-arterial (A-a) oxygen difference seen as proportion of lung perfusion defects increase • Normal A-a gradient and PaO2 >80 makes PE less likely, but neither excludes PE ♦ Echocardiogram

• Normal in half of patients with confirmed PE • Use echo to detect RV dysfunction = independent predictor of mortality • Transesophageal echocardiogram can diagnose emboli in main, right, and left pulmonary artery but not in lobar or segmental branches • Can be used to diagnose acute PE in hemodynamically unstable patient and initiate thrombolysis/embolectomy • Can diagnose conditions that mimic acute PE • Look for patent foramen ovale or atrial septal defect ▲ Risk for paradoxical embolism and stroke

• Patent foramen ovale is independent predictor of mortality • Predictive information ▲ Estimated systolic pulmonary artery pressure >50 mmHg at PE diagnosis

is associated with persistent pulmonary HTN at 1 year ▲ Cumulative incidence of pulmonary hypertension at 1 year with PE

– 3.1% ♦ Cardiac biomarkers

• Troponins – levels correlate with extent of RV dysfunction • Elevated levels usually transient and small ▲ May be seen in absence of angiographic CAD

• Troponins I and T similarly accurate

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• Elevated troponin + RV dysfunction on echo predicts 10 × risk of complicated hospital course and mortality of 20% • Elevated CKMB (isoenzyme of creatine kinase with muscle and brain subunits) associated with RV infarction • Elevated BNP (brain natriuretic peptide) and NT-pro BNP are associated with RV dysfunction in acute PE and are predictive of all-cause in-hospital mortality • NPV of cardiac biomarkers >97% for in-hospital death ♦ Chest CT

• Prognostic CT findings ▲ Ventricular septal bowing associated with death ▲ RV enlargement = RV/LV > 0.9

• RV enlargement on CT correlates with RV dysfunction on echo and may identify patients at risk of death from RV failure • Embolic burden not associated with increased risk of death ■

Treatment of massive PE ♦ High-dose UFH

• Bolus – at least 10,000 IU • Continuous infusion – at least 1,250 IU/h • Target aPTT >80 s ♦ Resuscitation: crystalloid vs. pressors

• • • •

Rapid infusion of 500–1,000 mL NS Dopamine and dobutamine = first line Norepinephrine and phenylephrine may help Switch pressors if BP not restored

♦ Thrombolysis

• Indication – Hemodynamically unstable patient with hypotension or signs of systemic hypoperfusion caused by PE • Current FDA-approved thrombolytic protocol for PE Alteplase – 100 mg/2 h continuous IV infusion, OR Bolus dose 0.6 mg/kg/15 min is equivalent Stop heparin Do not obtain aPTT until end of alteplase infusion Restart heparin if aPTT is <80 s (continuous infusion, no bolus) Timing – No difference (vs. heparin) in degree of embolic resolution at 5–7 days after PE onset ▲ Reduces risk of death or recurrent PE by 55% in massive PE (five RCTs) ▲ Thrombolysis can significantly reduce pulmonary vascular resistance and RV stress ▲ ▲ ▲ ▲ ▲ ▲

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W.C. Ziai ▲ IV rtPA appears to be equivalent to intrapulmonary rtPA ▲ Major hemorrhage risk with PE thrombolysis – 9.1% vs. 6.1% in

heparin-treated patients (11 RCTs) ▲ Fatal hemorrhage risk – 1–2%; ICH – 1.2–2.1%

♦ Embolectomy

• Indications ▲ Contraindication to thrombolytic therapy (1/3 of massive PE) ▲ Refractory hypotension ▲ Failure of systemic thrombolytic therapy in a highly compromised

patient • Open surgical embolectomy – 89% (26/29) survival rate in one study ▲ Consider in presence of right heart thrombi ± paradoxical embolism

• Minimally invasive procedures – catheter-directed thrombolysis, percutaneous embolectomy, embolus fragmentation, pulmonary artery stent placement • Catheter embolectomy – 83% (10/12) survival rate in one study ▲ Clinical success defined as improvement in hemodynamic parameters ▲ ▲ ▲ ▲

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immediately after procedure Reverses systemic hypotension Decreases peak airway pressure Improves cardiac output Several devices; all appear to be useful and are usually combined with thrombolytics

Treatment of submassive PE ♦ RCT of systemic thrombolysis vs. heparin alone found that alteplase + hepa-

rin reduced risk of clinical deterioration that would require treatment escalation but did not reduce risk of death

Key Points ■ ■

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High index of clinical suspicion is paramount in making a prompt diagnosis of PE Algorithms using pretest clinical probability to direct diagnostic tests are the standard of care For massive PE, catheter-directed embolectomy with or without local lytic therapy is preferred over systemic thrombolysis in centers with experience Current evidence does not support use of thrombolytic agents in hemodynamically stable patients with right ventricular dysfunction Choice of thromboprophylaxis in acute ischemic stroke patients depends on individual risk assessment of VTE and bleeding complications

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LMWH can be started safely within 24 h after elective neurosurgery As long as patients are at risk for major bleeding, systemic anticoagulation is contraindicated, and a vena cava filter should be considered

Suggested Reading Antevil JL, Sise MJ, Sack DI et al (2006) Retrievable vena cava filters for preventing pulmonary embolism in trauma patients: a cautionary tale. J Trauma 60:35–40 Gross PL, Weitz JI (2008) New anticoagulants for treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol 28(3):380–386 Kamphuisen PW, Agnelli G (2007) What is the optimal pharmacological prophylaxis for the prevention of deep-vein thrombosis and pulmonary embolism in patients with acute ischemic stroke? Thromb Res 119:265–274 Sandercock PA, Counsell C, Tseng MC (2008) Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischaemic stroke. Cochrane Database Syst Rev (3):CD000119 Sherman DG, Albers GW, Bladin C et  al (2007) The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison. Lancet 369:1347–1355 Simosa HF, Petersen DJ, Agarwal SK et al (2007) Increased risk of deep venous thrombosis with endovascular cooling in patients with traumatic head injury. Am Surg 73:461–464 Skaf E, Stein PD, Beemath A et al (2006) Fatal pulmonary embolism and stroke. Am J Cardiol 97:1776–1777 Tapson VF (2008) Acute pulmonary embolism. N Engl J Med 358:1037–1052 Vergouwen MD, Roos YB, Kamphuisen PW (2008) Venous thromboembolism prophylaxis and treatment in patients with acute stroke and traumatic brain injury. Curr Opin Crit Care 14:149–155 Young T, Tang H, Aukes J, Hughes R (2007) Vena caval filters for the prevention of pulmonary embolism. Cochrane Database Syst Rev (4):CD006212

Chapter 33

Neurocritical Illness During Pregnancy and Puerperium Chere Monique Chase and Cindy Sullivan

Introduction ■

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Critical care support and admission to an ICU is a relatively infrequent occurrence during pregnancy and the postpartum period Retrospective analyses of hospital admissions and complication rates indicate that 0.11–1.1% of deliveries are complicated by maternal ICU admission Patient demographics and hospital type clearly vary and affect outcomes differently; therefore, understanding the true risk of obstetric complications is somewhat difficult Literature suggests that these complications may account for most or only a portion of ICU admissions in pregnant patients (i.e., 19–93%); however, it is clear that maternal morbidity and mortality can be substantial when pregnant women require critical care In one study, 71% of obstetric patients transferred to the ICU required ventilatory support; other studies that indicate mortality ranges from 5 to 20% Treatment of critically ill pregnant women is challenged by limited information regarding safety profiles of therapeutic agents and the necessity to simultaneously manage mother and pregnancy viability Survival depends on care algorithms that allow for early detection of maternal problems and prompt referral to tertiary centers with ICUs Proactive and aggressive measures, including optimal cardiopulmonary management, minimize the incidence of multiorgan failure and mortality

C.M. Chase, MHS, MD (*) Forsyth Comprehensive Neurology, 2025 Frontis Plaza Boulevard, Greystone Professional Center, Suite 102, Winston-Salem, NC 27103, USA e-mail: [email protected] C. Sullivan, RN, MN, ANP-C, CNRN Neurocritical Care Program, Novant Health Systems, Forsyth Medical Center, Winston-Salem, NC, USA A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_33, © Springer Science+Business Media, LLC 2011

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Admission criteria for appropriate triage are essential; decisions may be based on several models (which utilize prioritization) or diagnostic and objective parameters The American College of Critical Care Medicine summarized qualifications for ICU admission; this diagnostic model (Table 33.1) uses specific conditions or diseases to determine appropriateness of ICU admission General criteria for admission to an obstetric intermediate care unit are listed in Table 33.2

