handbook of neurocritical care

Handbook of Neurocritical Care

Anish Bhardwaj, MD, FAHA, FCCM, FAAN Marek A. Mirski, MD, PhDEditors

Handbook of Neurocritical Care

Second Edition

EditorsAnish BhardwajChairman Department of NeurologyTufts University School of MedicineProfessor of Neurology Neurological Surgery, and NeuroscienceNeurologist-in-ChiefTufts Medical Center Boston, MA, [email protected]

Marek A. MirskiVice-Chair, Department of Anesthesiology and Critical Care MedicineDirector, Neurosciences Critical Care DivisionChief, Division of Neuro AnesthesiologyDirector, Anesthesia Perioperative Clinical Research ProgramCo-Director, Comprehensive Stroke ProgramProfessor of Anesthesiology, Neurology, NeurosurgeryJohns Hopkins Medical Institutions Baltimore, MD, [email protected]

ISBN 978-1-4419-6841-8 e-ISBN 978-1-4419-6842-5DOI 10.1007/978-1-4419-6842-5Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2010934376

© Springer Science+Business Media, LLC 2011All 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)

v

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 manage-ment 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 state of thisrapidly 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.

the current

vii

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, diagnos-tic, and therapeutic modalities in a variety of brain and spinal cord injury para-digms. This growth and maturation are clearly exhibited by the emerging fellowship training programs at various facilities, the recently instituted subspecialty certifica-tion 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 interven-tions 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 pro-viders 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 neu-rocritical care. We have focused further on management algorithms for making and confirming the clinical diagnosis with appropriate ancillary radiologic and labora-tory tests and algorithms for managing acute neurologic diseases. Tables and illus-trations provide quick and easy bedside reference. At the end of each chapter, key points and references highlight essential elements and should serve as quick sum-maries of salient features. We hope that this second edition of the handbook

viii Preface

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 par-ticularly 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, FAANMarek A. Mirski, MD, PhD

ix

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 deci-sion 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 hyper-thermia, meningitis and encephalitis, and intraventricular hemorrhage. Useful algo-rithms, 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 of Neurology Harvard Medical School Vice Chair, Department of Neurology Beth Israel Deaconess Medical Center

xi

Contents

Part I General Principles of Neurocritical Care

1 Establishing and Organizing a Neuroscience Critical Care Unit ....... 3Marek A. Mirski

2 Electrolyte and Metabolic Derangements ............................................. 13Nikki Jaworski and Ansgar Brambrink

3 Fever and Infections ................................................................................ 37Neeraj Badjatia

4 Cerebral Blood Flow and Metabolism: Physiology and Monitoring........................................................................................ 51Jeremy Fields and Anish Bhardwaj

5 Multimodality Monitoring in Acute Brain Injury ............................... 61Kristine H. O’Phelan, Halinder S. Mangat, Stephen E. Olvey, and M. Ross Bullock

6 Cerebral Edema and Intracranial Hypertension ................................. 73Matthew A. Koenig

7 Cardiac Dysfunction, Monitoring, and Management .......................... 89Andrew Naidech

8 Airway Management and Mechanical Ventilation in the NCCCU ......................................................................................... 99Paul Nyquist

9 Blood Pressure Management ................................................................. 115Ameer E. Hassan, Haralabos Zacharatos, and Adnan I. Qureshi

10 Nutrition in Neurocritical Care ............................................................. 123Tara Nealon

xii Contents

11 Sedation, Analgesia, and Neuromuscular Paralysis ............................ 145Marek A. Mirski

12 Postoperative Care .................................................................................. 173W. Andrew Kofke and Robert J. Brown

13 Care Following Neurointerventional Procedures ................................. 217Yahia M. Lodi, Julius Gene Latorre, Jesse Corry, and Mohammed Rehman

14 Ethical Issues and Withdrawal of Life-Sustaining Therapies ............ 247Wendy L. Wright

15 Collaborative Nursing Practice in the Neurosciences Critical Care Unit.................................................................................... 265Filissa M. Caserta

Part II Specific Problems in Neurocritical Care

16 Coma and Disorders of Consciousness ................................................. 277Edward M. Manno

17 Acute Encephalopathy ............................................................................ 287Robert D. Stevens, Aliaksei Pustavoitau, and Tarek Sharshar

18 Traumatic Brain Injury .......................................................................... 307Geoffrey S.F. Ling and Scott A. Marshall

19 Acute Myelopathy ................................................................................... 323Angela Hays and Julio A. Chalela

20 Ischemic Stroke ....................................................................................... 341Neeraj S. Naval and Anish Bhardwaj

21 Intracerebral Hemorrhage ..................................................................... 353Neeraj S. Naval and J. Ricardo Carhuapoma

22 Intraventricular Hemorrhage ................................................................ 365Kristi Tucker and J. Ricardo Carhuapoma

23 Subarachnoid Hemorrhage .................................................................... 371Eric M. Bershad and Jose I. Suarez

24 Brain Injury Following Cardiac Arrest ................................................ 389Romergryko G. Geocadin

xiiiContents

25 Meningitis and Encephalitis ................................................................... 409Barnett R. Nathan

26 Cerebral Venous Sinus Thrombosis ...................................................... 421Agnieszka A. Ardelt

27 Neuroleptic Malignant Syndrome, Malignant Hyperthermia, and Serotonin Syndrome ........................................................................ 435Panayiotis N. Varelas and Tamer Abdelhak

28 Brain Tumors .......................................................................................... 445Sherry Hsiang-Yi Chou

29 Hydrocephalus ......................................................................................... 469Michel T. Torbey

30 Neuromuscular Disorders ...................................................................... 475Jeremy D. Fields and Anish Bhardwaj

31 Status Epilepticus .................................................................................... 489Marek A. Mirski

32 Deep Venous Thrombosis and Pulmonary Embolism ......................... 505Wendy C. Ziai

33 Neurocritical Illness During Pregnancy and Puerperium ................... 523Chere Monique Chase and Cindy Sullivan

34 Brain Death and Organ Donation ......................................................... 533Alexander Y. Zubkov and Eelco F.M. Wijdicks

Index ................................................................................................................. 541

xv

Contributors

Tamer Abdelhak Departments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, MI, USA

Agnieszka A. ArdeltUniversity of Chicago, Departments of Neurology and Surgery (Neurosurgery), Division of Neurocritical Care, 5841 South Maryland Ave MC2030, Chicago, IL 60637, USA

Neeraj BadjatiaDepartments of Neurology and Neurosurgery, Columbia University, New York, NY 10032, USA

Eric M. BershadDepartment of Neurology, Baylor College of Medicine, One Baylor Plaza, MS NB302, Houston, TX 77030, USA

Anish BhardwajDepartment of Neurology, Tufts University School of Medicine, Tufts Medical Center, Box 314, 800 Washington Street, Boston, MA 02111, USA

Ansgar BrambrinkDepartment of Anesthesiolgy, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA

Robert J. BrownDepartment of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

M. Ross BullockDepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

xvi Contributors

J. Ricardo CarhuapomaNeurosciences Critical Care Division, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA

Filissa M. CasertaNeurosciences Critical Care Unit, Johns Hopkins University School of Medicine, 600 N. Wolfe Street - Meyer 8-140, Baltimore, MD 21287-7840, USA

Julio A. ChalelaMedical University of South Carolina, PO BOX 250606, Charleston, SC 29425, USA

Chere Monique ChaseForsyth Comprehensive Neurology, 2025 Frontis Plaza Boulevard, Greystone Professional Center, Suite 102, Winston-Salem, NC 27103, USA

Sherry Hsiang-Yi ChouDivision 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 CorryUpstate Medical University, Syracuse, NY, USA

Jeremy D. FieldsDepartment of Neurology, Oregon Health and Science University, Portland, OR, USA

Romergryko G. GeocadinDivision of Neuroscience Critical Care, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA

Ameer E. HassanZeenat Qureshi Stroke Research Center, Department of Neurology, University of Minnesota, Minneapolis, MN

Angela HaysMedical University of South Carolina, Charleston, SC, USA

Nikki JaworskiDepartment of Anesthesia and Peri-operative Medicine, Oregon Health and Science University, Portland OR

Matthew A. KoenigAssociate Medical Director of Neurocritical Care, The Queen’s Medical Center, Neuroscience Institute–QET5, 1301 Punchbowl Street, Honolulu, HI 96813, USA

xviiContributors

W. Andrew KofkeDepartments 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 LatorreNeurosciences Critical Care Unit and Neurocritical Care Fellowship Program, Upstate Medical University, Syracuse, NY, USA

Geoffrey S.F. LingCritical Care Medicine for Anesthesiology and Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd. Bethesda, MD 20814, USA

Yahia M. LodiDivision 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. MangatDepartment of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA

Edward M. MannoMayo Clinic School of Medicine, 200 First St. SW, Rochester, MN 55905, USA

Scott A. MarshallUniformed Services University of the Health Science, Bethesda, MD, USA

Marek A. MirskiDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA

Andrew NaidechDepartment of Neurology, Northwestern University, Feinberg School of Medicine, Neuro/Spine ICU, Northwestern Memorial Hospital, Chicago, IL 60611-3078, USA

Barnett R. NathanDepartment of Neurology and Internal Medicine, University of Virginia School of Medicine, PO Box 800394, Charlottesville, VA 22908, USA

Neeraj S. NavalNeurosciences Critical Care Fellowship Program, Oregon Health and Science University, Portland, OR, USA

xviii Contributors

Tara NealonJohns Hopkins University School of Medicine, Baltimore, MD, USA

Paul NyquistDepartment of Neurology, Anesthesiology and Neurological Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street – Phipps 126, Baltimore, MD 21287, USA

Stephen E. OlveyDepartment of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA

Assistant Professor, Director of Neurocritical Care Department of Neurology, University of Miami Miller School of Medicine, Miami, FL

Tarek SharsharHospital Raymond Poincare, University of Versailles, Versailles, France

Robert D. StevensNeurosciences 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. SuarezDepartment of Neurology, Baylor College of Medicine, One Baylor Plaza, MS NB302, Houston, TX 77030, USA

Kristine H. O’PhelanDepartment of Neurology, University of Miller School of Medicine, Miami, FL, USA

Kristi TuckerDepartments of Neurology and Anesthesiology/Critical Care, Wake Forest University Health Sciences, Winston-Salem, NC, USA

Panayiotis N. VarelasDepartments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, MI, USA

Aliaksei PustavoitauJohns Hopkins University School of Medicine, Baltimore, MD, USA

Kristine H. O’Phelan

xixContributors

Adnan I. QureshiZeenat Qureshi Stroke Research Center, Department of Neurology, University of Minnesota, Minneapolis, MN

Mohammed RehmanDepartment of Neurology, Upstate Medical University, Syracuse, NY, USA

Cindy SullivanNeurocritical Care Program, Novant Health Systems, Forsyth Medical Center, Winston-Salem, NC, USA

M.T. TorbeyDepartment of Neurological Surgery and Neurology, Medical College of Wisconsin, Department of Neurology, 9200 W.Wisconsin Avenue, Milwaukee, WI 53226, USA

Eelco F.M. WijdicksDepartment of Neurology and Neurological Surgery, Mayo Clinic School of Medicine, 200 First Street SW, Rochester, MN 55905, USA

Elco A. WidjicksProfessor of Neurology Chair, Division or Critical Care Neurology Mayo Clinic and Mayo College of Medicine, Rochester, MN

Wendy L. WrightEmory University School of Medicine, 1365B Clifton Rd., NE, Ste. 6200, Atlanta, GA 30322, USA

Haralabos ZacharatosZeenat Qureshi Stroke Research Center, Department of Neurology, University of Minnesota, Minneapolis, MN

Wendy C. ZiaiDepartment of Neurology and Neurological Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street – Meyer 8-140, Baltimore, MD 21287, USA

Alexander Y. ZukbovStroke Center, Fairview Southdale Hospital, Minneapolis Clinic of Neurology, Rochester, MN, USA

Part IGeneral Principles of Neurocritical Care

3A. 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

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 ♦

backgroundGreater 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♦

Chapter 1Establishing and Organizing a Neuroscience Critical Care Unit

Marek A. Mirski

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]

4 M.A. Mirski

Probable conflicts must be defined and respected; strategies to overcome con-■

flicts must be defined

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 •populationsNeurology – 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 hospi-•tal LOS and improved the disposition of patientsPatients with ICH, improvement in outcome as defined by percent of mor-•tality, percent to home, and rehabilitation versus nursing home, despite lower Glasgow Coma Scale score in comparative grouping in NCCU ver-sus general ICU (Fig. 1.2)

Fig. 1.1 Cumulative survival curve demonstrating a benefit in lower mortality of patients suffer-ing 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

51 Establishing and Organizing a Neuroscience Critical Care Unit

Improvement in ICU efficiency of care and ICU LOS♦

Shorter ICULOS leads to reduction in cost and increased case-load •profitabilityFor 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 MICUFor 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 examina-tion and interpretation of findings; e.g., reduction of imaging requisitions and lower cost of pharmaceuticals can be expected with expertise at bed-side (Fig. 1.4)Further subdivision among costs for imaging studies, pharmacy, and labo-•ratory testing found reduction across all aspects of clinical management

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

6 M.A. Mirski

Improvement in ICU efficiency of care and documentation♦

Data from a sampling of records with three diagnoses: traumatic brain •injury, ICH, and subarachnoid hemorrhage – pre- and post-appointment of neurointensivistDocumentation 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 effective-•ness (15% reduction), full implementation of intensivist-model ICUs would save ~53,850 lives each year in the US

Fig. 1.3 National database [HBS International, Inc. (HBSI, Bellevue, WA)] comparative differ-ence (%) in ICU length of stay from the benchmark standard (0 on axis) for neuroscience subspe-cialty 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


Fig. 1.4 National database [HBS International, Inc. (HBSI, Bellevue, WA)] comparative differ-ence 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 timeReturn >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

http://www.leapfroggroup.org/media/file/Leapfrog

8 M.A. Mirski

Cost savings of intensivist coverage♦

Data demonstrate intensivist coverage renders considerable savings to medi-•cal centerNeurointensivists offer additional ICU staffing options for hospital in pro-•viding necessary expertise to critical careSurvey 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•

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

Key components to NCCU successful staffing model■

Specialty-trained neurointensivists♦

2-Year accredited fellowship•

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 assump-tions (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


Ideal: three intensivists for 8–12-bed NCCU; intensivists perform aca-•demic activity or other non-ICU clinical duty 2 of 3 weeksOn-service 1–2 weeks per shift; 24/7 responsibility most common current •formatIf 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 effective10–14 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 •managementIntelligent patient and family interaction; allay concerns and fears of dif-•ficult 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)

Literature does not clearly support one model of critical care delivery p

over anotherDedicated ICU personnel, specifically the intensivist, the ICU nurse, p

respiratory care practitioner, and pharmacist, all work as a teamMultidisciplinary group-practice model should be led by a full-time p

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 p

have no competing clinical responsibilities (Grade E recommendation)ICUs with an exclusive critical care service and operating in the closed p

format, as described previously, may have improved outcomes; when

http://www.guideline.gov

http://www.guideline.gov

10 M.A. Mirski

geographic constraints, resource limitations, and manpower issues allow, this organizational structure for the delivery of critical care ser-vices may be optimal (Grade E recommendation)The presence of a pharmacist as an integral part of the ICU team, p

including but not limited to making daily ICU rounds, improves the quality of care in the ICU and reduces errors; integration of a dedi-cated pharmacist into the ICU team is recommended (Grade C recommendation).Physician practitioners in the ICU should have hospital credentials to p

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


Costs■

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 regu-•lated rates of return per DRGIncome 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

Neurointensivist-managed NCCU offers expertise to provide improved outcome ■

with lower cost/patient and ICU LOSThis model has historically been financially beneficial to hospital administra-■

tion, 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 ser-vices and compliance with Leapfrog recommendations. Crit Care Med 34:1016–1024

Diringer MN, Edwards DF, Aiyagari V, Hollingsworth H (2001) Factors associated with with-drawal of mechanical ventilation in a neurology/neurosurgery intensive care unit. Crit Care Med 29:1792–1797

12 M.A. Mirski

Mirski MA, Chang CW, Cowan R (2001) Impact of a neuroscience intensive care unit on neuro-surgical 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: finan-cial 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


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 acido-■

sis is defined as pH <7.35pH is a measure of the hydrogen ion concentration in the extracellular fluids and ■

is determined by the pCO2 and HCO

3 concentration

[H♦ 2] (meq/L) = 24 × (PCO2/HCO

3)

The initial change in PCO■2 or HCO

3 is called the primary disorder; the subse-

quent change is called the compensatory or secondary disorderCompensatory changes frequently will not return the pH to the normal range but ■

will serve to limit the effect of the primary derangementAcid – 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 blood-■

brain 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 CO■2 +

H2O to H+ and HCO

3 by carbonic anhydrase

Chapter 2Electrolyte and Metabolic Derangements

Nikki Jaworski and Ansgar Brambrink

N. Jaworski, MDDepartment 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]

14 N. Jaworski and A. Brambrink

The pH of the CSF returns to normal after 6–8 h, as HCO■3 is either retained or

extruded across the BBB despite ongoing hyper- or hypocapnia, respectivelyAs the CSF pH returns to normal, CBF also trends toward normal■

Primary Acid: Base Disorders

Respiratory acidosis – increased PaCO■2

Compensation – subsequent increase in HCO♦3

Neurologic consequence♦

CBF increases 1–2 mL/100 g/min for each 1 mmHg change in PaCO•2

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 CO•

2 production from hypermetabolic state such as hyperthermia,

fever, or seizuresDecreased cardiac output, resulting in accumulation of CO•

2 in blood and

tissues

Respiratory alkalosis – decreased PCO■2

Compensation – subsequent decrease in HCO♦3


CBF decreases 1–2 mL/100 gm/min for each 1 mmHg change in PaCO•2

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 herniationEtiology♦

Hyperventilation•

Metabolic acidosis – decreased HCO■3

Compensation – subsequent decrease in PaCO♦2 (hyperventilation)


Primarily a result of the compensatory change in PaCO•2

Hypoxia (PaO•2 <60 mmHg) rapidly increases CBF most likely due to cere-

bral vasodilation induced by lactic acidDifferential includes anion gap vs. non-anion gap♦

152 Electrolyte and Metabolic Derangements

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, sali-•cylate toxicity

A normal anion gap acidosis is due to a net gain in chloride ions♦

Diarrhea, early renal insufficiency, resuscitation with isotonic or hyper-•tonic saline, renal tubular acidosis, acetazolamide

Metabolic alkalosis – increased HCO■3

Compensation – subsequent increase in PCO♦2 (hypoventilation)


Again, this is primarily due to the compensatory change in PaCO•2, result-

ing in increased CBF

Etiology♦

Administration of NaHCO•3

Contraction alkalosis from overdiuresis (kidney retains HCO•3 ions to

maintain electrical neutrality while losing Cl- ions)Any time the loss of chloride ions exceeds the loss of sodium ions (naso-•gastric suctioning)

Electrolyte Disorders

Electrolyte disorders are common and important in any critically ill patient and ■

are of particular concern in patients with CNS disturbancesThey may occur as a part of the disease process, or they may be iatrogenic■

If unrecognized or persistently severe, the consequences of electrolyte derange-■

ment may become life threateningSodium■

Sodium cannot move freely across cell membranes and is the primary deter-♦

minant of tonicity or effective osmolarityIsosmotic 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 dissolvedExample – 150 mM NaCL added to plasma is approximately isosmotic & •isotonic to brain, and little water is therefore passed between plasma and brain.


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 concentrationFor 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 mech-anisms 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 stateAzotemia – 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 statePsychogenic polydipsia▲

Syndrome of inappropriate antidiuretic hormone secretion (SIADH)▲


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

detected by the hypothalamus or a decrease in plasma volume is detected by the peripheral and central baroreceptorsADH secretion is considered inappropriate when the above criteria are N

not present or when it is secreted in the setting of low serum osmolarityFindings includeN

Urine is inappropriately concentrated (>100 mOsm/kg H°2O)

Urine volume will be normal or low°

Plasma is hypotonic (<280 mOsm/kg H°2O)

Patients demonstrate normal sodium handling by the kidneys, and °

urine sodium excretion remains >20 meq/LExtracelluar fluid volume remains normal or slightly elevated°

EtiologyN

Exact etiology is unclear°

SIADH may be associated with brain tumors, subarachnoid hemor-°

rhage (SAH), traumatic brain injury, stroke, meningitis or encepha-litis, or may be drug induced (e.g., carbamazapine)

Other reasons for excessive ADH secretion must be ruled out; e.g., N

hypothyroidism, mineralocorticoid insufficiency, hypotension, hypov-olemia, 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 waterAdrenal insufficiency – decreased ACTH (adrenocorticotropic hor-▲

mone) secretion or primary insufficiency (Addison disease), resulting in insufficient release of mineralocorticoid (aldosterone)Cerebral salt wasting (CSW) – a special form▲

Characterized by excessive sodium loss accompanied by excess N

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

Laboratory evaluation is similar to that for SIADH, with exception N

of extracellular fluid volume

Urine volume will be normal or high°

Plasma is hypotonic (<280 mOsm/kg H°2O)

Urine sodium excretion remains >20 meq/L°

Extracellular fluid volume becomes increasingly depleted°


Primary distinguishing features between CSW and SIADH are pres-N

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

recent evidence suggests that many conditions previously thought to be associated with SIADH such as meningitis, SAH, TBI, and pitu-itary surgery are more likely to be associated with CSW due to the presence of hypovolemiaRestoration of a positive sodium balance requires the infusion of N

hypertonic saline and may require the use of fludrocortisone, a syn-thetic mineralocorticoidSAHN

Hyponatremia is the most common and severe electrolyte abnor-°

mality after SAHHypovolemia 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 hyponatremiaSymptoms include headache, anorexia, nausea, vomiting, malaise, confusion, •or lethargyIf untreated, symptoms may progress to metabolic encephalopathy associ-•ated with cerebral edema, elevated ICP, and tonic-clonic seizuresAs extracellular hypotonicity develops, water shifts intracellularly to rees-•tablish 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 volumeThe sodium deficit may then be calculated to guide further therapy•

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


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

A synthetic mineralocorticoid▲

May be used for mineralocorticoid replacement in patients with pri-▲

mary adrenal insufficiencyMay 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 ponsSymptoms progress over hours to days and include spastic paralysis, ▲

pseudobulbar palsy, and decreased level of consciousnessCorrection 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

Diabetes insipidus (DI)N

Most frequently occurs after pituitary or diencephalic surgery°

May occur with brain neoplasms, anoxic brain injury, meningitis, °

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

rendering the kidneys unable to concentrate urine in the face of a rising serum osmolarityDiagnosis°

— High urine output— Serum Osm >290 mOsm/kg— Urine specific gravity <1.010

Associated with loss of other electrolytes due to high urine °

outputIs often temporary, lasting 3–5 days°

Treatment includes vasopressin (DDAVP); sodium and serum °

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


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)

Excessive sweating, vomiting, or diarrhea without volume replacementN

IatrogenicN

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 hyper-▲

tonic fluid)

Frequently iatrogenic in the NCCU; hypertonic saline is used for N

treatment of cerebral edema due to stroke or TBI as well as to replace sodium losses during CSWTo avoid development of symptoms, an upper limit to treatment N

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 levelsSymptoms primarily include a decreased level of consciousness and confu-•sion that may progress to tonic-clonic seizuresIntracellular fluid in the brain becomes hypotonic relative to the extracel-•lular 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 infu-sion 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 restoredChronic hypernatremia results in brain accumulation of organic osmolytes •over several days (myoinositol, b taurine, small-chain amino acids); resto-ration 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


Treatment♦

Volume status should be assessed, and hypovolemia should be treated with •isotonic fluids to maintain hemodynamic stabilityFree 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 P▲Na

/Current PNa

)Replacement Volume = TBW deficit × (1/1 – X)▲

X = concentration of sodium in the replacement fluidN

As described above, acute hypernatremia may be corrected over a few •hours as the brain is able to rapidly eliminate accumulated electrolytesTo avoid the risk of cerebral edema, chronic hypernatremia should be cor-•rected 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

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 potassiumTotal body potassium is ~50 meq/kg■

Large intracellular stores of potassium are very effective at replenishing extra-■

cellular potassium losses; as a result, the relationship between the changes in total body potassium and serum potassium is curvilinear such that serum potas-sium changes occur twice as rapidly when potassium stores are in excess than they do when potassium stores are depletedHypokalemia■

Defined as serum K < 3.5 meq/L♦

Etiology♦

Transmembraneous shift•

Catecholamines (i.e., ▲ b agonists) stimulate Na+/K+ ATPase activityAlkalosis – hydrogen ions are shifted extracellularly in exchange for ▲

potassium ionsHypothermia▲

Insulin enhances Na/K ATPase activity▲

Hypertonicity – the increase in electricochemical gradient favors the ▲

movement of ions out of cells

Potassium depletion♦

Renal losses•


Diuretic therapy increases the distal tubular flow and sodium delivery ▲

to the distal tubule, stimulating the secretion of potassium via Na+/K+ ATPase

Mannitol is a frequently used diuretic to treat elevated ICP in the N

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

Mineralocorticoids▲

Aldosterone stimulates the reabsorption of sodium and the secretion N

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

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 effectsMagnesium depletion▲

Impairs potassium reabsorption across the renal tubulesN

High-dose steroids used to treat spinal cord injury and mineralocorti-▲

coid 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 •conductionHypokalemia can be associated with nonspecific EKG changes, including •U waves, flattening or inversion of T waves, and prolongation of the QT intervalHypokalemia promotes cardiac dysrhythmia when combined with other •pro-dysrhythmic conditions such as ischemia, digitalis toxicity, or magne-sium depletion

SAH is frequently associated with EKG changes and sinus dysrhyth-▲

mia; 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 dysrhythmiaStroke 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


Hyperkalemia■

Defined as serum K♦ + >5.5 meq/LTransmembraneous shift♦

• b antagonists/digitalisAcidosis•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 hepa-▲

rin infusionAntibiotics – trimethoprim-sulfamethozaxole, potassium penicillin▲

Blood transfusion•

Potassium leaks from erythrocytes in stored blood▲

The extra potassium is normally cleared by the kidneys, but in circula-▲

tory shock that requires transfusion greater than one blood volume, potassium can accumulate and result in hyperkalemia


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


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 toneRegulates calcium influx into neuronal cells via glutamate receptor – associated ♦

ion channels; magnesium partially blocks the receptor and reduces calcium cur-rents, 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


Symptoms include exacerbation of neurologic dysfunction, apathy, delir-•ium, muscle weakness, hyperreflexia, muscle spasms, ataxia, nystagmus, and seizuresAssociated electrolyte abnormalities•

Hypokalemia and hypocalcaemia can be refractory to replacement ▲

therapy in the setting of hypomagnesemiaLow magnesium impairs the release of parathyroid hormone and end-▲

organ 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

Acts as an endogenous calcium-channel antagonistN

Inhibition of release of excitatory neurotransmitters such as N

glutamate


NMDA-receptor antagonismN

Direct vascular smooth muscle relaxationN

Currently, the use of hyperacute magnesium therapy to provide neuro-▲

protection after stroke is under investigation

SAH•

~30% of patients who present with SAH have coexisting hypomag-▲

nesemia upon admissionRelationship between low magnesium levels, SAH, and myocardial ▲

stunning remains unclearCombination 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 thresh-•old, 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 •preeclampsiaHemolysis•Adrenal Insufficiency•Lithium intoxication•Hyperparathyroidism•


Hypermagnesemia becomes symptomatic at levels >4 meq/L•Progress of symptoms – hyporeflexia • → first degree AV Block → complete heart block → respiratory failure → cardiac arrestNot 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), anion-■

bound (inactive), and ionized (active) formsTightly 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


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 channelsInflux 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 calciumClinical 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 dysrhythmiasNeuromuscular 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 thiaz-ide diureticsClinical manifestations involve the gastrointestinal, cardiovascular, renal, and ♦

neurologic systems

Cardiovascular – increased vascular resistance, QT shortening, occasional •dysrhythmiasNeurologic – confusion, lethargy, memory impairment, weakness, • hypotonia, and hyporeflexia leading to progressive obtundation and coma


Phosphate

The most abundant intracellular anion; phosphate is important for membrane ■

structure, cellular energy, the production of ATP, cell transport, and intracellular signaling cascadesDepletion 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 ischemiaHypophosphatemia■

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


Phosphate is a major component in the production of cellular energy •(ATP); therefore, phosphate depletion is concerning but can be compen-sated 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 com-▲

mon among chronic alcoholicsHypophosphatemia can be profound and occurs as tissues begin to ▲

rebuild themselves upon the initiation of nutritional support

May lead to muscle weakness, including respiratory muscle weak-N

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

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


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

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 reasonsMetabolic disorders and endocrinopathies should always remain in the differen-■

tial diagnosis of encephalopathyMetabolic disorders may occur as comorbidities in any patient, including neuro-■

surgical or neurologic patientsHyperglycemia■

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 outcomeIn animal studies, hyperglycemia before or during ischemic injury has been ♦

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

likely due to the physiologic stress caused by the injuryThe 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 diseaseTwo 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 stressEncephalopathy usually presents as altered mental status but may ▲

progress to focal deficits and seizuresFindings▲

Blood glucose usually >1,000 mg/dLN

Persistent osmotic diuresis leads to profound hypovolemiaN

Treatment▲

Volume resuscitation with isotonic fluids or colloidsN


Replacement of free water once intravascular volume has been N

restored; pseudohyponatremia is likely to be present, and resuscita-tion of hypovolemic state requires high degrees of NaCl, as the serum glucose level decreases with treatmentRestoration of brain cell volume may occur rapidly; therefore, vol-N

ume replacement should occur slowlyInsulin therapy can be initiated after volume status has been restoredN

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 glu-cose 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 diabetesMay be seen in a previously well-controlled diabetic who is experienc-▲

ing acute physiologic stress such as infection or sepsisFindings▲

Blood glucose usually > 250 mg/dL but <800 mg/dLN

Serum bicarbonate <20 meq/LN

Elevated anion gapN

Ketones in blood and urineN

Treatment▲

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

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

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 reachedReplace potassium; correction of underlying acidosis in combina-N

tion 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 metab-•olism; EEG changes can be seen at levels of 40 mg/dL, and the EEG begins to show suppression at 20 mg/dL; seizures may developHypoglycemia increases CBF which may be detrimental to patients with •elevated ICP


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 T

3, T

4, and rT

3

Free (non-protein bound) T♦3 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 treatmentMost 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 cardiomegalyHyponatremia – kidneys are unable to properly secrete free water due to •decreased GFR and increased vasopressin secretionHypoglycemia, hypoxemia, and hyponatremia may result in reduced CBF •and seizuresFindings 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 hypothermiaUrinary sodium excretion is normal•Elevated TSH and low total and free T•

4 and T

3

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


Treatment♦

Ventilatory support•Cautious warming – rapid rewarming may result in vasodilation and refractory •hypotensionGlucocorticoid 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, depend-•ing on severity; sodium levels <120 meq/L are considered more severeThyroid 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 tachyar-rhythmias and myocardial ischemia

Hashimoto Encephalopathy

Hashimoto encephalopathy is an autoimmune disorder that is related to Hashimoto ■

thyroiditisAlso known as STEAT (steroid-responsive encephalopathy associated with auto-■

immune 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 encephalopathyDisorder 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 psy-chosis with a gradual or subacute onsetSeizures, 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 presentTSH may be normal or elevated♦

Free T♦4 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


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 subjectiveMortality 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 stormFindings■

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 CO•2 production/O

2 consumption)

Gastrointestinal dysfunction♦

Nausea/vomiting•Jaundice•Hyperglycemia may be present•

Adrenocortical dysfunction♦

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


Diagnosis♦

Elevated free T•4 and free T

3 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 hormoneA thionamide (propylthiouracil or methimazole) should be given first to •inhibit thyroid gland synthesisIodine 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 conditionAcetaminophen 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 T▲4 to T

3

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 stimu-■

lates the anterior pituitary to release ACTH; ACTH subsequently stimulates the zona fasciculata of the adrenal gland to release cortisolBasal 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 supportThis 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 mani-•festing as hypotension, hypovolemia, and shock


Secondary (inadequate production of CRH or ACTH)♦

Iatrogenic•

Chronic suppression▲

Cortisol naturally participates in a negative feedback loop with N

ACTH secretionChronic administration of exogenous glucocorticoids results in N

adrenal gland atrophy and chronic suppression of the hypothalamus-anterior pituitary axisThe adrenal gland is then unable to mount an appropriate response N

to stress, resulting in profound hypotension, muscle weakness, and hypoglycemia

Etomidate▲

Etomidate directly inhibits cortisol synthesis by the adrenal gland; N

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 complaintsManifests 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 abnormal15–35 • 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 resus-citation 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


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 unrec-■

ognized or persistently severeDerangements of serum sodium are common, and etiologies include SIADH, ■

CSW, and DIMetabolic 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 strate-gies for prevention and management. Curr Opin Crit Care 12:78–84

Wartofshy L (2006) Myxedema coma. Endocrinol Metab Clin North Am 35:687–698


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♦

Chapter 3Fever and Infections

Neeraj Badjatia

N. Badjatia, MD, MSc (*) Departments of Neurology and Neurosurgery, Columbia University, New York, NY 10032, USA e-mail: [email protected]

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 hStool 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 •ORIbuprofen 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•

CardiovascularMyocardial infarctionPericarditisDeep venous thrombosis

PulmonaryAtelectasisPulmonary embolism

Hepatobiliary/GastrointestinalAcalculous cholecystitisAcute pancreatitisToxic megacolonNon infectious hepatitis

EndocrineHyperthyroidismAdrenal insufficiencyPheochromocytoma

OtherDrug reactions (“drug fever”)Transfusion reactionsTumorsMalignant hyperthermiaNeuroleptic malignant syndromeSerotonin syndromeDrug withdrawal (alcohol, heroin, opiates)

Table 3.1 Secondary evaluation of fever: noninfectious causes of fever

393 Fever and Infections

Induction and maintenance of normothermia (37°C)♦

Utilized for patients with fever refractory to above interventions•Application of advanced therapeutic temperature-modulating device (intra-•vascular or surface) set to 37°CMonitoring 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

30 mg buspirone orally q 8 hN

Surface counterwarming (43°C)N

1,000 mg acetaminophen q 4–6 hN

Step 2 – For persistent shivering, utilize a combination of medications▲

MgSON4, 4 g IV bolus; then, 0.5–1.0 g/h; Goal Serum Mg level:

3–4 mg/dLDexmedetomidine, 0.2–1.5 N mg/hMeperidine, 25–75 N mg IV q 4–6 h as needed OR 0.5–1.0 mg/kg/h infusion; do not administer in patients with renal insufficiencyDantrolene, 2.5 mg/kg IV q 6 h as neededN

Step 3 – Uncontrolled, moderate to severe shivering (BSAS 2–3)▲

Propofol, 30–50 N mg/kg/min continuous infusionRe-evaluate need for ongoing therapeutic normothermiaN

Thoracic Infections

Community-acquired pneumonia■

Risk factors♦

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

Table 3.2 The Bedside shivering assessment scale (BSAS)

Score Definition

0 None. No shivering noted on palpation of the masseter, neck, or chest wall1 Mild. Shivering localized to the neck and/or thorax only2 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

40 N. Badjatia

Diagnosis♦

Hospitalized for • £3 days at time of infectionPresence of clinical features•Fever (>38.0°C)•Elevated WBC•Purulent sputum•Infiltrate on chest X-ray•P•

aO

2/FiO

2 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 availableFluoroquinolone plus • b-lactamMacrolide 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▲

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


Pharmacologic▲

Chlorhexidine mouth wash, ranitidineN

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

Nonintubated and hospitalized for >3 days prior to infection▲

Microbiology•

Gram-positive▲

Streptococcus pneumonia and N Staphylococcus aureus

Gram-negative▲

N H. influenza, K. pneumonia, S. aureus, Pseudomonas aeruginosa, Enterobacter spp., Klebsiella spp.

Treatment•

General principle▲

Empiric broad antibiotic coverage to cover methicillin-resistant N

S. aureus (MRSA), gram-negative organisms

Vancomycin plus aminoglycoside or fluoroquinolone▲

Ventilator associated pneumonia (VAP)♦

Prevention•

Nonpharmacologic▲

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

elevated 30–45°

Pharmacologic▲

Chlorhexidine mouth wash, ranitidineN

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▲

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

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▲


IV drug abuse▲

Bacteremia▲

Diagnosis•

Clinical findings▲

New heart murmurN

Splinter hemorrhagesN

Retinal hemorrhages (Roth spots)N

Red/purple nodules on toes/fingers (Osler nodes)N

Flat red lesions on palms/soles (Janeway lesions)N

Laboratory findings▲

Persistent feverN

Elevated WBCN

Blood culture positiveN

Echocardiography▲

TEE better than TTE in diagnosis of valvular vegetations, abscessesN

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 ▲

valvesCommon group – ▲ Haemophillus spp., Actinobaccillus actinomycetemo-comitans, Cardiobacterium hominus, Eikenella corrodens, and Kingella spp (HACEK)

Treatment•

Broad-spectrum gram-positive and gram-negative coverage with van-▲

comycin 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 gram-•negative organismsSigmoidoscopy 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•


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 cul-▲

ture data available

2 g ceftriaxone IV q 12 hN

1 g vancomycin IV q 8–12 hN

50–100 mg/kg ampicillin IV q 6 hN

Viral encephalitis■

Risk factors♦

Environmental exposures•Immunocompromised•

Diagnosis♦

Clinical signs•


Headache▲

Fever▲

Alteration in mental status▲

CSF findings•

Elevated WBC with lymphocytosis▲

Normal glucose▲


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▲


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 gram-▲

negative organism

1.0–1.5 g vancomycin IV q 12 h (goal trough, level >15)N

Second- or third-generation cephalosporin with good CNS penetra-N

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 pend-•ing 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


Etiologic considerations for risk factors, clinical suspicion, ancillary laboratory ■

and microbiologic data are required to institute appropriate therapies in a timely fashionMonitoring 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

51

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/minCBF 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:

P•aCO

2

An acute 1 mmHg decrease in P▲aCO

2 causes CBF to decrease by 4%

Chronic (>12–24 h) changes in P▲aCO

2 do not affect CBF due to changes

in physiologic set points

P•aO

2

CBF does not correlate with P▲aO

2 when it exceeds 50 mmHg; however,

when PaO

2 is <50 mmHg, CBF increases dramatically

Temperature•

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

Chapter 4Cerebral Blood Flow and Metabolism: Physiology and Monitoring

Jeremy Fields and Anish Bhardwaj

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

52 J. Fields and A. Bhardwaj

Mean arterial pressure (MAP)•

CBF is maintained across a MAP of 50–150 mmHg by changes in ▲

blood vessel caliber

Below this range, cerebral vessels are maximally vasodilated and N

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

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 viscosityBlood viscosity is inversely proportional to CBF▲

CBF increases due to vasodilation in response to decreasing ▲

hematocrit

Under normal conditions, a decrease in hematocrit from 35 to 25% N

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

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 func-•tion, particularly the generation of electrical signals; 45% is used for basal metabolic processes such as maintenance of ion gradients and synthesis of structural molecules

Fig. 4.1 Chemical autoregulation: Effect of PaO

2 and P

aCO

2 on CBF

534 Cerebral Blood Flow and Metabolism: Physiology and Monitoring

>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 spaceNeurons take up lactate for aerobic metabolism and release glutamate, ▲

aspartate, and potassium into the extracellular spaceGlutamate, 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 CBFKey cerebral metabolic parameters♦

Arterial venous difference in oxygen content (AVDO•2)

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 ▲

saturationIncreases with enhanced brain activity, assuming constant CBF▲

Cerebral metabolic rate of oxygen consumption (CMRO•2)

Represents the total oxygen consumption by the brain in a given time ▲

periodCalculated as CBF ▲ × AVDO

2

Increases with increased brain activity▲

Cerebral metabolic rate of glucose consumption (CMRGlu)•

Represents the total glucose consumption by the brain in a given time ▲

periodIncreases 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)


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 pressuresCBF does not change in response to changes in CO▲

2, O

2, or hematocrit

Uncoupling – When autoregulation is impaired, physiologic parameters that ♦

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

Loss of relationship between metabolic energy expenditures (CMRO•2 or

CMRGlu) and CBFUncoupling of lactate utilization by neurons and uptake of excitatory neu-•rotransmitters 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 hypertensionTherefore, decreasing MAP to the lower range in a chronically hyperten-•sive 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 periodIn 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 stateFollowing this period, the brain becomes hypometabolic; the degree is ▲

correlated with the depth of comaPoorer clinical outcomes are associated with greater degrees of initial ▲

hypermetabolism, as measured by CSF lactate, and subsequent hypo-metabolism, as measured by CMRO

2

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 patientsHyperemia (day 1–3) – CBF normal or above normal; may lead to ▲

increased ICP


Vasospasm (day 4–15) – CBF decreases below normal until conscious-▲

ness 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 CBFOligemia – increased in OEF in response to a decline in CBF, with ▲

maintained CMRO2

Reversible ischemia – increase in OEF inadequate to sustain CMRO▲2

Irreversible ischemia – decrease in OEF, with very low CBF and CMRO▲2

Loss of autoregulation occurs in the ischemic penumbra (the area of •reversibly injured brain surrounding the core of irreversible damage), lead-ing 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 injuryIn rare cases of persistent large-vessel occlusion with blood pressure ▲

dependence, it may be necessary to augment blood pressure with pres-sors (with MAPs in the 120–140 mmHg) to preserve CBF as collateral vessels formSome collateral circulation is available immediately after arterial occlu-▲

sion; other vessels must be recruited – a process that takes days to weeksExcessive 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 ele-vated CBF or CBVWhen 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 21Vasospasm associated with SAH or systemic hypotension may decrease •CBF still further, into the range of reversible or permanent ischemiaCMRO•

2 decreases during the first week and then normalizes; uncoupling

of CBF and metabolism are most common during the first weekThe rationale of hypertensive and hypervolemic therapy is, therefore, to •increase CBF to avoid cerebral ischemia


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/minEEG 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, PO

2, 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 cere-bral 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 CBFPET also allows for direct measurement of metabolism of oxygen and glucose♦

Imaging modalities are compared in Table ♦ 4.2

SjVO■2 (jugular venous oxygen saturation) and PbrO

2 (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 (C

1–C

2)


• PbrO2 – Microsensor (0.5 mm in diameter) introduced into the brain paren-

chyma through bolt or tunneled catheter to continuously measure brain oxygen tension (and in some cases, PbCO

2 and pH)

Interpretation♦

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

Increased metabolism (increased CMRO▲2), or

Decreased oxygen delivery due to decreased arterial oxygen and ▲

decreased CBF

An elevated SjVO♦2 is most often due to hypometabolism (or decreased OEF)

or equipment failure; elevated PbrO2 usually represents equipment failure

Limitations♦

SjVO•2 measures mixed venous blood from entire hemisphere and is insen-

sitive to more restricted ischemiaPbrO•

2 measures local oxygen tension in the area of the probe only (~15 mL

volume) and does not reflect metabolism in other brain regions

Table 4.1 Bedside tests for evaluating CBF and metabolism

Technique Parameters Test Response

Change MAP or CPP to assess cerebral vasoreactivity

CPPICPFV

Increase MAP using pressor

ORDecrease MAP with

vasodilator or progressive deflation of blood pressure cuff applied to leg

ANDMonitor ICP or TCD FV

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

Change MAP or CPP to assess PbrO

2

CPPPbrO

2

Increase MAP using pressor and measure change in PbrO

2

Normal (autoregulation intact): small increase in PbrO

2

Abnormal: substantial increase in PbrO

2, suggesting either

failure of autoregulation or inadequate CPP/CBF

Oxygen challenge PBrO2

Patient placed on 100% FiO

2 for 15 min

Normal: rapid rise in PbrO2

followed by plateau (intact autoregulation)

Abnormal: prolonged rise in PBrO

2

MAP mean arterial pressure; CPP cerebral perfusion pressure; ICP intracranial pressure; FV flow velocity; TCD transcranial Doppler; PbrO

2 oxygen tension in brain tissue; FiO

2 fraction of

inspired oxygen


Equipment issues♦

Probes for measuring both parameters are subject to substantial drift•PbrO•

2 probe may cause hemorrhage or, rarely, infection

SjVO•2 catheter and sheath may cause infection or thrombosis of internal jugu-

lar 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 ♦

catheterDepending on catheter, this technique can measure:♦

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

Table 4.2 Imaging techniques for measurement of CBF and brain metabolism

Technique Measures Output/advantages Limitations

Xenon CT 131Xenon concentration after inhalation

Quantitative map of CBF in up to six CT slices

• UnderestimatesCBFin patients with lung disease

CT perfusion Standard iodinated CT IV contrast agent

Qualitative map of CBV, MTT, and CBF. Relatively cheap, potentially widely available, and rapid

• Qualitativemeasuresof CBF relative to a specified arterial input function

• Contrastagentsmaycause renal failure

• Accuracydependsoncontrast not crossing the BBB

MR perfusion Standard gadolinium MR IV contrast agent

Qualitative map of TTP, CBV, and CBF. May be compared with DWI images to determine areas of reversible ischemia

• Thresholdsdefininganalysis of raw data not yet identified

• Qualitativemeasuresof CBF relative to a specified arterial input function

• Difficulttotransportpatient to MRI emergently

PET 15O or 18FDG Quantitative. Can measure both blood flow and metabolism, including CBF, CBV, CMRO

2, OEF, and

glucose metabolism

• Poorspatialresolution• Expensiveandnot

widely available for inpatient clinical use

CBF cerebrospinal fluid; CBV cerebral blood volume; MTT Mean transit time; BBB blood–brain barrier; TTP thrombotic thrombocytopenic purpura; DWI diffusion-weighted imaging; CMRO

2

cerebral metabolic rate of oxygen; OEF oxygen ejection fraction


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 PbrO•2, microdialysis technique measures local metabolic param-

eters in the area of the catheter only and does not reflect metabolism in other brain regionsAbsolute 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 importantInvasive, and may cause hemorrhage or infection•

Key Points

Understanding normal cerebral physiology and metabolism and in pathophysi-■

ologic states is critical in the management of critically ill neurologic and neuro-surgical patientsConventional methods for measuring and monitoring CBF are not readily available ■

and are tedious

Table 4.3 Monitoring of brain metabolism in the neuro-ICU

Technique Parameter Normal range Abnormal conditions

Jugular venous oximetry

SjVO2

50–75% >80% → reduced OEF/hyperemia

<50% → increased OEF/ischemia

Brain tissue oxygen PbrO2

20–50 mmHg in grey matter

35–40 mmHg in white matter

<15 mmHg → ischemia

Cerebral microdialysis

pHGlucose LactatePyruvateLactate/pyruvateGlycerolGlutamate

7.21.7 (SD 0.9) mmol/L

2.9 (SD 0.9) mmol/L166 (SD 47) mmol/L23 (SD 4)82 (SD 44) mmol/L16 (SD 16) mmol/L

<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; PbrO

2 oxygen tension in

brain tissue


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 neuro-critical 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


Introduction

Major advances in microelectronics have produced new techniques for monitor-■

ing the injured brain; some, such as ion sensitive microelectrodes and continu-ous 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 brainCombining these techniques with global cerebral mapping techniques such as ■

PET, MRI, and MR spectroscopy offers enormous power in understanding the pathophysiology of the injured brainMost 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

Chapter 5Multimodality Monitoring in Acute Brain Injury

Kristine H. O’Phelan, Halinder S. Mangat, Stephen E. Olvey, and M. Ross Bullock

62 K.H. O’Phelan et al.

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

outcomeDetermine 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 limitedWithin 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 PTiO♦2 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 oxime-■

try, 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 hemor-rhage (SAH), spontaneous intracranial hemorrhage (ICH), acute ischemic stroke, and large brain tumors with mass effectStructural 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 metabolismIntermittent 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 activityCommonly 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♦

635 Multimodality Monitoring in Acute Brain Injury

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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 professionalsProvides 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 methodsMay 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 ♦

craniotomyRequires expertise in placing monitor♦

Provides global vs. regional Pressure data♦

Because brain is noncompressible, measured fluid pressure should repre-●

sent pressure throughout cranial vault and is generally thought of as a global measurementHowever, gradients may develop within the cranial vault and the pres-●

sure 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 therapeuticWaveform analysis can provide information about brain compliance, with ♦

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

outcomeAANS 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 <90Low cost♦

Transcranial Doppler■

Uses ultrasound technology♦

Cerebral arteries are insonated via thin temporal bone (window) or transor-♦

bitallyInadequate 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 neurointensivistsMean velocities measured are proportional to blood flow♦


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♦

ICP MANAGEMENT PROTOCOL

TARGETSOverall aim is to optimize brain perfusion and avoid secondary damage

CPP, 60–70; ICP, <20; Temp, <37.5°C; CVP, 6–10Maintain CPP with fluids and vasopressors as needed

STAGE 1Head up 30°

Sedation with propofol, 40 mcg/kg/min, titrated to RASS-2Analgesia with opiate infusion

Ventilation with normocarbia—pCO2, 34–36 mmHgNormothermia—36–37.5°C

EVD for 5 min at a time if ICP >20, for >5 min

STAGE 2Mannitol 20%, 0.5 g/kg bolus dose q 4 hr prn; ICP >20 mmHg

Hold if plasma Osm is >315 mmol/L

STAGE 3Neuromuscular paralysis with cisatracurium and/or vecuronium

Mild hyperventilation—pCO2, 32–35 mmHgHead CT (?)—if not recent, consider repeat.

STAGE 4Hypertonic saline 3%, 250 mL bolus dose q 4 hr prn; ICP >20 mmHg

Hold if serum sodium is >150 mEq/LMild hypothermia @ 34–35°C—using cooling catheter or surface cooling device, change

propofol to benzodiazepine infusion before starting therapeutic cooling

STAGE 5Decompressive craniectomy

STAGE 6Barbiturate 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 burstsuppression, with continuous EEG

CPP, cerebral perfusion pressure; ICP, intracranial pressure; Temp, temperature; CVP,cerebrovascular pressure; RASS, Richmond Agitation-Sedation Scale; EVD, externalventricular drainage; Osm, osmolality.

Fig. 5.1 ICP monitoring


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

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

latory arrest associated with brain deathCost 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 EEGCan be used for seizure detection♦

20% incidence of nonconvulsive status epilepticus or subclinical seizures in ♦

this at-risk populationCan be used to detect other detrimental neurophysiologic changes such as ♦

ischemia and elevated ICPInterpretation difficult for untrained practitioners♦

Can be used to titrate medication levels during metabolic suppression with ♦

barbituratesICU electrical equipment frequently produces artifacts♦

Less Commonly Used Neuromonitoring Tools

Parenchymal brain tissue oxygen (PbtO■2) (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 ICP >20 mmHg

Administer FiO2 100% × 15 min

to test probeAdminister FiO

2 100% × 15 min

to test probe↑PaCO

2 to 40–45 mmHg range as tolerated;

carefully monitor both ICP and PbtO2

Drain CSF

Optimize CPP Optimize CPPAdminister fluids to euvolemia; watch for

signs and symptoms of fluid overloadAdminister fluids to euvolemia

Give blood products for anemia Give blood products for anemiaCooling measures for brain;

temperature >37°CAdminister mannitol, 0.25–0.5 m/kg

Optimize sedation/analgesia; consider paralytics

Administer hypertonic saline for ICPOptimize sedation/analgesia; consider paralyticsCooling measures for brain

temperature of >37°C


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

ing properly, 100% FiO2 administered for 15 min, and PbtO

2 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 hemisphereRegional measurement – 14 mm♦ 3 of tissue reflectedValue not reliable if placed in area of severe injury (contusion) or if hema-♦

toma forms at probe siteThresholds – after TBI with normal CPP and ICP, PbtO♦

2 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 ischemiaLow PbtO♦

2 has been associated with worse outcomes; a randomized trial to

evaluate if targeted therapy improves outcome will begin soonAANS Guidelines – Level III recommendation for use in severe TBI, with a ♦

lower limit of 15 mmHg as threshold for treatmentExpensive♦

Brain temperature monitoring■

Measures temperature with a thermocouple probe placed in brain ♦

parenchymaIncluded in brain oximetry probes♦

Invasive♦

Used with other invasive monitoring such as ICP and PbtO♦2

Brain temperature is typically 1–1.5°C warmer than core temperature♦

Fever has been associated with worse outcome in SAH, TBI, and acute ♦

strokeBrain 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 trendsNoninvasive♦

Can detect pupillary constriction even in small pupils♦

Correlates with ICP CV <0.6 mm/s; associated with ICP >20 mmHg or midline ♦

shiftDifficult 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


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 bed-side 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 sedationCan 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 (SjVO■2) (Fig. 5.2)

Measures oxygen saturation of venous blood returning from the brain in jugular ♦

bulb, i.e., oxygen extractionCatheter 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 areasCan be used in combination with a regional monitor such as PbtO♦

2

Correlates well with PbtO♦2 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 placementMay 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 ♦

contami nationAANS Guidelines – Level II recommendation for use in severe TBI with a ♦

lower limit of 50% as threshold for treatmentLow 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


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

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


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

from remote tissueMicrodialysis 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 CPPCost 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 CBFRegional 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 ♦

conductance of heat between two electrodesMay 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 tissueBased on light absorption in near-infrared range transmitted from an emitting ♦

source to a sensor nearbyNot quantitative♦

Noninvasive – probe is placed on forehead♦

Regional (frontal)♦

Used more commonly in neonates – more reliable with thin skull and open ♦

fontanellesUnreliable in presence of underlying hematoma or fluid collection♦

Monitors and probes are expensive♦

Not validated clinically; essentially, a research tool♦


Tabl

e 5.

3 N

orm

al a

nd p

atho

logi

c co

ncen

trat

ions

of

brai

n m

etab

olic

ana

lyte

s in

hum

an m

icro

dial

ysis

stu

dies

, as

repo

rted

in

the

liter

atur

e fo

r pe

rfus

ion

rate

of

0.3

mL

/min

Pa

thol

ogy

Glu

cose

Lac

tate

Pyru

vate

L/P

rat

ioL

/G r

atio

Glu

tam

ate

Nor

mal

val

ues

Rei

nstr

up P

et a

l (20

00)

Neu

rosu

rger

y 47

:701

–710

Post

erio

r fo

ssa

(aw

ake)

1,70

0 ±

900

2,90

0 ±

900

166

± 4

723

± 4

–16

± 1

6

Pat

holo

gic

valu

esSt

ahl N

et a

l ( 2

001)

Act

a A

naes

thes

iol S

cand

45

:977

–985

TB

I10

0 ±

200

8,90

0 ±

6,5

0031

± 4

745

8 ±

563

–38

1 ±

236

Schu

ltz M

K e

t al (

2000

) J

Neu

rosu

rg 9

3:80

8–81

4SA

H N

o is

chem

ia2,

120

± 1

503,

040

± 3

2015

0 ±

11.

419

.7 ±

21.

62 ±

0.1

719

.4 ±

3.2

4SA

H S

ever

e is

chem

ia54

0 ±

150

6,73

0 ±

1,0

9084

.2 ±

35.

897

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32.

216

.7 ±

4.7

011

9 ±

58.

4

Dat

a fo

r th

e si

ngle

ana

lyte

s ar

e ex

pres

sed

in m

mol

/L a

nd a

re p

rese

nted

as

mea

n ±

sta

ndar

d de

viat

ion.

TB

I tr

aum

atic

bra

in i

njur

y; S

AH

sub

arac

hnoi

dhe

mor

rhag

e; L

/P la

ctat

e/py

ruva

te; L

/G la

ctat

e/gl

ucos

e


Key Points

Major advances in microelectronics have produced new techniques for monitoring ■

the injured brainMost commonly used neuromonitoring tools include serial neurologic exams, ■

ICP monitoring, TCD, and EEGLess 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 saturationRarely 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 neuroin-tensive 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


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 contusionsDue to disruption of the blood – brain barrier (BBB) and diffusion of water ♦

into the interstitial spaceTends 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 MRIIncreased signal on T2, diffusion-weighted (DWI), and apparent diffusion ♦

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

tions, resulting in movement of water from the vascular space into the inter-stitium, 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 ♦

intoxicationDue to disruption of normal cellular osmotic gradients across the cellular ♦

membrane resulting in ingress of water into the intracellular spaceNot 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

Chapter 6Cerebral Edema and Intracranial Hypertension

Matthew A. Koenig

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]

74 M.A. Koenig

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 gradientsMechanism in water intoxication and other hypoosmolar states is passive •movement of water down diffusion gradient into the intracellular spaceMechanism 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 tran-sependymal dissection of cerebrospinal fluid (CSF) into the interstitium sur-rounding 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 ♦

independentlyNormal ICP 5–20 cmH♦

2O or 3–15 mmHg (1.36 cmH

2O = 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 existsICP elevation is an independent risk factor for bad outcomes after head ♦

trauma, with a direct association between duration of ICP >20 mmHg and outcomesEven if CPP is maintained within the normal range, sustained intracranial ♦

hypertension has been demonstrated to increase brain injury in animal models of head traumaIntracranial hypertension causes brain injury due to compression and shifts of ♦

brain tissues, resulting in mechanical injury and vascular compromiseNormal 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

756 Cerebral Edema and Intracranial Hypertension

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

contents 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 pro-•cess, increases in parenchymal volume minimally impact ICP; after com-pensatory mechanisms are exhausted, further small increases may dramatically increase ICP

Clinical Presentation

Because clinical signs and symptoms of intracranial hypertension lack specific-■

ity and sensitivity, a high index of clinical suspicion should be maintained in the appropriate settingsThe classic Cushing triad of bradycardia, hypertension, and abnormal respira-■

tions is only present in ~50% of patients with intracranial hypertension and is most commonly observed in the terminal stages of herniationThe earliest signs and symptoms include new onset of hypertension and headache■

Bradycardia may be masked by pain, agitation, or blood loss, resulting in para-■

doxic tachycardiaOther signs and symptoms include decrease in mental status, abnormal ■

periodic breathing patterns (e.g., central hyperventilation), vomiting, hic-coughs, diplopia from bilateral sixth nerve palsies, dysrhythmias, and pupillary abnormalitiesFor acute lesions, level of consciousness is associated with the extent of shift of ■

midline structures, as measured by lateral displacement of the pineal body (eas-ily 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 consciousnessCerebral herniation syndromes (Table ■ 6.1)

Cerebral herniation refers to displacement of brain tissue into an adjacent ♦

compartment due to local gradients in ICP

76 M.A. Koenig

Tabl

e 6.

1 Ty

pes

of c

ereb

ral h

erni

atio

n sy

ndro

mes

Etio

logy

Clin

ical

fin

ding

sC

ompl

icat

ions

Tre

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Subf

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late

gyr

us h

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und

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Con

tral

ater

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ess

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late

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ante

rior

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ebra

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ery

com

pres

sion

Dec

ompr

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f un

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ass

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Tra

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ial

(Unc

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Med

ial t

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ral l

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hern

iate

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m

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Dec

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Upw

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, usu

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to

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Herniation causes ischemic stroke and venous hemorrhages due to compression ♦

of adjacent arteries and veins, often resulting in permanent, devastating neu-rologic injury, even if quickly reversedAlthough 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 declineStroke 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 MonroeAllows continuous ICP monitoring and intermittent drainage of CSF ▲

when ICP is elevatedAlternative strategy is continuous CSF drainage at a given ICP “pop-▲

off” (the ICP threshold that must be reached for CSF drainage to occur) and intermittent measurement of ICPMajor 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 occlusionCatheter 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

78 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 hydrocephalusRelative contraindications include collapsed ventricles, coagulopathy ▲

(i.e., fulminant liver failure carries a 10% risk of catheter tract hemor-rhage), and infection over insertion siteAntibiotic impregnated catheters decrease the rate of iatrogenic menin-▲

gitis and ventriculitis; systemic antibiotics are optional in standard ventriculostomy cathetersCSF infection rates increase rapidly between days 5–10 and subse-▲

quently plateauCSF infection rates are decreased by aseptic insertion and access tech-▲

niques, 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 compartmentMay be coupled with brain tissue oximeter, microdialysis catheter, ▲

brain thermometer, ventriculostomy catheter, or other devicesAdvantages – 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 occlu-sion, easily placed in patients with collapsed ventriclesDisadvantages – 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 CSFAdvantages – low risk of infection or hemorrhage, easily placed in ▲

patients with collapsed ventriclesDisadvantages – cannot be used to drain CSF, accuracy of ICP mea-▲

surement 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 sacAdvantages – avoidance of craniotomy, lower risk of hemorrhage and ▲

infection than is associated with ventriculostomy catheter, allows thera-peutic drainage of CSF in addition to ICP measurement


Disadvantages – preferentially drains the subarachnoid space rather ▲

than intraventricular compartment; therefore, may be ineffective for patients with ventriculomegalyContraindicated in patients with significant shift of midline structures ▲

due to unilateral supratentorial lesions or crowding of the basal cistern by generalized supratentorial edemaIn lateral decubitus position, lumbar ICP should be equivalent to ven-▲

tricular ICPIn upright position, ventricular ICP (in cmH▲

2O) = 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 trans-•mission of arterial pulse to the brainP1; percussion (systolic) wave produced by transient increase in ICP from •transmission of arterial systolic pressure to the choroid plexus, resulting in production of CSFP2; elastance (tidal) wave due to restriction of ventricular expansion by •rigid dura and skull, resulting in a transient increase in ICPP3; dicrotic wave due to closure of the aortic valve associated with arterial •dicrotic notchWith normal intracranial compliance, P1 has the highest pulse pressure, •followed by P2 and P3Elevation 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 ICPNormal ICP pulse pressure is ~3 mmHg, increasing as high as 10–15 •mmHg in patients with poor intracranial complianceLundberg A (Plateau) wave – periodic, sustained elevation of ICP >50 mmHg •for 15 min or more, associated with poor intracranial compliance and poor prognosisLundberg B wave – periodic, self-limited elevation of ICP to 20–50 mmHg, •occurring every 1–2 min and lasting several secondsLundberg 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

80 M.A. Koenig

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

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

<150 mg/dL0.5–1 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 edemaIf 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 requiredMaintain normoglycemia with aggressive insulin therapy to maintain glucose ♦

<150 mg/dLOsmolar 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 tempo-rize for definitive therapyIf intracranial hypertension suspected, proceed to ventriculostomy for ICP ♦

monitoring and to ICP crisis treatment algorithmConsideration 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 orherniation

• 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 hyperventilateto PaCO2 ~30 mmHg

Repeat dosing of mannitol orhypertonic saline to serumosmolality ~320 mOsm/L

• Place ventriculostomy catheterand drain 5–10 mL CSF

• Place central line for hypertonicsaline; 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 orhemicraniectomy

Fig. 6.1 Sample algorithm for management of intracranial hypertension


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 mmHgHowever, in patients with hypotension, the small decrease in ICP may be •offset by a decrease in CPP, resulting in ischemiaStroke 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 raisedIn practice, the effect of raising the head of bed should be tested while •closely monitoring ICP and CPP, and the optimal height should be indi-vidualized to the patientOf 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 shiveringPain should be treated with short-acting narcotics such as fentanyl or ▲

remifentanil, either by continuous infusion (with frequent interruptions for neurologic examination) or serial bolusesAgitation should be treated with short-acting sedative/hypnotic medica-▲

tions such as midazolam, propofol, or dexmedetomidine, either by continuous infusion (with frequent interruptions for neurologic exami-nation) or serial bolusesCoughing at the endotracheal tube can be treated with systemic seda-▲

tion 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 comfortShivering 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 alkalosisMay provoke or worsen cerebral ischemia if PaCO▲

2 <28 mmHg

82 M.A. Koenig

Prolonged hyperventilation (>4 h) will lead to rebound intracranial ▲

hypertension when discontinued due to CSF bufferingPatients with refractory ICP elevation, especially those requiring sedation, ▲

should undergo early intubation to maintain control of the airway and PaCO

2

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 PaCO▲2 should be

28–32 mmHgFor patients on mechanical ventilation, manual bag breaths should be ▲

avoided because of the tendency for excessive ventilation, and hyper-ventilation should be accomplished by increasing the minute ventila-tion by ~20% and titrating to an end-tidal CO

2 monitor

Hyperventilation begins to reduce ICP within 10 min, with a peak ▲

effect in 20–40 minThe effect of hyperventilation on ICP may last as long as 4–8 h, but ▲

rebound intracranial hypertension ensues thereafterIf hyperventilation is required prior to intubation, controlled breaths ▲

should be delivered by bag-valve at a rate of ~20, and excessive vol-umes and rates should be avoidedAfter 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 spaceMore effective against vasogenic than cytotoxic edema but may temporize ▲

malignant cytotoxic edema by selectively dehydrating uninvolved brainProlonged infusions of osmotic agents may ultimately worsen cytotoxic ▲

edema by sinking across a degraded BBB into infracted tissue bedsRebound cerebral edema may occur with rapid discontinuation of ▲

osmotic therapyIn stroke and intraparenchymal hemorrhage, selective osmotic dehydra-▲

tion of normal brain may actually worsen brainstem compression and shift of midline structuresSerum electrolytes and osmolality must be closely monitored during ▲

osmotic therapy due to the potential risks of dehydration, hypokalemia, hypomagnesemia, hypernatremia, hyperosmolality, and renal failureMannitol▲

Initiated as a 1–1.5 g/kg bolus of 20% mannitol for ICP crisis or N

herniationNot recommended for continuous infusion in stroke or head trauma N

due to potential to worsen cerebral edema


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

basis q 6 h to maintain a target serum osmolality of 300–320 mOsm/LTwo-stage mechanism of action – osmotic dehydration of brain N

followed by renal diuretic effect90% excluded by an intact BBB (reflection coefficient, 0.9)N

May produce massive, rapid diuresis of dilute urine due to osmotic N

load on renal tubules, leading to volume contraction and hypoten-sion, both of which may reduce CPP and produce ischemia in the setting of high ICPUrine output should be closely monitored in the first 4 h after N

administration and should be replaced by hypertonic or isotonic NaCl to maintain euvolemiaElectrolytes and serum osmolality should be monitored q 6 h during N

therapyIn addition to osmotic effects, other salutary effects include free N

radical scavenging, favorable rheologic effects, and neuroprotective mechanismsSide effects include acute tubular necrosis (which leads to renal N

failure if dehydration is permitted), hypokalemia, hypomagnesemia, hypotensionAlthough serum osmolality should be targeted to be <320 mOsm/L N

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▲

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

concentrations, including 2, 3, 7.5, and 23.4%Has similar osmotic effects as mannitol but is less potent diureticN

Serum osmotic load increases blood volume and MAP, contributing N

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

venous catheter due to the risk of phlebitis when given through peripheral cathetersIn addition to osmotic effects, other salutary effects include an N

improved rheologic profile and neuroprotective propertiesContinuous infusion of hypertonic solutions may cause rebound N

exacerbation of cerebral edema and tissue sinking with cytotoxic edema and disruption of the BBBIn the presence of an intact BBB, hypertonic NaCl is 100% excluded N

from the interstitium (reflection coefficient 1.0)Repeated doses or continuous infusion of concentrated NaCl leads N

to hyperchloremic acidosis unless buffered as a 50%/50% or 75%/25% solution of NaCl and NaHCO

3

84 M.A. Koenig

For transtentorial herniation, bolus infusion of 30–60 mL of 23.4% N

saline as part of a standard treatment algorithm will temporarily reverse clinical features of herniation and reduce ICP in 75% of patientsFor herniation or ICP crisis, a bolus infusion of 30–60 mL of 23.4% N

saline or 250–500 mL of 3% NaCl should be followed by a continu-ous 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 maintain-ing Na+ at 145–155 mg/L thereafterThe most feared potential complication, central pontine myelinoly-N

sis (CPM), has never been reported after use of hypertonic NaCl for treatment of intracranial hypertension or cerebral edemaRisk factors for CPM, including alcoholism, malnutrition, and N

chronic hyponatremia, should be considered a relative contraindica-tion for hypertonic NaCl23.4% Saline should be infused via IV pump over at least 10 min N

because rapid hand infusion produced transient hypotension in a significant number of patientsOther potential side effects include renal failure, dehydration, dys-N

rhythmia, hemolysis, and congestive heart failureTypically, serum [Na] should be maintained at <160 mg/L; however, N

in practice, concentrations as high as 180 mg/L are tolerated with-out apparent complicationsWith continuous infusion of hypertonic NaCl, most patients develop N

hypokalemia, requiring the addition of 20–40 mg of KCl per 1 L infusion

Choosing mannitol or hypertonic NaCl▲

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

ously and may have independent and complementary actions on erythrocyte morphology and secondary mediators of injuryBecause of its volume expansion effects, hypertonic NaCl is pre-N

ferred in the setting of dehydration or hypotensionIn patients lacking central venous catheters, osmotic therapy should N

not be delayed, and mannitol should be administered until central access can be establishedPatients with significant risk for development of CPM should prob-N

ably receive mannitol rather than hypertonic NaClIn patients with symptomatic congestive heart failure, mannitol is N

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


Suppressing brain metabolism by hypothermia and general anesthetic ▲

agents leads to decreased ICP by reducing cerebral blood volumePentobarbital▲

Barbiturate anesthetic most commonly used for metabolic suppres-N

sion for treatment of refractory ICP elevationHalf-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-N

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

increase in pentobarbital dose will not be effectiveAfter ICP control is established at a stable dose of pentobarbital, N

EEG monitoring can be performed periodically rather than continuouslyThe neurologic exam will be completely suppressed during EEG N

burst suppression or generalized suppression, often including the pupillary light reflexes, potentially masking brain deathMost patients experience hypotension, requiring vasopressor agents, N

immune suppression, hypothermia, generalized edema from third spacing, and ileusPatients are at high risk for infection and do not mount fever or N

other markers of inflammation; therefore, routine blood, sputum, and urine cultures should be obtained at least every other day during pharmacologic comaPentobarbital should be maintained for 48–72 h, after which, it can N

be discontinued without weaning due to the long half-lifeSerum drug levels may be useful after discontinuation to determine N

the rate of drug clearanceBrain death examination cannot be performed by clinical findings N

until the serum pentobarbital level is <5 mg/mL, requiring confirma-tory testing (i.e., SPECT scan or angiography) at higher levelsIn clinical trials for head trauma, pentobarbital has never been dem-N

onstrated to improve neurologic outcomes or mortality despite proven efficacy in reducing ICP

Propofol▲

Propofol has become more popular as an alternative to pentobarbital N

due to a shorter half-life (60–120 min after prolonged infusion)150 N mg/kg bolus, followed by 10–100 mg/kg/min infusionMore frequently causes severe hypotensionN