Table 33.1  Diagnosis model for ICU admission of pregnant women (American College of Critical Care Medicine) System Diagnosis Cardiac Acute myocardial infarction with complications, cardiogenic shock, complex dysrhythmias, acute congestive heart failure with pulmonary failure, hypertensive emergencies, unstable angina, cardiac arrest, cardiac tamponade, dissecting aortic aneurysms, complete heart block Pulmonary Acute respiratory failure, hemodynamically unstable pulmonary emboli, respiratory deterioration/failure in acute- or intermediate-care patients that may or may not require intubation, massive hemoptysis Neurologic Acute stroke with altered mental status, coma, intracranial hemorrhage, subarachnoid hemorrhage, meningitis with altered mental status, central nervous system or neuromuscular disorders with declining neurologic or pulmonary function, status epilepticus, brain death, vasospasm, traumatic brain injury Drug ingestion and overdose Drug ingestion with hemodynamic instability, altered mental status, and/or seizures Gastrointestinal disorders Gastrointestinal bleeding (including hypotension, angina, persistent bleeding, or with comorbid conditions), fulminant hepatic failure, severe pancreatitis, esophageal perforation Endocrine Hemodynamic instability with diabetic ketoacidosis (altered mental status, respiratory insufficiency, or severe acidosis), thyroid storm or myxedema coma, hyperosmolar state with coma, adrenal crises, severe hypercalcemia with altered mental status, hypo/hypernatremia with seizures, altered mental status, hypo/hypermagnesemia, hypo/ hyperkalemia with dysrhythmias or muscular weakness, hypophosphatemia with muscular weakness Surgical Postoperative patients who require hemodynamic monitoring/ ventilatory support or extensive nursing care Miscellaneous Septic shock, hemodynamic monitoring, clinical conditions that require ICU-level nursing care, environmental injuries (lightning, near drowning, hypo/hyperthermia), new/ experimental therapies with potential for complications Adapted from Guidelines for Intensive Care Unit Admission, Discharge and Triage. Crit Care Med 27(3):633–638

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Table 33.2  Criteria for obstetrical admission to ICU Intermediate care unit

Obstetric complications – severe preeclampsia, severe eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets), severe hemorrhage and/or coagulation disorders, acute fatty liver of pregnancy, sepsis Surgical or anesthesia complications Medical or surgical disorders – diabetic ketoacidosis, thyrotoxicosis, hemofiltration/plasmapheresis, cholecystitis, pancreatitis, appendicitis Medical-surgical intensive care unit Mechanical ventilation, inotropic drugs, life-threatening dysrhythmia, coma Data from Zeeman GG (2006) Obstetric critical care: a blueprint for improved outcomes. Crit Care Med 34:S208–S214

Neurologic Conditions in Pregnancy ■

Mental status, coma, and seizure ♦ General medical problems can complicate and, in some instances, exacerbate

during pregnancy, resulting in neurologic complications ♦ ICU studies suggest that up to 50% of critically ill obstetric patients have

neurologic involvement, including altered mental status, coma, seizures, and paralysis (Tables 33.3–33.5) ■

Intracranial hemorrhage (ICH) ♦ ICH, subarachnoid and/or intracerebral, during pregnancy is rare but results

♦

♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

in significant maternal and fetal mortality or serious neurologic morbidity (Table 33.6) Rupture of an intracranial vascular anomaly (e.g., aneurysm or arteriovenous malformation (AVM)) accounts for >50% of all cases of ICH during pregnancy ICH from aneurysms is most commonly in the subarachnoid space and less commonly in intraparenchymal and intraventricular spaces AVMs bleed most often in the intraparenchymal space Eclampsia is the second most common cause of ICH in the gravid patient 40% of fatal eclamptic patients are found to have ICH Other less common causes include systemic coagulopathy, trauma, and intracranial tumors The clinical features and presentation of ICH in the obstetric population are similar to those in the general population Signs and symptoms are headache, nausea, vomiting, stiff neck, photophobia, seizures, and decreased level of consciousness Severity of subarachnoid hemorrhage can be scored using the same grading systems that are used in the general population (e.g., Hunt & Hess scale, Fisher Grade, and World Federation of Neurological Surgeons)

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Table 33.3  Common causes of altered mental status and coma Etiology Differential diagnoses Vascular Cerebral infarction, intracerebral hemorrhage, cerebral venous sinus thrombosis, subarachnoid hemorrhage, hypertensive encephalopathy Infections Bacterial meningitis, septic encephalopathy, cerebral malaria Intracranial space-occupying Gliomas, meningiomas, acoustic neuromas, pituitary tumors, lesions tuberculoma Metabolic disorders Hypoglycemia, hepatic encephalopathy, hyponatremia and other electrolyte abnormalities, acute intermittent porphyria Drugs and toxins Magnesium sulfate, sedative overdose, ethanol, illicit drug abuse, poisoning Miscellaneous Epilepsy, eclampsia, thrombocytopenic purpura, postpartum pituitary necrosis Adapted from Karnad DR, Guntupalli KK (2005) Neurologic disorders in pregnancy. Crit Care Med 33(10 suppl):S362–S371 Table 33.4  Common causes of seizure in pregnancy Pre-existing epilepsy Review past medical history New-onset seizures with Mass lesions normal blood pressure • Vascular malformations • Benign and malignant tumors • Cerebral abscess Infectious disorders • Viral • Bacterial • Parasitic infestations • HIV Cerebrovascular complications • Cerebral infarction • Cerebral hemorrhage • Subarachnoid hemorrhage • Cerebral venous thrombosis • Cerebral edema Metabolic disorders • Hypernatremia and hyponatremia • Hypoglycemia and hyperglycemia • Hypocalcemia • Hepatic failure • Central stimulants (e.g., cocaine, theophylline) Eclamsia New-onset seizures with hypertension Malignant hypertension Adapted from Karnad DR, Guntupalli KK (2005) Neurologic disorders in pregnancy. Crit Care Med 33(10 suppl):S3632–S3671, and Kaplan PW (1999) Neurological issues in eclampsia. Rev Neurol 155(5):335–341 ■

Preeclampsia and eclampsia ♦ Preeclampsia is a form of toxemia of pregnancy characterized by albuminuria

and hypertension ♦ If convulsions occur before, during, or shortly after childbirth, the syndrome

is classified as eclampsia

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Table 33.5  Common causes of paralysis in pregnancy other than cortical injury Spinal cord Trauma Demyelination Multiple sclerosis Acute transverse myelitis Peripheral nerve Guillain–Barré syndrome Porphyria Neuromuscular junction disorders Myasthenia gravis exacerbation Data from Karnad DR, Guntupalli KK (2005) Neurologic disorders in pregnancy. Crit Care Med 33(10 suppl):S362–S371 Table 33.6  Differential diagnosis of intracranial hemorrhage Vascular Aneurysm Arteriovenous malformations Intracranial venous or dural sinus thrombosis Intracranial arterial occlusion Pituitary apoplexy Mass Tumors Abscess Other space-occupying lesions Inflammatory/immune Meningitis Encephalitis Demyelinating disease Obstetric Eclampsia

♦ Eclampsia is the disorder most frequently confused with ICH from aneurysms

and AVMs during pregnancy; however, hypertension and albuminuria are two cardinal features of eclampsia ♦ Important laboratory values utilized to differentiate primary ICH from eclampsia include evidence of systemic hemolysis, elevated liver enzyme concentrations, and low platelet counts (HELLP) syndrome (Table 33.7) ♦ HELLP syndrome is more likely to occur when hypertension or preeclampsia is diagnosed before 34 weeks (Table 33.8) ♦ Preeclampsia and eclampsia also may be associated with a variety of liver diseases other than the HELLP syndrome including hepatic rupture, hepatic hematoma, and hepatic failure

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Table 33.7  Hallmarks of HELLP syndrome Hemolysis Diagnosis requires at least two of the following: • Abnormal peripheral smear (schistocytes, burr cells) • Elevated serum bilirubin (³1.2mg/dL) • Low serum haptoglobin • Significant drop in hemoglobin levels, unrelated to blood loss Elevated liver enzymes • Aspartate aminotransferase or alanine aminotransferase at least the upper level of normal • Lactate dehydrogenase at least twice the upper level of normal; this value is also elevated in severe hemolysis Low platelets • <100,000/mm3 Data from Sibai BM (April, 2005) A practical plan to detect and manage HELLP syndrome. OBG Manag 52–69

Table 33.8  Conditions that heighten the risk of HEELP • Preeclampsia-eclampsia early onset • Severe gestational hypertension • Early-onset hypertension or severe intrauterine growth restriction • Thrombophilias • Abruptio placentae • Nonspecific viral syndrome like symptoms • Right upper quadrant, epigastric, or retrosternal pain • Persistent nausea or vomiting in third trimester • Bleeding from mucosal surfaces • Unexplained hematuria or proteinuria • Petechial hemorrhages or ecchymosis Data from Sibai BM (April, 2005) A practical plan to detect and manage HELLP syndrome. OBG Manag 52–69

♦ In addition to supportive therapy, treatment for preeclampsia-related liver

disease consists of delivery of the fetus as soon as possible; Obrien et al. suggest that corticosteroids may also have a role in this particular setting ■

Epilepsy ♦ Epilepsy in pregnancy, especially in the critically ill, continues to represent a

challenging paradigm ♦ Consideration must be given to maternal and fetal risks associated with

uncontrolled seizures and to the potential teratogenic effects of antiepileptic drugs (AEDs) ♦ The physician must understand the risks of AEDs, the effects of pregnancy on seizure control, and of gestational effects on AED disposition

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♦ Uncontrolled tonic-clonic seizures are potentially hazardous to the mother

and assumed to be more harmful to the fetus than are AEDs ♦ Fetuses exposed to AEDs in utero are twice as likely to have congenital

malformations than are the general population ♦ Data have indicated higher malformation rates with exposure to valproic acid