Patients often develop tachyphylaxis, requiring higher doses over N

time to maintain burst suppression

86 M.A. Koenig

Relatively contraindicated in children, dehydration, heart failure, N

renal failure, hepatic failure, and elderly patients due to risk of propofol-infusion syndromePatients receiving >50 N mg/kg/h should undergo daily screening for metabolic acidosis and serum triglyceride and creatinine kinase levelsPropofol infusion syndrome is a fatal syndrome of refractory N

metabolic acidosis (with or without elevated lactate levels), rhab-domyolysis, renal failure, and cardiovascular collapsePropofol may cause pancreatitis due to hypertriglyceridemia from N

the lipid carrier vehicleOther complications, including hypothermia and immune suppres-N

sion, are similar to those associated with pentobarbital

Hypothermia▲

Presumably reduces ICP through metabolic suppression, but mech-N

anisms remain unclearProven neuroprotective therapy for comatose survivors of cardiac N

arrest, but disappointing neuroprotection in clinical trials of stroke and traumatic brain injuryExternal or invasive cooling devices used to maintain core tempera-N

ture at ~32°C for 48–72 hRewarming should occur in a controlled fashion over 12–24 h to N

prevent rebound intracranial hypertensionHypothermia masks the fever response to infection; therefore, N

routine blood, sputum, and urine cultures are recommended for surveillanceOther side effects include coagulopathy and dysrhythmiasN

Shivering must be suppressed as described above because it causes N

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 edemaDemonstrated mortality and functional outcome benefit for patients <60 •years of age with malignant MCA strokes who were treated prior to hernia-tion and within 24–48 h of stroke onsetFor MCA strokes, hemicraniectomy was equally beneficial in patients with •dominant and nondominant strokesEvidence for efficacy in intraparenchymal hemorrhage, subarachnoid hem-•orrhage, and head trauma is less strongShould 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


Bilateral hemicraniectomy can be performed for patients with bilateral •cerebral edema due to head trauma or encephalitis, but large outcome stud-ies are lackingAs with all salvage therapies, the possibility that hemicraniectomy may •increase the chances of a patient (who would have otherwise died) surviv-ing in a dependent state with severe neurologic deficits must be discussed with surrogate decision makersHemicraniectomy reduces the need for osmotherapy and other interven-•tions for cerebral edemaThe bone flap can be replaced or substituted with a prosthesis ~3 months •after the initial surgeryComplications include persistent subdural hygromas, hydrocephalus, hem-•orrhage due to compression at the edge of the craniectomy, and infectionPatients 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 existTherapy based solely on maintenance of CPP at >50–60 mmHg has inher-•ent limitations - CPP is a global measure that does not necessarily account for focal ischemiaA rigid approach to maintaining CPP at all costs may result in systemic •injury from volume overload and vasopressor use leading to ARDSIn 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 formationTherapy based on increasing MAP to augment CPP may, therefore, worsen •cerebral edema and systemic complications

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

88 M.A. Koenig

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 contri-▲

bution of hydrostatic pressure to cerebral edema formationAlbumin is given to maintain the capillary oncotic pressure and draw ▲

water into the vascular spaceTissue hydrostatic pressure is limited by reducing ICP through sedation ▲

and metabolic suppression

Key Points

Cerebral edema, intracranial hypertension, and cerebral herniation may occur ■

independently or may exist on a spectrum of diseaseClinical signs and symptoms of intracranial hypertension are unreliable, and a ■

high index of suspicion is required for relevant diseasesThe BBB is disrupted in cytotoxic edema, rendering it less amenable to treat-■

ment with osmotic agents or corticosteroids and more prone to worsening of edema with CPP augmentationSustained ICP elevation and cerebral herniation are medical emergencies best ■

managed by a protocol that includes osmotic therapy and hyperventilationMedical 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 38:3084–3094Bhardwaj A, Ulatowski JA (1999) Cerebral edema: hypertonic saline solutions. Curr Treat Opt

Neurol 1:179–187Hutchison P, Timofeev I, Kirkpatrick P (2007) Surgery for brain edema. Neurosurg Focus

22:E14:1–9Jüttler 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 malig-nant 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

89

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•


~10–20% of patients have pulmonary edema or cardiac dysfunction•

More common in patients with devastating TBI that leads to brain ▲

deathStatus 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•

Chapter 7Cardiac Dysfunction, Monitoring, and Management

Andrew Naidech

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]


90 A. Naidech

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). Catecholamine-induced 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 dysrhythmiasSubclinical 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 TBIcTI is more often positive than CK-MB•In SAH, early cTI elevation is associated with later complications and poor •response to hyperdynamic therapy

917 Cardiac Dysfunction, Monitoring, and Management

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 hypoten-sion 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 inflammation-•mediated changes in alveolar and capillary cellsMay 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 NPETypically 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 supplementationIf abnormal Mg• 2+ is not corrected, ↓K+ cannot be normalized

• ↑K+

92 A. Naidech

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 feasibleAntibiotic-coated central lines prevent infection >1 week after catheter •insertion

Pneumonia♦

Ventilator associated if presentation is >48–72 h after intubation; antibiotics •depend on sensitivitiesConsider 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 ♦

contraindi catedConsider routine compression stockings♦


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 mmHgSome 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 interactionscTI 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 outcomesAnticonvulsants♦

Many anticonvulsants (valproic acid, barbiturates, benzodiazepines, etc.), •and in particular, phenytoin may lead to hypotension, dysrhythmia, or prolonged QTc on ECGMultiple 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:•

94 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 riskWhen suspected, discontinue propofol immediately and choose an alternative •sedativeConsider 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 useRemove offending cause (antibiotics, propofol, anticonvulsants, etc.), if •possibleInterruption 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

resistanceMay require peripheral vasopressors to maintain adequate blood pressure; ▲

a-agonists (e.g., phenylephrine) most helpfulMay 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.♦


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 NSMElevated 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 resis-•tance (phenylephrine, norepinephrine, higher-dose dopamine, etc.) with worsening hemodynamicsConsider 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 angiography-based intervention in lieu of hyperdynamic therapyConsider 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)

Fig. 7.1 General cardiac monitoring in the NCCU

Admission/ComplicationPhysical exam

Correct hypovolemiaTelemetry

Check e-lytes/ABG/cTI12-lead ECG Echocardiography

Dysrhythmia

Re-check electrolytesRe-check cardiac enzymes

Refer to ACLS protocols

Hypotension

Re-check cardiac enzymesConsider echocardiographyIn SCI, consider α agonists

Screen for infectionConsider screen for PEScreen for causative Rx

Acute coronary syndrome

Consider:b blocker

ACE InhibitorHigh-dose statin

OxygenNitrates

96 A. Naidech

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 contraindicatedShould 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 perfusionCautious use of peripheral vasodilators in SCI•

Outcomes

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

Elevatedcardiac

enzymes

DepressedLV function

Increasedvaso-

pressors

BP

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


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 throm-bosis, PE, etc.)

Cardiovascular instability and hypotension are associated with increased length ■

of stay, resource utilization, and costsMost 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 injuryTelemetry 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 6:473–489Daniele O, Caravaglios G, Fierro B, Natale E (2002) Stroke and cardiac arrhythmias. J Stroke

Cerebrovasc Dis 11:28–33Hays A, Diringer MN (2006) Elevated troponin levels are associated with higher mortality following

intracerebral hemorrhage. Neurology 66:1330–1334Kothavale A, Banki NM, Kopelnik A et al (2006) Predictors of left ventricular regional wall

motion abnormalities after subarachnoid hemorrhage. Neurocrit Care 4:199–205Lehmann 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

99

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 incorpo-■

rate novel ventilatory strategies due to a unique constellation of symptoms and neurologically based problems centering on the need to preserve brain functionThese ventilator strategies often operate outside the norms established for medi-■

cal 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♦

Chapter 8Airway Management and Mechanical Ventilation in the NCCCU

Paul Nyquist

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]


100 P. Nyquist

Primary neurologic disorders that result in primary neuromuscular disorders ■

with type II respiratory failure and often require intubation include:

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 postop-■

eratively 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 comaLoss 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 intubationThree 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 deteriorateIn 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

1018 Airway Management and Mechanical Ventilation in the NCCCU

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

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 patientsInjury affecting these patients may be mild, and these alterations in breathing ■

patterns can be seen in patients who appear to be neurologically intactChange in respiratory rate can be associated with a change in awareness and an ■

improvement or decline in the neurologic examDuring hyperventilation, the patient maybe more alert and may awaken if uncon-■

scious, 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 (PaCO

2) 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 structuresNeural control of respiration depends on both conscious and automatic compo-■

nents 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 pres-sure (ICP) that lead to a herniation; these altered patterns of respiration include:

Cheynes–Stokes breathing♦

Apneustic breathing♦

102 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 sizesOften called the • atrial fibrillation of breathingAssociated 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 frac-■

tional 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 PaCO■2; hypocapnia induces

vasoconstriction and reduces CBF by causing a reduction in the volume occu-pied by the vascular component of the cranial vault


Hyperventilation to induce hypocapnia is a rapidly effective strategy to acutely ■

reduce ICP

Hyperventilation is used to reduce PaCO♦2 from its normal range of 40–60

mmHg to a reduced range of 25–35 mmHgAcute 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 minuteMediated by arterial responses to changes in pH and occurs in the perivascu-♦

lar space of the small arterioles of the brainChanges 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 systemAs 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 ran-domized prospective study has been conducted that addresses the effects of chronic hyperventilation on clinical outcomes in patients with TBI

100 200

Normocapnia

Increasing risk ofhypertensive

encephalopathy

Increasing riskof ischemia

50 150 250

Hyperventilation

Cerebral Blood Flow

MAP (mmHg)

0

Fig. 8.1 The cerebral autoregulation curve

104 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

Clinical studies have documented the relationship of elevated positive end-■

expiratory 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 H

2O 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 ICPClose proximity of the thoracic cavity and the cranial vault allows the direct trans-■

mission 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 pronePEEP 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 injuryIn 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 declinesIn patients with severe lung injury, the effects of PEEP on increases in intratho-■

racic 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


Effects of High-Frequency Ventilation on ICP

High-frequency ventilation (HFV) is an innovative mode of mechanical ventila-■

tion 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 pres-sure 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 accom-■

plished 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

106 P. Nyquist

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 levelsClinical studies have focused on two types of monitoring devices♦

Jugular bulb oximetry•Monitoring of brain tissue oxygen tension (PbrO•

2)

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•


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 PaCO♦2

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♦

Permissive hypercapnia has not been shown to induce brain injury and is fre-■

quently 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 ICHHas 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 spe-■

cific pulmonary complications caused by their neurologic illness; these associ-ated 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

108 P. Nyquist

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 ICHCombat 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 instantaneousSupportive 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

NPE is caused by extravasation of a proteinaceous fluid across the alveolar ■

membrane; this is secondary to injury to the alveolar membrane from the cate-cholamine storm associated with severe neurologic injuryNPE 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 pro-teinaceous material is produced from the pneumocytes within the alveolar wallThe diagnosis of NPE is often difficult to separate from other forms of lung ■

injury, including ARDS, ALI, and heart failure from stunned myocardiumWhile 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 NPEOther 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♦

Definition of ARDS and ALI can be quite similar to NPE■

Bilateral pulmonary infiltrates on chest X-ray♦

Alteration of the PaO♦2/FiO

2 ratio to <300 within 24 h for ALI and <200 over

48 h for ARDS

In general, NPE is different from pulmonary edema from heart failure, ARDS, ■

and ALI:

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♦


Elevated FiO♦2

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

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 echocardiographyDiagnosis of stunned myocardium focuses on the detection of:■

Increased serum troponin and CK-MB, usually with disproportionately high ♦

troponin levelsEKG 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, hypoki-•nesis on the echocardiogram, usually with an apical distribution

Treatment of the stunned myocardium■

Inotropic support♦

Fluid restriction♦

Diuresis♦

Early detection and appropriate treatment are required to avoid potentially fatal ■

outcomesIntubation 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

110 P. Nyquist

Liberation from Mechanical Ventilation in Neurologic Disorders

Little data exist to guide the appropriate decision-making pathways in liberating ■

patients with primarily neurologic injury from the ventilatorThe Society of Critical Care Medicine suggests that best evidence supports the ■

weaning pathway that utilizes a standard breathing trial, with aggressive libera-tion from the ventilator if the patient passes this trialWeaning 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 literatureMany 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 ventilationLiterature 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

Liberating patients who are mechanically ventilated in the setting of neurologic ■

injury can be accomplished safely and quickly; predicting the success of libera-tion and the long-term viability of that process can be difficultImportant considerations when evaluating the patient with respiratory impair-■

ment 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


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 ventilationTracheostomy 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 driveOften 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 pneumoniaPatients 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 breathingEarly 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 injuryCare must be taken to identify the mechanical limits caused by their neu-•rologic injury prior to liberationPatients in general should not be liberated until they have demonstrated a •prolonged period of independent ventilation such as tolerance of a pro-longed CPAP trial or T-piece trial

Weaning in Pure Type II Respiratory Failure

Extubation of patients with severe peripheral nerve disease can be attempted ■

when sufficient respiratory muscle recovery occursExtubation 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♦

112 P. Nyquist

Mean inspiratory pressure <−20 to −50 cm H♦2O

FiO♦2 requirement <40% and PEEP ³5 cm H

2O

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 wellHigh 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 ♦

dependencyPatients often exhibit a form of breathing known as ♦ paradoxical breathingThe 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 dysfunc-■

tion; injury from C1 to C

3 causes apnea

Injury from C♦3 to C

5 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 independentInjury below C♦

5 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 inflationAggressive 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 H♦2O

Vital capacity >15–20 mL/kg of patient’s ideal body weight♦

Pitfalls to be avoided involve the rapid extubation of patients with cervical spine ■

injury within the first 72 h


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 respira-tory failureAdditionally, 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

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 bed-side personnelIntubation and extubation criteria depend on mental status examination and ■

status of neuromuscular strengthCertain patterns of breathing are associated with specific lesion locations, often ■

seen in ICU patients with intracranial mass lesions and elevated ICPNeurologic injury causes direct effects on the pulmonary system that manifest ■

as NPE and pulmonary edema from stunned myocardiumA 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, PhiladelphiaThe 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


Introduction

The cerebrovascular system is highly vulnerable to fluctuations in systemic ■

blood pressure (BP) through structural and functional alterationsIn a normal brain, cerebral blood flow (CBF) is autoregulated over a wide range ■

of BPCBF remains relatively unchanged over a range of cerebral perfusion pressure ■

(CPP) under normal circumstances secondary to changes in cerebrovascular resistance (CVR) via vasoconstriction and vasodilationCBF = CPP/CVR■

CPP is the difference between the mean arterial pressure (MAP) and the intrac-■

ranial 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 hemorrhageRegarding hypotension – the goal is to prevent BP from falling below the threshold ■

that maintains adequate CPP, thereby avoiding secondary ischemic brain injuryA MAP in the range of 60–150 mmHg helps to maintain a constant CBF in ■

normotensive individualsMean arterial hypertension may be gradually reduced below 120 mmHg in per-■

sons with a history of chronic hypertension, but a reduction of >20% should be avoided in the acute setting

Chapter 9Blood Pressure Management

Ameer E. Hassan, Haralabos Zacharatos, and Adnan I. Qureshi

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]

116 A.E. Hassan et al.

Pathophysiology of Hypertension

Chronic hypertension contributes to decreasing the elasticity of arteries, thereby ■

increasing the likelihood of rupture in response to acute elevations in intravas-cular pressureThe spectrum of lesions due to arterial hypertension, at the level of the intra-■

parenchymal 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♦

Long-standing and persistent hypertension leads to cerebral vascular wall dam-■

age that can be seen with the hyalinization of excessive fibrillar material from arteriolar wall or from basement membranes, otherwise termed sclerosis (arte-riolar and capillary) with hyalinosis

Intracerebral Hemorrhage

Hypertension is the most frequent and most important risk factor for intracere-■

bral hemorrhage (ICH)After an acute ICH, BP initially reaches a maximum over 24 h and then declines ■

spontaneouslyHemorrhages that involve the putamen, globus pallidum, thalamus, internal capsule, ■

periventricular white matter, pons, and cerebellum are often attributed to hyperten-sive small-vessel disease, particularly in a patient with known hypertensionElevated early-mortality rates have been clearly demonstrated in ICH patients ■

who present with high arterial pressuresHematoma 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 rebleedingEmphasis on BP reduction is especially true for hemorrhage that results from ♦

a ruptured aneurysm or arteriovenous malformation, in which the risk of con-tinued bleeding or rebleeding is presumed to be highestHematoma enlargement occurs more frequently in patients with elevated ♦

systolic BP. However, it is not known whether this represents a direct contrib-uting cause to the hematoma expansionThe 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

1179 Blood Pressure Management

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 BPDecreased 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 BPEdema 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

Patients with ischemic stroke often suffer from chronic hypertension, and their ■

cerebral autoregulatory curve is shifted to the rightThe elevation in BP may be a result of many factors including the stress of the ■

cerebrovascular event, anxiety, nausea, pain, baseline hypertension, a physio-logic response to hypoxia, or a response to increased ICP

Table 9.1 Recommended AHA/ASA guidelines for treating elevated blood pressure in spontaneous ICH

SBP/MAP

Suspicion and/or evidence of elevated ICP CPP

BP check/clinical re-examination Comment

If SBP >200 mmHg OR

If MAP >150 mmHg

Every 5 min Consider aggressive BP reduction with continuous IV infusion

If SBP >180 mmHg OR

If MAP >130 mmHg

Yes >60–80 mmHg

Consider monitoring ICP and reducing BP using intermittent or continuous IV medications to keep CPP >60–80 mmHg

If SBP >180 mmHg OR

If MAP >130 mmHg

No Every 15 min Consider a 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

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


Many patients have spontaneous declines in BP during the first 24 h after onset ■

of strokeHigher MAP levels are better tolerated by hypertensive stroke patients■

Stroke patients with a history of hypertension are at risk of critical hypoperfu-■

sion for MAP levels usually well tolerated by normotensive individualsFor 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♦

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 brainIt 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

Intracerebral

hemorrhage

Reduce BP if

>185/110 mm Hg using

short acting IV medication

Treated with

thrombolysis

Maintain BP

<180/105 mm Hg using short

acting IV medication

or infusions

for 24 hours

Suspect high

ICP

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

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

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

Candidate for

thrombolysis

Not a candidate

for thrombolysis

Reduce BP if

>220/120 mm Hg using short

acting IV medication

and avoid and treat

hypotension

(<100/70 mm Hg)

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


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 startedIf 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 therapyConsensus 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 strokeResearch testing the effects of early treatment of arterial hypertension on ♦

outcomes after stroke is under wayIt 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)

Drugs recommended for use in lowering BP in acute stroke include labetalol, ■

hydralazine, nicardipine, and nitroprussideDue to the high rates of dysphagia and impaired consciousness within the acute ■

neurocritical care setting, IV therapy is the route of choice for treatmentAdvantages 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/minEnalapril 1.25–5 mg IVP q 6 ha NAEsmolol 250 mg/kg IVP 25–300 mg/kg/minNicardipine 5 mg/h IVP 5–15 mg/hNitroprusside NA 0.1–10 mg/kg/minNitroglycerin NA 20–400 mg/minLabetalol 5–20 mg q 15 min 2 mg/min (maximum 300 mg/day)Urapidil 12.5–25 mg 5–40 mg/ha The enalapril first test dose should be 0.625 mg due to the risk of precipitous lowering of blood pressure


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 hypertensionIV nicardipine has a rapid onset of action (1–2 min) with an elimination half-♦

life of 40 ± 10 min, and the major effects last from 10 to 15 minIt 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 ♦

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

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

first-line agent in patients with ICH who require acute antihypertensive therapyIV labetalol treatment has the benefit of minimal side effects with a rapid ♦

onset of action and the disadvantage of sustained hypotensive effect with prolonged usageLabetalol is metabolized by the liver♦

Hydralazine■

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

cle cells, leading to the reduction of arterial BPHydralazine has a latency of ♦ £15 min following an IV dose and a therapeutic duration of up to12 hHeadache, hypotension, and palpitations are the common side effects associ-♦

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

to <160 mmHgLow 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 stoppedSNP is often not the antihypertensive of choice in patients with ICH due to its ♦

potent venodilatory effects, which may increase ICP in susceptible patients


Key Points

Fundamental principles of BP management in neuro-critical care include avoid-■

ance of systemic hypotension and hypertension, maintaining CPP > 60–70 mmHg for preventing secondary brain and spinal cord injuryReduction of CPP below 70 mmHg can trigger reflex vasodilatation and ICP ■

elevationIdeal agents should be short acting, can be administered intravenously and that ■

have minimal effects on ICP and CBF autoregulationDrugs 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


Epidemiology and Etiology

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 com-■

plications, and increased morbidity and mortality rates, all resulting in increased costsAll patients admitted to the neurocritical care unit should be screened for risk or ■

presence of malnutritionCritically ill patients with neurologic impairment often require specialized nutri-■

tion support because of intubation, dysphagia, or altered mental statusAcute neurologic injury can result in metabolic and physiologic alterations and ■

nitrogen wastingEarly 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 outcomeNeurosurgical patients who require major spinal or intracranial interventions ■

experience the same intense catabolism characteristic of major surgery patientsParenteral nutrition should be reserved for those patients with impaired gastro-■

intestinal (GI) function or those who cannot meet their nutritional needs via EN alone

Chapter 10Nutrition in Neurocritical Care

Tara Nealon

T. Nealon, RD, CNSC (*) Johns Hopkins University School of Medicine, Baltimore, MD, USA e-mail: [email protected]

124 T. Nealon

Clinical Presentation (Signs and Symptoms)

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 supportComponents of a nutritional assessment■

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▲

Women – 100 lb (45 kg) for the first 5 ft (152 cm) and add 5 lb (2.3 N

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

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

frame size can be used for interpretation

Classification of IBW▲

% of IBW = weight/IBW × 100N

80–90% = mild malnutritionN

70–79% = moderate malnutritionN

0–69% = severe malnutritionN

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 (m• 2)Interpretation•

12510 Nutrition in Neurocritical Care

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▲

85–95% = mild malnutritionN

75–84% = moderate malnutritionN

0–74% = severe malnutritionN

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 carbohy-drate metabolism from fat, which greatly alters insulin levels and concomi-tant serum electrolyte levels

The syndrome typically occurs within 4 days of refeeding; Hypophosphatemia •is common as is a fall in potassium, magnesium, glucose, and thiamineVisceral organ function (cardiac, neuromuscular, hematopoietic, etc.) is •subsequently dysfunctional as a consequenceSpecial 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 recoveryNegative acute-phase reactants because they decrease at least 25% in ▲

response to chronic or acute inflammationIn addition to inflammation, serum concentrations are affected by renal and ▲

liver function, hydration status, blood loss, iron deficiency, and pregnancy

126 T. Nealon

Half-life▲

Albumin – 14–20 daysN

Prealbumin – 2–3 daysN

Transferrin – 8–10 daysN

Can identify those patients who are at risk for malnutrition due to ▲

hypermetabolism/hypercatabolismIf 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:▲

Urine output <1 L/dayN

Renal or liver failure with nitrogen accumulating in the bloodN

Nitrogen losses from large open wounds, fistulas, or diarrheaN

Urine collection <24 hN

Metabolic response to neurotrauma♦

Initial “ebb” phase•

General decrease in metabolism, body temperature, cardiac output, and ▲

energy expenditureUsually 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 massCan 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 determin-•ing energy requirements; IC obtains REE (resting energy expenditure)


Many factors limit the use of IC such as patient stability, inconsistent ven-•tilator settings, air leaks, and calibration errors; therefore, it may be diffi-cult to obtain accurate resultsWhen IC is used, a 5 min steady state must be achieved to validate the use •of data obtainedTraditionally, various multipliers are added to measured REE; however, •recent research concluded that patients should be fed 100% REE without addition of factorsThe 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 0.67–1.3Therefore, when using IC, care must be taken not to adjust a nutritional •regimen based on the value of the RQWhen IC is not available, predictive equations and kcal/kg can be used to •estimate energy requirementsNot 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 illIf 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 accurateFor 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 simplis-•tic; The American Society for Parenteral and Enteral Nutrition (ASPEN) Guidelines recommend 20–35 kcal/kg/day for adults25 kcal/kg is recognized as a starting point for the critically ill patient, as •it is important to avoid overfeeding in this populationIn those patients at risk for refeeding syndrome, nutritional needs may be •estimated at 20 kcal/kg initially and, after slow advancement and determi-nation of tolerance to feeding, will be adjusted appropriately; Careful monitoring and repletion of electrolyte levels is also recommended in these patientsHypocaloric 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 complicationsGoal 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 appropriateAfter the acute phase of critical illness, caloric provision can be evalu-▲

ated on an individual basis to be increased to support the recovery phase

128 T. Nealon

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 massInflammatory 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 ade-quacy of nutritional intakeThe current recommendation is to provide 1.5–2 g/kg/day of protein•

Fluid requirements♦

Table 10.1 Estimation of energy requirements in critically Ill (in order of accuracy)

For nonobese patientsPenn State:

Resting metabolic rate (RMR) (kcal/d) = HBE(0.85) + VE(33) + T

M(175) – 6,433

Equation uses basal metabolic rate calculated with the Harris–Benedict equation (HBE), minute ventilation (V

E) in liters per min (L/min), and maximum temperature (T

max) 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 patientIreton–Jones, 1992:

Same as abovePenn State, 1998:

Resting metabolic rate (RMR) = Basal metabolic rate (BMR)(1.1) + VE(32) + T

max(140) – 5,340

Equation uses basal metabolic rate calculated with the Harris–Benedict equation, minute ventilation (V

E) in liters per min (L/min), and maximum temperature (T

max) 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 evidence-based nutrition practice guideline, 2008


By weight – 25–35 mL/kg/day, depending on age, sex, activity, clinical •conditionBy 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 failureIncreased 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 supportIn 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 duode-•num that cannot be resolvedSevere GI bleed•Gut ischemia•Hemodynamically unstable: MAP <60–70 mmHg, • ↑ dose of pressors

Table 10.2 Possible consequences of underfeeding and overfeeding

UnderfeedingDecreased respiratory muscle strengthFailure to wean from mechanical ventilationPoor wound healingImmunosuppressionImpaired organ functionIncreased risk of nosocomial infection

OverfeedingHyperglycemiaFailure to wean from mechanical ventilationHypertriglyceridemiaHepatic steatosisAzotemiaImmunosuppressionElectrolyte imbalanceAlterations in hydration status

130 T. Nealon

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 ICUEarly EN is associated with a decrease in infectious complications and •may reduce LOS

Location♦

Short term•

Nasogastric or orogastric tube▲

Commonly placed in the neurocritically ill patientN

Made in various sizes (5–18 F), but 8–12 F most appropriate for N

administration of enteral feedsEasily placed at bedsideN

Nasoenteric tube (nasal duodenal/Dobhoff, nasojejunal, nasogastric-▲

jejunal)

Placement of a feeding tube in the small bowel should be consid-N

ered when a patient is supine or under heavy sedation or when serial measurements of gastric residual volumes >250 mL are not respon-sive to prokinetic agentsNasogastric-jejunal tube can allow for gastric decompression with N

simultaneous small bowel feedingCan be more difficult to place – may need fluoroscopic or endo-N

scopic placementX-ray verification of tube placement remains the gold standardN

The smallest bore feeding tube possible should be used for patient N

comfort

Long term•

If anticipated that a patient will require enteral feeding for >4 weeks, a ▲

gastrostomy or jejunostomy tube should be placedGastrostomy (PEG, open G-tube)▲

Available in sizes from 14 to 28 FN

Can be placed endoscopically, radiologically, and surgicallyN

Allow for bolus feeding and administration of medicationN


Jejunostomy (PEJ, open J-tube, PEG/J, G-JT)▲

Smaller bore tubes (8–14 F); gastric port larger, if placedN

Ideal for patients with gastroparesis, recurrent aspiration of gastric N

contentsCan have a tube with both gastric and jejunal ports to allow for N

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 formulationsTypically provided as 40–90% of total kcals•Most formulas are lactose free because of prevalence of lactose •intoleranceMost 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 formulationsMay be soluble or insoluble▲

Soluble – can help to control diarrhea because of its ability to N

increase sodium and water absorption. Enteral formulations with soluble fiber have been shown to reduce the incidence of diarrheaInsoluble – may help to decrease transit time by increasing fecal N

weight. No studies to date have supported the decrease in incidence of diarrhea with insoluble fiberFiber-containing formulas should not be given to patients with N

decreased gastric emptying or who are at risk for bowel ischemiaSome enteral formulas contain FOS (fructo-oligosaccharides), a N

nondigestible oligosaccharide that is fermented in the colon to pro-duce short-chain fatty acids that may aid in maintaining gut integ-rity 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)

132 T. Nealon

The fat in enteral formulas serves as a source of concentrated energy ▲

and prevents essential fatty acid deficiencyVegetable oils are commonly used as the fat source to provide essential ▲

fatty acidsMany 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 malabsorptionOmega-3 fatty acids are thought to be anti-inflammatory, whereas omega-6 ▲

fatty acids are thought to be proinflammatory and immunosuppressive

Some enteral formulas contain a higher amount of omega-3sN

While studies have shown promising results, it is not recommended N

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 proteinPeptide-based formulas contain a protein source that has undergone ▲

enzymatic hydrolysis. Peptides are absorbed as efficiently as free amino acidsElemental 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 ▲

containsPercentage of water from enteral formulations should be included in ▲

patients’ total fluid intakeMost 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 tubeShould not be added directly to the tube feeding formula except if done ▲

under sterile conditionsProtein powders▲


Most commonly used modular product, contains 7–12 g protein per N

servingUsed to add additional protein to tube feeding regimen without N

significantly increasing caloric provision

Carbohydrate powder▲

PolycoseN

Fat▲

MCT oilN

Fiber▲

Soluble fiber supplementN

Micronutrients▲

When provided in a sufficient volume (usually 1,000–1,500 mL/N

day), most enteral formulas meet 100% RDI for vitamins/mineralsPatients not receiving 100% RDIs from tube feeding should receive N

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 formulaSelection of an appropriate tube feeding formula should be based on GI func-•tion, fluid status, presence of renal failure, and needs for wound healingWhile 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 productStandard, 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 patientRenal formulas may be appropriate for patients whose serum electrolyte •and mineral levels are difficult to controlDiabetic formulas are not supported for routine use in the critically ill popu-•lation. Published evidence that these formulas improve glycemic control is limited, and the high-fat content can contribute to delayed gastric emptyingSemi-elemental and elemental formulas should be used only in cases of •malabsorption, maldigestion, short bowel syndrome, or pancreatic exo-crine insufficiency

134 T. Nealon

The use of immune-enhancing formulas is not recommended for routine •use in the critically ill population

American Dietetic Association (ADA) Analysis Library:▲

Immune-enhancing EN is not associated with reduced infectious N

complications, LOS, reduced cost of medical care, days on mechan-ical ventilation, or mortality in moderately to less severely ill ICU patientsTheir use may be associated with increased mortality in severely ill N

ICU patients, although adequately powered trials evaluating this question have not been conducted

Initiation♦

In critically ill patients, conservative tube feeding initiation and advance-•ment is indicatedGastric feeding is acceptable as a starting point and well tolerated by most •neurocritically ill patientsTube 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 hIn the stable neurocritically ill patient who is tolerating gastric feeds, tube •feeding regimens may be adjusted on an individual basis to a bolus or grav-ity 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 diarrheaPresence or absence of bowel sounds is not always a good indicator of •bowel function; therefore, absence of bowel sounds is not a contraindica-tion to enteral feedingDiarrhea 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 strate-▲

gies belowStrategies to alleviate diarrhea▲

Increasing fluid replacementN

Addition of soluble fiberN

Addition of anti-motility agentN

If possible, change of offending medicationN


Switch to tube feeding formula with lower osmolality or lower fat N

content, if indicatedChange of formula to semi-elemental or elemental should be the last N

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 •narcoticsNeurocritically 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 empty-ing, regurgitation, vomiting, pneumonia, or mortalityIn 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 mis-placement of the tip of a feeding tubeStrategies to reduce risk of aspiration include elevation of the head of the •bed to 45°, X-ray confirmation of feeding tube placementAn 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 volumeMost institutions have a specific protocol regarding checking and moni-▲

toring 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 volumesIf a patient is not responsive to the prokinetic agents, feeding tube place-•ment beyond the ligament of Treitz may be beneficialBlue dye has traditionally been added to enteral formulas to detect aspira-•tion 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 benefitThe presence of blue dye in tracheal secretions is not a sensitive indica-▲

tor for aspiration and therefore should not be routinely used in the criti-cally ill population

136 T. Nealon

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 stomachKinking of the tube▲

Clogging of the tube▲

Most common cause is inadequate flushingN

Other causes include inadequately crushed medications, medica-N

tions administered together, inadequate amount of water given with each medicationTube should be flushed before, between, and after medication N

administrationWarm water is the optimal choice for unclogging the tubeN

Can use pancreatic enzymes if unsuccessful with warm waterN

Tube feeding formula is rarely the cause of cloggingN

Oral intake♦

Candidates for oral intake should have a bedside swallowing evaluation •before initiation of oral intakeMany patients may require concurrent administration of enteral feeds until •able to meet caloric and protein requirements via oral intake aloneEnteral feeds can be changed to nocturnal, cyclic, or bolus in efforts to •facilitate oral intakeMany 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 malnutritionA 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▲


Severe catabolism with or without malnutrition when GI tract is not ▲

usable within 5–7 daysLengthy GI work-up, requiring NPO status for several days in malnour-▲

ished patientAcute 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 acidsLimitations on meeting nutritional needs▲

Not the optimal choice for feeding patients with significant malnutri-▲

tion, 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 formulasAvailable 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

138 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% emulsionsTotal of 2.5 g/kg/day of lipids in healthy patients and 1 g/kg/day in the ▲

critically ill should not be exceededPropofol 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 syndromeHigher 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 adultsVitamin 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 zincMTE-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 solutionsIron 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


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 hospitalCan also be cycled in stable patients with PN-associated liver abnormali-•ties to rest the liverCycled 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 trig-lyceride 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 stableTriglyceride level should be obtained before starting IV lipids; weekly •thereafterFingersticks 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▲

Avoid overfeedingN

Limit dextrose in CPN to 150 g/day initiallyN

Review other sources of IV dextrose that the patient is receiving N

(antibiotic drips, continuous venovenous hemodialysis, peritoneal dialysis, etc.). Adjust PN if indicatedTighten sliding-scale insulin coverageN

Increase frequency of fingersticksN

140 T. Nealon

Start insulin dripN

Stop CPN for 24 h; resume once glucose levels are under controlN

Hepatic•

Fatty liver due to over infusion of dextrose, lipid, and/or total calories▲

Biliary•

Cholestasis▲

Initiate enteral/oral intake as soon as possible, even with malabsorp-N

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 prob-•ably the most commonly known drug–nutrient interactionMany studies and case reports have been published, but few are prospec-•tive, randomized, controlled trialsThe practice of holding tube feeding before and after phenytoin adminis-•tration is cumbersome and often results in inadequate nutrient intake. This practice has not been validatedMany 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 feed-ings are held for medications

Carbidopa/Levodopa♦

No trials have evaluated absorption of carbidopa/levodopa with concurrent •enteral feedingsExtrapolations have been made from the data that show a decreased effect •when the medication is taken with a high-protein mealThe 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■



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 essentialNitrogen losses of up to 30 g/day have been documented in acutely ill •patients with head injuryGoal 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 lossesEN 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 ENIf intolerance to gastric feeding is noted, placement of the tube should be •advanced into the small bowelPatients for whom EN was initiated rapidly had fewer infectious complica-•tions, earlier hospital discharge, and better neurologic outcomes at 3 months as compared to patients whose EN formula rate was slowly increased over timeFor patients receiving barbiturate coma therapy, energy expenditure will be •decreased. Small bowel feedings have been shown to be well toleratedPropofol 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 regimenPN 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 agentsThe 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 nutri-•tional requirements over the course of injuryIn 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 imple-mented via nasogastric or nasojejunal tubes within the first 48 hImmobilization leads to high nitrogen losses in acute phases of injury; •however, over time, it may lead to an increase in body fatBody weight should be adjusted by 4.5 kg for paraplegic and 9 kg for •quadriplegic patientsInitial caloric guidelines for paraplegic patients are 28 kcal/kg/day; for quad-•riplegic patients, 23 kcal/kg/day. These levels may change depending on the clinical status of the patient at time of initiation of nutritional supportMany patients with spinal cord injuries will require a more permanent •feeding device. Placement of tube may depend on location of injury

142 T. Nealon

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 nutri-•tional support may be requiredEnteral 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 warrantedDysphagia is a common complication, and efforts to regain swallowing •function should be implemented earlyEven 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 transi-•tion into the recovery (rehabilitation) phase of illnessOngoing immobility and denervation continue to generate muscle losses; •therefore, care should be given to maintain adequate protein intakeHydration status should be closely monitored, as fluid intake is often com-•promised 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-feedingPEG placement may be a potential option for many of these patients; how-•ever, may not improve outcome

Key Points

Malnutrition is associated with longer hospital stays, slower healing, more com-■

plications, and increased morbidity and mortality ratesNutritional support should be initiated in those patients unable to tolerate oral ■

diet within 48 h of admission to the neurointensive care unitEN support is the preferred route in the neurocritically ill patient who requires ■

specialized nutritional supportMost neurocritically ill patients can tolerate gastric feedings; however, if intoler-■

ance is present, the use of prokinetic agents and placement of a tube past the ligament of Treitz should be utilized


PN should be reserved for those patients with severe GI impairment or docu-■

mented intolerance to ENPatients with TBI exhibit a hypermetabolic response that is proportional to the ■

severity of injury and motor dysfunctionPatients 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 supportA swallowing evaluation should be completed before initiating oral diet. Even ■

when tolerance is established, many patients will also require long-term EN sup-port to achieve adequate nutrient intake

Suggested Reading

ADA Evidence Analysis Library (2006) Critical illness evidence-based nutrition practice guide-lines. 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 case-based 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–S84Todd SR, Kozar RA, Moore FA (2006) Nutrition support in adult trauma patients. JPEN J Parenter

Enter Nutr 21:421–429

http://www.adaevidencelibrary.com


General Issues of ICU Sedation

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 ■

patientSedatives and analgesics may compromise exam and cerebral physiology■

More need for conscious sedation due to recent reduction in pharmacologically ■

induced paralysis in ICU patientsEmphasis 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”

■ Sedation – commonly used to indicate provision of analgesia, anxiolysis, anti-psychosis, or a combinationCorrect diagnosis of a single or overlapping disturbance thus becomes starting point■

Medications may have narrow or broad overlapping therapeutic effects■

Chapter 11Sedation, Analgesia, and Neuromuscular Paralysis

Marek A. Mirski

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]

146 M.A. Mirski

Management of Pain: Recognition

Prerequisite for analgesic therapy is discomfort■

Etiologies of pain in the ICU are depicted in Table ♦ 11.1Not 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 syndromeNevertheless, 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 suboptimalIn a recent large series of mechanically ventilated patients, procedural discom-♦

fort was specifically managed in <25% of the population, and the use of guidelines for analgesia and sedation promoted less – not more – therapy for pain managementSpecific to procedure, patients express differences between pre- and post-♦

procedural levels of discomfort with interventions of drain removal, deep breathing and coughing exercises, suctioning, and line removal; often patients do not receive pre-procedural analgesiaImportant 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 Neurologic Complex

Surgical wound Acute abdomen Intracranial hemorrhageBone fracture Myocardial ischemia Headache/migraine Mechanical ventilationUlceration Pneumonia Elevated intracranial

pressureDiffuse joint pain/

arthralgiaPleurodynia Myocarditis Compressive neuropathy Sickle cellInvasive procedure Pulmonary embolus Subarachnoid hemorrhage Metabolic disordersLocal burn injury Vascular ischemia Cranial neuritis Febrile/sepsisCompartment

syndromesGastritis Diabetic neuropathy

Ureteral stone Pancreatitis Reflex dystrophyAppendicitis Bowel obstruction Meningismus

14711 Sedation, Analgesia, and Neuromuscular Paralysis

The BPRS and the BPS have undergone complete content, criterion, and con-♦

struct validity testing, and the BPS has further documented inter-rater reliability testingStudies have demonstrated that self-reporting of discomfort has the greatest ♦

correlation with multi-domain behavioral ratings compared with single-item scoringPain 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

Table 11.2 Pain assessment scale for awake, responsive patients

ICU pain scale Self-rating scale

Numerical Rating Scale (NRS) 1–10Visual 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)

148 M.A. Mirski

Psychologically demanding circumstances in critical care are numerous, with ■

common general ICU stressors being the psychological responses to a life-threatening illness, unfamiliar surroundings, near constant noise and activity, disturbed sleep-wake cycles, and overall sense of lack of controlPain and anxiety are commonly combined; important to discern if pain is para-■

mount; 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: a

2 agonists, ketamine, and some narcotics (morphine,

meperidine) in low doses

Delirium

Delirium is a dysfunctional cognitive state; recently gained great interest as a ■

predictor of poor outcome in hospitalized patients, particularly in the ICUNot easily diagnosed unless the condition is specifically entertained■

Specific scoring batteries have been designed for diagnostic purpose; their intro-■

duction has led to data supporting that delirium is an independent predictor of longer hospital stay, greater mortality, and ICU costsHowever, it remains unclear whether all forms of delirium are equally hazardous; ■

especially in the ICU setting, a breadth of conditions can incite the encephalopathic

Table 11.4 Common classes of analgesic agents

Drug class ExamplesAnalgesic mechanism Other action Major toxicity

Nonsteroidal Aspirin, acetaminophen, ketorolac

COX-1 or COX-2 inhibition

Antiplatelet Bleeding, hepatotoxicity

Opioids Morphine, hydromorphone, fentanyl

µ-Receptor agonists

Respiratory control, sedation

Ventilatory depression, addictive behavior

a2 Agonists Clonidine,

dexmedetomidinea

2-Receptor agonist

Cardiovascular tone and heart rate control

Hypotension, bradycardia

Local anesthetics

Lidocaine, bupivacaine

Nerve Na+ channel blockade

Sensory and motor blockade, cardiac conduction

Motor weakness, cardiac arrest

NMDA antagonist

Ketamine NMDA antagonist

Dissociative anesthesia, cerebral activation

Hallucinations, seizures, ICP elevation

COX cyclooxygenase; NMDA N-methyl, d-Aspartic acid


state and delirium in a transient or persistent manner, each with likely different effects on the patient’s physiologic stateSeveral etiologies include metabolic dysfunction, electrolyte abnormalities, rela-■

tive 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

Many classes of drugs exist, including the narcotics, benzodiazepines, barbitu-■

rates, propofol, neuroleptics, a2-adrenergic agents, ketamine, and several other

lesser classes of chemical agents. Within each class are agents with varied phar-macokinetics, routes of administration, titratability, adverse reactions, and hemodynamic profileIt 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 importantIt 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

To monitor administration of sedatives, numerous sedation scoring systems have ■

been craftedFirst scale popularized was the Ramsay Scale, introduced in 1974; focused pri-■

marily on patients post-cardiac surgery and emphasized deep levels of sedationRecent scoring tools include the Riker Sedation-Agitation Scale (SAS, 1999), ■

Motor Activity Assessment Scale (MAAS, 1999), the Richmond Agitation-Sedation Scale (RASS, 2002), and recently, the ATICE (Adaptation to the Intensive Care Environment) and AVRIPAS (four components: agitation, alert-ness, heart rate, and respiration)Only the RASS has been validated for its ability to detect changes in sedation ■

status over consecutive daysSome 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 toolHence, 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

150 M.A. Mirski

Tabl

e 11

.5

Phar

mac

olog

ic p

rofil

e of

com

mon

IC

U s

edat

ive

agen

ts

Dru

gTy

pe o

f m

edic

atio

nSe

datio

nA

nalg

esia

Mec

hani

sm o

f ac

tion

Adv

anta

ges

Adv

erse

eff

ects

Fent

anyl

Opi

oid

++

++

µ-R

ecep

tor

agon

ist

Pote

nt, r

ever

sibl

e, r

apid

on

set,

shor

t dur

atio

nR

espi

rato

ry d

epre

ssio

n,

ches

t wal

l rig

idity

, ga

stri

c dy

smot

ility

, hy

pote

nsio

nR

emif

enta

nil

Opi

oid

++

++

µ-R

ecep

tor

agon

ist

Pote

nt, r

ever

sibl

e, r

apid

on

set,

shor

t dur

atio

nR

espi

rato

ry d

epre

ssio

n,

ches

t wal

l rig

idity

, ga

stri

c dy

smot

ility

, hy

pote

nsio

nM

orph

ine

sulf

ate

Opi

oid

++

++

µ-R

ecep

tor

agon

ist

Rev

ersi

ble,

pro

mot

es

slee

pR

espi

rato

ry d

epre

ssio

n,

gast

ric

dysm

otili

ty,

hypo

tens

ion,

ha

lluci

natio

nsH

ydro

mor

phon

eO

pioi

d+

++

+µ-

Rec

epto

r ag

onis

tR

ever

sibl

e, lo

nger

du

ratio

nR

espi

rato

ry d

epre

ssio

n,

gast

ric

dysm

otili

tyK

etam

ine

Non

barb

itura

te

anes

thet

ic/a

nalg

esic

ag

ent

++

++

++

NM

DA

ago

nist

Pres

erve

s ve

ntila

tory

dr

ive,

pha

ryng

eal-

la

ryng

eal r

efle

xes,

an

d ca

rdio

vasc

ular

st

abili

ty

Dis

soci

ativ

e st

ate,

ha

lluci

natio

ns,

delir

ium

, ta

chya

rrhy

thm

ia

Dia

zepa

mB

enzo

diaz

epin

e+

++

+G

AB

Aa-

rece

ptor

ag

onis

tR

ever

sibl

e, s

hort

du

ratio

nR

espi

rato

ry d

epre

ssio

n,

hypo

tens

ion,

co

nfus

ion,

long

-act

ing

activ

e m

etab

olite

Lor

azep

amB

enzo

diaz

epin

e+

++

–G

AB

Aa-

rece

ptor

ag

onis

tR

ever

sibl

e, lo

nger

du

ratio

nR

espi

rato

ry d

epre

ssio

n,

hypo

tens

ion,

co

nfus

ion

Mid

azol

amB

enzo

diaz

epin

e+

++

–G

AB

Aa-

rece

ptor

ag

onis

tR

ever

sibl

e, s

hort

du

ratio

n, ti

trat

able

, w

ater

sol

uble

Res

pira

tory

dep

ress

ion,

hy

pote

nsio

n,

conf

usio

n


Hal

oper

idol

Neu

role

ptic

(b

utyr

ophe

none

)+

++

–B

lock

s do

pam

ine,

ad

rene

rgic

, se

roto

nin,

ac

etyl

chol

ine,

hi

stam

ine

rece

ptor

s

Pres

erve

s le

vel o

f

arou

sal,

airw

ay

refl

exes

Ext

rapy

ram

idal

sig

ns,

may

low

er s

eizu

re

thre

shol

d

Dro

peri

dol

Neu

role

ptic

(b

utyr

ophe

none

)+

++

+B

lock

s do

pam

ine,

ad

rene

rgic

, ser

oton

in,

acet

ylch

olin

e,

hist

amin

e re

cept

ors

Com

bine

d se

datio

n,

antip

sych

otic

. an

tiem

etic

, ana

lges

ia

in h

eada

che

sy

ndro

mes

Ext

rapy

ram

idal

sig

ns,

may

low

er s

eizu

re

thre

shol

d, Q

T

prol

onga

tion

Clo

nidi

nea

2 A

goni

st+

++

+a

2 A

goni

st (

pre-

and

po

st-s

ynap

tic)

Use

ful i

n se

tting

of

al

coho

l or

drug

w

ithdr

awal

Dry

mou

th, b

rady

card

ia,

hypo

tens

ion,

reb

ound

hy

pert

ensi

onD

exm

edet

omid

ine

a2

Ago

nist

++

++

a2

Ago

nist

(pr

e- a

nd

post

-syn

aptic

)Sh

ort a

ctin

g, li

ttle

effe

ct

on c

onsc

ious

ness

an

d bl

ood

pres

sure

Dry

mou

th, b

rady

card

ia,

hypo

tens

ion,

adr

enal

su

ppre

ssio

n, a

tria

l fi

brill

atio

nPr

opof

olN

on-b

arbi

tura

te

seda

tive

hypn

otic

++

+–

Unc

lear

GA

BA

a-

rece

ptor

ago

nist

Ver

y sh

ort d

urat

ion,

tit

rata

ble

Hyp

oten

sion

, res

pira

tory

de

pres

sion

, m

etab

olic

aci

dosi

s,

rhab

dom

yoly

sis,

an

aphy

laxi

s, s

epsi

s,

pain

at v

enou

s si

te

152 M.A. Mirski

Tabl

e 11

.6

Phar

mac

okin

etic

s an

d do

sing

of

com

mon

IC

U s

edat

ives

Dru

gH

alf-

life

Star

ting

dose

Titr

atio

nPr

otei

n

bind

ing

Met

abol

ism

Act

ive

met

abol

ite

Fent

anyl

30–6

0 m

in

(sin

gle

IV d

ose)

, if

rep

eate

d

is h

ours

12.5

–50 mg

IV

q

20–3

0 m

inIn

fusi

on 0

.01–

0.03

m

g/kg

/min

and

tit

rate

q 1

5–30

min

, up

to 5

0–10

0 mg

/h

80–8

6%H

epat

ic–

Rem

ifen

tani

l3–

10 m

in a

fter

si

ngle

dos

e0.

5–1.

0 mg

/kg

IV

bol

usIn

fusi

on 0

.05–

0.2

mg

/kg/

min

92%

Plas

ma

es

tera

ses

–

Mor

phin

e

sulf

ate

1.5–

4.5

h IV

, IM

, SQ

5–20

mg

IM q

4

h; 2

–10

mg

IV

q 4

h

Cau

tion:

met

abol

ites

m

ay a

ccum

ulat

e

for

post

oper

ativ

e

pain

(PC

A):

0.2

–3.0

m

g an

d 5–

20 m

in

lock

out i

nter

vals

20–3

0%H

epat

icM

orph

ine-

3-gl

ucur

onid

e;m

orph

ine-

6-

gluc

uron

ide

Dia

zepa

m30

–60

h2

mg

IV q

30

–60

min

–99

%H

epat

icD

esm

ethy

l-di

azep

am,

oxaz

epam

, hy

drox

ydia

zepa

mL

oraz

epam

10–2

0 h

0.25

–0.5

mg

IV

q 1

–2 h

–91

–93%

Hep

atic

–

Mid

azol

am1–

2.5

h0.

5–1

mg

IV

q 5–

30 m

inIn

fusi

on 0

.25–

1.0

mg

/kg/

min

97%

Hep

atic

1-H

ydro

xym

ethy

lmid

azol

am

Hal

oper

idol

12–3

6 h

0.5–

5.0

mg

IV–

92%

Hep

atic

–D

rope

rido

l4–

12 h

0.62

5–2.

5 m

g IV

–92

%H

epat

ic–


Clo

nidi

ne12

–16

h0.

1 m

g PO

q 8

–24

h;

incr

ease

0.

1 m

g/da

y q

1–2

da

ys u

p to

0.

6 m

g/da

y

–20

–40%

Hep

atic

(50

%)

and

urin

e (u

ncha

nged

, 50

%)

–

Dex

med

etom

idin

e2

h1 mg

/kg

IV o

ver

10

min

Infu

sion

0.2

–0.7

mg

/kg/

h94

%H

epat

ic–

Prop

ofol

4–10

min

1.0–

2.5

mg/

kg I

V

(ane

sthe

sia

in

duct

ion)

; 5 mg

/kg/

min

for

5

min

IV

(se

datio

n)

Incr

ease

infu

sion

by

5–1

0 mg

/kg/

min

q

5–10

min

to

mai

nten

ance

of

25–

100 mg

/kg/

min

up

to 1

00–3

00 m

g/kg

/m

in

Not

fou

ndH

epat

ic a

nd

extr

ahep

atic

–

154 M.A. Mirski

Physiologic and Brain Function Monitors

Neither heart rate nor blood pressure changes have been useful parameters for ■

sedation guidanceNeurologic monitors have their origin in the raw electroencephalogram (EEG) ■

and typically have been variants of signal-processed EEG and, more recently, the BIS monitorThe 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 prob-ability of unconsciousness; sedation targets are typified by ranges of 60–75BIS 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 statesAgents such as the benzodiazepines, narcotics, or other classes of sedatives differen-■

tially 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 schemeFurther 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•

Table 11.7 Physiologic etiologies for agitation

Hypoxemia Hepatic or renal insufficiencyHypercarbia Myocardial ischemiaAcidosis – metabolic, respiratory Cerebral ischemiaHyponatremia HypotensionHypoglycemia Psychoactive medicationsHyperammonemia CorticosteroidsHypercalcemia Anticonvulsants


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 “over-shoot” 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-antagonistsBasis for pharmacologic effects – analgesia, decreased level of conscious-•ness, respiratory depression, miosis, gastrointestinal hypomotility, antitussive effects, euphoria or dysphoria, and vasodilatationAlthough 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 responseEach 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 com-•pounds (e.g., fentanyl, remifentanil) having shortest time of onsetMajority of morphine does not cross the blood–brain barrier•Peak effect – IV administration of morphine: 15 min; fentanyl: 5 min; •remifentanil: 1–2 minIn 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) Half-life (min) Clinical effect (min)

Morphine 15 90–270 120–240Hydromorphone 20 120–400 240–360Fentanyl 5 200 30–60Remifentanil 1–3 5–15 1–10

156 M.A. Mirski

Remifentanil incurred the risk of higher degrees and longer duration of ▲

pain upon discontinuation than did fentanylEmphasized 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 achievedCumulative 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 minContinuous infusions above 2 ▲ mg/kg/h – not recommended in narcotic-naïve patients unless endotracheally intubatedFor deeper sedation, as adjunct to general anesthesia, or in narcotic-tolerant ▲

patients, continuous infusions greater than those above may be advocatedNot 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 ▲

infusionDosing range, ~0.02–0.05 ▲ mg/kg/min, to typical maximum of 0.1 mg/kg/minLarger doses rapidly lead to apnea and subsequently general anesthetic ▲

dosesNo 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 regimenFor analgesic dosing, 5–20 mg IM q 4 h or 2–10 mg IV over 4–5 min q ▲

2–4 h is recommendedPreference 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 reasonableAppropriate for PCA▲

High somnolence effect (potential good sleep aid in ICU)▲

Hydromorphone (Dilaudid)•

Long acting: 4–6 h duration▲

Minimal somnolence▲

Appropriate for PCA▲


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 pressurePer 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 elec-trographic seizure activityMeperidine is renally eliminated active metabolite; normeperidine ▲

associated with an excitatory syndrome that includes seizuresPruritus, 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♦

158 M.A. Mirski

Predominant anxiolytic action; some analgesic effect has been suggested for ♦

diazepam via GABAergic receptor functionMechanism of action♦

Potentiation of inhibitory neurotransmitter, gamma aminobutyric acid •(GABA); increase frequency of opening of the GABA

a chloride channel in

response to binding of GABASubsequent effects include anxiolysis, sedation, muscle relaxation, antero-•grade 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 •lipophilicityRapidly distributed to the brain, followed by redistribution to muscle and fat•With multiple doses or continuous infusions, the time to offset is more depen-•dent on the agent’s half-life and presence or absence of active metabolitesDiazepam•

Most rapid onset and most rapidly redistributed due to high lipophilicity, ▲

followed by midazolam and lorazepamLongest 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▲


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 patientsBecause of short duration of action, re-sedation can occur▲


Benzodiazepines provide often-needed relief from the stressful ICU •environmentSmall, titrated doses are effective without overt compromise of cognitive •functionAnterograde amnesia is useful attribute for discomforting procedures, •although analgesia should also be offeredSimilar 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 entertainedAlone, benzodiazepines have little or no effect on ICP; decreases in mean •arterial pressure associated with midazolam administration may impair cerebral perfusionAs with opioids, high doses of benzodiazepines may induce respiratory •dysfunction and apnea, and hypercapnia may stimulate an increase in ICPRisk of benzodiazepines•

Frank delirium, which is diagnosed if:▲

Change occurs in features of acute onset of mental status, orN

Fluctuating levels of consciousness occur, along with inattention, andN

Either disorganized thinking or altered level of consciousness is N

present

Recent developed measures for the screening of delirium•

Confusion Assessment Method for the Intensive Care Unit (CAM-▲

ICU) orIntensive 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

160 M.A. Mirski

An absolute dosing threshold has not been identified, reported in ▲

patients receiving higher doses (lorazepam infusion >18 mg/h) for pro-longed periods of timeCalculation of osmolar gap can be used as a surrogate for serum pro-▲

pylene glycol concentrationsShould be monitored closely in patients receiving high doses, with an ▲

osmolar gap >10, suggestive of potentially toxic propylene glycol concentrationsOther 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 epilepticusLorazepam is recommended drug for this life-threatening condition•Benzodiazepines inhibit many types of experimentally induced seizure •activity but not allWhen seizures are provoked by mechanisms other than antagonism of the •GABA receptor, such as theophylline-induced seizures, benzodiazepine therapy is typically unsuccessfulHowever, 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 interac-•tions; metabolized by cytochrome P

450 family of enzymes; inducers (e.g.,

rifampin, carbamazepine, phenytoin, and phenobarbital) may enhance clear-ance of these agents, while inhibitors (e.g., macrolides, azole antifungals, non-dihydropyridine calcium-channel blockers) may inhibit clearanceLorazepam 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 doseFor 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


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 depres-sant effects limit its utilityDexmedetomidine is approved for postoperative and ICU settings; has shown ♦

promise in reducing discomfort of mechanical ventilation while permitting rapid patient arousal for neurologic examinationBoth agents markedly enhance efficacy of inhalational anesthetics and opioids, ♦

decreasing requirements for other substancesMechanism 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 a

2-

adrenergic receptors coupled to potassium-channel-activating G-proteinsSummation of effects – decrease in sympathetic outflow from the locus •coeruleus, a decrease in tonic activity in spinal motor neurons and spinotha-lamic pain pathways, and subsequent decreases in heart rate and blood pressure; at recommended doses, respiratory drive is not compromised


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 functionOnly 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 therapyTime of onset for transdermal clonidine – 24–72 h; not useful as a seda-▲

tive agent; however, may be useful in setting of alcohol or drug with-drawal in ICU patients or as adjunct for reduction of sympathetic hyperactivity in severe TBI patients

162 M.A. Mirski

Dexmedetomidine•

Given as IV infusion only; rapidly distributed to the brain; equilibrium ▲

half-life of 6–9 minElimination half-life is 2 h; may increase to 7.5 h in individuals with ▲

hepatic insufficiencyAt recommended doses, elimination follows linear kinetics▲

Due to short half-life, dexmedetomidine is easily titrated▲

Excretion via kidney as inactive methyl and glucuronide conjugates▲


Advantages•

Nominal effect on reduction of level of arousal; may induce sedation ▲

without concomitant loss of attentive behavior and cognition fol-lowing low levels of auditory or tactile stimulation; thus, ability to conduct neurologic assessment is preserved while achieving sedative goalCombined effect – sedative/anxiolytic and analgesic action may permit ▲

single-drug use for both sedation and modest pain controlIn 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 useIn 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 dexmedetomidineParadoxical hypertension – following loading dose of dexmedetomidine▲

With prolonged use, dexmedetomidine may lead to suppression of ▲

adrenocorticoid release


May exacerbate effects of other centrally acting depressants▲

Hypotension and bradycardia may be worsened by concomitant admin-▲

istration of antihypertensive and antidysrhythmic medicationsIn vitro studies suggest inhibition of P▲

450 microsomal system by dexme-

detomidine; however, no clinically significant effects are noted


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


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 patientsDiscussion limited to two agents commonly used in the ICU – the butyrophe-♦

nones, haloperidol and droperidolMechanism of action♦

Block cerebral and peripheral (but not spinal) dopamine, adrenergic, sero-•tonin, acetylcholine, and histamine receptors; variable selectivity, depending on agentEffects include sedation (tolerance develops with repeated dosing), anxi-•olysis, 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 effectsHaloperidol and droperidol – limited anticholinergic properties compared •with other neuroleptics


Haloperidol is highly lipophilic and plasma-protein bound; sedative effects •within min of IV administrationPlasma half-life, 12–36 h; effective half-life may be much longer (• ³1 week) due to accumulation in brainIV droperidol – rapid onset of action (1–3 min); peak effects, 30 min; duration •of action varies from 2 to 12 hSystemic elimination mirrors hepatic blood flow; metabolism is similar to •haloperidol


Advantages•

Major utility – treatment of acute agitation secondary to psychosis or ▲

deliriumAdverse effects negate use for mild sedation; however, where appropriate, ▲

the effects can be dramatic and greatly enhance ICU management

164 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 utilityExtrapyramidal 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 droperidolPossible other CNS effects▲

Droperidol has little effect on ICP, although cerebral perfusion pres-N

sure can decrease via systemic hypotensionLowering seizure threshold – neuroleptics induce slowing and syn-N

chronization (with associated increased voltage) of the EEG; halo-peridol 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▲

Increased prolactin secretion, orthostatic hypotension (rare with N

haloperidol and droperidol), neuroleptic malignant syndrome, and jaundice (rare with butyrophenones)Both haloperidol and droperidol can induce QT prolongation and N

torsades de pointes; warnings have been issued with even low doses of droperidol, limiting its useDroperidol is contraindicated in patients with preexisting QT pro-N

longation, and should be used with extreme caution in those at risk for cardiac dysrhythmiasSignificant hemodynamic side effects are rare with haloperidol and N

droperidol


Selective serotonin reuptake inhibitors (SSRIs) compete with neuroleptics •for hepatic oxidative enzymes; may increase circulating levels of haloperidol and droperidolCo-administration with any agent that can prolong the QT interval may •increase the likelihood of torsades de pointes, and routine EKG monitoring is necessary


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


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

Additional dosages – not to exceed 0.625–1.25 mg every 2–4 hN

Propofol■

Propofol, an ultra-short-acting alkylphenol, is extensively used both as a ♦

sedative agent in critically ill patients and a general anestheticAlthough 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 barbituratesOther advantages include less emetic property than barbiturates and mood ♦

enhancer rather than frank depressantHowever, 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 sedationMechanism of action♦

GABAergic mechanism of action, according to both in vivo and in vitro •binding studies; evidence that propofol directly binds to GABA

a receptors

and activates inhibitory chloride channels in absence of GABAOther studies suggest nonspecific but structurally dependent effect on neu-•ronal plasma membrane fluidity; thus, the specific mechanism(s) of action of propofol remain unclear


Similar to thiopental in lipophilicity; propofol is rapidly distributed to •brain following IV administrationDistribution half-life of 1–8 min; shorter in time than most sedative agents with •equally rapid recovery following redistribution to other less-perfused tissuesRepeated 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 statesAdministered IV – premixed concentration of 10 mg/mL (1%), continuous •infusion

166 M.A. Mirski

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 brokenDosing•

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


Ultra-short duration of action; readily titratable and rapidly eliminated•Produces stereotypic suppression of EEG activity similar to the barbitu-•rates: increasing theta and delta to flat EEG pattern during deep general anesthesiaCan 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 •maneuversMay 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, hypov-olemia, in those on other cardiodepressant medications, or the elderlyFor severe TBI patients, propofol may impair cerebral perfusion even as it •induces a fall in ICPDose-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 personnelContinuous 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 adminis-•tration 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


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 unclearMost cases involve critically ill patients on multiple medications (may •initiate the metabolic disarray)Careful monitoring of electrolytes, lactic acid, creatine kinase, and triglyc-•erides is highly recommended when doses >80 mg/kg/min are given for prolonged periods of time


Propofol may potentiate effects of alcohol, opioids, benzodiazepines, barbi-•turates, other general anesthetics, antihypertensives, and antiarrhythmicsDoes 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, tho-•racic, or extremity musculature, including muscles for ventilationUnintended consequence of NMB use – inability for patient to communi-•cate, ability to assess for pain, anxiety, or other discomfort, and removes patient from decision-making processOther indirect consequences – loss of muscle tone (risk of pressure-•induced injury, nerve palsies, joint misalignment), ophthalmic keratitis, diminished venous returnUse 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

168 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 dyssynchronyImprove 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 intuba-•tion; 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)▲

No cardiovascular side effects; a preferred NMB in ICUN

Cisatracurium – long (60 min)▲

Pancuronium – long (120 min)▲

Complications of ICU use of NMBs♦

Potentiation of NMB•

Antibiotics (gentamycin)▲

Ca▲ 2+ blockers, b blockers, magnesium sulfate


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; rareSteroid-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 diseasesDue to loss of cortical and NM junction connectivity•Sensitization process, muscle end plate synthesizes many AChR (immature •fetal) complexesSensitization to succinylcholine and resistance to nondepolarizing NMB•AChRs exposed to depolarization of succinylcholine – documented • ↑ serum K+, as high as 12–15 mEq/LProportional risk to muscle mass involved; clinical risk if two or more •limbs with paresisOften 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

Table 11.9 Properties of common NMBs

Nondepolarizing NMB

Bolus dose (mg/kg)

Continuous infusion (mg/kg/min) Metabolized Adverse effects

Mivacurium 0.2 N/A Plasma esterases MinimalAtracurium 0.4 2.5–3 Plasma esterases HistamineVecuronium 0.08 0.8–1.5 Hepatic MinimalRocuronium 0.6 8–10 Hepatic MinimalCisatracurium 0.2 2–8 Plasma esterases MinimalPancuronium 0.08 N/A Renal excreted Vagolytic

170 M.A. Mirski

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 anesthesiaCause of any acute change in mental status must be investigated for new intrac-■

ranial pathology, metabolic or toxic disarray, infection, or adverse reaction to medications before treating symptomaticallyAny medication that impairs respiratory drive may lead to hypercarbia and con-■

comitant elevations in ICPNondepolarizing NMB must be used with great caution in patients with neuro-■

muscular pathologyDepolarizing 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 mani-festations 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 neuromus-cular 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 284:4–5Puntillo 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


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 two-dimensional sedation rating scale for critically ill adults. Chest 126:1883–1890


Postoperative care of patients in the NCCU generally encompasses management after neurosurgery but can also encompass issues associated with non-neurosurgical pro-cedures; proper management requires an understanding of general post-anesthesia care and issues specifically related to the neurosurgical procedure.

General Issues

Problems can be categorized as those that develop in the first 24 h after surgery ■

and those that develop after 24 hImportant issues can arise during transport; report must be made in the proper ■

manner, and new and ongoing general medical issues must be managedPost-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 trans-•port and provision of medical assistance as neededCommon problems•

Hypoventilation from airway obstruction▲

Hypoxemia from a variety medical and pharmacologic issues▲

Alterations in mental status▲

Hemodynamic abnormalities▲

Chapter 12Postoperative Care

W. Andrew Kofke and Robert J. Brown

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

174 W.A. Kofke and R.J. Brown

Continuous monitoring of the airway, gas exchange, oxygen saturation, •and blood pressure (BP) is mandatoryBring 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 corridorsIf a ventriculostomy is in place•

Generally best to clamp it so that no untoward ingress or egress of CSF ▲

occursDo not allow CSF in the collection chamber to touch the filter at the top ▲

of the collection chamberInadvertent overdrainage can cause a subdural hemorrhage or predis-▲

pose 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 sur-▲

gical procedureThe 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 thereafterAnticipate the need for fluid boluses (typically, 500–1,000 mL normal saline) ♦

for decreases in BP or urine output

17512 Postoperative Care

Pain medications■

Some prefer prn codeine, whereas others may employ morphine, fentanyl, or ♦

nonopioid analgesics, e.g., acetaminophenPatient-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 sedationIf delirium arises in the first 1–2 h after surgery, physostigmine (1–2 mg IV) ♦

should be considered, especially in the elderlySedative hypnotic drugs given before anesthetic drugs have been fully elimi-♦

nated may prompt a return to unconsciousnessBenzodiazepines may exacerbate agitation before they induce sedation or ♦

unconsciousness, but the effects can be reversedAntipsychotic 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, inter-•mittent 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)


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 rela-•tionship of bed height to ventriculostomy height; if patient decides to sit up more than the bed height, overdraining can occur with potentially seri-ous 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 dayProphylaxis – consider:■

GI prophylaxis♦

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


H•2 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 complica-■

tions are listed in Table 12.1Craniotomy or craniectomy for tumor■

Posterior fossa – be vigilant for neurogenic issues in consciousness, circula-♦

tion, and respirationA variety of positions may be used for these procedures♦

A sitting position entails risk of venous air embolism (VAE) but is associ-•ated with less blood loss and easier exposure for the surgical procedure

These patients often arrive with antecubital CVP catheters in place▲

Catheters should be treated as normal central lines; they predispose N

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 drugsSubsequent 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 ♦

effectsICP monitoring may be needed if major issues arise, related to edema or ♦

hemorrhage with significant otherwise unexplained decrement in level of consciousness


Craniotomy for aneurysm clipping■

Entail a craniotomy with careful dissection down to expose and clip a prob-♦

lematic intracranial arterial aneurysmTypically, 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 clippedProblems that can arise during surgery♦

Difficulty getting aneurysm properly clipped with associated prolonged •temporary focal ischemiaPossible need for brain protection with anesthetic drugs or hypothermia•Aneurysmal rupture; presence or absence of prior SAH determines •managementWith aneurysmal SAH•

Concerns – first 24 h▲

Table 12.1 Neurosurgical procedures and associated complications

Operation

Complication

Immediate 24–48 h

Craniotomy/ Tumor resection

• Cerebraledema • SubgalealCSFleak• Intracranialhemorrhage • Infection

Aneurysm clipping • Strokefromprolonged temporary clip or permanent clip misplacement

• Cerebraledema

• Vasospasm(day5–10afterSAH)AVM resection • Hemorrhageorcerebraledema • HemorrhageorcerebraledemaTranssphenoidal

hypophysectomy• Diabetesinsipidus • Diabetesinsipidus• Visualloss • CSFleak

Carotid endarterectomy

• Myocardialischemia • Myocardialinfarction• Hypotension • Cerebraledema• Cerebraledema• Cerebralhemorrhage• Neckhematoma

Posterior fossa tumor resection

• Posteriorfossahemorrhage • Hydrocephalus• Apnea • Aspiration• Bradycardia

Back surgery • Transfusioncomplications • Visualloss• Visualloss • Spinalhematoma• Spinalhematoma• Retroperitonealhemorrhage

Cerebral arteriography • Embolicstroke • Retroperitonealhematoma• Arterialdissection• Inguinalhematoma • Femoralpsuedoaneurysm• Retroperitonealhematoma• Legischemia


Stroke from vascular manipulation or clip, cerebral edema, cerebral N

hemorrhage, subdural hemorrhage, and hydrocephalusRebleeding is also a concern if residual unclipped aneurysm or other N

aneurysms existIf patient had a significant decrement in consciousness preopera-N

tively, it can be expected after surgery as well

Delayed problems▲

Vasospasm with stroke or cerebral edema, among others, is dis-N

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 mmHgStandard 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 procedureIf no intraoperative ischemia or aneurysmal rupture, most of the issues ▲

resemble those of patients after craniotomy for tumorConcerns – first 24 h▲

Stroke from vascular manipulation or clip misplacementN

Cerebral edemaN

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


Cerebral hemorrhageN

Subdural hemorrhageN

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 practiceConcerns – 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 corpec-■

tomy and multilevel fusions

Cervical corpectomy♦

May entail a one-level or multilevel resection of the vertebral body, usu-•ally followed by fusionApproach is typically anterior•Patient’s return from the OR with cervical collar or, occasionally, halo •frameConcerns – first 24 h•