♦ ♦ ♦ ♦

♦

♦

♦ ♦ ♦ ♦

compared with other major AEDs; this appears to be a dose-dependent relationship with higher risks at dosage levels >1,000mg/day In the critically ill patient, especially those in status epilepticus, the use of polypharmacy and polytherapy is likely Polytherapy with AEDs, compared to monotherapy, also appears to be associated with an increased risk of birth defects Most women with epilepsy have no change in seizure frequency during pregnancy, despite a decline in plasma drug concentration with AEDs Clinicians should note that patients who take lamotrigine and possibly oxcarbazepine can have break-through seizures; therefore, regular monitoring of drug concentrations during pregnancy is recommended General guidelines suggest monotherapy at lowest effective dosages to avoid generalized tonic-clonic seizures, risks to the fetus, and limited exposure through breast feeding The absolute risks have been reported as carbamazepine, 2.2%; lamotrigine, 3.2%; phenytoin, 3.7%; untreated women with history of seizures 3.5%, with VPA as the outlier at 6.2% (Harden, 2008) For women in childbearing years, it is important to have therapeutic management of seizures prior to conception Seizure freedom in 9–12 months before pregnancy is associated with seizure freedom during pregnancy Often delivery of the fetus is part of the solution for critically ill obstetric patients Clinicians must be aware that neonates born to epileptic mothers who take AEDs should receive 1mg of vitamin K intramuscularly at birth to decrease the risk of hemorrhagic disease in the newborn

Special Considerations for Critically Ill Obstetric Patients ■

Diagnostics ♦ Imaging with ultrasound is safe in all trimesters of pregnancy; safety data for

MRI imaging is scant ♦ To date, no harmful effects have been reported to be associated with MRI

scanning during pregnancy, but some advise restricting to the second and third trimesters of pregnancy ♦ CT may be used during pregnancy when clearly indicated; the risk of exposure to the fetus is low in CT scans that do not involve the abdomen or pelvis

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♦ CT scans may be performed safely in any trimester of pregnancy; CT scans

of the abdomen and pelvis result in a maximum fetal dose of ~1–2rad • Although this is well below the threshold dose of 10–20rad for fetal loss or malformation, concerns regarding a small increased risk of childhood cancers in exposed infants have been raised

Prediction of Maternal Death ■

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Ultimately, the neurointensivist will have to prognosticate regarding morbidity and mortality of obstetric patients in the ICU Maternal mortality rates vary widely, depending on the country, type of hospital, available services, and personnel Several scoring systems are used in the critical care setting ♦ The acute physiologic and chronic health evaluation (APACHE) scoring sys-

♦ ♦

♦ ♦

tem, the simplified acute physiologic score (SAPS), and mortality prediction model (MPM) are the most frequently used scores Unfortunately, none of these scoring systems adjust for normal obstetric physiologic changes In that laboratory abnormalities in the obstetric population that may signal a sentinel event are not included in these scoring systems, their applicability may be limited In contrast, the scoring systems may also overestimate mortality risk in the critically ill pregnant patient As the neurocritical care literature expands, future studies to provide reliable and reproducible severity scales in pregnancy should be conducted

Key Points ■

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Treatment of critically ill pregnant women is challenged by limited information regarding safety profiles of therapeutic agents and the need to simultaneously manage mother and pregnancy viability Up to 50% of critically ill obstetric patients have neurologic involvement, including altered mental status, coma, seizures, and paralysis Rupture of an intracranial vascular anomaly (e.g., aneurysm or AVM) accounts for >50% of all cases of ICH during pregnancy Treatment of epilepsy during pregnancy requires careful consideration of maternal and fetal risks that are associated with uncontrolled seizures and of the potential teratogenic effects of AEDs Eclampsia is the disorder most frequently confused with ICH from aneurysms and AVMs during pregnancy; however, hypertension and albuminuria are two cardinal features of eclampsia

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Suggested Reading Guidelines for intensive care unit admission, discharge, and triage. Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine. (1999) Crit Care Med 27:633–8 Afessa B, Green B et  al (2001) Systemic inflammatory response syndrome, organ failure, and outcome in critically ill obstetric patients treated in and ICU. Chest 120(4):1271–1277 Barton JR, Sibai BM.Care of the pregnancy complicated by HELLP syndrome. (1991) Obstet Gynecol Clin North Am. 18:165–79 Battino D, Tomson S (2007) Management of epilepsy during pregnancy. Drugs 67(18):2727–2746 Clardy PF, Reardon CC. Critical illness during pregnancy and the peripartum period. (2010) www. uptodate.com 2010 Dias MS (1994) Neurovascular emergencies in pregnancy. Clin Obstet Gynecol 37(2):337–354 Germain S, Wyncoll D, Nelson-Piercy C (2006) Management of the critically ill obstetric patient. Curr Obstet Gynecol 16:125–133 Harden CL (2008) Antiepileptic drug teratogenesis: what are the risks for congenital malformations and adverse cognitive outcomes? Int Rev Neurobiol 83:205–213 Harden CL, Sethi NK (2008) Epileptic disorders in pregnancy: an overview. Curr Opin Obstet Gynecol 6:557–562 Kaplan PW (1999) Neurological issues in eclampsia. Rev Neurol 155(5):335–341 Karnad DR, Guntupalli KK (2005) Neurologic disorders in pregnancy. Crit Care Med 33(10 suppl):S362–S371 Male DA, Stockwell M, Jandowski S (2000) Critical care in obstetric infections. Curr Obstet Gynecol 10:196–201 Martin SR, Foley MR (2006) Intensive care in obstetrics: an evidenced-based review. Am J Obstet Gynecol 195(3):673–689 Mallampalli A, Guy E (2005) Cardiac arrest in pregnancy and somatic support after brain death. Crit Care Med 33(10):S325–S331 Nasraway SA, Cohen IL, Dennis RC et al (1998) Guidelines on admission and discharge for adult intermediate care units. American College of Critical Care Medicine of the Society of Critical Care Medicine. Crit Care Med 26(3):607–610 O’Brien JM, Milligan DA, Barton JR (2000) Impact of high-dose corticosteroid therapy for patients with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Am J Obstet Gynecol 183(4):921–924 Price LC, Slack A, Nelson-Piercy C (2008) Aims of obstetric critical care management. Best Pract Res Clin Obstet Gynaecol 22(5):775–799 Raps EC, Galetta SL, Flamm ES (1994) Neuro-intensive care of the pregnant woman. Neurol Clin 12(3):601–611 Sibai BM, Coppage MD (2004) Diagnosis and management of women with stroke during pregnancy/postpartum. Clin Perinatol 31:853–868 Williams J, Mozurkewich E, Chilimigras J et  al (2008) Critical care in obstetrics: pregnancyspecific conditions. Best Pract Res Clin Obstet Gynaecol 22(5):825–846 Zeeman GG (2006) Obstetric critical care: a blueprint for improved outcomes. Crit Care Med 34:S208–S214 Zeeman GG, Wendel GD Jr, Cunningham FG (2003) A blueprint for obstetric critical care. Am J Obstet Gynecol 188(2):532–536

Chapter 34

Brain Death and Organ Donation Alexander Y. Zubkov and Eelco F.M. Wijdicks

Basic Principles ■

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In the US, the Harvard Ad Hoc committee and the Presidents Commission in 1981 defined criteria for brain death in 1968, which were later codified in the Uniform Determination of Death Act (UDDA) in 1981 The UDDA reads: “An individual who has sustained either: (1) irreversible cessation of circulatory and respiratory functions or (2) irreversible cessation of all functions of the entire brain, including brain stem, is dead; A determination of death must be made in accordance with accepted medical standards” A determination of brain death is left to the discretion of the physician. In the US the examination is usually performed in accordance with the guidelines proposed by published by the American Academy of Neurology In general, the diagnosis of death by neurologic criteria requires ♦ Clinical and radiographic evidence for catastrophic and irreversible brain

injury ♦ Exclusion of confounding factors ♦ Comprehensive assessment to evaluate the absence of any brain function

A.Y. Zubkov, MD, PhD Stroke Center, Fairview Southdale Hospital, Minneapolis Clinic of Neurology, Rochester, MN, USA E.F.M. Wijdicks, MD, PhD (*) Department of Neurology and Neurological surgery, Mayo Clinic School of Medicine, 200 First Street SW, Rochester, MN 55905, USA e-mail: [email protected] A. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, DOI 10.1007/978-1-4419-6842-5_34, © Springer Science+Business Media, LLC 2011

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Clinical Criteria for Brain Death ■

Confounding factors should be excluded: ♦ No prior sedation with medications, illegal drugs or any lingering effects

• Of note, hypothermia significantly slows the metabolism of such medications as lorazepam and fentanyl • A reasonable guideline is to calculate 5–7 times the elimination half-life in hours and allow that time to pass before clinical examination is performed • Examples of long elimination half-life medications are phenobarbital (100 h), diazepam (40 h), amitriptyline (24 h), primidone (20 h), lorazepam (15 h), and fentanyl (6 h). Half-life of commonly used midazolam is only 3 h • The legal alcohol limit for driving (blood alcohol content 0.08%) is a practical threshold, and below this level, it is acceptable to determine brain death ♦ Absence of neuromuscular blockade (defined by the presence of four twitches

with a train of four, with maximal ulnar nerve stimulation) • Absence of severe electrolyte, acid base, or endocrine disturbances (defined by marked acidosis or any substantial deviation from the normal values) ♦ Core temperature >36°C

• Patients who have lost all brain function become hypothermic but rarely with a core temperature <35°C ♦ Systolic blood pressure >90 mmHg

• The sudden appearance of hypotension is virtually always the first sign of transition to brain death • Brain-dead patients do not have any physiologic variability in pulse (as a result of loss of vagal function) ♦ CT scan should demonstrate massive brain destruction

• Abnormalities may include large mass and brain tissue shift, multiple hemorrhagic lesions, or diffuse cerebral edema with obliteration of basal cisterns • CT scan can be initially normal if patient is imaged very early after cardiopulmonary arrest ♦ Many patients with anoxic-ischemic brain injury do not fulfill brain death

criteria • In patients with anoxic-ischemic encephalopathy who eventually fulfill those criteria, early edema or hypodensity in thalami, caudate nuclei, and basal ganglia is commonly present • Even neuroimaging findings of severe brain injury do not exclude search for potential confounders

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♦ The following neurologic tests must be performed:

• Evaluation of consciousness; patient must be comatose, unresponsive to verbal or painful stimuli ▲ Standard noxious stimuli – compression of the supraorbital nerves,

forceful pressure to the nail bed, or bilateral temporomandibular joint compression ▲ Eye opening to noxious stimuli must be absent ▲ No nonreflexive motor responses are observed ▲ Spinal reflexes may be preserved and are still compatible with brain death. These are uncommon but include triple flexion responses, finger flexion, head turning, and slow arm lifting ♦ Evaluation of pupillary responses; pupils should be mid-position (4–6 mm)

and must be unresponsive to light • Magnifying glass should be used when there is an uncertainty about reactivity of pupils • Atropine used during cardiopulmonary resuscitation may cause pupillary dilation ♦ Evaluation of corneal reflexes; must be absent bilaterally ♦ Evaluation of oculocephalic reflexes (doll’s eyes); must be absent bilaterally

• Produced by fast turning of the head to both sides; will not produce any ocular movement ♦ Evaluation of oculovestibular response (cold calorics) – must be absent

• The head is elevated 30°; ~50 mL of ice water is infused in the external auditory canal. No eye movements are observed. Patient is usually monitored for 2 min after testing to ensure no delayed responses • Pen markers on the lower eyelids at the level of the pupils may be useful to exclude minimal eye movements ♦ Evaluation of gag and cough reflexes – must be absent

• Gag reflex might be tested by movement of the endotracheal tube, and cough reflex should be tested by deep bronchial suctioning • Gag reflex is very unreliable in the intubated patient ♦ Apnea test (passive oxygen-diffusion method)

• No breathing drive with CO2 challenge • Systolic blood pressure should be >90 mmHg or supported by vasopressors above that level • Preoxygenation with 100% oxygen for at least 10 min • Obtain baseline ABG and confirm normal PaCO2 and increased PaO2 (>150 mmHg)

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• Reduce positive end-expiratory pressure to 5 cmH2O and observe for deoxygenation • Disconnect ventilator • Oxygenate patient with 100% oxygen at 6 L/min by placing catheter through endotracheal tube to the level of the carina • Monitor for respiration movements by observation and palpation of the chest and abdomen • Normally, Pa increases at the rate of 3 mmHg/min; therefore, allow ~8 min to increase PaCO2 by 20 mmHg from baseline • Monitor oxygen saturation and blood pressure. Significant hypotension or hypoxia may lead to early termination of apnea test • Repeat ABG to confirm Pa increase ▲ PaCO2 should rise above 60 or 20 mmHg above baseline

• Reconnect patient to ventilator ▲ If patient is unable to tolerate or complete the apnea test, an ancillary

test is required ▲ If spontaneous respirations occur during test, test can be repeated in

several hours

Ancilary Tests for Brain Death ■

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Ancillary tests are required in children (different requirements in different age brackets (Fig. 34.1) These tests should not be used to diagnose brain death CT angiogram, CT perfusion and evoked potentials are poorly validated tests In adults, ancillary test are advised when: ♦ ♦ ♦ ♦

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Patient is unable to tolerate apnea test Patient has high cervical injury, precluding apnea testing as useful Patient is a known CO2 retainer Parts of the clinical evaluation are unreliable due to facial trauma

The experience with Electroencephalography is maintained but arti facts are problematic ♦ No electrical activity and lack of reactivity to somatosensory or audiovisual ♦ ♦ ♦ ♦

stimuli should be demonstrated A minimum of eight scalp electrodes should be used Interelectrode impedance should be between 100 and 10,000 W Integrity of the entire recording system should be tested Distance between electrodes should be at least 10 cm • Sensitivity should be increased to 2 mV for 30 min • High-frequency filter settings should not be set below 30 Hz, and the lowfrequency setting should not be set above 1 Hz

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Fig. 34.1  Brain death diagnosis and guidelines for confirmatory testing. *Evidence preferably based on CT scan or cerebrospinal fluid exam. **Confirmatory test such as cerebral angiography, nuclear scan, or transcranial-Doppler ultrasonography may obviate observation over time. ***Criteria vary worldwide. PaCO2 partial pressure of arterial CO2; EEG electroencephalogram. From Wijdicks EFM (2010) The practice of emergency and critical care neuorology. Oxford University Press, Oxford

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Transcranial-Doppler ultrasonography is an easy bed test ♦ Small systolic peaks in early systole without diastolic flow or reverberating flow ♦ Complete absence of flow might be not diagnostic because ~10% of the popu-

lation does not have adequate ultrasonographic windows ♦ Should be bilateral insonation through temporal windows (carotid system)

and through suboccipital windows (vertebral arteries) ■

Cerebral scintigraphy is more ♦ Isotope should be injected within 30 min after its reconstitution

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A.Y. Zubkov and E.F.M. Wijdicks

♦ A static image of 500,000 counts should be obtained immediately after injec-

tion, at between 30 and 60 min later ♦ A correct IV injection should be confirmed, with additional images of the

liver demonstrating uptake (optional) ♦ No isotope intake within the intracranial circulation (hollow skull phenomenon) ♦ No tracer in superior sagittal sinus ■

Conventional cerebral angiography is the a gold standard of ancillary tests ♦ Contrast media should be injected selectively in both posterior and anterior

circulation ♦ No intracerebral filling at the level of the carotid bifurcation or circle of

Willis ♦ External carotid circulation should be patent

Documentation ■

■

■

The time of death is determined by the time the arterial PaCO2 reached the target value If apnea test was aborted, brain death is the time at which the confirmatory test has been completed Complete documentation of comprehensive brain death evaluation is very important

Organ Donation ■

■

Organ procurement agencies will ask the family for organ donation and explain the logistics (decoupling principle) The organ procurement process is complicated by problems that emerge after brain death: ♦ ♦ ♦ ♦ ♦ ♦ ♦

■

Hypotension Diabetes insipidus Hypothermia Electrolyte abnormalities Lactic acidosis Coagulopathy Cardiac dysrhythmias

Two types of organ donation ♦ Donation after brain death ♦ Donation after cardiac death

34  Brain Death and Organ Donation

539

• Donation after cardiac death might be considered in patients with catastrophic injury who do not fulfill criteria for brain death • The assumption is that the patient will develop circulatory arrest within 45–60 min after extubation and discontinuation of medical therapy • The diagnosis of cardiac arrest is determined in the operating room, followed by organ-preserving measures

Key Points ■ ■

■

■

■

Brain death is a clinical diagnosis and cannot be replaced by a diagnostic test A single examination is sufficient for adults; in children, two examinations are necessary Time of death is determined by either time of completion of the apnea test or by confirmatory test Clinical examination should be documented carefully, and organ transplantation agency should be notified A patient who does not meet the criteria of brain death after a reasonable time of observation can be an organ donor after cardiac death

Suggested Reading Pollack M (2007) Clinical issues of brain death in children. Lancet Neurol 6:88–89 Robertson KM, Cook DR (1990) Perioperative management of the multiorgan donor. Anesth Analg 70:546–556 Wijdicks EFM, Vakelas PN, Gronseth GC, Greek DM, Evidence-based guideline update: Determining brain death in adults report of the quality standards subcommittee of the American Academy of Neurology; Neurology 210: 74 1911–1918 Wijdicks EFM (2001) The diagnosis of brain death. New Engl J Med 344:1215–1221 Wijdicks EFM (2002) The determination of brain death criteria worldwide: accepted fact but not much of a global consensus in diagnostic criteria. Neurology 58:20–25 Wijdicks EFM, Rabinstein AA, Manno EM, Atkinson J (2008) Pronouncing brain death: contemporary practice and safety of the apnea test. Neurology 71(16):1240–1244 Zubkov AY, Wijdicks EFM (2008) Plantar flexion and flexion synergy in brain death. Neurology 70:E74 (includes a video of the response)