Bleeding in the surgical site that may become severe enough to com-▲

promise the airway

May be particularly problematic with multilevel corpectomy and if N

a halo frame is in place

Neurologic changes; arm and leg sensation and strength must be ▲

assessed every 2 h


Management•

Control systolic BP (SBP) at <160 mmHg▲

Close monitoring of airway for development of stridor or desaturation▲

This is an emergencyN

Secure airway; then evaluate for surgeryN

Simply opening the wound at the bedside can be lifesavingN

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 postoperativelyHigh 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 bleedingCardiovascular 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

Administer oxygen with serial oxygen saturation measurement and, N

as needed, arterial blood gas evaluation and chest X-ray

Imaging studies must be ordered, including a chest X-ray for possible ▲

pneumothoraxDetection of a change in neurologic function mandates immediate ▲

evaluation and possible surgical interventionOrders related to vertebral column stability may be required, e.g., log-▲

rolling, c-spine collar, brace placement, physical therapy evaluation

Postoperative visual loss•

Rare event associated with the prone position (including prone cran-▲

iotomy/ectomy in pins)

Risk factors•

Prolonged procedure, hypotension, anemia▲

Intraocular pressure increases during these procedures▲


Glaucoma▲

Periorbital edema can result in a delay in diagnosis▲

Pathogenesis is unclear, and no therapy is established•Common-sense management approach•

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 sec-•ondary problemsAirway management problems related to redundant tissue in the hypo-•pharynx and glottisObstructive sleep apnea•Hypertension•Cardiomegaly•Diabetes•Renal problems•

Non-acromegaly procedures may have other associated endocrine issues, par-•ticularly if there is an ACTH oversecreting lesion, which leads to Cushing dis-ease and the sequelae of chronic oversecretion of glucocorticoidsCraniopharyngioma•

Embryonic tumors can be slow growing and present problems related to •their massTend to be difficult dissections, not shelling out easily, and can be associ-•ated 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 pituitaryPolyuria in patients having undergone pituitary surgery raises the pos-▲

sibility of DIHowever, it is not necessarily automatically DI▲

DI after pituitary surgery is associated with one of three patterns•

Transient DI▲

Permanent DI▲

A triphasic pattern▲

An initial polyuric phase of several days’ duration is thought to be N

related to posterior pituitary injury; urine volume increases with concomitant decrease in urine osmolarity and specific gravity


A second antidiuretic phase of 4–6 days arises; thought to be related N

to release of supraoptic stores of ADH; urine volume decreases as urine osmolarity and specific gravity increaseThe third, possibly permanent phase of polyuria then occurs with N

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 defini-tions exist for this condition, which is made more problematic because the patient may have partial DI syndromeClassic 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 serumDifferential diagnosis includes▲

Normal physiologic response to intraoperative fluids and/or N

overhydrationHyperglycemiaN

Mannitol or other diuretic administrationN

Nephrogenic DIN

Partial DI, perhaps complicated by any of the above singly or in N

combination

Postoperative DI can be managed in two ways•

Let patient drink▲

Water is placed at awake patient’s bedside, and drinking is allowed N

ad libitumPresupposes that patient is awake enough to manage drinking, that N

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 concentrationSleep deprivation may ariseN

Administer desmopressin (DDAVP) or ADH; doses are as follows:▲

DDAVP can be given 1–2 N mg IV/SC q 12 h with close monitoring of serum sodium, urine output, and urine specific gravityIf urine output increases with specific gravity falling below 1.005–1.008, N

the dose is inadequate and should be increased; alternatively, the DDAVP can be given as needed when these criteria are metUrine losses must be replaced if oral intake is inadequate, with ¼–½ N

normal saline adjusted as needed and adjusted according to urine output and serum sodium responsePostoperative intranasal administration is not possible; if permanent N

DI develops, the patient may be transitioned to this route


Vasopressin (ADH) can also be used with similar monitoring caveats; N

it can be given in adults 5–10 U IM/SQ q 6–12 h as needed; alterna-tively, 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 requiredSerial sodium determinations must be made as frequently as q 4–6 h during •the initial management phase and whenever sodium homeostasis changesThe changing nature of DI after pituitary surgery makes a uniform proto-•col difficult to establishBedside 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 •leakingIf CSF leak arises, a lumbar drain may be necessary to decrease ICP•Instrumentation of the nasopharynx is contraindicated after packing has •been removed

Attempts to place a nasogastric tube, for example, can lead to intracra-▲

nial placement and infection, fistula, or patient deathIf reintubation or another anesthesia is required, try to avoid positive ▲

pressure to the nasopharynx to prevent pneumocephalus and the pos-sibility 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 malig-nant brain edema and for traumatic brain injuryEntails 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 syndromesA more difficult procedure, which is occasionally employed, is a bifrontal ♦

craniectomyTypically, 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 illnessConcerns in the acute phase include:♦

Cerebral hemorrhage•Subdural hemorrhage•CSF leak•Herniation syndromes•


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 surgeryConcerns – 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 dayPotential drug interactions of common epileptic drugs need to be consid-•ered and reviewed (Chap. 31)SBP <160 mmHg•Order appropriate imaging studies•Patients generally go to an epilepsy monitoring unit if they have had elec-•trodes 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 ♦

closedThe 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•


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 hyperemiaMyocardial ischemia may not be accompanied by chest pain (as after any •surgery)

Myocardial ischemia diagnosis is complicated by immediate postop-▲

erative carotid sinus dysfunction producing low vascular resistance and bradycardiaMyocardial ischemia is detected by bedside EKG and/or echocardiog-▲

raphy and myocardial injury/infarction by cardiac enzyme

Cerebral ischemia is detected by serial bedside neurologic examination•

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 warrantedICH, in situ thrombosis, and cerebral emboli are also important com-▲

plications for which monitoring is requiredIn 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 bleedingOccasionally 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 AVM-▲

induced intracranial hypotension; theoretically, this leads to a lower CBF autoregulatory curveNormal BP, as typically defined, may produce a state of malignant ▲

hypertension if the “normal” BP exceeds the upper autoregulatory range of a given patientNPPB is associated with resection of large AVMs and can lead to ▲

edema and bleeding


A day or more of postoperative intubation with an IV drug-induced ▲

state of anesthesia/deep sedation may be required to enforce the strat-egy 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 stimuliDecrease 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/kgEffective half-life (▲ b) of 19 min and an 8 h elimination half-life, during which most of the drug is extravascularA 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 minLess 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 anes-thesia being induced at the higher dosageMetabolized by plasma esterases and has an extremely context-insensi-▲

tive half-life, i.e., duration of effect is not affected by prior dosing historyDiscontinuation of a low or high dose infusion results in emergence ▲

within minAssociated with hyperalgesia on discontinuation, especially if inade-▲

quate long-acting analgesic drugs were given during the procedureEnsure 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


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 postoperativelyPostoperative doses are 1–5 mg IV, with dosage adjusted according to ▲

patient tolerance and needsHistamine release can arise, with concerns that central histamine is ▲

neurotoxic in animalsLeast 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 dura-▲

tion of actionNo 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/minLower bolus doses occasionally helpful as sedative▲

Produces hypotension and respiratory depression▲

Short duration of action and antiemetic▲

Propofol-infusion syndrome▲

High dose or prolonged useN

Lactic acidosisN

HypertriglyceridemiaN

Rhabdomyolysis with very high CPK levelsN

Difficult to predict susceptibilityN

Thought to be more likely in children and young adultsN

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 propo-▲

fol, with no antiemetic effectLower doses can predispose to seizure, airway hyper-reactivity, or hiccups▲

Etomidate•

Etomidate has minimal hemodynamic or respiratory effects▲


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 minAdrenal suppressant; when used in high doses or as an infusion, this ▲

may be a concern postoperativelyContains propylene glycol, which can produce toxicity manifest as ▲

lactic acidosis when used as a prolonged infusionCommonly used when intraoperative motor-evoked potentials are used▲

Neuromuscular blocking drugs♦

Depolarizing drug (cholinergic agonist) is succinylcholine•Nondepolarizing drugs (competitive cholinergic antagonists) include pan-•curonium, vecuronium, rocuronium, and cis-atracuriumNondepolarizing drugs interact with most of the first-line anti-epileptic •drugs, with a significant shortening of their actionAll can be deadly in untrained hands, as they can all stop breathing and •require skill with airway managementSuccinylcholine•

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

Increases ICP, likely related to fasciculationsN

Excessive infusion dosing produces type II block similar to that seen N

with nondepolarizing agentsRepeat dosing can produce bradycardiaN

1 in 10,000 do not have plasma cholinesterasesN

Prolonged effect°

Elimination only by renal excretion, probably in the NCCU°

If in doubt, don’t use it!N

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▲


Pancuronium•

Steroid-based muscle relaxant▲

Duration is ~60 min, with mostly renal elimination but some hepatic ▲

eliminationProduces 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 ▲

glycopyrrolateAlternate 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 simi-•lar to folate deficiencyDiffusion 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


Local anesthetic issues♦

Potential local anesthetic toxicity•Bupivacine, ropivacine, and lidocaine can produce neuroexcitatory phe-•nomena with seizureBupivacine 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 blockPatient 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 deepenedDrugs 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 difficultiesLight 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 examinationMallampati 4 is an expected difficult intubation, with posterior pharyngeal •structures difficult to visualize on physical examinationTypically part of the preoperative evaluation•

Laryngoscope view and ease of ventilation should have been documented by ♦

the anesthesia teamEase 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 proceduresDifficult 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


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 surgeryPatient is sedated, topical anesthesia is applied, and a fiberoptic scope ▲

is used to identify and enter the tracheaThe 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 NCCUSome institutions place specific identification bands on patients with his-•tory 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, tempera-ture issues, and rarely, transfusion-associated lung injuryHypotension associated with intraoperative blood loss may indicate •increased risk of multiorgan dysfunction

Mannitol♦

Frequently given during neurosurgical procedures to facilitate brain •exposure


Significant diuresis during surgery•Determine if urine output was replaced•If mannitol-induced polyuria has not been replaced, patient will be arriv-•ing 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 osmo-•larity 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 bal-anced 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 careIntraoperative brain ischemia■

Causes include edema, retractors, hemorrhage, arterial inflow obstruction, ♦

head position, or global blood flow and blood pressure problems; residual effects may persist postoperativelyNeuroprotective 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 postopera-▲

tive periodProlonged 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 secureCan 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


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 surgeryAll 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 hemorrhageBleeding from arterial structures is managed by gaining proximal control; ♦

may produce arterial ischemia with residual postoperative deficitsBleeding from large venous structures brings the risk of venous occlusion, ♦

venous thrombosis, and VAE, all of which require consideration in the post-operative periodExtensive 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 antiepi-leptic drugs such as phenytoin or levetiracetamIf patient’s skull is in pins when a motor seizure arises, laceration to the skull ♦

may occur, which may require attention postoperativelyAttention to ensure antiepileptic drug levels is required intra- and post-♦

operatively

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


Significant VAE can produce an airlock in the heart and produce hypotension ♦

or cardiac arrestWith less severe (and much more common) VAE, patient may have a decrease ♦

in BP, a decrease in end-tidal CO2, increased PaCO

2, and increased end-tidal

nitrogenIf a precordial Doppler was employed, the anesthesiologist will report having ♦

heard the air transit through the heartVAE can be precipitated in a previously stable case by hypovolemia from ♦

blood loss or diuresisPostoperative management requirements may include hemodynamic support ♦

with ventilatory support and 100% oxygenParadoxical 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 syn-dromes; 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 FiO♦2, V/Q mismatch, diffusion

abnormalities, and low cardiac output in the context of pulmonary parenchy-mal abnormalitiesConsideration must be given to continuation of these problems and their ♦

causes postoperatively

Hypercapnia■

Produced by an imbalance between CO♦2 elimination and CO

2 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 outputCauses of low minute ventilation include equipment problems or problems ♦

with the patientConsideration 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 lossMost common causes are blood loss and relative anesthetic drug overdose; if ♦

hypotension persists on arrival in the ICU, these are the leading candidates


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 therapyAnesthesia 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 steroidsIf any of these drug therapies were omitted, administering them may be ♦

among the first steps to be taken in the postoperative periodIf 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 surgeryAssociated problems include hypercapnia, hypertension, tachycardia, shock, ♦

rhabdomyolysis, and renal failureMH mandates immediate cessation of offending anesthetic agents and stop-♦

ping the surgery as soon as possibleTherapy 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 functionCauses include transfusion, prior antiplatelet or antithrombotic (warfarin) ♦

therapy, or as a result of preexisting disease processesScrupulous attention must be given to maintaining all of clotting factors at ♦

normal during and after neurosurgery


Intraoperative injuries■

A variety of injuries can occur during surgery that are unrelated to the surgery ♦

itselfOcular injuries♦

Visual changes after anesthesia for nonocular surgery are relatively infre-•quent, with an incidence of 0.0008% for all noncardiac surgery and 0.2% following spine surgeryTransient blurring of vision can be due to cycloplegia from anticholinergic •medicines, use of ocular lubricantsOphthalmologic 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 com-•plaints after intubation and laryngeal mask airway (LMA)

Usually a minor problem; resolves without treatment or with just symp-▲

tomatic therapeutics such as gargling with viscous lidocaine or other such local anestheticsSevere 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 ▲

anestheticsObtain dental consultation▲

If a tooth is missing and cannot be found, a radiographic search is ▲

requiredIf 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 ProjectThe 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


Extravasation injury•

Results from injection or leakage of IV fluids or medications into the ▲

extravascular spaceInjury can be related to chemical effects of drugs or the pressure that ▲

was employed in injecting themIf 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 resultExtravasation of vasopressors might be treated by early infiltration with ▲

phentolamineSurgical 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 proceduresFactors 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▲

Trimethobenzamide, 100 mg IM or PRN

Prochlorperazine, 5–10 mg IV or 25 mg PRN

D2 antagonist – metoclopramide, 10 mg IV or IM▲

Glucocorticoid – dexamethasone, 4 mg IV▲

Butyrophenone neuroleptic – droperidol, 0.625–2.5 mg IV▲


Black box warning for possible QT prolongationN

Not a recommended first-line drug because of this warning, notwith-N

standing years of widespread use as a first-line agentCan produce sedated appearance but with anxietyN

H-1 antihistamine – hydroxyzine, 25–100 mg IM▲

Sedative side effectN

Central anticholinergic – scopolamine, topical patch (best used prophy-▲

lactically) or 0.2–0.6 mg IM, SQ, or IV

Can produce delirium; reversible with physostigmineN

Airway issues■

A variety of airway problems can arise immediately after surgery, and these ♦

issues and their management followUpper airway obstruction♦

Contributors – anesthetics; neurologic problems; anatomic abnormalities, •injuries, or edema; or residual neuromuscular blockadeAnatomic 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▲

Orohypopharyngeal obstructionN

Snoring type respirationsN

Triple airway maneuver (i.e., chin lift, head extension, open mouth) N

usually fixes obstructionOropharyngeal or nasopharyngeal airway insertion can helpN

Decrease sedative level if possible or await subsidence of anesthetic N

effectsNasopharyngeal airway use contraindicated with pituitary surgery N

and can produce a nose bleed but tends to be better tolerated if suc-cessfully insertedOropharyngeal airway helps but requires blunted or absent gagN

Laryngeal obstruction▲

Stridor presentationN

Airway swelling with glottic edema; consider this cause after pro-N

longed surgery with the head down or in prone positionLaryngospasm; reflex closure of the glottis associated with light N

anesthesia with lower airway stimulation; it can also be a posterior fossa injury sign


Vocal cord paralysis; can be due to nerve or brainstem injury related N

to the surgery or may be preexisting; when bilateral, it can mimic laryngospasm

Extrinsic airway compression▲

Stridor or bronchospasm presentationN

Consider after neck or cervical vertebral surgery with a neck N

hematoma.Especially consider after:N

Carotid endarterectomy°

Multilevel cervical corpectomy°

A rapidly expanding hematoma can cause marked tracheal deviation N

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 manuallyTracheostomy 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

Low alveolar ON2 concentration

VQ mismatchingN

Anatomic shuntN

Diffusion abnormalitiesN

These may be further exacerbated by alterations in cardiac output if the ▲

pulmonary shunt is highCommon medical problems that may arise in the immediate postopera-▲

tive time to produce hypoxemia

Low FiON2

Ensure adequate supplemental oxygen and that paCO°2 is not so

high as to displace O2 from the alveoli with CO

2

Another short-lived cause is diffusion hypoxia as nitrous oxide °

leaves the blood to flood the alveoli and displace oxygen

Small airway closureN

Can be related to any combination of factors, such as preexisting °

lung disease, habitus, or drug-induced hypoventilation


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

V/Q mismatch from blunted hypoxic vasoconstriction; can occur with:N

Vasodilator infusion°

Early sepsis°

Liver failure°

Infiltrates or atelectasis –N

Check the chest X-ray and treat as appropriate°

New infiltrates may be associated with position or aspiration°

Diagnostic Approach to Hypoxemia

Check CXR

Assess ABC’sCheck ABG increased Aa Gradient*

Abnormal

Assess respiratorydrive and/or

negative inspiratoryforce

Normal**

Atelectasis

Focalinfiltrate

Consider Swan-Ganz catheterization

ConsiderChest CTfor PE

ConsiderUpper orLower AirwayObstruction

Pneumonia

Diffuse infiltrates

elevatedPCWP

normalPCWP

CHF ARDS/ALI

Fibrosis

Pneumothorax

V/Qmismatch

Confirm FiO2

MicroAtelectasis:

ObesityHypoventilationChest wallpain

Blunted hypoxicvasoconstriction:

SepsisVasodilatorsLiver failure

Brainstem lesion - mass- hemorrhage- herniation

Neuropathy - Critical illness- GBS

Myopathy - Critical illness- Hypophosphatemia- ALS or MG- Disuse atrophy

Decreasedrespiratory drive

Sedatives/ anesthetics

DecreasedNIF/FVC

Residual NeuromuscularBlockade

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 FiO

2 by 6 and comparing that expected

paO2 with the actual paO

2. The alveolar gas equation is pAO

2 = 713 *fiO

2 – paCO

2/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 exac-erbate hypoxemia due to low mixed venous oxygen level


Atelectasis may be related to endotracheal tube position or post-°

operative hypoventilation

Diffusion problemsN

Evaluate for and treat pulmonary edema°

High cardiac output can worsen diffusion-related hypoxemia°

Consider preexisting problems such as pulmonary fibrosis or °

sarcoid

Low cardiac outputN

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 CO•2 production relative to CO

2

elimination

Increased CO▲2 production; consider and treat, if present:

FeverN

MHN

ThyrotoxicosisN

Decreased CO▲2 elimination

Decreased minute ventilationN

Evaluate for drug-induced causes (residual propofol, volatile °

anesthetics, opioid, etc.)Naloxone may be helpful to diagnose and treat opioid-induced °

depressionFlumazenil 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

Increased dead spaceN

Can be produced through alveolar distension caused by excessive °

PEEP; therapy is to decrease PEEPVAE, 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•


With severe chronic obstructive pulmonary disease and administration of •fluids, a suboptimal state may be presentDo 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 secretionsGastric contents can enter the trachea during induction or emergence or •even after emergence from anesthesia in the NCCUSeizure 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 gas-•tric acid, whereas aspiration pneumonia refers to inhalation of contents that are colonized by bacteria and produce bacterial pneumoniaTreatment of significant aspiration•

Supplemental oxygen▲

Suctioning▲

Bronchoscopy may be helpful to remove particulate matter; unclear ▲

value if nonparticulate matter aspirationBronchodilators 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


based on better outcome with earlier institution of antibiotic therapy of pneumonia

Some risk-benefit judgment may be needed, as each decision has asso-N

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▲

Arises from increased pulmonary capillary pressureN

Can be treated by measures to improve cardiac function and to N

decrease capillary pressure with dieresis, along with supportive measures such as oxygen and sedationWhen severe, mechanical ventilator support and PEEP may be neededN

Consideration for myocardial ischemia as a contributing cause may N

be indicated

Noncardiogenic edema ▲

Usually due to increased permeability of pulmonary capillariesN

Treatment includes supplemental oxygen, sedation as needed, N

diuretics, mechanical ventilator support, and PEEPIf due to sepsis, pressors may be needed, along with appropriate anti-N

microbial therapy

Negative pressure pulmonary edema▲

Caused by upper airway obstruction with forceful inspiratory efforts N

against a closed glottis

Pulmonary embolism♦

Arises when a clot from the periphery transits to the lung and produces •significant hypoxemiaImportant postoperative problem, and efforts to prevent deep venous •thrombosis are requiredThe diagnosis is challenging but generally entails the existence of hypox-•emia out of proportion to the abnormality on chest X-ray with confirma-tory evidence by CT angiography or formal angiographyTreatment of pulmonary embolism is supportive, with volume infusion, vaso-•pressors, and mechanical ventilation as needed, as anticoagulation or throm-bolytic therapy generally is not an option immediately after neurosurgeryAn inferior vena cava filter may be warranted urgently•


Pneumothorax♦

Accumulation of air in the plural space with collapse of a lung and •impaired gas exchange with hypoxemiaTension 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 hypotensionTherapy 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 contextCauses 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 elevationsAbsence of chest pain does not rule out postoperative myocardial ▲

ischemiaOccurs 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 causeManagement includes▲

Treat hypoxemia, tachycardia, anemia, and hypotensionN

Serial ECG, enzymes, echocardiographyN

N b blockade when BP permitsAspirin when feasible after surgeryN

Nitroglycerin may be helpful if hemodynamically permissibleN

Cardiology consultation; note – do not withhold the above therapy N

waiting for the cardiologist to arrive


Dysrhythmias•

Most perioperative dysrhythmias are benign, but if pathologic, precipi-▲

tating factors must be considered and treatedElectrolyte 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▲

Can be supraventricular or ventricular (Chap. 9)N

Immediately after surgery, consider and treatN

Pain°

Hypovolemia°

Anxiety°

Intrinsic dysrhythmia°

Atrial fibrillation is a common SVT after neurosurgeryN

If hemodynamically stable, ° b blockers, diltiazem, or amiodarone can be given for rate control and/or conversionHypervolemia can stretch the atrium to precipitate atrial fibrilla-°

tion; if this is the case, a diuretic trial is reasonable, with electro-lyte replacementIf hemodynamically unstable, cardioversion is indicated°

Magnesium may be helpful°

Glycopyrrolate or atropine given with the reversal of neuromuscular N

blockade should also be considered in genesis of postoperative tachycardia

Bradycardia▲

Consider causes, and as feasible, treat:N

Neostigmine administration (atropine or glycopyrrolate are °

antidotes)Sinus node dysfunction°

Excessive ° b-blocker useInferior wall myocardial ischemia°

Bradycardia in the absence of hypotension is probably not really a N

problemPossible therapies include atropine, N b-agonist therapy, or transtho-racic pacemaker


Postoperative ECG changes▲

Extremely common after anesthesia and surgeryN

If nonspecific, changes generally do not suggest a problem with myo-N

cardial ischemia; 18% incidence of T-wave changes reported in the postoperative population and not associated with evidence of myocar-dial ischemia or injury; most ECG changes resolve within 24 hNonetheless, if an ischemic process is suspected, the T-wave N

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 hyperten-•sion; 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, cloni-dine, and propranolol become reasonable therapeutic options

Clonidine can produce unwanted sedationN

N b blockers can produce bronchospasm and excessive bradycardia

Table 12.2 Antihypertensive medications

Drug Mechanism Neuro side effects Other side effects

Labetalol, Metoprolol, Propanolol

b-adrenergic and a- adrenergic (labetalol) blockade

• Neuroprotective • Bradycardia

• NoICPeffects • BronchospasmHydralazine Systemic vasodilation Increase ICP • Tachycardia

• Myocardialischemia• Increased

catecholaminesEnalopril ACE inhibitor No ICP effects Renal ischemia if renal

artery stenosisSodium

nitroprussideSystemic vasodilation Increase ICP • Tachycardia

• Myocardialischemia• Increased

catecholamine• Cyanidewithhigh

dosesNicardipine Systemic vasodilator • Possibly

neuroprotectiveCoronary vasodilation

• ModestICPeffect

ICP intracranial pressure, ACE angiotensin-converting enzyme


ACE inhibitors also exhibit neuroprotective qualities in animals and do ▲

not produce the intracranial hypertension or tachycardia that might exacerbate myocardial ischemia

Use with caution with preexisting renal ischemiaN

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 extentHydralazine can be used if there are no issues with coronary artery ▲

disease or intracranial hypertension

Can increase ICPN

Can cause tachycardia and exacerbate myocardial ischemiaN

Urinary and renal dysfunction■

Bladder distension♦

May induce pain, hypertension, restlessness, and delirium•If severe and untreated, can lead to prolonged problems with bladder •functionCan be diagnosed with ultrasound bladder scanning and treated with ure-•thral 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 infusionBlood 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 obstructionCatheterization 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

Pretreatment with acetylcysteine or bicarbonate may be helpful N

prophylaxis


The only practical therapy is to maintain normal-to-slightly elevated ▲

intravascular volume status and avoid vasoconstricting drugs

Diuretics have not been proven to affect outcome, although they N

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 problemsDelirium♦

A transient fluctuating disturbance of consciousness, attention, cognition, •and perceptionMay delay recovery and prolong hospital stay•Often has accompanying cardiovascular abnormalities and behavioral •abnormalities that may endanger the patient and staffNutrition becomes nearly impossible to implement•

Diagnostic approach to postoperative mental status change

Perform neurologic exam

Focal deficitspresent*

Focal deficitsabsent

Obtain stat brain imaging Signs or symptomsof ↑ ICP absent

Signs or symptomsof ↑ 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)

Assess ABC’s

Normal imaging Consider stat brainimaging

Consider EEG

Labs unremarkable

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


Sometimes efforts to treat delirium create other problems as serious as the •inciting eventOccurs 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 effectsManagement approach to delirium•

Rule out contributing physiologic abnormalities such as hypoxemia, ▲

hypotension, and acidosisAdequately evaluate and treat pain (including bladder distension)▲

Evaluate for and treat metabolic causes such as blood sugar abnormali-▲

ties, electrolyte disturbances, and sepsisPhysostigmine is helpful when delirium is believed to be the result of ▲

central anticholinergic drugs; often worth giving empirically, as side effects are minimalHaloperidol or an atypical antipsychotic such as quetiapine may pro-▲

vide symptomatic relief, although probably does not treat cause, and an overdose cannot be reversedBenzodiazepines 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 neu-•rologic injury related to the recent neurosurgeryMetabolic abnormalities•

Evaluate and treat problems such as▲

Hypoglycemia/hyperglycemiaN

Severe azotemiaN

Severe anemiaN

Hyperammonemia related to hepatic failureN

Severe sodium imbalanceN

Severe hypercapnia (PaCON2 >80 mmHg) or

Hypoxemia (PaON2 <60 mmHg)


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 factorAntagonist drugs may be employed in an effort to reverse some anes-▲

thetic drugs if it is important to have a faster wake-up; antagonist drugs may include

Physostigmine (1–2 mg)N

Naloxone (serial boluses of 40 N mg IV)Flumazenil (0.2 mg q 1 min × 5 titrated)N

If neuromuscular blockade is a potential problem, neostigmine and N

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

Table 12.3 Residual anesthetic effects – 1 h after surgery

Drug Effect Treatment options

Volatile anesthetics Blunt hypoxic drive to breathe OxygenNitrous oxide Pneumocephalus OxygenOpioids Respiratory depression: Stimulation

Hypoxemia NaloxoneHypercapnia Oxygen

Vecuronium, Rocuronium, Pancuronium, Cisatracurium

Residual blockade: Neostigmine/ glycopyrrolate

Dyspnea Noninvasive ventilationProximal twitching (chorea-like)

movement of extremitiesOxygen

Hypoxemia Endotracheal intubationHypercapnia

Propofol Propofol infusion syndrome Physiologic support (stop propofol)

HypotensionMetabolic acidosisRhabdomyolysisResidual CNS depression Observation and

physiologic supportThiopental Residual CNS depression Observation and

physiologic supportDroperidol Residual CNS depression Observation and

physiologic supportExtrapyramidal immobility

and anxietyReassurance


Perioperative stroke♦

Incidence ranges from 0.1 to 1% and varies according to type and com-•plexity of surgery and preexisting cerebrovascular condition

After neurosurgery, many apparent ischemic stroke syndromes are ▲

related to retractor injury and will self-resolveSometimes, 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 insufficiencyIn patients with ischemic stroke, management early on is similar to ▲

principles outlined in Chap. 20

Risks and benefits of antiplatelet therapy and anticoagulation must N

be seriously weighed after neurosurgery

Hemorrhagic stroke can also occur▲

Common types are subdural and intraparenchymal in area of the N

surgery; occasionally see epidural and distant intraparencymal sitesSBP > 160 mmHg has been associated with post-neurosurgery N

intracranial hemorrhageOther problems with associated intracranial vascular dysautoregula-N

tion (e.g., after AVM surgery or carotid endarterectomy) also must be individually considered and may lead to judgment-based varia-tion 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 shiveringIf patient is still intubated, propofol infusion can also be effective▲


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 helpfulDiagnosis primarily based on observation of extremely high CO▲

2 pro-

duction and an extremely high temperatureAssociated problems can include▲

Metabolic acidosisN

Respiratory acidosisN

Extreme shivering and consequent rhabdomyolysisN

Renal failureN

Hemodynamic lability leading to shock stateN

Therapy for MH▲

Symptomatic control of temperatureN

Cold saline infusion IV and, if needed, nasogastric irrigation and °

enemasIce bags topically placed°

Cooling blankets°

Intubation with neuromuscular blockade and high minute volume, if N

neededDantrolene (10 mg/kg IV) (block the ryanodine receptor)N

Treatment of renal failure and rhabdomyolysis with fluid infusion; N

treatment of acidosisCall for helpN

Call MH hotline for assistance (1-800-644-9737 in US and 0011-N

315-464-7079 outside the US)

If patient has been in the hospital for >1 or 2 days, evaluation and pos-▲

sible 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 hyper-glycemic after surgeryIn 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


Overly aggressive treatment of hyperglycemia may produce deleterious ♦

hypoglycemia; thus, treatment must be aggressive but carefulPatients 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 illnessAcceptable 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♦

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 associ-ated with exacerbation of brain damage


Patients may complain of cognitive or personality changes early on, which ♦

improve over the months after surgery10–15% of elderly patients continue to have POCD at 6 months or later after ♦

noncardiac surgeryPOCD has not been prospectively evaluated specifically after neurosurgery; ♦

exact causative factors have not been elucidated; however, they include surgi-cal 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

Care of the postoperative neurosurgical patient begins with a comprehensive ■

report from the anesthesia and surgery team on arrivalIn caring for the postoperative patient, knowledge of the neurosurgical proce-■

dure and its common complications is vital to rapidly evaluating and reversing any adverse eventIn order to not confound the neurologic examination, sedatives in the NCCU ■

should be used judiciouslySuccessful preservation of neurologic status requires prompt resuscitation of ■

systemic complicationsHypertension increases the risk of ICH following craniotomy; in this setting, SBP ■

>160 mmHg should be treated using agents with favorable side-effect profilesPostoperative hypotension may be caused by hyovolemia, vasodilation, or ■

decreased cardiac dysfunction and should be treated accordinglyHyperglycemia and hyperthermia have deleterious effects on neurologic out-■

come and should be treated intensivelyBecause 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 cran-iotomy: 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


Coplin WM, Pierson DJ, Cooley KD et al. (2000) Implications of extubation delay in brain-injured 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. Churchill-Livingstone, 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):690–701Manninen PH, Raman SK, Boyle K et al. (1999) Early postoperative complications following

neurosurgical procedures. Can J Anaesth 46(1):7–14Ortiz-Cardona J, Bendo AA (2007) Perioperative pain management in the neurosurgical patient.