Index

A Abdominal infections, 43–45 Acid-base disorders, 13–15 ACNP. See Acute care nurse practitioner Acromegaly, 182 Acute adrenal insufficiency, 33–35 Acute brain injury, multimodality monitoring ICU, 62, 63 monitoring techniques, 61–62 neuromonitoring tools (see Neuromonitoring tools, acute brain injury) Acute care nurse practitioner (ACNP), 269–271 Acute coronary syndromes (ACS), 95, 96 Acute disseminated encephalomyelitis (ADEM), 303–304 Acute encephalopathy diagnosis, 292–293 differential diagnosis, 293–295 epidemiology, 288 management, 295–297 nomenclature and classification, 287–288 pathophysiology conscious awareness, 290 etiologic classification, 289 inflammatory mechanisms, 291–292 injury pattern, 290 metabolic alterations, 290 neurotransmitter alterations, 290–291 selected syndrome ADEM, 303–304 alcohol withdrawal delirium, 302 brain dysfunction, 299 DDS, 299–300 endocrine disorders, 300–301 HE, 297–299 nonendocrine disorders, 301 PRES, 302–303

uremic encephalopathy, 299 Wernicke encephalopathy, 302 Acute myelopathy clinical presentation, 328 definitions, 323 diagnosis, 332–333 differential diagnosis, 331–332 epidemiology, 325–326 etiology, 324–325 ICU management autonomic dysreflexia, 337 cardiocirculatory, 336 corticosteroids, 337 gastrointestinal and nutritional, 336–337 respiratory, 334–336 pathophysiology, 326–327 physical examination, 330–331 prognosis, 337–339 spinal cord syndromes, 328–330 Acute pulmonary edema, 387 Acute respiratory distress syndrome (ARDS), 106–107 ADEM. See Acute disseminated encephalomyelitis Adrenal crises. See Acute adrenal insufficiency Advanced practial registered nurse (APRN) ACNP, 269–270 category, 268 CRNP, 269 education, 268 neurocritical care, 271–272 outcomes, 271 practice scope, 268 roles, 268–269 safety, 271 AED. See Antiepileptic drugs

541

542 a2 agonists action mechanism, 161 adverse reactions, 162 dosage recommendations, 162–163 drug-drug interactions, 162 ICU use, 162 pharmacokinetics and dynamics, 161–162 Airway management and mechanical ventilation ARDS network protocol and permissive hypercapnia, 106–107 cervical cord injury, 112–113 coma or brainstem injury, 113 extubation strategies, 110–111 gas exchange, 102 ICP and brain oxygenation, 106 controlled to spontaneous ventilation, 105 fiberoptic bronchoscopy, 106 HFV effects, 105 hyperventilation, 102–104 ventilatory modes effect, 104 intubation criteria, 99–101 NPE, 107–109 stunned or neurogenic myocardium, 109 ventilation control, 101–102 ventilator liberation, 110 weaning, type II respiratory failure, 111–112 Alcohol withdrawal delirium (AWD), 302. See also Delirium tremens Alexia without agraphia, 346 Alzheimers disease, 142 Analgesia classes, 147–148 pain assessment, 145–146 pain etiology, 146 Anaphylaxis, 196 Anesthesias, 437–438 Aneurysmal subarachnoid hemorrhage (aSAH), 492 Anterior circulation stroke syndromes, 345 Anticonvulsants, 461–463 Antidopaminergic agent, 436 Antiepileptic drugs (AEDs), 528 Antipsychotic drugs, 435 Anton syndrome, 345 Anxiolysis, 147–148 Apnea test, 535–536 Apneustic breathing, 6102 APRN. See Advanced practial registered nurse ARDS. See Acute respiratory distress syndrome

Index Arteriovenous malformation (AVM) resection, 186–187 Aspiration pneumonia, 40, 111, 203, 283 Ataxic breathing, 102 Atelectasis, 334 Atrial fibrillation, 342 Autonomic dysreflexia, 337 Autonomic nervous system, 477, 479 B Bacterial meningitis blood cultures, 411 CNS infection, 45–46 CSF analysis, 412 definitions and epidemiology, 409 predominant causative pathogens, 410 symptoms and signs, 411 treatment, 412–413 Bacterial ventriculitis, 47–48 Balint syndrome, 345 Benedikt syndrome, 346 Benzodiazepines (BDZ) action mechanism, 158 adverse reactions, 159–160 dosage recommendations, 160–161 drug–drug interactions, 160 ICU use, 159–160 pharmacokinetics and dynamics, 158 reversal, 159 sedation, analgesia, and neuromuscular paralysis, 499 seizure therapy, 160 Bispectral index monitor (BIS), 68, 154 Blood pressure (BP) management AHA/ASA stroke treatment, 117 CBF and CPP, 115 ICH, 116–117 ischemic stroke, 117–119 pathophysiology, 116 pharmacologic treatment, hypertension control, 119–120 Blood viscosity, 52 Botulism, 487–488 Bradycardia, 220 Brain death, 262 Brain death, organ donation ancillary tests, 536–538 confounding factors, 534–536 documentation, 538 neurologic criteria, 533 procurement process, 538 types, 538–539 Brain injury, cardiac arrest approach, 391

Index CA estimation, 389 neurologic complications management cerebral edema and elevated ICP, 399–400 cerebral perfusion and oxygenation, 398 glucose control, 400 seizure and myoclonus, 399 temperature elevation, 398–399 neuronal injury, 389–391 post-resuscitative period, 391–392 prognostication AAN guidelines, 400–401 post-CA factors, 401–405 pre-and intra-CA factors, 401 shivering management, 397 therapeutic hypothermia clinical impact and post-trail experience, 394 complications, 397–398 delivery, 394–397 neurologic prognostication, 405 and neuroprotective strategies, 392–394 Brain tumors diagnosis and differential diagnosis MRI/CT imaging, 459 MR spectroscopy (MRS), 459 PET, 459 progressive multifocal leukoencephalopathy, 460 epidemiology, 445 etiology, 445–456 management cerebral edema, 460–461 hydrocephalus, 461 pituitary insufficiency, 461–464 seizure treatment and prophylaxis, 461–463 tumor-related complications, 460 VTE, 464 symptoms and signs altered mental status, 458 headache, 456 intracerebral hemorrhage, 458 intracranial pressure elevation, 458 progressive focal neurologic deficits, 457 seizure, 456–457 treatment chemotherapy, 465–467 radiation therapy (XRT), 465 surgery, 464–465 Bronchospasm, 334–335 Bulbar muscles, 477, 479

543 C Carbidopa/Levodopa, 140 Carcinomatous meningitis, 446 Cardiac dysfunction diagnosis and differential diagnoses, 91–94 epidemiology, 89 etiology, 90 management, 94–96 outcomes, 96–97 signs and symptoms, 90–91 Cardiac ischemia, 222 Cardiopulmonary stabilization, 285 Cardiovascular dysfunction postoperative hypertension, 207–208 postoperative hypotension dysrhythmias, 206–207 hypovolemia, 205 myocardial ischemia, 205 vasodilation, 205 Carotid artery stenting (CAS) angiographic criteria, 219 antiplatelet regimen, 223 clinical characteristics, 219 follow-up, 223 intraoperative and postoperative management bradycardia, 220 groin hematoma and retroperitoneal hemorrhage, 222 hypotension, 220–221 ICH, 221–222 instant thrombosis, 222–223 ischemic stroke, 221 seizure, 221 patient preparation, 220 Carotid endarterectomy (CEA), 185–186, 219 Carotid occlusive disease carotid stenosis classification, 218 CAS (see Carotid artery stenting) clinical presentation, 218 etiology, 218 incidence, 217–218 management, 219 recurrent events, 218 Carotid stenosis, 342–343 Catheter-related infections, 48 CEA. See Carotid endarterectomy Central nervous system dysfunction delayed awakening, 210–211 delirium, 209–210 perioperative stroke, 212 Central parenteral nutrition (CPN), 137, 139, 140

544 Cerebral blood flow (CBF) and metabolism cerebral physiology, 51–53 monitoring cerebral microdialysis, 58–59 EEG and CPP, 56 imaging, 56–58 SjVO2 and PbrO2, 56–59 TCD, 56 pathophysiology, 53–55 Cerebral edema. See also Intracranial hypertension diagnosis and differential diagnoses, 77–79 etiology cytotoxic edema, 73–74 hydrocephalic and hydrostatic |edema, 74 vasogenic edema, 73 management cytotoxic edema, 80 vasogenic edema, 79–80 sedation and analgesia decompressive hemicraniectomy, 86–87 hypertonic solutions, 83 Lund concept, 87–88 mannitol, 82 signs and symptoms, 75–77 Cerebral herniation syndromes, 75–77, 80, 411 Cerebral metabolism, 52–53 Cerebral microdialysis, 58–59, 68–71 Cerebral perfusion pressure (CPP), 56, 57, 87, 115, 316 Cerebral salt wasting (CSW), 17–18 Cerebral scintigraphy, 537–538 Cerebral venous sinus thrombosis (CVST) anatomy anatomic variations, 424 normal anatomy, 423 occlusion, frequency, 424 clinical differential diagnosis, 426 complications intracranial hypertension, 431–432 persistent headache, 432 seizures and epilepsy, 432 diagnostic tests brain MRI, 427–428 CCA, 428–429 electroencephalography, 429 head CT, 427 lumbar puncture, 429 epidemiology, 421 etiology, 421–422

Index management monitoring, 429 systemic anticoagulation, 429–430 therapy, 431 thrombolysis, 430 outcome adults, 432–433 pediatric patients, 433 pathophysiology, 424–425 symptoms and signs, 425–426 Cerebrospinal fluid (CSF), 469 Certified registered nurse practitioner (CRNP), 268–270 Cervical cord injury, 112–113 Cervical corpectomy, 180 Chemotherapeutic agent, 465–467 Chest trauma, 335 Cheynes–Stokes breathing, 101, 102 Cholecystitis, 44 Claude syndrome, 346 Clinical diagnosis, 539 Closed unit design, 9 Clostridium tetani, 485 Cluster breathing, 102 CNS infections, 45–48 Coagulopathy, 196 Collaborative nursing practice APRN (see Advanced practial registered nurse) clinical nurse mentor, 267 nurse manager, 267–268 registered nurse, 265–266 Coma. See also Consciousness disorders assessment, 281–283 cardiopulmonary stabilization, 285 management, 283–284 prognosis, 284–285 Communicating hydrocephalus, 470 Community-acquired pneumonia, 39–40 Consciousness disorders definitions, 277–278 etiology, 279–281 terminology, 278–279 Contractures, 484 Conventional cerebral angiography (CCA), 428–429 CPN. See Central parenteral nutrition CPP. See Cerebral perfusion pressure Craniotomy for aneurysm clipping, 178–180 for ICH, 180 for tumor, 177–178 CSW. See Cerebral salt wasting

Index D Dandrolene, 436, 439 Deep venous thrombosis (DVT) clinical presentation, 508 diagnostic approach intermediate, high pretest probability, 511–512 Wells prediction rule, 511 diagnostic tests MRI venography, 510 venous Doppler ultrasound, 509 management acute ICH, 514 AIS, 513–514 VTE treatment (see VTE treatment) Dejerine–Roussy syndrome, 346 Delayed cerebral ischemia, 385 Delirium alcohol withdrawal, 302 altered mental status algorithm, 296 diagnosis, 148, 292–293 differential diagnosis, 293–295 epidemiology, 288 etiology, 149 injury pattern, 290 neurotransmitter alterations, 290–291 SPECT, 290 Delirium tremens, 302 Diabetes insipidus (DI) accurate fluid intake, 184 after pituitary surgery, 182–183 classic signs, 183 and hypernatremia, 19–20 postoperative, 183–184 Dialysis disequilibrium syndrome (DDS), 299–300 Dilated cardiomyopathy, 343 Drowsy, 278 Drug toxicity, 500–502 DSM-IV-TR criteria, 435–436 Dural sinuses, 423 Dysautonomia, 486 Dysphagia, 480 Dyspnea and respiratory distress, 258–259 Dysrhythmia, 91–92, 94–95, 206–207 E Early endotracheal intubation, 285 Eclampsia, 526–528 Electroencephalography (EEG), 56, 66, 403–404, 429, 536 Electrolyte and metabolic derangements acid-base disorders, 13–14

545 adrenal crises, 33–35 calcium, 25–26 electrolyte disorders, 15–21 Hashimoto encephalopathy, 31–32 magnesium, 23–25 metabolic disorders and endocrinopathies, 28–31 phosphate, 27–28 potassium, 21–23 primary acid-base disorders, 14–15 thyroid storm, 32–33 Electrolyte disorders, 15–21 Elevated cTI, 95–96 Embolectomy, 520 Emergent endovascular revascularization acute vessel occlusion, 225–226 efficacy, 226 end point and assessment, 226–227 interventional treatment, 223–224 intervention indications, 224–225 intracranial AVMS, 243–245 intraoperative and postoperative medical management, 229–230 nonpharmacologic techniques, 225–226 outcome predictors, 228 perioperative anesthetic consideration, 228–229 preoperative medical management, 228 procedural complications, 231–232 Qureshi grading system, 227–228 relative contraindications, 224–225 stenotic artery/dissection, 225 unruptured and ruptured intracranial aneurysms (see Intracranial aneurysms) Empyema, 42 Encephalitis definitions and epidemiology, 415–416 diagnosis, 417–419 management, 419 signs and symptoms, 416–417 Endocrine disorders absolute AI and diabetes mellitus, 301 Hashimoto encephalopathy, 300–301 myxedema, 300 thyroid storm, 300 Endocrinopathies, 28–31 Endovascular coiling, 234, 384 Enteral nutrition (EN). See also Parenteral nutrition (PN) aspiration, 135 formula composition, 131–133 formula selection, 131, 133–134 initiation, 134

546 Enteral nutrition (EN). See also Parenteral nutrition (PN) (cont.) location, 130–131 mechanical complications, 136 neurologic impairment, 129 oral intake, 136 potential contraindications, 129–130 timing, 130 tolerance, 134–135 Ependymomas, 368 F Fondaparinux, 514, 515 Fosphenytoin (fPHT), 500 G Gastric feeding, 134, 141 Gastrointestinal ulcer prophylaxis, 383 Generalized convulsive SE (GCSE) EEG presentation, 496–498 morbidity, 494–495 subtype, 490 Genetic syndromes, 445, 455–456 Groin hematoma, 222 Guillain–Barré syndrome (GBS), 475 H Hakim triad, 471 Hashimoto encephalopathy, 31–32, 300–301 Hemicraniectomy, 184–185 Hemolysis, elevated liver enzyme concentrations, and low platelet counts (HELLP) syndrome, 527–528 Hepatic encephalopathy (HE), 297–299 Herpes encephalitis (HSE). See also West Nile Virus (WNV) encephalitis diagnosis, 417 management, 419 pathophysiology, 416 signs and symptoms, 416 High-frequency ventilation (HFV), 105 Hospital-acquired pneumonia, 40–43 Hydralazine, 119, 120, 207, 208, 358 Hydrocephalus in brain tumor, 461 classification communicating hydrocephalus, 470 CSF, 469 diagnosis, 471–472 noncommunicating hydrocephalus, 470–471

Index NPH, 470 treatment, 472–473 epidemiology, 469 Hypercalcemia, 26, 154 Hypercapnia, 195 Hypercarbia, 10, 28 Hyperglycemia, 28–29, 139–140, 213–214, 400 Hyperkalemia, 23, 169, 439 Hypermagnesemia, 25, 478 Hypernatremia, 16, 19–20, 526 Hyperphosphatemia, 28 Hypertension. See Blood pressure (BP) management Hyperthermia, 32, 48, 213, 281, 440 Hyperventilation, 81–82, 102–104, 316 Hypocalcemia, 26, 526 Hypoglycemia, 29, 154, 285, 491, 526 Hypokalemia, 21–22, 24 Hypomagnesemia, 23–24 Hyponatremia, 16–21, 388 Hypophosphatemia, 27, 125, 280 Hypoplasia, 424 Hypotension, 195–196, 220–221 Hypothermia clinical impact and post-trail experience, 394 complications, 397–398 delivery, 394–397 in metabolic suppression, 86 neurologic prognostication, 405 and neuroprotective strategies, 392–394 shivering, 397 temperature abnormalities, 212 Hypovolemia, 18, 92–93, 205 Hypoxemia, 195 Hypoxia, 284, 285 I ICP elevation, 458 ICP waveform analysis, 79 Ideal body weight (IBW), 124 Infective endocarditis, 42–43 Inferior sagittal sinus, 423 Instant thrombosis, 222–223 Intracerebral hemorrhage (ICH) BP management, 116–117 clinical presentation, 355 diagnosis, 355–356 epidemiology, 353 indication, 356–357 management emergent, 357

Index IV medication, 358–359 primary injury, 358 secondary injury, 359 pathophysiology, 353–355 prognosis, 357 recurrence prevention, 360–362 surgical options, 359 Intracranial aneurysms ruptured classification, 238 epidemiology, 237 follow-up, 242–243 intraprocedural management, 239–240 post-procedural management, 240–242 pre-procedural care, 238 risk factors, 237–238 symptomology, 238 unruptured epidemiology, 232 follow-up, 235, 237 intra-procedural management, 235 patient preparation, 234 patient selection, 233–234 post-procedure care, 235, 236 pre-procedure care/counseling, 233 risk factors, 232–233 symptomology, 233 treatment risks, 234 Intracranial atherosclerosis, 343 Intracranial AVMS current treatments, 243 endovascular embolization, 244 follow-up, 245 operative management, 244 postoperative care, 244–245 preoperative management care, 244 Intracranial hemorrhage (ICH), 146, 211, 318, 525–528 Intracranial hypertension. See also Cerebral edema diagnosis and differential diagnoses, 77–79 etiology, 74–75 management, 80–81 sedation and analgesia hyperventilation, 81–82 metabolic suppression, 84–86 osmotic therapy (see Osmotic therapy) signs and symptoms, 75 Intracranial mass lesions, 101 Intracranial neoplasm, 459 Intracranial pathology, 28 Intracranial pressure (ICP) and brain oxygenation, 106 controlled to spontaneous ventilation, 105

547 fiberoptic bronchoscopy, 106 HFV effects, 105 hyperventilation, 102–104 ventilatory modes effect, 104 Intraoperative brain swelling, 193–194 Intraoperative hemorrhage, 194 Intraventricular hemorrhage (IVH) clinical presentation, 367 epidemiology, 365–366 management, 368 pathophysiology, 367 Ischemic stroke and BP, 117–119 and CBF, 55 complications, 350–351 definitions, 341 emergent endovascular procedures types, 225–226 epidemiology, 341 etiology, 342–344 indications, 224 interventional treatment, 223–224 investigations, 347 management, 349–350 relative contraindications, 224–225 risk factors, 342 subsequent care, 351 subtypes, 342 anterior circulation stroke syndromes, 345 brainstem syndromes, 346 posterior circulation stroke syndromes, 345–346 symptoms, 344 treatment, 348–349 J Jugular venous oxygen saturation (SjVO2), 56–59, 68, 69 L Labetalol, 119, 120, 207 Lacunar strokes, 343 Lacunar syndromes, 346 Laser-Doppler flowmetry (LDF), 70 Leapfrog ramification, 8 Leptomeninges, 446 Life-sustaining therapies advance directives, 250–251 comfort measures goals, 255–256 communicating prognosis communicating obstacles, 252–253