Anesthesiol Clin 25(3):655–674Ropper 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 prophy-laxis. AACN Adv Crit Care 18(2):119–126


Postoperative management following interventional procedures is equally as ■

important as the procedure itselfPostprocedural management must be coordinated with intraoperative manage-■

ment to optimize outcomes and avoid complicationsMeticulous preoperative and intraoperative planning leads to streamlined ■

postinterventional careA 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 isch-■

emic stroke

Chapter 13Care Following Neurointerventional Procedures

Yahia M. Lodi, Julius Gene Latorre, Jesse Corry, and Mohammed Rehman

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, NYand 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

218 Y.M. Lodi et al.

More common in men than women■

Affects more Whites than Blacks■

Etiology

Atherosclerotic process is most common cause of extracranial carotid artery ■

stenosis and associated with reduced ratio of lipoprotein B:AOther 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


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

Recurrent events depend on the severity of the stenosis and morphology of the ■

plaqueHighest 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 ■

recurrencePresence of collateral circulation is protective and associated with fewer events■

21913 Care Following Neurointerventional Procedures

Management

Prompt diagnosis and treatment of carotid stenosis is mandatory to prevent life-■

threatening disabling stroke and recurrent eventsTreatment 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 managementFor symptomatic carotid stenosis ■ ³70%, revascularization is associated with 13.5% absolute risk reduction (RR), and number needed to treat to observe benefit is 8For symptomatic carotid stenosis ■ ³50%, revascularization is associated with 6.5% absolute RR, and number needed to treat to observe benefit is 15Women 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 recur-■

rent events and good outcome if perioperative complication remains £3%

Cas

CAS is an alternative to CEA, especially for those who have high risk of periop-■

erative complications associated with CEAAngiographic criteria are considered to be high perioperative risk for CEA■

Contralateral occlusion of carotid artery♦

Ipsilateral intracranial carotid stenosis♦

Ipsilateral external carotid artery stenosis♦

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♦


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 isch-emia is accomplishedMost 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 procedureBasic 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 impairmentOral 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 thromboembolismIn 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 clopi-dogrel 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 threat-ening, 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 necessaryIf 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 baselineIf 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 rateAdjusted 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


Hypotension is well treated with dopamine in addition to volume ▲

expansionDopamine 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 ischemiaIs not very common and develops in those patients who do not have ▲

good collateralsSeizure instantly stops after deflation of balloon and does not require ▲

treatmentIf 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 ischemiaIncidence of thromboembolic events has reduced after introduction of ▲

distal protection device during CASIn the event of clinical ischemic event, a complete angiogram of ▲

head and neck must be performed to identify site of blood vessel occlusionIf an angiographic occlusion exists, attempt to restore blood flow ▲

should be initiated, using either clot retriever device or intra-arterial thrombolysis with thrombolyticsBecause all patients undergoing CAS are already on aspirin, clopi-▲

dogrel and therapeutic heparin, caution is advised in excessive use of thrombolytic agents during thrombolysis to prevent unwanted hemor-rhagic conversionIf angiogram is not consistent with occlusion of blood vessels, an ▲

urgent CT scan of the head should be obtained to identify any potential intraoperative hemorrhageIf 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 ▲

CASMost common cause is perforation of a blood vessel during mechanical ▲

maneuver of devicesOther causes of ICH are associated with anticoagulation during proce-▲

dure and reperfusionIn case of a hemorrhagic event that is either identified by cerebral angiogra-▲

phy or brain CT, heparin should be reversed immediately with protamine


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 transfusionIf the craniotomy is indicated, immediate transfusion of platelets ▲

before and during craniotomy will reverse platelets for urgent safe surgeryAfter 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 patientsThought to be associated with poor coronary perfusion that occurs with ▲

bradycardia and hypotension, induced during angioplastyProper screening of patient prior to the procedure and optimal man-▲

agement of heart rate and blood pressure may prevent unwanted car-diac ischemiaEach institution should follow its own protocols for cardiac ischemia▲

Post-stenting hypertension must be avoided to prevent hyperperfusion-▲

induced brain injuryThere 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 necessarySystolic blood pressure (SBP) of 120–160 mm Hg may be easily toler-▲

ated 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 devicesRecent studies have revealed that morbidity and mortality associated ▲

with CAS increase significantly in the event of retroperitoneal hem-orrhages, which further amplify in the presence of hemodynamic instabilityEvery effort must be undertaken to prevent groin hematoma; in the ▲

event of retroperitoneal hemorrhage, prompt hemodynamic stability must be achievedAn urgent vascular surgery consultation should be initiated for ▲

surgical repair of the puncture site to prevent further hemody-namic instability

Instant thrombosis•

Instant thrombosis is a rare complication associated with CAS; it ▲

occurs in ~1% of cases


Stent thrombosis may begin immediately after deployment of a carotid ▲

stent and is most commonly seen in the first 24 h; therefore, a post-proce-dure carotid ultrasound is recommended within 24 h for all CAS patients prior to their discharge home to identify any acute in-stent thrombosesUnderlying mechanisms are platelet activation by the stent and inade-▲

quate inhibition of plateletsIf stent thrombosis is detected during procedure, IV or intra-arterial ▲

administration of GPIIbIIIa-receptor antagonist (integrelin) usually resolves thrombosis and restores blood flowThe IV infusion of GPIIbIIIa-receptor antagonist (integrelin) may need ▲

to be continued for 24 hA carotid ultrasound is recommended within 24 h for all CAS patients ▲

prior to their discharge home to identify acute in-stent thrombosesIf the follow-up carotid ultrasound demonstrates no stent thrombosis, ▲

patient can be discharged homeIf an in-stent thrombosis is detected within 24 h by ultrasound, IV infu-▲

sion 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 thrombosisIt takes almost 4 weeks for the endothelium to grow over the stent, when the ♦

stent becomes part of the wall of the carotid arteryAfter 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 studiesIt is recommended that carotid duplex evaluation of stent patency be con-♦

ducted 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 FDA-■

approved therapy for acute ischemic stroke but must be administered within 3 h and is relatively ineffective for proximal occlusions


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 strokeMechanical 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 territoryLarge 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■


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♦

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▲


Balloon angioplasty and/or stenting▲

Suction thrombectomy▲

Discontinued devices▲

Angiojet – suction-inducing saline jetsN

Latis laser deviceN

EPAR (endovascular photo acoustic recanalization) laser systemN

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▲


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 ▲

perfusionTICI 2 – Partial perfusion▲

2a – Partial filling <2/3 of vascular territoryN

2b – Complete filling but slowN

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 perfusionGrade 2 – Rapid collaterals to the periphery of ischemic site and partial ▲

perfusion

Table 13.1 Quareshi grading system

Grade Description

Grade 0 No occlusionGrade 1 MCA occlusion M3 segment ACA occlusion A2

or distal segment1 BA/VA branch occlusion

Grade 2 MCA occlusion M2 segment ACA occlusion A1 and A2 segment

>1 BA/VA branch occlusion

Grade 3 MCA occlusion M1 segment3a Lenticulostriate arteries spared and/or leptomeningeal collaterals visualized3b No sparing of lenticulostriate arteries and/or leptomeningeal collaterals not

visualizedGrade 4 ICA occlusion collaterals

presentBA occlusion collateral present

4a Collaterals fill MCA Anterograde filling4b Collaterals fill ACA Retrograde fillingGrade 5 Complete occlusion

MCA middle cerebral artery, ACA anterior cerebral artery, BA basilar artery, VA vertebral artery


Grade 3 – Slow collateral flow but complete reperfusion by the late ▲

venous phaseGrade 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 SaO■2 > 95%; supplement with O

2 as necessary

Perform elective intubation if:■

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 administrationFor 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 procedureInsert 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)


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 sever-ity of cardiac dysfunction, and emergent cardiology referral may be war-ranted for concurrent coronary interventionConfirm 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 edemaRepeat imaging as necessary to assess progression of hemorrhage or edema•

Oxygenation♦

Keep SaO•2 Sat >95%, supplement with O

2 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 HgThose who have poor recanalization despite intervention may be main-•tained 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 •outcomeAggressive 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


Fever control♦

Hyperthermia from any cause is a poor predictor of outcome; keep •temperature below 38°C using acetaminophen, cooling blanket, ice packsSurface or endovascular cooling for normothermia enables tight and uni-•form temperature control without over- or under-shooting (thereby pre-venting additional complications) and may be preferable

Antiplatelet therapy♦

Patients who had angioplasty and stenting require adequate antiplatelet •therapy to prevent rethrombosis/reocclusionBoth 325 mg ASA and 75 mg clopidogrel are recommended maintenance •medications for at least 4 weeksAntiplatelet therapy is contraindicated in patients who received systemic or •intra-arterial thrombolysisIf patient received both thrombolysis and stenting, decision to institute anti-•platelet 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 restIt is important to examine the groin puncture site for development of •hematoma, pseudoaneurysm, or worsening tenderness and loss of distal pulsesIncidence of groin hematoma is declining due to the availability and use of •micropuncture femoral access kit and closure devicesDespite this, retroperitoneal hemorrhage occurs and may induce hemody-•namic instability and cause impaired cerebral perfusion if not addressed fullyUrgent vascular surgery consultation may be needed if hemostasis cannot •be achieved


Complications and Their Management

Procedural complications■

Hematoma♦

Manual compression for at least 20–30 min to achieve hemostasis and •prevent further expansionIf 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 achievedFor space-occupying hemorrhage or brain edema, manage with aggressive •intracranial hypertension protocolSurgical decompression may be considered in patients <60 years old with •nondominant hemisphere involvement and/or with some language preser-vation and impending sign of herniationSeizure 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 •procedureTelemetry monitoring and serial cardiac injury panel determination iden-•tify most acute cardiac injury in the perioperative periodIf 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•


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 patientsScreen patients with CT or MR angiography▲

Hereditary connective tissue diseaseN

Patient with N 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 elasti-cum, familial aldosteronism type I, polycystic disease of the kidneys)


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 14Hypertension▲

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%/year5-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 sizeBenefit 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 •yearsSelection of patients•

Any aneurysm ▲ ³7 mmAny aneurysm in patient with SAH▲

If intradural and symptomatic▲

Familial aneurysm of ▲ ³5 mmWide-necked ruptured aneurysm▲

Fusiform aneurysm of ▲ ³7 mm

Table 13.2 Five-year rupture rates for intracranial aneurysms

Size (mm) Cavernous ICA (%) Anterior circulation (%) Posterior circulation (%)

7–12 0 2.6 14.513–24 3 14.9 18.4³25 6.4 40 50


Selection of patients specific to stent-assisted endovascular coiling•

Wide-necked aneurysm with diameter of ▲ ³7 mmAny symptomatic Wide-necked aneurysm ▲ ³2 mmWide-necked familiar aneurysm ▲ ³5 mmWide-necked ruptured aneurysm▲

Fusiform aneurysm of ▲ ³7 mm

Wide-necked aneurysms are defined as having dome-to-neck ratios N

<2 or a neck >4 mm in diameterAn intracranial aneurysm is defined as fusiform if the aneurysm was N

an out-pouching dilatation of the parent blood vessel affecting at least 270° of circumference of the lumen and possessing no discern-ible neck

Treatment risks (Table ♦ 13.3)

Poor outcome risk increases with age, 6% risk if 40–49 years, and 30% if •>70 yearsSurgery 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 studiesAll 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 aneu-rysms who may require stent-assisted coiling; this loading dose provides platelet inhibition of 55% in 1 h and 80% within 5 h of administrationAs stent-assisted treatment of aneurysms requires general anesthesia, all •prospective candidates must be evaluated for candidacy of general anesthesiaPreoperative mandatory laboratory testing – CBC, basic metabolic panel, •PT, PTT, urine analysis, 12-lead EKG, chest x-ray, and echocardiographyTreat 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 12.6Endovascular coiling 9.3 9.8


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 hypertensionAll hypertensive events must be treated with appropriate antihypertensive •medications such as labetalol, hydralazine, or nicardipine; sodium nitrop-russide must be preserved for the refractory casesBaseline ACT must be obtained, and IV heparin should be administered to •obtain a recommended ACT ³250 s prior to implantation of intracranial stentStent-induced spasm could be treated with intra-arterial verapamil and/or •nitroglycerineInstant thrombosis is usually treated with intra-arterial IIB/IIIa receptor •antagonist and intraoperative thromboembolism is treated with intra-arte-rial 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 hGroin 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 hAll stent-assisted coiling must be monitored in a NCCU setting or at least •in the medical ICU with nurses trained in caring for neurosurgical patientsBlood pressure – after stent-assisted coiling procedure, liberalized blood •pressure is allowedAdequate hydration and oxygenation must be maintained; adequate pain •control must be obtained, preferably with IV short-acting narcotics such as fentanylAll patients must have orders for appropriate anti-emetics•Diet – if the patient is wake and alert without any neurologic and swallow-•ing impairment, diet could be advanced as toleratedIf any neurologic deterioration occurs, patient requires an urgent CT of •head after the stability of airway and hemodynamics; the treating neuroin-terventionalist 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 place-ment in wide-necked aneurysm


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/•clopidogrelEase of intubation/extubation; use and reversal of neuromuscular •blockade; net volume after case; use of colloid and/or vasopressorsUse of closure device at angiopuncture sight/duration of extremity •immobilityPast 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 HgECG 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)


Patients with unruptured aneurysm may be discharged to home after 24 h •if they are back to their baseline conditionAll 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 noticeAll patients must be evaluated in the clinic in 2 weeks after discharge to •home and require a 3-month follow-up cerebral angiographyHeadaches – coil headaches are usually transient, last from a few days to a •few weeks, and are treated with oral acetaminophen with codeine, gabap-entin, 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 midbrainArterial dissection (vertebral artery > carotid artery > intracranial); ▲

30–70% will rebleed, and these are often fatalArteriovenous malformation (AVM); 10–20% will have associated sac-▲

cular aneurysmDural AV fistula▲

Cocaine abuse (“crack:” form > alkaloid form)▲

Risk factors♦

Hypertension, heavy EtOH intake, connective tissue diseases, cigarette •smoking, and estrogen deficiencyFamilial•

If SAH, ~4% of first-degree relatives have aneurysm; familial saccular ▲

aneurysms tend to burst at a smaller size and younger age than do spo-radic aneurysms


10-year prospective risk of SAH with one first-degree relative with ▲

SAH is 0.8%; if two, then 7.1%

Classification♦

Shapes•

Saccular (berry) aneurysms▲

Most often at bifurcationN

Wide-necked aneurysms are defined as having dome-to-neck ratios N

<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, coma10–43% of patients with headache report prior headache or “sentinel” ▲

headache30% occur at night▲

LBP and meningismus common later after bleed▲

Pre-procedural care♦

Endovascular therapy carries a lower risk of adverse outcomes and in-•hospital death, shorter length of stay, and decreased hospital chargesPatients eligible for endovascular treatment must have an aneurysm with-•out thrombus, willing to have repeated angiography, and a favorable fun-dus-to-neck ratioPreoperative mandatory laboratory testing - CBC, basic metabolic panel, •PT, PTT, urine analysis, 12-lead EKG, chest x-ray, and echocardiographyPeriprocedural 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 methylpred-nisolone IV, and 0.5 mg IM epinephrine q 5 min prn or epinephrine drops @ 2–10 mg/min

NPO•


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 preven-tion of hypertension; if a ventriculostomy catheter is inserted, adequate cerebral perfusion of 70 mm Hg must be maintainedAll hypertensive events must be treated with appropriate antihypertensive •medications such as labetalol, hydralazine, or nicardipine; sodium nitrop-russide must be preserved for the refractory casesOnce 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 baselineA baseline ACT must be obtained, and IV heparin should be administered •to obtain a recommended ACT ³250 s prior to the implantation of intrac-ranial stentStent induced spasm could be treated with intra-arterial verapamil and/or •nitroglycerineIn-stent thrombosis is usually treated with intra-arterial IIB/IIIa receptor •antagonist, and intraoperative thromboembolism is treated with intra-arte-rial administration of thrombolytic or mechanical retriever of clotCoils/Stents/Balloons•

Titanium and platinum wire are used to make microcoils and 3D ▲

spheresOnce 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 aneurysmHydrogel coils (Microvention) are platinum coils covered with an expand-▲

ing polymer; with exposure to blood, the coil increases volume 3–4 times, with nearly equivalent recanalization rates to those of Matrix coilsBalloon-assisted GDC (Guglielmi detachable coil) therapy has been ▲

shown to be safe and effective for wide-necked aneurysms with a neck-to-body ratio close to 1; balloon assistance forces the coils to assume the shape of the aneurysm without coils abutting the parent arteryBalloon use does have the inherent risk of induced vasospasm, throm-▲

bus formation, rupture, and ischemiaStent-assisted endovascular coil occlusion of wide-necked saccular aneu-▲

rysms achieves ³95% occlusion in 73–100% of patients in recent studiesLiquid-based embolic polymer, Onyx, is a treatment for AVM and, ▲

potentially, aneurysms; on contact with blood, it transforms into a pul-pous substance; the major drawback is migration of the substance to the parent artery and distal embolization5–14.5% 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


Post-procedural management (Box ♦ 13.2)

Good outcomes rely on skilled observation•Post-procedure problems – hydrocephalus, hypothalamic dysfunction, sei-•zures, cardiac abnormalities, contrast reaction, infection, arterial dissection, pseudoaneurysm, parent artery occlusion, groin hematoma, thromboembo-lism, and rupture associated with coil/stent/balloon (30–40% mortality)Upon return, a complete neurologic examination must be performed imme-•diately 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, re-•hemorrhages, etc.)Any remaining aneurysms?•Any vasospasm noted? Treatments?•Pre-procedure ASA, clopidogrel; use of stents; duration of ASA/•clopidogrelEase of intubation/extubation; use and reversal of neuromuscular •blockade; net volume after case; use of colloid and/or vasopressorsUse of closure device at angiopuncture sight/duration of extremity •immobilityPMH and medications•

Neurologic♦

Continue neurologic assessments sequentially following case; if sud-•den change in MS, consider rebleed vs. seizure vs. hydrocephalus vs. ischemia vs. ICH vs. vasospasmAssess 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 daysICP•

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 prnCardiac▲

(continued)


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

Box 13.2 (continued)

Hold any home meds; MAP • £130 mm HgIf patient on chronic ▲ b blockade, follow for signs of tachycardia and resume at lower doseFirst-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 echocar-•diogram prnMonitor urinary output and follow for evidence of IV contrast neph-•ropathy; optimize risk reduction with adequate hydrationSerial extremity pulses to assess perfusion distal to puncture•At day 4 from SAH, maintain intake approximately equaling outputs •until day 15If 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, con-sider lower extremity Doppler ultrasound for DVT screeningIf 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)


Blood pressure – once the aneurysm is secured, allow MAP to rise to •£130 mm HgAdequate hydration and oxygenation must be maintained; adequate pain •control must be obtained preferably with IV short-acting narcotics such as fentanylAll patients must have orders for appropriate anti-emetics and stool •softenersDiet – if patient is wake and alert without any neurologic and swallowing •impairment, diet can be advanced as toleratedIf any neurologic deterioration occurs, patient requires urgent head CT •after the stability of airway and hemodynamics; the treating neurointerven-tionalist and neurosurgeon must be notified immediately for the appropri-ate management

Follow-up♦

Acute medical management•

Neurologic▲

Seizure prophylaxis – a number of retrospective series report poorer N

outcome associated with phenytoin; thus, in the acute window, sug-gest agent such as 500 mg levetiracetam PO/PT q12 h × 3 days if no seizuresVasospasm – window, day 4–21; peaking days, 7–8N

Risk factors include dehydration, hyperglycemia, high Fisher °

grade, and <50 years of age7% of patients die from vasospasm; use of lumbar drainage or °

statins may ameliorate this riskKeep 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 improvementMore distal vasospasm can be amenable to IA vasodilators, °

resulting in improved clinical outcome scoresRecent 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 pres-ence of U wavesPulmonary – DVT prophylaxis with 5,000 U heparin SQ q 12 h or 40 U ▲

SQ q d Lovenox after first post-procedure dayGI – stool softeners to limit valsalva strain and serum glucose ▲

£180 mg/dL


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 coiling6–12-month follow-up typically occurs with an angiogram; thereafter, ▲

with MRA or CTAImproved long-term outcomes associated with coiling▲

Benefits in ISAT (International Subarachnoid Aneurysm Trial) N

reported to 7 years1-year outcome – clip vs. coil (Table N 13.4)Absolute risk reduction of death/dependency at 1 year, 6.9%; rela-N

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 rupturePresence of concomitant intracranial aneurysm and AVM increases twofold the ■

chance of hemorrhage in follow-up periodIntracranial 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 casesOther presentations include headaches (15%), focal neurologic deficit (<5%) ■

and pulsatile tinnitus

Current Treatments

Surgery■

Radiosurgery■

Embolization■

Combined treatment■

Table 13.4 One-year outcome – clip versus coil

Outcome (mRS) Surgery (%) Endovascular (%)

0–2 69.1 76.53–6 30.9 23.5


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 seizuresAll patients must have preoperative testing, including anesthesia clearance, as ■

described previouslyArrangement 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 procedureDuring the procedure, a normal SBP of 110–140 mm Hg must be maintained■

Any hypertension must be avoided to prevent complications related to the poten-■

tial “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 seizuresTo prevent fluctuations of blood pressure, an IV continuous infusion of antihy-■

pertensive medication must be used at least for first 24–48 hIf the procedure is performed under general anesthesia, intraoperative neu-■

romonitoring 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 obtainedIn case of an ICH, patient must be urgently evaluated by Neurosurgeon for the ■

evacuation of blood


If CT scan is normal but patient still has change in mental status, an urgent EEG ■

must be obtained to diagnose nonconvulsive seizuresSBP must be maintained at 110–140 mm Hg■

To prevent fluctuations of blood pressure, an IV continuous infusion of antihy-■

pertensive 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 proceduresPre-, intra- and post-procedural management is critical for enhancing good out-■

comes in patients undergoing neurointerventional proceduresUse of stents, placement of coils, and liquid polymer use must be assessed ■

adequately for need for heparin and clopidogrel and potential for distal embolizationIn patients with intracranial aneurysms, endovascular coiling, compared to sur-■

gery, 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):928–939Molyneux 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 neo-plasms. 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


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 disabilityWhen rendering that care, it is important for providers to maintain respectable ■

standards of ethics and to be compassionate toward critically ill patients and their familiesIn 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 healthHowever, 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•

Chapter 14Ethical Issues and Withdrawal of Life-Sustaining Therapies

Wendy L. Wright

W.L. Wright, MD (*) Emory University School of Medicine, 1365B Clifton Rd., NE, Ste. 6200, Atlanta, GA 30322, USA e-mail: [email protected]

248 W.L. Wright

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 interestFor example, withholding information about a poor prognosis and only offering •the treatment options that the physician thinks are most appropriatePaternalism 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 dyadThe 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

24914 Ethical Issues and Withdrawal of Life-Sustaining Therapies

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 consentEven in an emergency, however, it is not permissible for a physician to per-♦

form any treatment, test, or procedure that he knows goes expressly against a patient’s wishesThree criteria are required to make consent valid: capacity, adequate informa-♦

tion, and lack of coercion

Capacity•

Capacity is the patient’s physical ability to exercise rational decision-▲

makingIncludes the ability to understand the consequences of a decision, which is ▲

often best assessed by having a conversation with the patient to that effectDifficult to assess in patients who are mechanically ventilated, but if ▲

they can write or use alternative forms of communication, capacity can be assessedCapacity is decided based on a physician’s clinical judgment▲

However, “capacity” is often mistakenly used interchangeably with the ▲

word “competence” by cliniciansCompetence 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 compe-tency is a legal declarationMany 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 decisionWould 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

250 W.L. Wright

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 decidingIf 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 illOften address fluid, hydration, and ventilatory support preferences if the patient ♦

were to have a terminal illness or enter into a persistent vegetative stateMay 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 illnessHowever, 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 arrestDepending 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


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 inadequateHowever, 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 futileIn fact, honoring a request to provide medically futile treatment may violate ♦

the principles of nonmaleficence and justiceThe 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 consentMedical futility can be difficult to establish. As it is based on training and ♦

clinical expertise of the treating physicians, there may be room for debateMany hospitals have a policy to establish futility♦

Often incorporating that no one physician should establish futility •unilaterallyFutility cannot be established without explaining to the patient and/or fam-•ily 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 measuresHas been shown to invariably lead to patient deaths in the NCCU and to particu-♦

larly be a problem in patients with large intracerebral hemorrhageFurther hinders the collection of accurate prognostic information♦

Slows or altogether halts opportunities for therapeutic advances♦

252 W.L. Wright

Obstacles in communicating prognoses■

One of the biggest obstacles is physician anxiety about delivering the news of ♦

a poor prognosisThis 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 litera-•ture 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 goalsIn actuality, it is important to try to understand and work toward patients’ •desired goals

Fig. 14.1 How to deliver “Bad News”

In person, whenever possibleIdeally in a private room that has seating for everyone; At least

in a private, quiet settingDemonstrate compassion and empathyMake eye contact, extending a comforting touch when appropriateAvoid medical jargon


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 discus-sions; 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 state-ment 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 careWhen 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 valuesThe benefits of ethics consultations often arise from promoting regular com-♦

munication between the patient’s family and healthcare teamThe 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 providersEthics consultants can incorporate cultural sensitivity into the discussion, ♦

help to address uncertainty regarding value-laden issues, and offer a range of morally acceptable optionsWhen conflicts exist among the healthcare team about whether or not to with-♦

draw 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

254 W.L. Wright

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 tumorAdministering 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 deathAllows 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 patientMedical 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•


Palliative Care

Palliative care is a branch of medicine that focuses on the relief of physical, ■

emotional, social, and spiritual sufferingPalliative 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 managementPrinciples 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 occursImplementation 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 barrierEducation 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 focusThe absence of pain, dyspnea or other symptoms is a primary indicator of high-■

quality end-of-life careSome common goals■

Provide adequate pain and symptom management♦

Avoid prolongation of the dying process♦

Respect cultural beliefs and meet cultural expectations when possible♦

256 W.L. Wright

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 patientsCommunicate with the family or decision makers (In the NCCU, communica-■

tions 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 ■

removedDocument 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 causesWithdraw 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 fashionUnless there is diagnostic uncertainty, therapies that lead to death in a delayed ♦

fashion tend to be withdrawn firstWithdraw therapies that are thought to be expensive, in short supply, or ♦

artificial


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 ventilationPhysicians 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 mem-•bers 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 exam-•iner 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 choiceA 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 one10. To be fed, hydrated and rested

Adapted from Truog et al. (2001)

258 W.L. Wright

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 familyWarning 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 accessFentanyl▲

Causes less hypotension than morphineN

Much shorter acting than morphine and less likely to cause euphoria N

and sedation

Hydromorphone▲

Less likely to cause sedation and euphoria than is morphineN

Meperidine is not commonly used in end-of-life care because it can ▲

cause excitation of the central nervous system

Can potentially lead to anxiety, tremors, and seizuresN

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▲


Table 14.1 Common medications used during end-of-life care

Symptom Medication Typical starting dose Comments

Pain Morphine 2–10 mg IV q 2–4 h or 0.05–0.1 mg/kg/h infusion

If no IV access, consider •oral, rectal, subcutaneous or transdermal dosingIM dosing is less preferred •due to pain at the injection site

Fentanyl 25–100 mcg/h IV infusion or 50–100 mcg/h transdermal patch

Very short-acting, •so infusion must be maintained judiciouslyPatch 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

Hydromorphone 0.5–1 mg IV q 2–4 h Less nausea and sedation •than morphine

Dyspnea Morphine As abovePropofol 0.5–2 mg/kg/h IV

infusionAs an anesthetic agent, many •hospitals will only allow infusion in a mechanically ventilated patientCan be painfully when •administered via peripheral IV

Albuterol/Ipratropium 2–4 puffs q4 h and prnDelirium Haloperidol 0.5–10 mg IV q 4–6 h

or 3 mg/h IV infusion

Titrate up at 30 min •intervals as needed to control patient’s delirium

Anxiety Lorazepam 0.5–2 mg IV or po q 2–4 h

Used most commonly•

Diazepam 2.5–5 mg IV or po q 2–4 h

Can be painful when •administered via peripheral IV

Midazolam 2–4 mg IV q1–2 h or 2–4 mg/h via continuous IV infusion

Propofol 0.5–2 mg/kg/h IV infusion Many hospitals will •only allow infusion in a mechanically ventilated patientCan be painful when •administered via peripheral IV

Fever Acetaminophen 650 mg po/pr q4 hNausea Ondansetron 4 mg IV q 8 h

Phenergan 25–50 mg po/pr q6 h prn or 12.5–25 mg IV q 4–6 h prn

260 W.L. Wright

This effect is more pronounced with morphine compared to other N

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 ventilatedAs 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 discomfortFood 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 careHowever, some patients who are having life-sustaining treatment withdrawn ♦

will have been on NMBAsA 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


However, a clinician must weigh the burdens of reversing the paralytics or •waiting for them to wear off with the risks of continuing ventilatory sup-port 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 dosagesDosages 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 givenThe 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 with-drawing 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 careDuring ♦ 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 comfortThe 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 patternsHowever, 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

262 W.L. Wright

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 machineryDisadvantages are that the patient may have stridor or secretions that are •uncomfortable and must be adequately managed from a symptomatic standpointEven 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 deadFamilies 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 NCCUAs 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


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 capacityWhen 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 •principlesMost notably, to ensure that death is not hastened in the donor in order to •retrieve organsCustomary end-of-life practices should be provided with the goal of relieving •pain and sufferingDonation after cardiac death should not be done without a prospectively •developed institutional protocolMost 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 harmA patients’ right to self-determination dictates that they (or their surrogate decision ■

maker) have access to as much prognostic information as they physician hasThere is no ethical distinction between withholding and withdrawing care, but ■

there is a distinction between killing and letting dieBe 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 patientEthics 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 patientsWhen 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 patientStandardized order forms improved end-of-life care■

264 W.L. Wright

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.

http://www.lastacts.org


Introduction

Neurocritcial care is best delivered with a collaborative, organized, and efficient ■

model of careUtilizing a combination of nursing roles offers a unique opportunity to pro-■

vide 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 neuroscienceNeurospecific 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:♦

Chapter 15Collaborative Nursing Practice in the Neurosciences Critical Care Unit

Filissa M. Caserta

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]

266 F.M. Caserta

Cerebrovascular insults (ischemic and hemorrhagic stroke, including aneu-•rysmal 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 edu-■

cation, 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 careCredentialing 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 ♦

nursingImportance: 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 neuro-•sciences or retest

26715 Collaborative Nursing Practice in the Neurosciences Critical Care Unit

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 ulti-mately, recruitment and retention are improvedImplementing the role of CNM can provide a constant, visible clinical presence ■

to the nurses in the NCCUThe CNM position should either be a dedicated position or rotated among the ■

experienced staff on the unitThe 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 experi-ence and intuitionShould possess patience, openness, trustworthiness, positive attitude, good ♦

communication, and listening skillsShould not have a patient assignment, as that would render the CNM inacces-♦

sible to the unit nursing staffShould 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 ♦

populationPersonal experience with the intricacies of the assessment and management ♦

of the neurocritical care patient

268 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 RNThe 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 performanceRole has expanded beyond clinical practice to include education and con-•sultation; in some states, the CNS has prescriptive authorityGoal 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 familyOffers 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 patientsCreates protocols for practice based on the most current guidelines▲


Offers “hands-on” education of various neurospecific devices such as ▲

those indicated for monitoring of intracranial pressure and brain tissue oxygenation, extraventricular drainage, and microdialysisUtilizes the research process to improve outcomes▲

Collaborates with senior investigators and the NCCU interdisciplinary ▲

team to conduct researchEvaluates the quality of nursing on the team▲

Participates in obtaining initial primary stroke center certification and ▲

maintaining ongoing certificationParticipates in obtaining initial trauma certification and maintaining ▲

ongoing certification

CRNP♦

A CRNP is an APRN who provides a wide range healthcare services, includ-•ing prescribing medications, diagnosing and treating illnesses/injuries, and performing proceduresComprise 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 areasCurrently, 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 certificationFamily 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▲

Obtains a detailed history and physical, diagnoses patient, creates a N

plan of care, writes orders to carry out the plan, and evaluates the plan

270 F.M. Caserta

Interprets lab and radiographic studiesN

Provides ventilator managementN

Interprets hemodynamic measurementsN

Performs procedures; the type and degree of invasive procedural work N

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 cathetersIntubation°

Bronchoscopy°

Thoracentesis°

Lumbar punctures°

Placement of lumbar drains°

Placement of intracranial pressure monitoring devices°

Nursing support▲

Assists bedside nurse in understanding many of the complexities of N

managing the neurocritical care patient by:

Utilizing the rounding process to review pathophysiology and °

explain rationales for interventionsPerforming the initial neurologic assessment and the daily °

assessment with the novice neuroscience nurse to reinforce the intricacies of the neuro exam

Participates in formal educational offerings, that enable the neuro-N

science nursing staff to maintain clinical expertise

Research▲

Identifies potential patients for clinical trialsN

Educates nurses, patients, and families about such trials and assists N

with data collection.Measures outcomes of the impact of a nurse practitioner service to N

help increase ACNP role recognition and acceptance and ensure longevity.

Billing▲

Passage of the Balanced Budget Act of 1997 allowed CRNPs and N

CNS to be directly reimbursed by Medicare for services providedACNPs capture possible lost charges due to:N

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▲


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 careBenefits 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

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 falls13 Encourage patients’ active involvement in their own care as a

patient safety strategy15 Identifies safety risks inherent in its patient population16 Improve recognition and response to changes in a patient’s

conditionaNoncontiguous 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

272 F.M. Caserta

Holding regularly scheduled meetings with the CNM, NM, CNS, ACNP, and ♦

senior nursing staffEnsuring 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

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

Certified registered nurse practitioner

• Advanced practice registered nurse with master’s or doctoral preparation

• 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

http://www.aann.org/credential/pdf/CNRNBrochure07.pdf


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 descrip-tion. 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

http://www.jointcommission.org/PatientSafety/NationalPatientSafetyGoals/08_hap_npsgs.htm

http://www.jointcommission.org/PatientSafety/NationalPatientSafetyGoals/08_hap_npsgs.htm

Part IISpecific Problems in Neurocritical Care


Definitions

Consciousness can be defined as the state of awareness of self and one’s rela-■

tionship with the environment

Consciousness consists of two components: ♦ wakefulness or arousal and awarenessBoth 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 forebrainThe 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 cortexCortical activity is simultaneously modulated through a series of direct inputs ♦

from monoaminergic neurons that originate in the upper brainstem and pos-terior hypothalamusInteraction 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

Chapter 16Coma and Disorders of Consciousness

Edward M. Manno

E.M. Manno, MD (*) Mayo Clinic School of Medicine, 200 First St. SW, Rochester, MN 55905, USA e-mail: [email protected]

278 E.M. Manno

■ Disturbance in consciousness, therefore, must involve a process that affects the RAS, the cerebral hemispheres, or both simultaneouslyA 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 cortexHowever, in general, a change in consciousness mediated through the cerebral ♦

cortex must involve a process that affects the cortex diffusely; e.g., a meta-bolic encephalopathy, head trauma, anesthesia, etc.Conversely, a small lesion strategically placed in the brainstem or in the thala-♦

mus can lead to profound disturbance in consciousnessDisturbances 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

■ 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 (represent-ing 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 condi-tion must be present for 1 monthPermanent 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

27916 Coma and Disorders of Consciousness

■ 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 environmentBoth 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 structuresCommunication may only be possible through eye movements or eye blinking♦

■ Brain death refers to the irreversible loss of all functions of the entire brainOther terminology, such as ■ apallic state and akinetic mutism, are historical terms that refer to specific conditions that were previously described but less well characterizedTerms 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♦

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, malingeringHead trauma is a leading cause of an alteration of consciousness●

Trauma may mediate a disturbance of consciousness through several ▲

different mechanismsDiffuse axonal injury can occur due to shearing of the cortical and ▲

subcortical grey matter structuresSecondary hemorrhages (i.e., subdural and epidural hematomas) may ▲

lead to distortion of the brainstemIschemic changes can result from large increases in intracranial pres-▲

sure or abrupt decreases in cerebral perfusion

280 E.M. Manno

Electrolyte disturbances●

Most commonly hypo- or hypernatremia can lead to alterations of ▲

consciousnessHyper- or hypocalcemia in malignancies is often encountered▲

Less commonly, disturbances in magnesium and phosphate levels can ▲

depress the sensoriumRefeeding hypophosphatemia is a concern in the surgical patient who ▲

has been without nutrition for a period of timeHypercapnia 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 commonOther deficiencies include B▲

12 deficiency and pellagra due to niacin

deficiency

Drug intoxication and poisoning can lead to an encephalopathy, either ●

through a direct intoxication (arsenic, ethylene glycol) or due to secondary organ failureNeoplasms 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 meningesIschemia, either global or focal, can lead to alterations in consciousness●

Global anoxia after cardiac arrest is a common form of an ▲

encephalopathyIschemic stroke that involves the brainstem or diencephalic structures ▲

will depress consciousnessAn acute focal hemispheric ischemic stroke can depress consciousness ▲

if a lesion previously existed that involved the opposite cerebral hemi-sphere thus leading to bi-hemispheric damage

Intracerebral hemorrhage involving the brainstem or diencephalon will ●

diminish consciousness

Intraventricular hemorrhage similarly depresses consciousness▲


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 Marchiafava-Bignami diseaseInfections 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▲

Seizures and status epilepticus is a common cause of neurologic deterioration●

Sleep disturbances, including the parasomnias, somnambulism, and narco-●

lepsy, may lead to chronic fatigue and sleepinessDisturbances in cerebral autoregulation, commonly encountered in eclamp-●

sia, malignant hypertension, and the recently described posterior reversible encephalopathy (PRES), can depress consciousness

Assessment of Coma and Stupor

Assessment of the patient with a depressed level of consciousness involves ■

several stepsAs 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 dete-rioration of consciousnessImportant details to elicit would include any preexisting conditions, the circum-■

stances of the event, and/or the progression of the loss of consciousnessPrevious deterioration of consciousness and focal signs or symptoms preceding ■

a worsening level of consciousness may provide additional informationMedications and a history of substance abuse must be explored■

Focused general physical exam can provide clues to a source of neurologic ■

deteriorationScalp lacerations, periorbital ecchymosis, or bruising behind the mastoids sug-■

gests a skull fractureTongue 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

282 E.M. Manno

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 featuresGlasgow 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 responsesMore 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 gasLiver 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 Four score

Eye opening Eye opening

Spontaneous 4 Open and tracking 4To voice 3 Open but not tracking 3To pain 2 To voice 2None 1 To pain 1

None 0

Motor response Motor response

Follows commands 6 Follows commands 4Purposeful 5 Localizes to pain 3Withdrawal to pain 4 Flexion to pain 2Flexion to pain 3 Extension to pain 1Extension to pain 2 No response 0No response 1

Verbal Response Respiration

Oriented 5 Regular 4Confused 4 Cheyne-Stokes 3Inappropriate 3 Irregular 2Incomprehensible 2 Above ventilator rate 1None 1 At ventilator rate 0

Brainstem Reflexes

Pupil and corneal reflexes

Present 4Unilateral dilated pupil 3

Pupil or corneal reflexesAbsent 2Pupil and corneal reflexes

Absent 1Pupil, corneal, and cough

Reflex absent 0


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 comaSubsequent evaluations utilizing electroencephalography, spinal fluid, or intracranial ■

pressure monitoring can be tailored according to the presentation of the patientAn algorithm for the assessment of the unresponsive patient is provided in ■

Fig. 16.1

Management

Patients with a depressed level of consciousness are at an increased risk for ■

aspiration pneumoniaPatients 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 circu-lation, are paramount in the care of the comatose patient