548 Life-sustaining therapies (cont.) ethics consultation, 253 medical futility, 251 prognostic information, 251 self-fulfilling prophecy, 251 dosing and titration, medications, 261 ethical issues, 247–248 informed consent, 248–250 managing symptoms anxiety, 260 delirium, 260 dyspnea and respiratory distress, 258–259 fever, 260 hunger and thirst, 260 nausea and vomiting, 260 NMBAs, 260–261 pain, 258 palliative care, 255 specific situations, 262–263 withdrawal, 254 pitfall, 256–258 standardized order forms, 256 ventilatory support, 261–262 Low-grade gliomas, 456 Low-molecular-weight heparin (LMWH) prophylaxis regimens dalteparin (fragmin), 514 enoxaparin (lovenox), 514 fondaparinux, 514 vs. vitamin K, 515–516 VTE prevention AIS, 513–514 elective neurosurgery, 513 traumatic brain injury, 513 warfarin, 515 Lumbar catheter, 78–79 Lumbar puncture, 377, 379, 429 Lung abscess, 42 M Malignant hyperthermia (MH) differential diagnoses, 438–439 epidemiology, 437–438 management, 439–440 postoperative care, 196 symptoms and signs, 438 Mannitol, 82–84, 192–193, 315, 461 Mean arterial pressure (MAP), 52, 57, 115 Meningitis definitions and epidemiology, 409–410 diagnosis, 411–412

Index etiology, 410 management, 412–415 signs and symptoms, 410–411 Meta-analysis, 7 Metabolic disarray, 28. See also Toxic disarray Metabolic disorders, 28–31 Metastatic tumor, 368 Multimodality monitoring, acute brain injury ICU, 62, 63 monitoring techniques, 61–62 neuromonitoring tools BIS, 68 brain temperature, 67 cerebral microdialysis, 68–71 continuous EEG (cEEG), 67–68 EEG, 66 ICP monitoring, 64, 65 LDF and NIRS, 70 PbtO2, 66–67 pupillometry, 67 serial neurologic exam, 62, 64 SjVO2, 68, 69 TCD, 64–66 thermal dilution flowmetry, 70 Multimodality neuromonitoring, 60 Multi-slice CT angiography, 426 Myasthenia gravis (MG), 481–483 Myocardial ischemia, 93, 146, 178, 205, 207 Myxedema coma, 30–31, 300 N Narcotics action mechanism, 155 adverse reactions, 157 ICU use, 157 pharmacokinetics and dynamics, 155–156 sedative-hypnotics, 154 tolerant patients, 157 Near-infrared spectroscopy (NIRS), 70 Neurocritical illness criteria, obstetrical admission, 524–525 critically ill obstetric patients, 525 diagnosis model, admission, 524 maternal death, prediction, 530 maternal ICU admission, 523, 524 pregnancy epilepsy, 528–529 ICH, 525–526 mental status, coma, and seizure, 525–527

Index preeclampsia and eclampsia, 526–528 Neurogenic myocardium. See Stunned myocardium Neurogenic pulmonary edema (NPE), 107–109 Neurogenic stunned myocardium (NSM), 90, 95–96 Neurointensivists, 7–9 Neurointerventional procedures carotid occlusive disease (see Carotid occlusive disease) emergent endovascular revascularization (see Emergent endovascular revascularization) Neuroleptic malignant syndrome (NMS) differential diagnosis, 436 epidemiology, 435 management, 436–437 symptoms and signs, 435–436 Neuroleptics action mechanism, 163 adverse reactions, 164 dosage recommendations, 164–165 drug–drug interactions, 164 ICU use, 163–164 pharmacokinetics and dynamics, 163 Neurologic test, 535 Neuromonitoring tools, acute brain injury BIS, 68 brain temperature, 67 cerebral microdialysis, 68–71 continuous EEG (cEEG), 67–68 EEG, 66 ICP monitoring, 64, 65 LDF and NIRS, 70 PbtO2, 66–67 pupillometry, 67 serial neurologic exam, 62, 64 SjVO2, 68, 69 TCD, 64–66 thermal dilution flowmetry, 70 Neuromuscular blockade, 534 Neuromuscular blocking agents (NMBAs), 260–261 Neuromuscular disorders bedside assessment, 476–477 botulism pathophysiology, 487 treatment, 487–488 comprehensive ICU care, 476 critical illness neuropathy/myopathy epidemiology and risk factors, 483–484

549 presentation, 484 treatment and prognosis, 484–485 differential diagnosis, 477 GBS acute motor and sensory axonal neuropathy (AMSAN), 479 admission, NCCU, 480 electrophysiology, 480 epidemiology, 477 features, 477 ICU management, 481 intubation, 480 Miller–Fisher syndrome, 479 MG cholinergic crisis, 483 epidemiology, 481–482 features, 482 myasthenic crisis, 482–483 treatment, 483 prolonged neuromuscular blockade, 485 tetanus pathophysiology, 485–486 treatment, 486 ventilation mode/intubation sequence, 475 Neuromuscular paralysis common indications, 167–168 complications, 168 depolarizing agent, 168 myopathic disorders, 169 nondepolarizing agents, 168 pharmacology, 168 succinylcholine-induced hyperkalemia, 169 Neuroscience critical care unit (NCCU) costs, 11 goals and benefits, 3 hospital argument, 5–7 hospital financial analysis, 11 key components National Guideline Clearinghouse, 9–10 neurointensivists, 6 specialty-trained NCCU nursing, 9 national, 6–8 nutrition (see Nutrition, NCCU) postoperative care (see Postoperative care, NCCU) physician argument, 4–5 revenue sources, 10–11 Nicardipine, 119, 120, 207, 358 Nitroprusside, 119, 120 Nonaneurysmal SAH, 372 Noncommunicating hydrocephalus, 470–471

550 Nonconvulsive SE (NCSE) diagnosis, 495 EEG presentation, 495–498 effects, 495 SE Nonconvulsive SE (NCSE) (cont.) epidemiology, 489 subtype, 490 TBI, 491–492 Nonendocrine disorders ADEM, 303–304 AWD, 302 PRES, 302–303 septic encephalopathy, 301–302 Wernicke encephalopathy, 302 Nonketotic hypersmolar coma (NKHC), 28–29 Nonobstructive hydrocephalus. See Communicating hydrocephalus Normal-pressure hydrocephalus (NPH), 470 Nutrition, NCCU epidemiology and etiology, 123 management drug nutrient interactions, 140 enteral nutrition, 129–136 nutritional considerations, 140–142 parenteral nutrition, 136–140 signs and symptoms nutritional assessment components, 124 premorbid nutritional status, 124–129 O Obstructive hydrocephalus. See Noncommunicating hydrocephalus Oculovestibular response, 535 Organ donation, 263 Osmotic demyelination syndrome, 19 Osmotic therapy hypertonic saline, 83–84 mannitol, 82–83 rebound cerebral edema, 82 Oxygen tension in brain tissue (PbrO2), 56–59 P Paralytics, 169 Parenchymal brain tissue oxygen (PbtO2), 66–67 Parenteral nutrition (PN). See also Enteral nutrition (EN) additives, 138–139 administration, 139 complications, 139–140

Index CPN, 140 formulations, 137–138 indications, 136–137 monitoring and initiation, 139 Parkinson disease, 142 Passive oxygen-diffusion method. See Apnea test Patent foramen ovale (PFO), 343 Peduncular hallucinosis, 346 Pentobarbital, 85 Perimesencephalic nonaneurysmal hemorrhage (PMNAH), 377 Periodic lateralizing epileptic discharges (PLEDs), 496 Peritonitis, 43–44 Permissive hypercapnia, 107 PFO. See Patent foramen ovale Pituitary surgery acromegaly, 182 CSF leak, 184 diabetes insipidus (DI) (see Diabetes insipidus (DI)) PLEDs. See Periodic lateralizing epileptic discharges PMNAH. See Perimesencephalic nonaneurysmal hemorrhage Pneumonia, 334 Polytherapy, 529 Positive end-expiratory pressure (PEEP), 104, 107 Positron emission tomography (PET), 459 Post-concussive syndrome, 311 Posterior circulation stroke syndromes, 345–346 Posterior reversible encephalopathy syndrome (PRES), 302–303 Postoperative care, NCCU airway issues, 199–200 anaphylaxis, 196 anesthetics and anesthetic techniques fluid management, 192–193 hypnotic drugs, 188–189 neuromuscular blocking drugs, 189–190 opioids, 187–188 perioperative airway issues, 191–192 regional awake, 190–191 volatile anesthetic agents, 190 arteriovenous malformation (AVM) resection, 186–187 cardiovascular dysfunction (see Cardiovascular dysfunction) carotid endarterectomy, 185–186 CNS dysfunction (see Central nervous system dysfunction) coagulopathy, 196