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; NH

3 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

284 E.M. Manno

Subsequent treatment of the unresponsive patient includes the administration of ■

thiamine and glucoseNarcan and flumazenil are also typically administered if drug intoxication is suspected■

However, overall management of the unresponsive patient is based upon the ■

underlying etiologyTrauma is managed supportively, with surgical options utilized to treat expand-■

ing hematomas or massesElectrolyte, 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 arrestApplication of hypothermia to patients with head trauma has not proven to be ■

effectiveHowever, subgroup analysis suggests that young patients who present hypother-■

mic may benefit from prolonged hypothermiaUse of psychostimulants and dopamine agonists for the treatment of prolonged ■

coma or vegetative states is anecdotal

Prognosis

Prognosis for coma is generally poor, with mortality ranging between 40 and ■

50% for traumatic brain injury and 50 and 88% for cardiopulmonary arrestPrognosis 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 neuro-logic findings, and concurrent medical illnessesPrognosis 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 injuryMarkers 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 predictiveLoss 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●


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 developedIndicators of poor outcome after cardiopulmonary resuscitation include:■

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

Cardiopulmonary stabilization is critical to prevent secondary brain injury in ■

comatose patients; early endotracheal intubation and maintaining cerebral perfu-sion are crucialThe overriding goal is to provide oxygen/ventilation and maintain a euv-■

olemic stateSerial 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, OxfordWijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL (2005) Validation of a

new coma scale: the four score. Ann Neurol 58:585–593

286 E.M. Manno

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 perspec-tive McGraw-Hill, Philadelphia, PA


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 disorderA number of synonymous terms exist in the literature, including ■ organic brain syndrome, acute confusional state, delirium, acute toxic-metabolic encephalo pathy, 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 delir-ium 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

Chapter 17Acute Encephalopathy

Robert D. Stevens, Aliaksei Pustavoitau, and Tarek Sharshar

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

288 R.D. Stevens et al.

♦ Anatomic classification: primary brain disorders that result from a direct insult to cerebral tissues (e.g., traumatic brain injury, stroke, brain tumors); second-ary brain disorders that result from an extracerebral disturbance (e.g., anoxic-ischemic 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

Many hospitalized patients develop an encephalopathy in which, even after an ■

extensive diagnostic workup, the underlying etiologic factor cannot be defini-tively identified or is presumed to be multifactorial; this is arguably the most common form of encephalopathy encountered in acutely ill patientsSome 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 patientsSelected surgical populations are at particular risk for delirium, such as those ♦

who have undergone cardiac surgery or repair of hip fracturesAmong 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 ven-tilation, and restraintsDelirium 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

28917 Acute Encephalopathy

Table 17.1 Etiologic classification of acquired acute encephalopathies

VascularIschemic strokeIntracerebral hemorrhageSubarachnoid hemorrhageCerebral venous thrombosisVasculitisPosterior reversible encephalopathy syndrome (PRES)

TraumaFocal brain lacerations and contusionsExtra-axial hematomasDiffuse axonal injury

NeoplasmPrimary or secondary brain tumors

Seizures/status epilepticusGeneralized seizures (convulsive, nonconvulsive)Complex partial seizures

Organ failureCardiac arrest (anoxic-ischemic encephalopathy)Respiratory (encephalopathies associated with hypoxia, hypercapnia)Hepatic encephalopathyUremic encephalopathy

MetabolicSevere electrolyte imbalanceHypoglycemia; hyperglycemic statesCofactor deficiency (Wernicke encephalopathy)

EndocrineHypothalamic and pituitary failureThyroid (myxedema coma, thyrotoxicosis)Adrenal (Addison disease)

Pharmacologic/toxicPrescription 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 infectionMeningitisEncephalitis

Systemic infectionSeptic encephalopathy

Inflammatory and immune-mediated encephalitisPostinfectious encephalitisPost-vaccine encephalitisParaneoplastic encephalitisLupus encephalitisNeurosarcoidosisAcute disseminated encephalomyelitis (ADEM)


Conscious awareness is the integration of multiple cognitive domains ♦

subserved by networks of neuronal populations located primarily in the cere-bral cortex, but it is also dependent on neuronal arousal systems that originate in the brainstem, hypothalamus, and thalamus and project directly or indi-rectly to the cerebral hemispheres; these systems can be disrupted by the physiologic imbalances that occur in severely ill patientsAmong 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 fron-tal and parietal lobes, the corpus callosum, basal ganglia, and thalamusStudies 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 symptomsLesions of the cerebral hemispheres, diencephalon, midbrain, or rostral pons ♦

will result in decreased arousal, ranging from somnolence to lethargy, stupor, and comaComa-inducing lesions must involve both hemispheres or must be unilateral ♦

lesions large enough to displace midline structuresDiencephalic and brainstem injuries that result in coma may be relatively small, ♦

but only bilateral or paramedian lesions will significantly affect arousalTranstentorial and central herniation syndromes that result from space- ♦

occupying hemispheric lesions are typically associated with significant dam-age 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, neu-rotransmitter metabolism, and the processing of energetic substratesAcute brain dysfunction may result from♦

Impaired oxygen or substrate delivery to the brain, as may be seen in hypoten-●

sion, hypoxemia, hypoglycemia, and carbon monoxide or cyanide toxicityImpaired cellular energy metabolism, e.g., mitochondrial dysfunction ●

associated with cyanide toxicity or thiamine deficiencyChanges 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


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 exposuresA higher risk of delirium has been linked to elevated endogenous anticholin-●

ergic activity measured in serum and in cerebrospinal fluid; these findings are consistent with data that show that cholinergic antagonists are delirio-genic and that their effects can be reversed with cholinesterase inhibitors such as physostigmineGABA-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 symp-toms 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 levelsIn clinical practice, the rate and severity of delirium is reduced by the ▲

administration of antipsychotic agents with dopamine receptor antago-nist activity

Elevated brain serotoninergic activity may present as “serotonin syn-●

drome,” 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 syndromesSystemic 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 adap-tive immune systems, and induction of neuronal and glial dysfunction and death

Expression of toll-like receptors and cytokines within the brain is a key ●

step in relaying and amplifying peripheral inflammatory signalsThe 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


Vagal nerve activation downregulates peripheral cytokine production ▲

(cholinergic anti-inflammatory pathway)The sympathetic nervous system has both pro- and anti-inflammatory ▲

actions

Diagnosis

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 etiologiesThe 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♦

The Diagnostic and Statistical Manual of Mental Disorders, 4● th edition (DSM-IV) defines delirium as an acute onset (hours to days) of a distur-bance of consciousness and characterized primarily by a reduced ability to focus, sustain, or shift attentionThis 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 medi-cal conditionSubsyndromal 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 deliriumAdditional 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 ▲

reflexesSigns 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 hypoac-tive 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, with-drawn, and have minimal interaction with health providers or family


▲ 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

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 interven-tions and outcomesDifferential diagnosis of delirium■

Many of the clinical findings of delirium are transiently induced by pharma-♦

cologic agents with sedative/hypnotic propertiesDisagreement exists as to whether the reversible neurologic changes induced ♦

by sedation should be classified as deliriumDelirium must be distinguished from dementia, psychosis, manic episode, ♦

and major depressive episode

Dementia is generally not associated with an acute disturbance in con-●

sciousness; 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 findingPerceptual disturbances are less common in patients with dementia, and ▲

sleep-wake cycles are usually normal

Psychosis is characterized by delusions, hallucinations, and grossly disor-●

ganized thought and behavior

Table 17.2 Confusion assessment method for the ICU (CAM-ICU)

Feature 1: Acute onset of mental status changes or a fluctuating courseFeature 2: InattentionFeature 3: Disorganized thinkingFeature 4: Altered level of consciousnessDelirium present if patient has features 1 and 2, plus either feature 3 or 4Data from Ely et al. (2001)


The disturbances in the level of consciousness, abrupt onset, and fluc-▲

tuating course seen in delirium are not typical in psychosisHallucinations in psychotic patients are more commonly auditory than ▲

visual, while the reverse is true in deliriumPsychotic 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, distractibil-ity, 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

Table 17.3 Intensive care delirium screening checklist (ICDSC)

1. Altered level of consciousnessA. Exaggerated response to normal stimulation (score 1 point)B. Normal wakefulnessC. Response to mild or moderate stimulation (score 1 point)D. Response only to intense and repeated stimulation (e.g., loud voice and pain) – Stop

assessmentE. No response – Stop assessment

2. Inattention (Score 1 point for any of the following abnormalities)A. Difficulty in following commands, ORB. Easily distracted by external stimuli, ORC. 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 hallucinationsB. 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, ORB. Hypoactive or clinically noticeable psychomotor slowing or retardation

6. Inappropriate Speech or Mood (Score 1 point for either)A. Inappropriate, disorganized, or incoherent speech, ORB. Inappropriate mood related to events or situation

7. Sleep-Wake Cycle Disturbance (Score 1 point)A. Sleeping <4 h at night, ORB. Waking frequently at night, ORC. 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)


Major depressive episodes are notable for markedly diminished interest or ●

pleasure in most activities, alterations in appetite, sleep disturbance, psy-chomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or guilt, diminished ability to think or concentrate, indeci-siveness, 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 collarA 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 eliminatedCommonly diagnosed etiologies/precipitants include primary brain lesions, ▲

exposure to medications that affect the CNS, alcohol and substance with-drawal, 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 deliri-●

ous after elimination of precipitants, when patient safety is a concern


(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

Consider alternativediagnosis: 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

Consider symptomatictreatment (haloperidol, olanzapine)

Consider delirium: inattention,fluctuating course cognitive orperceptual change, evidence of

an underlying cause

Arousable*No focal deficit **

Unconscious patient(see Fig. 2)

Unarousable*Abnormal brainstem reflexesNonlocalizing motor response

Acute change in mental status

Neurologic examination: mental status, cranial nerves,motor and sensory function, reflexes, coordination

Arousable*Focal deficit **

Evaluate forCNS lesion

*Minimum criteriaLocalizes (GCS motor score 5 or greater)Is able to verbalize (GCS verbal score3 or greater)

**Focal deficit, suggesting a brain or spinalcord lesion

Assess/treat Airway, Breathing, Circulation

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


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

Unconscious patient

Coma evaluation: LOC, brainstem reflexes, motor responses, breathing pattern

Persisting etiologic uncertainty:Consider MRI, EEG, LP

Immediate serum glucose, electrolytes, arterial blood gas,complete blood count, liver and endocrine tests, toxicology

screen; pan-cultures

1. If hypoglycemia <60 mg/dL thiamine,100 mg IV, then glucose 25 g (50 mL D50%)

2. If suspected seizure activity, lorazepam1–2 mg IV, maximum 0.1 mg/kg

3. If suspected opioid overdose,4. naloxone 0.4– 2.0 mg IV q 3 min5. If suspected benzodiazepine overdose,

flumazenil 0.2 mg/min, maximum 1 mg IV6. If drug intoxication suspected, gastric

lavage with activated charcoal

If herniation syndrome/increased ICP:

1. Hyperventilation PaCO2 35–30 mmHg2. Mannitol 0.5–1.0 g/kg3. Thiopental, 3–5 mg/kg or Propofol, 2–3 mg/kg4. Neurosurgical consultation

Assess/treat Airway, Breathing, Circulation

Etiology not immediately identifiable/reversible:Emergent head CT

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


Pathophysiology of HE is incompletely understood♦

Liver failure induces a profound metabolic brain disturbance that leads to ●

varying degrees of brain edemaBrain 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) mechanismsOther factors that contribute to HE include neurotoxins (ammonia, short- ●

and medium-chain fatty acids, mercaptans, phenols), changes in neurotrans-mitter function (GABA, glutamate, neurosteroids, false neurotransmitters, endogenous benzodiazepines), alterations in BBB permeability, decreased cerebral glucose utilization, increased production of reactive oxygen spe-cies, 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 alcoholDiagnosis 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

Table 17.4 Classification and grading of hepatic encephalopathy

Classification of hepatic encephalopathya

A Encephalopathy associated with acute liver failureB Encephalopathy associated with portal-systemic bypass and no intrinsic

hepatocellular diseaseC Encephalopathy associated with cirrhosis and portal hypertension or portal-systemic

shuntsGrading of hepatic encephalopathy (West Haven criteria)b

Grade 1 Trivial lack of awarenessEuphoria or anxietyShortened attention spanImpaired performance of addition

Grade 2 Lethargy or apathyMinimal disorientation for time or placeSubtle personality changeInappropriate behaviorImpaired performance of subtraction

Grade 3 Somnolence to semistupor, but responsive to verbal stimuliConfusionGross disorientation

Grade 4 Coma (unresponsive to verbal or noxious stimuli)aFerenci et al. (2002) bAtterbury et al. (1978)


Work-up should include a head CT, which will help to determine the pres-●

ence and severity of brain edema and will exclude associated intracranial hemorrhageBrain MRI typically will show T1-hyperintense lesions in the basal ganglia ●

and increased brain water suggested by an increased apparent diffusion coefficientElectroencephalography (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 coagulopa-thy, 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 mecha-●

nisms of encephalopathy such as thiamine deficiency, hypertensive enceph-alopathy, 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 comaPathophysiology has been linked to the accumulation of dialyzable “ure-●

mic neurotoxins,” including urea, guanidino compounds, uric acid, hippu-ric acid, various amino acids, polyamines, phenols and phenol conjugates, phenolic and indolic acids, acetone, glucuronic acid, carnitine, myoinosi-tol, and phosphatesGuanidino-succinic acid may contribute to central and peripheral nervous ●

system demyelination by inhibiting transketolase, a thiamine-dependent enzyme of the pentose phosphate pathway of myelinEvidence also links uremia to deficient sodium-potassium-ATPase func-●

tion, leading to elevation of intracellular sodium and increased neuronal excitability. Renal failure has also been associated with endocrine distur-bances, including raised levels of parathyroid hormone; parathyroid hormone-induced increases in tissue calcium have been implicated as a pathogenic mechanismDialysis or kidney transplantation effectively reverses uremic encephal-●

opathy; 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


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 acido-●

sis are at higher risk of DDS. DDS is typically self-limiting and resolves with slowing or interruption of dialysisTwo 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 brainAlternatively, 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 infarctionVery 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 levelsTreatment 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, thermoregula-tory, gastrointestinal, and cardiovascular signs

Neurologic manifestations range from restlessness and anxiety to ▲

delirium and comaDiagnosis depends on the demonstration of elevated serum T4 and T3 ▲

levels usually associated with very low TSHTreatment 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 enceph-alopathy associated with autoimmune thyroiditis”) is a recently described syndrome of presumed autoimmune origin that occurs in association with


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 (sec-ondary 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 pres-ence 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 hyper-osmolar 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 profileThis 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 conscious-ness of these patients predicted mortalityPathophysiology 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 deathCell 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 diseaseManagement is nonspecific and consists of treating the underlying infection●


Wernicke encephalopathy■

Wernicke encephalopathy is an acute syndrome that results from thiamine ♦

deficiency

Typically encountered in the setting of malnutrition, alcoholism, gastroin-●

testinal diseases, cancer, chemotherapy, magnesium deficiency, or AIDSNeurologic findings classically include ophthalmoplegia, ataxia, and ●

altered mental statusTherapy 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 alcohol-dependent patientsLike other forms of delirium, it is characterized by an acute disturbance of ♦

consciousness with a fluctuating course and cognitive and perceptual abnormalitiesUsually develops within 48–72 h of the last drink, although earlier presenta-♦

tions are possiblePsychomotor agitation and autonomic signs (hyperpyrexia, tachycardia, ♦

hypertension, and diaphoresis) are prominentUntreated, AWD may evolve to seizures, lethargy, and coma, and may result ♦

in aspiration, respiratory failure, metabolic acidosis, tachyarrhythmias, myo-cardial infarction, and injury to the patient or healthcare providersBenzodiazepines are the cornerstone of management and have been associ-♦

ated 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 associ-ated with neuroimaging evidence of vasogenic edema involving, most typically, the parietal and occipital lobes bilaterallyThe older term “posterior reversible leukoencephalopathy” is misleading ♦

because PRES involves both grey and white matter


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 chemotherapyPathophysiology of PRES is unknown; two theories prevail:♦

Severe hypertension exhausts cerebral autoregulatory mechanisms, leading ●

to hyperperfusion, endothelial injury, BBB breakdown, and vasogenic edemaSevere vasoconstriction and hypoperfusion leads to brain ischemia and ●

subsequent vasogenic edema

Management involves identifying and, when possible, treating or removing ♦

the underlying causeClinical 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 childrenADEM classically has a monophasic course, distinguishing it from multi-●

ple 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 venulesAssociation of ADEM with recent infections or vaccinations has suggested ●

that exposure to microbial antigens may elicit a cross-reactive anti-myelin response through molecular mimicryAlternatively, ADEM may be caused by a nonspecific inflammatory ●

response involving T-cell clonesA 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 proteinTypical 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,


and spinal cord; lesions are also often identified in the thalamus, basal ganglia, and periventricular white matterData 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 behav-ioral impairments

Treatment is high-dose IV methylprednisolone, followed by a prednisone taper♦

Plasmapheresis, IV immunoglobulin, and cyclophosphamide may be con-●

sidered in steroid-refractory patients

Key Points

Acute encephalopathy is a pathologic change in cognition and/or behavior second-■

ary to a rapidly developing structural or metabolic brain disorderIn hospitalized and critically ill patients, the most common clinical descriptors ■

of encephalopathy are delirium and comaDelirium 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 deathComa is the loss of arousal and awareness mechanisms and is a universal predictor ■

of increased mortality and morbidityEtiologies 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 infectionManagement of encephalopathy must consider the severity of neurologic ■

impairmentComa is a true emergency, mandating control of the airway, cardiopulmonary ■

stabilization, brain imaging, and selected additional studies to evaluate for underlying mechanismsDelirium 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


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, viiiStevens RD, Bhardwaj A (2006) Approach to the comatose patient. Crit Care Med 34:31–41Wijdicks EF, Bamlet WR, Maramattom BV et al. (2005) Validation of a new coma scale: the

FOUR score. Ann Neurol 58:585–593


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 careCenters with neurointensivists and neurosurgical assets deliver care with a ♦

full array of treatment optionsEvidence 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

Chapter 18Traumatic Brain Injury

Geoffrey S.F. Ling and Scott A. Marshall

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

308 G.S.F. Ling and S.A. Marshall

Long-term burden of TBI■

Survivors of moderate or severe TBI will likely require some form of ♦

rehabilitationVictims are usually young; thus, societal loss includes cost of long-term care of ♦

disease as well as diminished productivity and societal impact of that individualNearly 80% of mild-to-moderate TBIs have evidence of residual symptoms ♦

of brain injury 3 months after injuryBrain 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 AfghanistanFuture 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

Goal of neurocritical care management of TBI is prevention and minimization ●

of (a) secondary injury and (b) development of comorbiditiesSecondary injury may result in the most significant neurologic sequelae ●

from TBIMultifactorial etiologies for secondary injury include ischemic injury, hypoxia ●

(local or global), excitotoxicity, free radical damage, ionic dysregulation, inflammatory mediators, intracranial hypertension, and hyperthermiaSupportive measures are the mainstay of therapeutic interventions and ●

focus mainly on ensuring adequate CPP and tissue oxygenation, minimization of cerebral edema, and normalization of ICPIdeal 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 injuryTraumatized brain has an increased susceptibility to hypoxic-ischemic ▲

insults secondary to impaired autoregulation of the cerebral vasculatureDiffuse 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 TBIAreas that show the greatest susceptibility to hypoxic-ischemic insult ▲

include the hippocampus and the border zone regions of the middle

30918 Traumatic Brain Injury

cerebral artery and anterior cerebral artery, as well as those of the middle cerebral artery and posterior cerebral artery territoriesSingle 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 cra-●

nial structures in the direct and opposite direction of motion against the skull’s inner tableOften, a rotational component is associated with injury, and structures will ●

torque, with potential for shearing of microneuronal structuresShearing 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 factorsBlast 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 wavePathogenesis 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 injuryDevelopment 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, com-●

monly causing focal deficits and encephalopathyRadiographic evidence of DAI may be seen several hours following initial ●

traumaRadiographic appearance of DAI is most often identified as petechial white ●

matter hemorrhages on CT or MRI studiesHigher incidences of DAI with lateral impact or direction of force have ●

been reported versus frontal or even oblique orientation of forces


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 assaultsPenetrating TBI seen with projectiles such as shrapnel from a blast or gunshot ♦

wound, penetrating stab wounds, or non-blunt weapon assaultsPenetrating TBI involves violation of the cranium with neurologic and infec-♦

tious 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 present-●

ing complaints of nausea, vomiting, and headache, often with post-traumatic amnesiaTypically, 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 ●

deficitModerate TBI patients will require inpatient hospitalization and may ●

require some degree of neurosurgical interventionThis 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●

Table 18.1 Glasgow coma scale

Best motor response (M) Best verbal response (V) Best eye opening (E)

Follows commands 6Localizes to pain 5 Oriented, alert 5Withdrawal to pain 4 Confused, appropriate 4 Opens eyes spontaneously 4Flexor posturing Disoriented, inappropriate 3 Opens eyes to voice 3Extensor posturing 2 Incomprehensible speech 2 Opens eyes to pain 2No response 1 No response 1 No response 1


ICU care required, with institution of airway control, mechanical ventila-●

tion, neurosurgical evaluation or intervention, and ICP monitoringProtocol-driven ICU care for TBI patients in NCCUs has been shown to ●

improve long-term outcomes among surgical TBI and may improve out-comes 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 effectsSIS 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 hypertensionSevere 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 dizzinessIf symptoms persist for >1 year, resolution of postconcussive syndrome is less ♦

likely

Table 18.2 Return to play guidelines of the American academy of neurology

Grade I (mild) Remove from playExamine immediately and at 5-min intervalsMay return to duty/work if clear within 15 min

Grade I (mild) second event Above, and may return to duty/work in 1 weekGrade II (moderate) Remove from play for the remainder of the day

Examine frequently for signs of CNS deteriorationPhysician’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 observationReturn 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 monthGrade III (severe) third event Above, and neurologist evaluation indicatedLOC loss of consciousness


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 simultaneouslyOccult cervical spine injury is always assumed in any TBI patient with ▲

altered mental status or blunt injury above the clavicle until ruled out by imagingDisability or neurologic evaluation focuses on establishing initial GCS ▲

with attention to eyes, motor, and verbal responsePupil 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, gly-cemic 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)

Exam should commence immediately after correction of any obvious ●

abnormality seen in the primary surveyAssessment of neurologic status ideally should occur before paralysis or ●

sedation for intubation or other procedureOngoing neurologic assessments●

Neurologic exams should be performed at frequent intervals by neuro-▲

trained nurses and staffCare 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


Table 18.3 Focused neurologic exam

Neurologic system Components of exam Important considerations

Mental status exam

Orientation, language evaluation, and overall level of consciousness

May be accessed quickly while attending to other injuries

Cranial nerve evaluation

CN I: sense of smell CN I: not usually assessed unless mild TBICN II: vision CN II: pupil reactivity and presence of BTT

or field cut on confrontational testingCN III, IV, VI: vertical

and horizontal eye movements and identification of specific CN impairment, if any

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 V, VII: corneal reflex and facial symmetry to painful stimuli (grimace)

CN V, VII: corneal reflex testing more sensitive for subtle reactivity with cotton wisp than with saline drops

CN VIII: evaluation of hearing loss and rapid assessment of integrity of TM

CN VIII: gross testing and inspection indicated; always inspect TM prior to external canal irrigation with cold water for caloric testing

CN IX, X: gag or cough (if intubated) response

CN IX, X: commonly tested with in-line suction via the endotracheal tube

CN XI: SCM or trapezius movement

CN XI: ensure C-spine is cleared prior to 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

Motor response Evaluation of spontaneous movements, movements to pain, or strength on commanded movements in a cooperative patient

When administering pain for a motor response, give a stimulus in area where withdrawal, localization, or flexion responses will be distinct movements from each other (i.e., the axilla or the inner thigh)

Sensory response Pain sensation and temperature, vibration and position sense in cooperative patients

Pinprick sensation in the neck, arms, trunk, and legs with evaluation of perception via grimace or localization in the stuporous patient

Deep tendon reflexes

DTRs in the arms, legs, and Babinski responses

DTRs provide an objective exam finding that can help to confirm the presence of a lateralizing exam in an uncooperative patient

Cerebellar exam In the cooperative patient, simple dysmetria evaluation of the arms and legs with finger- nose-finger and heel- shin testing

Difficult to evaluate in the uncooperative or comatose patient

CN cranial nerve, TBI traumatic brain injury, BTT blink to threat, ICP intracranial pressure, TM tympanic membrane, SCM sternocleidomastoid, DTR deep tendon reflex


Early CT imaging may identify lesions that may benefit from operative ●

neurosurgical interventionImaging is repeated at any significant change in exam or with changes ●

in ICPSerial imaging may be used to assist with weaning from ventricular drainage ●

device if exam is poor and ICP remains lowClinical role of diffusion tensor imaging in prognosis is currently under ●

study

Fundamental concept of ICP♦

Contents of the intracranial cavity are enclosed in a fixed and rigid com-●

partment (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 ●

anotherFirst component to decrease is CSF in the intracranial vault, followed by ●

decrease in blood in the dural venous sinusesICP 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 placedExternal 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 drainageConcerns of hemorrhage or infection due to EVD placement should not ▲

deter ICP monitoring, if indicatedEVD 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 complicationsFiberoptic transducers used with an EVD offer similar accuracy to ▲

EVD with micro-strain gauge but at a greater expenseParenchymal ICP monitors (Codman) are not able to be recalibrated in ▲

situ, although they have a negligible drift during useFluid-coupled or pneumatic subarachnoid, subdural, and epidural ▲

devices are felt to be less accurate

Tissue oxygenation and metabolic monitoring♦

Goal is measurement of oxygen delivery to the brain with jugular venous ●

saturation (SJO

2) monitors, brain tissue oxygenation monitors (Licox), and

near-infrared spectroscopyAlternatively, the metabolic state of the brain is accessed with microdialy-●

sis cathetersS●

JO

2 monitoring provides an estimate of oxygen delivery to the brain with

goal mean values of 56–74%


Arteriojugular differences of oxygen content (AJDO●

2) as an indicator of

oxygen extraction of the brain may offer valuable prognostic information, with higher mean values desirablePeriods of low brain tissue oxygen tension (P●

BRO

2) may correlate with poor

outcome or deathAlthough 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 TBIS●

JO

2 < 50 or P

BRO

2 < 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 P●

aO

2 > 60 mmHg should be

maintained

Treatment■

Medical interventions to treat elevated ICP♦

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 ICPHead of bed should be elevated to 30° and the head kept midline so as not ●

to compress either internal jugular vein (which compromises venous drain-age 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 lineEmergent 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 jugu-lar lines may also elevate ICP by obstruction of internal jugular drainageIf 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 lineMannitol may be used to treat ICP, traditionally up to a serum osmolarity ▲

of ³320, based on effectOther 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 aci-dosis, and the percentages can be adjusted to complement an individual patient’s acid/base status3% hypertonic saline must be given via a central venous line and can ▲

be given in boluses of 250 mLA 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


Hyperventilation may be used emergently while other measures are being ●

prepared, but avoidance of persistent low PaCO

2 states (such as a P

aCO

2

<25 mmHg) is essential to maintaining cerebral perfusion

Precise P▲aCO

2 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

● Sodium thiopental in IV doses of 1–5 mg/kg can lower brain metabolic demand or cerebral metabolism (CMRO

2) 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 mortalityPromising animal data show evidence for induced hypothermia in treating ●

ICP, but it remains controversial in clinical useGoal core temperature for induced hypothermia is 32°–34°C, with shiver-●

ing controlled by warming of skin surface or hands with forced air onlyUse of induced hypothermia to control ICP in severe TBI currently main-●

tains only a level III recommendation in BTF guidelines, although this may be a tool of last resort to combat refractory ICPUse of hypothermia for more than 48 h may have a mortality benefit in TBI●

Surgical interventions for increased ICP♦

Decompressive craniectomy and/or lobectomy may be considered in ●

refractory casesDecompressive craniectomy permits the swelling brain to avoid compres-●

sion by the bony structures and provides an additional margin of error for ICP controlDecompressive surgery with a generous craniectomy may also reduce the ●

need to employ pharmacologic methods to control ICPIf the patient is not stable for surgical interventions and all other means to ●

control ICP have failed, the condition is likely fatal

Hemodynamics♦

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 fine-●

tuning of this value based on the hemodynamics of individual patientsRoutine maintenance of CPP at >70 mmHg with vasopressors or aggressive ●

volume expansion is not indicated and may be harmfulSystolic blood pressure should be maintained at >90 mmHg●


Prophylaxis with anticonvulsants♦

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 outcomePhenytoin and valproate are effective in reducing incidence of early ●

post-traumatic seizuresRoutine 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 hemorrhageProphylaxis with a well-tolerated agent with a limited side-effect profile ●

for 7 days, which is then discontinued, is a common and recommended practiceSuccessful prophylaxis for early post-traumatic seizures does not alter ●

incidence of late post-traumatic seizuresIn TBI patients with a poor exam and any concern for nonconvulsive sei-●

zures, EEG is indicated and should be obtainedCurrent outcome data are limited concerning implications of nonconvul-●

sive seizures in TBI

Nutrition♦

Severe TBI patients have a mean metabolic expenditure of ~140% of basal ●

rate despite comatose stateSignificant weight loss in general critical care patients confers an increased ●

risk of mortalityFeeding should be introduced as soon as possible after injury●

If feeds are begun no less than 72 h post-injury, evidence suggests a reduc-●

tion in overall infection and ICU complication rateBy 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

Table 18.4 Posttraumatic epilepsy

Brain injuries that predispose patients to increased risk of posttraumatic seizuresPenetrating traumatic brain injuryDepressed skull fractureContusional brain injuryEpidural or subdural hematomaSeizure activity within 1 day of injuryGCS <10Intracerebral hemorrhage


Prophylaxis for deep venous thrombosis♦

Patients with TBI have an elevated risk for the development of deep venous ●

thrombosis with subsequent venous thromboembolismSequential 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 contraindicationHeparin 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 heparinIn TBI with intracranial hemorrhage, timing for introduction of low-●

molecular-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♦

Agitation in TBI patients may often be due to pain, hypercapnia, hypoxia, ●

delirium, or poorly tolerated mechanical ventilationAgitation may be reduced by avoidance of polypharmacy and other con-●

servative measures, such as limitations of stimuli (television) and unnec-essary 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 TBIIn extremely difficult cases, infusion of either midazolam or propofol may ●

be neededIn the subacute period after TBI, the better-tolerated atypical antipsychotics ●

may be a better choice for controlling any persistent agitationPain should be treated with a short-acting narcotic analgesic such as fentanyl●

Longer-acting narcotics such as morphine or hydromorphone should be ●

avoidedReversal of narcotics with naloxone should be used in emergencies only, ●

as this likely causes severe discomfortBolus dosing of both fentanyl and sufentanyl has been associated with small ●

increases in ICP, a feature that may be reduced by continuous low-dose infusionInfusions 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


Autonomic dysfunction in TBI♦

● Paroxysmal autonomic instability with dystonia (PAID) is an emerging term for this syndrome of fever, elevated heart rate, diaphoresis, tachypnea, dystonia, and blood pressure abnormalitiesPAID is common in TBI patients and may be due to hypothalamic injury; ●

when present, infectious etiologies of fever must be aggressively sought and appropriately treatedOther treatable causes that must be excluded include thyroid hormone ●

abnormalities, alcohol or other toxin withdrawal, allergic reactions, malig-nant hyperthermia, serotonin syndrome, extrapryamidal reactions, and neuroleptic malignant syndromeIncidence of PAID is higher in severe TBI with some component of DAI●

Treatment is varied and includes beta-blocking agents (propranolol), nar-●

cotics, 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 presentationFor 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 findingsOlder 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 countriesAbsent pupillary reactivity was the third strongest predictor of poor outcome ♦

in all TBI patientsOn 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 outcomeDiffusion-tensor MRI protocols may also prove to be clinically helpful in the ♦

future for prognostication in TBI


Key Points

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 injuryFrequent neurologic examinations must be done in the acute period after TBI to ■

discover subtle changes and make necessary interventionsClinical management of TBI focuses on attention to ICP, CPP, and avoidance of ■

secondary injuryNew physiologic monitoring devices may illuminate the best emerging therapies ■

for TBIRoutine anticonvulsant use after 7 days in TBI is likely not helpful for preventing ■

development of late post-traumatic seizures or improvement of outcomeNutrition is a vital aspect of TBI care due to the hypermetabolism associated ■

with this conditionOver-sedation of patients with TBI must be avoided, as it confounds the ability ■

to note changes in the neurologic examRoutine steroid use is not recommended■

Autonomic changes are common in TBI but require ruling out other causes in ■

all casesPrognostic 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, OxfordKoenig MA, Bryan M, Lewin JL III et al (2008) Reversal of transtentorial herniation with hyper-

tonic saline. Neurology 70:1023–1029Lu J, Marmarou A, Choi S et al (2005) Mortality from traumatic brain injury. Acta Neurochirurgica

95:281–285MRC CRASH Trial Collaborators (2008) Predicting outcome after traumatic brain injury: practical

prognostic models based on large cohort of international patients. BMJ 336:425–429Patel HC, Menon DK, Tebbs S et al. (2002) Specialist neurocritical care and outcome from head

injury. Intensive Care Med 28:547–553Pompucci A, Bonis PD, Pettorini B (2007) Decompressive craniectomy for traumatic brain injury:

Patient age and outcome. J Neurotrauma ;24:1182Practice parameter: the management of concussion in sports (summary statement). (1997) Report

of the quality standards subcommittee. Neurology 48:581–5 [update in progress 2008]


Raslan A, Bhardwaj A (2007) Medical management of cerebral edema. Neurosurg Focus 22:1–12Ropper AH, Gorson KC (2007) Clinical practice: Concussion. New Eng J Med 356:166–172Rosenfeld JV, Cooper DJ, Kossmann T et al. (2007) Decompressive craniectomy. J Neurosurg

106:195–196Wang 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


Introduction

■ Acute myelopathy is a broad term used to describe spinal cord dysfunction of sudden, recent onsetDiagnostic possibilities are ample, but practicing neurointensivists deal mainly ■

with traumatic and inflammatory myelopathiesMain 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 dysfunc-tion, generally typified initially by lower motor neuron signs and/or sen-sory changes below the level of the lesion, which can result from a variety of etiologiesThe 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

Chapter 19Acute Myelopathy

Angela Hays and Julio A. Chalela

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]

324 A. Hays and J.A. Chalela

Etiology

Traumatic■

Fractures/dislocations♦

Ligamentous injury♦

Disc herniation♦

Epidural hematoma♦

Cord contusion♦

Degenerative spine disease■

Spondylosis♦

Disc herniation♦

Neoplastic■

Primary♦

Metastatic♦

Inflammatory■

Transverse myelopathies♦

Paraneoplastic♦

Parainfectious♦

Myelopathies associated with systemic disease■

Sarcoidosis♦

Systemic lupus erythematous♦

Behcet disease♦

Sjogren syndrome♦

Polyarteritis nodosa♦

Bacterial infections■

Epidural abscess♦

Bacterial myelitis♦

Tuberculosis♦

Viral infections■

Poliovirus♦

Varicella zoster♦

Herpes simplex♦

Cytomegalovirus♦

Human immunodeficiency virus♦

Human T-cell lymphotropic virus-1♦

32519 Acute Myelopathy

Other infectious agents■

Syphilis♦

Lyme disease♦

Schistosomiasis♦

♦ Toxoplasma gondii

Vascular■

Spinal cord infarction♦

Arteriovenous malformations♦

Hemorrhage♦

Toxic/Metabolic■

Vitamin B12 deficiency♦

Copper deficiency♦

Radiation♦

Medication related♦

Hepatic myelopathy♦

Epidemiology

Traumatic spinal cord injury (SCI)■

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 yearsMotor vehicle accidents account for ~50% of SCIs♦