Index craniotomy, 185 aneurysm clipping, 178–180 cervical corpectomy, 180–181 ICH, 180 multilevel thoracic fusion, 181–182 diet order, 175 epilepsy surgery, 185 general medical care, 174 hemicraniectomy, 184–185 hypercapnia, 195 hyperglycemia, 213–214 hypertension, 196 hypotension, 195–196 hypoxemia, 195 indwelling tubes, 175–176 intraoperative brain ischemia, 193 intraoperative brain swelling, 193–194 intraoperative hemorrhage, 194 intraoperative injury, 197–198 intraoperative seizure, 194 laboratory study, 176 malignant hyperthermia (MH), 196 medication reconciliation, 176 OR to NCCU transport, 173–174 pain medications, 175 pituitary surgery acromegaly, 182 CSF leak, 16 diabetes insipidus (DI) (see Diabetes insipidus (DI)) POCD, 214–215 PONV, 198–199 prophylaxis, 176–177 pulmonary dysfunction (see Pulmonary dysfunction) sedation, 175 temperature abnormalities, 212–213 urinary and renal dysfunction, 208–209 VAE, 194–195 Postoperative cognitive dysfunction (POCD), 214–215 Postoperative nausea and vomiting (PONV), 198–199 Preeclampsia, 526–528 Premorbid nutrition assessment body mass index (BMI), 124–125 energy requirements, 126–129 fluid requirements, 128, 129 hepatic protein, 125–126 IBW, 124 malnutrition, 125 nitrogen balance and neurotrauma, 126 protein requirements, 128 weight loss, 125

551 PRES. See Posterior reversible encephalopathy syndrome Primary and secondary (noninfectious) causes, 37–38 Primary brain tumors, 445–455 Primary CNS vasculitis, 343 Propofol action mechanism, 165 adverse reactions, 166 cautionary note, 167 dose-dependent respiratory depression, 166 drug–drug interactions, 167 hypotension-vasodilation, 166 ICU use, 166 in metabolic suppression, 85–86 pharmacokinetics and dynamics, 165–166 potential anaphylactoid reactions, 166 Propofol-infusion syndrome, 93–94 Prosopagnosia, 346 Pseudomembranous colitis, 44 Pulmonary dysfunction gastric contents aspiration, 203–204 hypercapnia, 202 hypoxemia, 200–202 pneumothorax, 205 preexisting lung disease, 202–203 pulmonary edema, 204 pulmonary embolism, 204 Pulmonary edema, 204, 335 Pulmonary embolism (PE), 204 clinical presentation, 508 diagnostic approach intermediate, high pretest probability, 511–512 Wells prediction rule, 511, 512 diagnostic tests CT pulmonary angiography, 510 pulmonary angiography, 511 V/Q scan, 509–510 differential diagnosis, 508 management AIS, VTE prevention, 513–514 VTE treatment (see VTE treatment) management algorithms high clinical probability, 513 intermediate clinical probability, 513 low clinical probability, 512–513 risk stratification ABG, 518 cardiac biomarkers, 518–519 categories, 517 chest CT, 519 clinical evaluation, 517

552 echocardiogram, 518 EKG, 517–518 massive PE, treatment, 519–520 submassive PE, treatment, 520 Pulmonary thromboembolism, 335–336 R Radiation therapy (XRT), 465 Radiographic pulmonary edema, 91 Radioisotope cisternography, 471 Refractory hypotension, 91, 93, 96 Renal failure encephalopathy brain dysfunction, 299 DDS, 299–300 uremic encephalopathy, 299 Respiration patterns, 101–102 Respiratory muscles, 477, 478 Reticular activating system (RAS), 277 Retroperitoneal hemorrhage, 222 Revenue sources, 10–11 Rhabdomyolysis, 439 Ruptured intracranial aneurysms, 237–243 Ryanodine receptor (RYR), 437 S SAH. See Subarachnoid hemorrhage Secondary brain injury, 285 Second-impact syndrome (SIS), 311 Sedation anxiolysis, 14/–148 classes a2 agonists, 161–163 benzodiazepines (see Benzodiazepines) narcotics (see Narcotics) neuroleptics, 163–165 neuromuscular paralysis (see Neuromuscular paralysis) propofol, 165–167 delirium, 148–149 general issues, 145 need identification, 145 physiologic and brain function monitor, 149, 154 propofol (see Propofol) scoring systems, 149 therapy pharmacokinetics and dosing, 149, 152–153 pharmacologic profile, 149–151 physiologic etiologies, 149, 154 Seizure prophylaxis, 382–383 Septic encephalopathy, 301–302

Index Serotonin syndrome (SS) differential diagnoses, 441, 442 epidemiology, 440 management, 441–442 symptoms and signs, 440 Serum sodium, 16, 19 Shunt placement, algorithm, 472 SIADH. See Syndrome of inappropriate antidiuretic hormone secretion Sinusitis, 45 Somatosensory-evoked potential (SSEP), 403, 405 Spinal cord infarction, 326, 331 Spinal cord injury (SCI), 89, 94, 141–142 SSEP. See Somatosensory-evoked potential Staffing models, 8 Status epilepticus (SE) anatomy, 490 definition, 489 drug interactions, 502–503 drug toxicity, 500–502 EEG presentation, GCSE and NCSE, 496–498 epidemiology, 489 etiologies of seizures aSAH, 492–493 cerebral neoplasms, 493 cerebrovenous sinus thrombosis, 493 neurologic (cortical) injury, 491, 492 non-neurologic injury, 491, 493 stroke, 492 traumatic brain injury (TBI), 491–492 in-hospital-based seizures, 493–494 medical and pharmacologic treatment, 500, 501 monitoring, 495–498 morbidity, 494–495 NCSE, 495 subtypes, 490 treatment first-line therapy, 499 second-line therapy, 499–500 Steroid-responsive encephalopathy associated with autoimmune thyroiditis (STEAT). See Hashimoto encephalopathy Stunned myocardium, 109 Stupor, 278, 281–283 Subarachnoid hemorrhage (SAH) cerebral blood flow, 55 definition, 371 diagnosis angiography, 378–379

Index head CT, 376–377 lumbar puncture, 377 epidemiology, 371–374 management operative, 383–384 postoperative, 384–388 preoperative, 380–383 signs and symptoms grading scales, 375, 376 headache, 374–375 mimics, 375 Surgical clipping, 383, 388 Surgical resection, 467 Sustained ICP elevation, 88 Symptomatic vasospasm, 384, 385 Syndrome of inappropriate antidiuretic hormone secretion (SIADH), 17, 18 Systemic inflammatory response syndrome (SIRS), 291 Systolic blood pressure, 534 T TBI. See Traumatic brain injury TCD. See Transcranial Doppler Telemetry monitoring, 91, 94, 231 Tentorial sinuses, 423 Tetanus, 485–486 Thermal dilution flowmetry, 70 Thoracic infections, 39–43 Thrombolysis, 519–520 Thyroid storm, 32–33, 300 Total parenteral nutrition. See Central parenteral nutrition (CPN) Toxic disarray, 170 Transcranial Doppler (TCD), 56, 64–66 Transcranial-Doppler ultrasonography, 537 Transverse myelitis epidemiology, 325–326 pathophysiology, 327 physical examination, 330 prognosis, 337–338 Transverse (lateral) sinuses, 423 Traumatic brain injury (TBI) in CBF, 54–55 clinical management examination, 312 focused neurologic, 312 fundamental concept, 314 imaging, 312, 314 sedation, 318 tissue oxygenation and metabolic monitoring, 314–315

553 epidemiology, 307–308 nutritional consideration, 140–141 pathogenesis, 308–309 prognosis, 319 taxonomy, 309–311 treatment autonomic dysfunction, 319 deep venous thrombosis, 318 gastrointestinal prophylaxis, 318 hemodynamics, 316 medical interventions, 315–316 nutrition, 317 prophylaxis with anticonvulsants, 318 sedation, 318 surgical interventions, 316 Treitz, 135 Tumor location, 467 U Uniform Determination of Death Act (UDDA), 533 Unremitting seizure activity, 494, 495 Unruptured aneurysms, 232–237, 374 Uremic encephalopathy, 299 Urinary and renal dysfunction, 208–209 Urinary tract infections, 44–45 V Vascular-metabolic coupling, 84 Vasospasm, 178, 242, 384–385 Veneus air embolism (VAE), 194–195 Venous thromboembolism (VTE). See also Deep venous thrombosis; Pulmonary embolism diagnostic approach, 464, 511–512 diagnostic tests contrast venography, 509 CT pulmonary angiography, 510 D-dimer, 509 MRI venography, 510 pulmonary angiography, 511 venous Doppler ultrasound, 509 V/Q scan, 509–510 epidemiology DVT, 505–506 PE, 505 management acute ICH, 514 AIS, 513–514 appropriate indications, 517 elective neurosurgery, 513

554 inferior vena cava (IVC) filters, 516–517 LMWH prophylaxis regimens, 514 traumatic brain injury, 513 VTE treatment (see VTE treatment) prevention, 464 Venous thromboembolism prophylaxis, 383 Ventilator associated pneumonia (VAP), 41–42, 230, 387 Vertebral/carotid dissection, 343 Viral encephalitis and CNS infection, 46–47 definitions and epidemiology, 415–416 diagnosis, 417–419 management, 419 signs and symptoms, 416–417 VTE treatment anticoagulation therapy, 464 bleeding complication, 515 catheter-directed thrombolysis, 516

Index fondaparinux, 515 heparin-induced thrombocytopenia, 516 IV heparin, 514 LMWH, 515–516 optimal duration, vitamin K, 516 warfarin, 515 W Wallenberg syndrome, 346 Warfarin, 515 Watershed infarcts, 343 Weber syndrome, 346 Wernicke encephalopathy, 302 West Nile Virus (WNV) encephalitis. See also Herpes encephalitis (HSE) diagnosis, 418–419 epidemiology, 416 management, 419 signs and symptoms, 417 Wisconsin algorithm, 473