Falls are the most common cause in patients older than 60 and account for ♦

24% of all SCIsOther common causes include sports (9%) and assault (11%)♦

More than half of all SCIs involve the cervical spine, whereas most nontrau-♦

matic 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


Progression to maximal deficit within 4 h to 21 days♦

Spinal fluid examination shows pleocytosis and/or elevated immunoglobulin ♦

G (IgG) indexMRI shows gadolinium enhancement♦

Spinal cord infarction■

Rare syndrome that may be underdiagnosed, as its clinical presentation and ♦

imaging characteristics are proteanMay occur infrequently as a complication of surgical repair of aortic aneu-♦

rysms and dissectionsOther mechanisms include systemic hypotension or cardiac arrest, cardiac ♦

emboli, occlusive vascular disease, and venous occlusionThe 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 myelopathySpinal 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 cordSegmental arteries arising from the subclavian, aorta, and iliac arteries provide ♦

collateral flowCentral arteries, arising from the anterior spinal artery, penetrate the spinal ♦

cord and perfuse the anterior horn and portions of the lateral funiculusThe artery of Adamkiewicz typically arises between T♦

8 and L

4 and supplies

the lower two-thirds of the cordThe middle and lower thoracic cord and the central gray matter of the cord ♦

are particularly vulnerable to watershed infarctionsAs with the cerebral vasculature, autoregulatory mechanisms maintain spinal cord ♦

blood flow at a constant level across a broad range of mean arterial pressuresIn 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 factorSpinal vascular malformations, including arteriovenous malformations and ♦

dural arteriovenous fistulas, produce an ischemic myelopathy that is thought to result from venous engorgement


Traumatic spinal cord injury■

Damage to the spine following trauma results from both ♦ primary and second-ary mechanismsPrimary mechanisms occur at the time of injury and may include shear injury, ♦

compression, distraction, laceration, and/or cord transaction; the latter is typi-cally seen with penetrating traumaPathologically, traumatic necrosis of the cord is characterized by hematomy-♦

elia, contusion, and destruction of the gray and white matterPathologic changes are most prominent at the level of the injury and one or ♦

two segments above and belowSecondary mechanisms result from associated injuries or biochemical cascades ♦

initiated by the traumatic event and may present therapeutic targetsIschemia may result from direct disruption of vascular structures, deranged ♦

autoregulation, vasospasm, systemic hypotension, or increased intrathecal pressureInflammatory reaction that involves macrophages, microglia, T-cells, neutro-♦

phils, 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 compoundsExcitotoxicity due to release of excitatory amino acids has also been ♦

implicated


The term applies to a group of disorders in which SCI results from inflamma-♦

tory and immune-mediated mechanismsInflammation is the hallmark, with infiltration by monocytes and lympho-♦

cytes noted on pathologic examination, particularly in patients with TM secondary to multiple sclerosisDemyelination and axonal changes are prevalent, but gray matter may also be ♦

affectedIn TM associated with autoimmune conditions, vasculitic lesions and spinal ♦

ischemia may be observedMolecular mimicry, resulting in production of autoantibodies, has been pos-♦

tulated as the underlying mechanism in parainfectious myelitisAntibody to aquaporin-4, called NMO-IgG (neuromyelitis optica antibodies-♦

IgG), has been linked to neuromyelitis opticaRecurrent TM has been associated with anti-Ro antibodies and with the ♦

antiphospholipid antibody syndromeImmunomodulatory therapies, including steroids and plasma exchange, are ♦

frequently employed



Presenting clinical syndrome is determined by the anatomic involvement of the ■

spinal cordSpinothalamic tract lesions■

Result in contralateral loss of pain and temperature sensation below the lesion♦

Located in the anterolateral white matter♦

Corticospinal tract■

Lateral corticospinal tract, located in the lateral funiculus, carries most of the ♦

descending motor fibersLesions result in ipsilateral loss of voluntary motor control below the level of ♦

the lesionUpper motor neuron findings (spasticity, hyperreflexia, and weakness without ♦

significant atrophy or fasciculations) appear in the subacute-to-chronic phaseCervical fibers are located more medially, and lumbosacral fibers more ♦

laterallyVentral 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 modalitiesCuneate 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–L

2

Parasympathetic cell bodies reside in the brainstem and in the lateral horns ♦

at S2–S

4

Autonomic injury is manifested by impaired sweating, autonomic dysre-♦

flexia, hypotension, bradycardia, and impaired sphincter function

Specific Spinal Cord Syndromes

Nosologic classification based on the presenting signs and symptoms is useful ■

in determining the location of the lesion and the likely etiologyCentral cord syndrome■

Characterized by motor impairment in the arms greater than in the legs, with ♦

variable sensory involvement


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 presentOccurs 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 involvementClassically seen with B♦

12 deficiency and syphilis

Brown-Sequard syndrome■

Characteristically results from cord hemisection, usually due to penetrating ♦

traumaMay 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 conusDue to nerve root involvement, upper and lower motor neuron findings will ♦

be presentPresents 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 anesthesiaPresents 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 outCare should be taken during the initial evaluation to ensure hemodynamic ♦

stability, patent airway, and adequate respiration


Cervical spine should be immobilized using a spine board or hard cervical ♦

collarLog-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 ♦

appreciatedPhysical examination must include an assessment of motor function, sensa-♦

tion to pin prick and light touch, rectal tone, deep tendon reflexes, and super-ficial reflexesThe impairment scale of the American Spinal Injury Association (ASIA) is ♦

widely used. Assessment involves testing of sensation bilaterally in all der-matomes, as well as motor and reflex assessment at each testable levelInjuries 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


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 soughtSigns and symptoms of autoimmune disorders or collagen vascular disease ♦

may be presentPresenting symptoms often include weakness, paresthesias, and hyperre-♦

flexia; band-like sensation around the chest or abdomen is often describedParaparesis 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 Complete lesion - no motor or sensory function below the level of the injuryB Incomplete sensory loss with absence of motor function below the lesionC Incomplete sensory loss, with motor strength of <3/5 in more than half

of the tested muscles below the lesionD Incomplete sensory loss, with ³ 3/5 motor strength in at least half

of the muscles tested below the lesionE Normal motor and sensory function


Spinal cord infarction■

As in ischemic cerebral strokes, the deficit is maximal at onset when brought ♦

about by arterial occlusionAnterior spinal artery is most commonly involved♦

Pain, motor dysfunction, loss of pain and temperature sensation, and sphinc-♦

ter dysfunction are commonRadicular pain at the level corresponding to the upper border of the lesion ♦

may occurSpinal cord infarction may rarely be preceded by spinal transient ischemic ♦

attacksSpinal arteriovenous malformations and dural arteriovenous fistulas result in ♦

an ischemic myelopathy that presents subacutely, with asymmetric weakness, imbalance, and variable sensory lossClaudication may be present♦

Lancinating or cramping pain may be the presenting symptom of intramedul-♦

lary arteriovenous malformations


Clinicians must utilize clinical, epidemiologic, laboratory, and imaging elements ■

to discern the cause of an acute myelopathyThe 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 olderProdrome of fever, malaise, and gastrointestinal or respiratory infection ♦

favors TMHistory 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 syndromePresence of acute symptoms with predominantly anterior cord symptoms ♦

suggests spinal cord infarctHistory of a prothrombotic state (deep venous thrombosis, pulmonary embo-♦

lism, factor V Leiden mutation, etc.) suggests a venous infarctionStuttering symptoms in patients older than 40 years suggest dural arterio-♦

venous fistula. Postural dependence of symptoms may also be presentFibrocartilaginous emboli are suggested by the presence of back pain and ♦

weakness following maneuvers that increase intra-abdominal or intrathoracic pressureHistory of radiation suggests (albeit, remotely) radiation-induced myelopathy♦


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 compres-■

sive myelopathy always must be ruled outSerologic markers, cerebrospinal fluid analysis, evoked potentials, and nerve con-■

duction studies are used mainly in the evaluation of noncompressive myelopathiesNeuroimaging■

Plain spine radiographs♦

CT of the spine♦

MRI of the spine♦

Contrasted myelogram♦

Serum studies■

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♦


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 C♦3–C

5 segments

Injury at C♦3–C

5 produces immediate ventilatory failure

Injuries below C♦3–C

5 preserve the diaphragm but compromise the intercostals

musclesInjuries below C♦

3–C

5 lead to contraction of the diaphragm without expansion

of the chest, resulting in decreased vital capacity and maximal inspiratory forceLoss of the contribution of the abdominal muscles to expiration leads to ♦

decreased expiratory forceSpasticity of the respiratory muscles ensues over time, and increases forced ♦

vital capacity and maximum expiratory forceIntubation♦

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 hSerial measurements of vital capacity may be useful, with intubation ●

becoming necessary when it falls below 1LPatients with impaired cough mechanism, copious secretions, or decreased ●

level of consciousness need to be intubated immediately, even if oxygen-ation and ventilation are normalOrotracheal intubation with in-line stabilization is safe in most patients ●

with cervical spine injurySuccinylcholine should be avoided in patients who have been weak or ●

paralyzed for >2 days (risk of fatal hyperkalemia; peak 2–7 days)


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 aureusPresence of two of the following: temperature >38°C or <36°C, leukocy-●

tosis or leucopenia, purulent secretions, or hypoxemia suggests ventilator-associated pneumoniaAntibiotic therapy should be guided by culture identification of an organ-●

ism, 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 mortalityAtelectasis is caused by impaired lung expansion, cephalad displacement ●

of the abdominal contents, retained bronchial secretions, and weak coughReduced surfactant production may contribute to atelectasis●

Aggressive pulmonary toilet, use of recruitment maneuvers, and adequate ●

patient positioning are the mainstay in the treatment of atelectasisIntermittent 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 secretionsIncreased secretions are a nuisance to the patient and may lead to mucus ●

pluggingSecretions return to normal a few weeks after SCI; during the early after-●

math, inhaled or systemic anticholinergic agents may be effectiveIntrapulmonary 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 secretionsUse of quad coughing (an assisted cough performed by delivering an ●

abdominal thrust in synchrony with a spontaneous or assisted breath) may assist in clearing secretionsUse 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


As in the case of increased secretions, the most likely explanation for bron-●

chospasm is an increased unopposed parasympathetic toneSympathetic supply to the lungs originates from the upper thoracic ganglia, ●

while the parasympathetic arises from the vagal nucleusInhaled 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 syndromeAggressive fluid administration used to treat hypotension leads to fluid ●

overload and is the leading cause of pulmonary edemaNeurogenic edema occurs likely due to exaggerated pulmonary and systemic ●

vasoconstrictionPlacement of a pulmonary artery catheter may help to determine the etiology ●

of the pulmonary edemaPositive-pressure ventilation, judicious use of diuretics, and inotropic sup-●

port are the main treatment options

Chest trauma♦

Chest trauma is a frequent and often overlooked cause of respiratory dys-●

function in patients with acute SCIPulmonary contusions, cardiac contusion (right ventricle), rib fractures ●

with flail chest, avulsion of a bronchus, diaphragmatic rupture, hemotho-rax, pneumothorax, and hemopericardium are common complications of thoracic traumaNormal chest x-ray and normal arterial gasimetry do not exclude the pos-●

sibility of a significant thoracic injuryHighest risk of respiratory complications (up to 51%) is seen with injuries ●

to T1–T

6

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 weeksMost 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 deathRisk factors for pulmonary embolism include tetraplegia, male gender, and ●

complete motor injuryPharmacologic prophylaxis with low-molecular-weight heparin should ●

commence as soon as possible after SCIVena cava filters should be used when pharmacologic prophylaxis is ●

contraindicated


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 ●

sinusitisTracheostomy improves patient comfort, facilitates secretion management, ●

reduces dead-space ventilation, and aids in weaning from the ventilatorTracheostomy should be separated from anterior cervical stabilization ●

surgery by a 1–2-week periodPatients with C●

2–C

4 injuries, ASIA A injuries (“complete” cord syndrome),

history of smoking, history of pulmonary disease, age > 45 years, pneumo-nia, and comorbid problems require tracheostomy more oftenPatients 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 hypotensionMost common dysrhythmia is sinus bradycardia, but supraventricular dys-♦

rhythmias can occurHypotension (spinal shock) occurs in the first few days as a result of the loss ♦

of vascular toneThe classic presentation findings are hypotension with inappropriately low ♦

heart rateHypotension often requires the use of IV fluids and vasopressors with alpha ♦

and beta action, as the cardiac accelerator fibers are affectedPlacement of a central venous line, arterial line, and assessment of cardiac ♦

filling pressures and vascular resistance may be needed to guide fluid replace-ment and pressor requirementsThe ideal spinal cord perfusion pressure has not been determined, but ♦

hypotension is known to worsen SCI. As with the brain, perfusion is auto-regulated 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 ♦

peristalsisMetoclopramide and erythromycin are useful agents to treat impaired ♦

gastrointestinal motilityStool softeners and laxatives are necessary to avoid constipation and fecal ♦

impaction


Oral naloxone may be used to counteract opioid-induced constipation♦

In the acute phase, patients are hypercatabolic and have increased nutritional ♦

requirementsIndirect 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 benefitHowever, 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 injuryIt is less common practice to administer 30 mg/kg methylprednisolone IV fol-♦

lowed by 5.4 mg/kg/h for 48 h in patients who present within 3–8 h of injuryThe 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 regimenRegardless, 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 T♦6 tend to produce autonomic dysreflexia

Common findings include paroxysmal hypertension (can be as high as 300 ♦

mmHg systolic), bradycardia, flushing, diaphoresis, and headacheCommon 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 recurrenceLong lesions on MRI tend to have a worse prognosis●

Female patients and younger patients are more likely to convert to multiple ●

sclerosisElevated serum glucose is associated with poor outcome●


Back pain, cervical sensory level, rapid progression to spinal shock, and ●

rapid progression of symptoms are associated with poor outcomeRoughly 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 monthsMost 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 muscleMuscle 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 touchMost motor recovery occurs within the first 6 months after injury●

Complete paraplegia♦

Potential for recovery is significantly higher in patients with SCI below T●

9

Up to 55% of patients with neurologic injury below T●

11 will recover func-

tion significantlyMost 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 yearRecovery 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 yearAt 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


Persistence of the delayed plantar flexor response has high correlation with ♦

complete injury and poor outcomePresence of cross adductor reflex in the acute stage is associated with good ♦

outcomeOlder 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 infarctionsEtiologic diagnosis and recognition of specific syndromes can provide valuable ■

insights into further management and prognosisICU management of patients with acute myelopathies centers on the cardiopul-■

monary systems and autonomic dysreflexiaDetermination 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–S30Berly M, Shem K (2007) Respiratory management during the first five days after spinal cord

injury. J Spinal Cord Med 30:309–318Brinar VV, Habek M, Brinar M,et al (2006) The differential diagnosis of acute transverse myelitis.

Clin Neurol Neurosurg 108:278–283de Seze J, Stojkovic T, Breteau G et al (2001) Acute myelopathies: Clinical, laboratory, and out-

come profiles in 79 cases. Brain124:1509–1521Ho 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–S54Hummers LK, Krishnan C, Casciola-Rosen L et al (2004) Recurrent transverse myelitis associates

with anti-Ro (SSA) autoantibodies. Neurology 62(1):147–149Kaplin AI, Krishnan C, Deshpande DM, et al. (2005) Diagnosis and management of acute myel-

opathies. Neurologist 11:2–18Kim JH, Lee SI, Park SI, Yoo WH (2004) Recurrent transverse myelitis in primary antiphospho-

lipid syndrome – case report and literature review. Rheumatol Int 24(4):244–246Novy J, Carruzzo A, Maeder P, Bogousslavsky J (2006) Spinal cord ischemia: Clinical and imag-

ing patterns, pathogenesis, and outcomes in 27 patients. Arch Neurol 63:113–1120Nowak DA, Mutzenbach S, Fuchs H-H (2004) Acute myelopathy. Retrospective clinical, labora-

tory, MRI, and outcome analysis of 49 cases. J Clin Neurosci 11:145–152Sekhon LHS, Fehlings MG (2001) Epidemiology, demographics, and pathophysiology of acute

spinal cord injury. Spine 26:S2–S12Wuerner 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


Definitions

Ischemic stroke: Focal neurologic deficit referable to the CNS that corresponds ■

to an arterial territoryTransient 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 ageOne 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)

Chapter 20Ischemic Stroke

Neeraj S. Naval and Anish Bhardwaj

N.S. Naval, MD Neuroscience Critical Care Fellowship Program, Oregon Health and Science University, Portland, OR, USA


342 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♦

34320 Ischemic Stroke

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 ovaleHigh 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 strokeIncidence 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 strokeIncreasing 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 intraproce-dural hypotension)Most commonly occurs between the middle cerebral artery (MCA) and ante-♦

rior cerebral artery (ACA) territories (man-in-barrel syndrome: bilateral proxi-mal 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 manifestationsUsually 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


Hypercoaguable states■

Could be ♦ embolic or thrombotic mechanism

Factor V Leiden mutation●

Antiphospholipid antibodies (lupus anticoagulant/anti-cardiolipin ●

antibodies)Factor C or S deficiency●

Antithrombin III deficiency●

Prothrombin Gene (G21201A) mutation●

Hyperhomocysteinemia●

Oral contraceptives●

Malignancy●

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 bilateralMCA 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


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 lossInferior 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 lobuleApraxias●

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; construc-▲

tional 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)●


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 pos-●

terior 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 arteryIpsilateral 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♦


Investigations

Head CT (noncontrast)■

Rules out hemorrhage♦

Early signs of stroke such as sulcal effacement or loss of grey-white matter ♦

differentiationSignificant 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 1weekPWI (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, PFOTTE 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♦

Lab testing■

Hypercoaguable work up (select cases)♦

Lipid profile♦

HbA1c♦

ANA, ESR♦

RPR♦


Treatment

tPA (tissue plasminogen activator)■

IV tPA is FDA approved for treatment of acute ischemic stroke within 3h of ♦

onset30% more likely to have no or minimal deficit at 90 days than those not ♦

receiving drugRisk 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 >400IA 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 thrombusEfficacy better for embolic strokes (red clot) compared to intracranial ath-●

erosclerosis (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 mido-drine and florinef, hold all home antihypertensivesSupportive 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♦


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♦

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% stenosisCEA 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 pulmo-nary disease, congestive heart failure, unstable anginaExtracranial-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 tPAHemicraniectomy for large strokes with intractable intracranial hypertension♦

Other treatments■

Peptic ulcer prophylaxis with H♦2 blocker or 5HT

3 blocker

DVT prophylaxis with subcutaneous heparin or, preferably, LMWH♦

Management of Acute Stroke in ED

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 tPAIf SBP >185 and not controlled with two IV boluses, DO NOT give IV tPA; use ■

of IV infusions prior to IV tPA not permittedIf IV tPA is administered, give 0.1mg/kg bolus over 1min, followed by 0.9mg/kg ■

infusion over 1h


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 recommendedTransfer to NCCU for closer monitoring♦

In setting of clinical herniation, consider 1g/kg mannitol or 23.4% saline ♦

30mL×1 doseFor definitive treatment, hemicraniectomy is advisable, especially if age ♦

<60years, independent of lateralization of strokeIn 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♦


Seizures■

Incidence, 4–8%, more common with embolic strokes, cortical strokes, and ♦

following hemorrhagic transformationNo 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 optionsStatins/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 othersEncourage 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 feedingSpeech 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 brainPatients 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 consideredAll patients with TIA or stroke should be investigated thoroughly to determine ■

etiology, and modifiable risk factors should be treatedNormonatremia, 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 insti-tution of physical and occupational therapy are paramount for good outcome


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, MassachusettsOsborn AG (1994) Diagnostic neuroradiology. Philadelphia, Mosby


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 strokeOnly 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)

Chapter 21Intracerebral Hemorrhage

Neeraj S. Naval and J. Ricardo Carhuapoma

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]

354 N.S. Naval and J.R. Carhuapoma

Table 21.1 Causes, means of diagnosis, and characteristics of intracerebral hemorrhage

CausesPrimary Means of Diagnosis Characteristics

Hypertension Clinical historya 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

Arteriovenous malformation

Imaging studies such as magnetic resonance angiography and conventional angiography

Rupture of abnormal small vessels connecting arteries and veins; the annual risk of recurrent hemorrhage of 18%7 can be reduced by surgical excision, embolization, and radiosurgery

Intracranial aneurysm

Imaging studies such as magnetic resonance angiography and conventional angiography

Rupture of saccular dilatation from a medium-sized artery that is usually associated with subarachnoid hemorrhage; risk of recurrent hemorrhage of 50% within the first 6 months, which decreases to 3% per year8; surgical clipping or placement of endovascular coils can significantly reduce the risk of recurrent hemorrhage

Cavernous angioma Imaging studies such as magnetic resonance imaging

Rupture of abnormal capillary-like vessels with intermingled connective tissue; annual risk of recurrent hemorrhage of 4.5%9 can be reduced by surgical excision or radiosurgery

Venous angioma Imaging studies such as magnetic resonance imaging and conventional angiography

Rupture of abnormal dilatation of venules; very low annual risk of recurrent hemorrhage (0.15%)10

Dural venous sinus thrombosis

Imaging studies such as magnetic resonance venography and conventional angiography

Result of hemorrhagic venous infarction; anticoagulation and, in rare cases, trans-venous thrombolytic agents can improve outcome; risk of recurrent dural venous thrombosis of 10% within first 12 months and of less than 1% thereafter11

Intracranial neoplasm Imaging studies such as magnetic resonance imaging

Results of necrosis and bleeding within hypervascular neoplasms; long-term outcome determined by the characteristics of the underlying neoplasm

(continued)

35521 Intracerebral Hemorrhage


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 brain-■

stem compression by supratentorial hemorrhageAirway compromise, irregular breathing, hypertensive crisis, Cushings triad (hyper-■

tension, 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

Table 21.1 (continued)

CausesPrimary Means of Diagnosis Characteristics

Coagulopathy 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 and cerebrospinal fluid markers; brain biopsy

Rupture of small or medium-sized arteries with inflammation and degeneration; immunosuppressive medications may be indicated

Cocaine or alcohol use

Clinical historya Underlying vascular abnormalities may be present

Hemorrhagic ischemic stroke

Imaging studies such as magnetic resonance imaging and conventional angiography

Hemorrhage in region of cerebral infarction as a result of ischemic damage to blood-brain barrier

a Imaging studies such as magnetic resonance imaging and conventional angiography can provide supportive evidenceReproduced from Spontaneous Intracerebral Hemorrhage, Qureshi et al., NEJM Volume 344: 1450–60


Other features visible on head CT■

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 fol-lowing 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), underly-■

ing 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 Age T1 T2

Hyperacute <7 h Isointense BrightAcute 7 h–3 days Isointense DarkEarly subacute 3 days–7 days Bright DarkLate subacute 7 days–3 weeks Bright BrightChronic >3 weeks Dark Dark


Location not typical for hypertensive bleeds (basal ganglia, thalamus, cerebel-■

lum, 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 lead-●

ing to aspiration and for hyperventilation in patients with elevated ICPConsider use of lidocaine to blunt increases in ICP during endotracheal ●

intubation

Breathing♦

Goal of PO●

2 >60 with strict avoidance of hypercabia, given risk of

increased ICPHyperventilation to goal PCO●

2 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●


Management of Primary Injury―Hematoma Stabilization (Tables 21.3 and 21.4)

Unclear if blood pressure control plays a significant role in hematoma stabiliza-■

tion; clinical trials (ATACH, INTERACT) are underwayBlood 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 hemorrhagesMore 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/hEsmolol 250 mcg/kg IVP loading dose 25–300 mcg kg-1 min-1

Enalapril 1.25–5 mg IVP q 6 ha NAHydralazine 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 applicablea Because of risk of precipitous lowering of blood pressure, the enalapril first test dose should be 0.625 mgb High risk of metabolic acidosis with prolonged infusions above 2 mcg/kg/min


Reverse coagulopathy secondary to warfarin with fresh frozen plasma and IV ■

(or PO) vitamin KProtamine sulfate should be used to reverse heparin-associated ICH, with the ■

dose dependent on the time from cessation of heparinRole 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 statusHyperventilation for acute lowering of ICP, with goal PCO■

2 28–32; chronic

hyperventilation not recommended but slow return to normocarbia to prevent rebound increase in ICPHyperosmolar 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/LNo 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/IVHPharmacologic 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 managementExceptions■

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 stereot-■

actic clot evacuation using clot lysis with tPA followed by clot aspirationDecompressive hemicraniectomy■

Efficacy demonstrated in ischemic infarction♦

Possible option in ICH♦


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♦

Consider continuous EEG monitoring in comatose patients or patients with neu-■

rologic deterioration with ICHPersistent hyperglycemia (>140 mg/dL), especially during the first 24 h to be ■

avoidedGoals of normothermia■

Use of hypothermia may be considered in the setting of refractory intracranial ♦

hypertension

DVT prophylaxis to be initiated immediately with TEDS (thromboembolic dis-■

ease 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

Rapid neurologic deterioration may occur secondary to hematoma expansion, ■

accompanying edema, or hydrocephalus, leading to elevated ICPControl of BP, anti-edema therapies, and control of ICP are cornerstones of ■

medical managementSurgical evacuation can be life saving but is tailored for the individual patient, ■

depending on age, size and location of hematoma, and comorbidities


APPROACH TO PATIENT WITH ICH

Signs and Symptoms

Sudden onset of headacheDecreased level of consciousness ± Lateralizing deficits

(aphasia, hemiparesis/hemiplegia, field deficits) Hypertension

Intraventricular catheterplacement with controlledCSF drainageICP monitoringMedical management

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

Medical ManagementControl BP to a target CPP >70 mmHg and SBP <160 mmHg; β blocker(labetalol), hydralazine, nicardipineCoagulation 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 to140–145 mEq/L GI and DVT prophylaxis NPO–close monitoring for aspirationInitiate stroke work-up

Emergent noncontrast CT scan of brain

Admit to ICU

ICH ± IVH

ICH with IVH ICH without IVH

Hydrocephalus No hydrocephalus

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


APPROACH TO PATIENT WITH CEREBELLAR HEMORRHAGE

Signs Symptoms

Ataxia (appendicular or truncal)Lower cranial neuropathiesRapid deterioration in level of consciousness, e.g., lethargy, comaDysarthria, nystagmus

Headache occipital and of sudden onsetDizziness, vertigo Inability to standDouble vision, oscillopsiaNausea and vomitingSlurred speech

Emergent non-contrast CT scan of brain

≥ 3 cm diameterhematoma in cerebellarhemisphere with rapid

decline in level ofconsciousness or

worsening brainstemfunction

<3 cm diameter hematoma incerebellar hemisphere with

stable neurologic exam

OR foremergent

evacuation

Admit to ICU

Medical Management Control BPLabetalolEnalaprilatHydralazineMaintain serum Na+ ≥140Check coagulation profile;correct coagulopathy

IVC placement and CSF drainage +medical

management

Surgical evacuationof hematoma and decompression

IVC placement + surgical

evacuation of hematoma and decompression

<3 cm hematomano hydrocephalus or

brainstem compression

>3 cm hematomawith hydrocephalus

<3 cm hematomawith hydrocephalus

>3 cm hematomano hydrocephalus

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


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 ran-domised 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


Epidemiology

Intraventricular hemorrhage (IVH) is defined as bleeding within the ventricular ■

systemIVH can occur as a primary event or in association with intracerebral hemor-■

rhage (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 ventriclesIVH 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 hydrocephalusMortality is even higher in those with IVH associated with warfarin use – 75% ♦

mortalityICH associated with IVH is often located in the caudate nucleus, thalamus, ♦

and basal ganglia

The conventional treatment of IVH when associated with symptomatic obstruc-■

tive hydrocephalus includes the use of external ventricular drainage (EVD)

Chapter 22Intraventricular Hemorrhage

Kristi Tucker and J. Ricardo Carhuapoma

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]

366 K. Tucker and J.R. Carhuapoma

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 ■

growthIVH 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 therapyIVH 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 injuriesOverall neurologic prognosis is determined by associated brain injuries♦

Primary IVH■

A rare occurrence, accounting for ~2% of all ICH admissions to large tertiary ♦

referral centersPatients commonly present with headaches, nausea and vomiting, and decline ♦

in mental statusSource of bleeding can be found using conventional angiography in 56% of ♦

casesMost 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)

36722 Intraventricular Hemorrhage

Pathophysiology

Brain injury induced by intraventricular blood can be due to hydrocephalus, local ■

mass effects within the ventricle, and/or potential inflammatory damage to ependy-mal and subependymal tissues from blood itself or from its degradation productsAlternative 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 regionsInflammation and fibrosis of ependymal lining♦


Presenting symptoms vary depending on the etiology, but most often, manifesta-■

tions of increased ICP, including altered mental status and nausea and vomiting are presentCT 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 scaleIf underlying aneurysm is suspected, patient will need four-vessel cerebral angio-■

gram; other diagnostic modalities such as MRA or CTA have an undetermined role in the early diagnosis of aneurysmal location following SAH at this pointPatients 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 systemLateral 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 blood3 = more than half of the ventricle filled with blood4 = ventricle filled with blood and expanded

Third and fourth ventricles Score 1 = blood present, ventricle size normal

2 = ventricle filled with blood and expandedLE ROUX system

Each ventricle is scored separately and a total score calculated. Maximum score = 16. Score 1 = trace of intraventricular blood

2 = less than half a single ventricle filled with blood3 = more than half the ventricle filled with blood4 = entire ventricle filled and expanded with blood

368 K. Tucker and J.R. Carhuapoma

Management

Systemic hypertension should be treated■

The ideal blood pressure goal is unclear at this point and may vary within ♦

individual patient populationsWhen elevated ICP is a concern, ICP monitoring is suggested to tailor blood ♦

pressure management to cerebral perfusion pressure goals

Check PT/PTT/INR and CBC, including platelets; coagulopathy must be rapidly ■

correctedMust perform serial neurologic examinations; watch for hydrocephalus, particu-■

larly if a large amount of blood is present within the ventriclesRepeat CT scan for any change in neurologic exam■

Neurosurgeons must be aware of these patients, as placement of an EVD system ■

may become rapidly indicatedUse 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 sur-rogates regarding involved risks

Key Points

In adults, IVH is associated with primary ICH (40%), SAH (10–28%), or ■

severe TBIPrimary IVH is rare, and secondary causes include intraventricular neoplasms ■

(meningiomas, ependymomas, metastatic tumors), cocaine use, pituitary apo-plexy, eclampsia, vascular malformations, and rarely, aneurysmsMortality 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 ventriculitisExternalized CSF drainage via placement of an EVD is usually indicated (espe-■

cially 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 intraven-tricular hemorrhage in patients with blunt head trauma. J Trauma 60:1010–1017

36922 Intraventricular Hemorrhage

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 relation-ships and clinical implications. Neurology 70:848–852

Longatti PL, Martinuzzi A, Fiorindi A et al (2004) Neuroendoscopic management of intraventricu-lar 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 aneu-rysm: 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 deter-minant 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


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■

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♦

Chapter 23Subarachnoid Hemorrhage

Eric M. Bershad and Jose I. Suarez

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]

372 E.M. Bershad and J.I. Suarez

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♦

Table 23.1 Rare causes of nonaneurysmal SAH

InflammatoryPrimary CNS vasculitisSystemic vasculitis

NeoplasticPituitary apoplexyGliomaSchwannomasMeningeal carcinomatosisAngiolipomaMeningiomaSpinal hemangioblastoma

VascularArterial dissectionArteriovenous malformations (brain and spinal cord)Dural arteriovenous fistulae (brain and spinal cord)Spinal artery aneurysmVenous sinus thrombosisAmyloid angiopathy

InfectiousMycotic arteritisLyme disease

DrugsCocaineAmphetamines

OtherCoagulopathy

37323 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

ModifiableSmokingHypertensionHeavy alcohol consumptionDrug abuse: cocaine and amphetaminesOral contraceptive use

NonmodifiableAdvancing ageFemale sexPregnancyBlack ethnicityFamily history (more than one first-degree relative)Autosomal dominant polycystic kidney disease (5–40% have aneurysms)Sickle cell diseaseMarfan syndromePseudoxanthoma elasticumEhlers–Danlos syndrome (type IV)Alpha-1-antitrypsin deficiencyNeurofibromatosis type IFibromuscular dysplasiaCollagen disorders


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 clini-■

cal factors (Table 23.3)

Size of aneurysm♦

History of SAH♦

Anterior vs. posterior circulation♦


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

Size of aneurysm (mm)

No history of SAH and anterior circulation aneurysm (%)

No history of SAH and posterior circulation or Pcom aneurysm (%)

History of SAH and additional aneurysm

<7 0 2.5 1.5 and 3.5%a

7–12 2.6 14.5 n/a13–24 14.5 18.4 n/a>25 40 50 n/aa 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


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%)•

Usually reversibleN

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 hemorrhageArteriovenous malformationHead traumaMeningitisHypertensive encephalopathySinus venous thrombosisPituitary apoplexyIschemic strokeDrug intoxication


Table 23.5 SAH grading scales

Grade Hunt and Hessa WFNS scaleb Fisher scalec Head CT scaled

0 Unruptured aneurysm

Unruptured aneurysm

n/a SAH absentANDIVH absent

1 Asymptomatic or mild HA

GCS 15ANDno motor deficit

No SAH on head CT

SAH minimalANDIVH absent

2 Moderate to severe HA, nuchal rigidity, ±CN deficits

GCS 13–14ANDno motor deficit

Diffuse SAH, <1 mm thickness, no clots

SAH minimalANDIVH in ventricles

bilaterally3 Confusion, lethargy,

or mild focal neurologic deficits

GCS 13–14ANDmotor deficit

Localized clots, or layers of blood >1 mm

SAH thicke

ANDIVH absent

4 Stupor and/or hemiparesis

GCS 7–12 ± motor deficit

IVH and ICH without significant SAH

SAH thicke

ANDIVH in ventricles

bilaterally5 Coma and/or extensor

posturingGCS 3–6 ± motor

deficitn/a n/a

WFNS World Federation of Neurological Surgeons; SAH subarachnoid hemorrhage; IVH intraven-tricular hemorrhage; HA headache; GCS Glasgow Coma Scale; CN cranial nerve; ICH intracere-bral hemorrhagea 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 gradesd 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•


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 fissureHydrocephalus may occur▲

Traumatic SAH•

Often associated with other signs of traumatic brain injury such as subdural ▲

and epidural hematoma, ICH, contusions, or diffuse cerebral edemaBleeding 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▲

OxyhemoglobinN

BilirubinN

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 poten-■

tially hazardous treatment of incidental aneurysms in a patient without SAHFailure to exclude SAH by LP may result in aneurysmal rebleeding, which is ■

associated with high mortality


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 treatmentAngiography■

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 •negativeCT angiography has been reported in rare cases to detect an aneurysm, •despite a negative contrast angiography studyIntraoperative angiography may be useful to ensure adequate clip place-•ment, perforator vessel status, and presence of vasospasmPotential complications of angiography•

Contrast nephropathy▲

Normal saline infusion may be helpful to attenuate riskN

Consider alkalinization of IV fluids for at-risk patients; more effica-N

cious than N-acetylcysteine (mucomyst)

Allergic reaction▲

Consider pretreatment with benadryl and steroidsN

Groin hematoma▲

Arterial dissection at the access site▲

Femoral neuropathy▲

Neurologic complications (1–2.5%)▲

0.1–0.5% risk of permanent neurologic impairmentN

Aneurysmal rebleedingN

StrokeN

Arterial dissectionN

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•


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 presentationsuggests SAH

Subarachnoidhemorrhage

No subarachnoidhemorrhage

No xanthochromiaXanthochromia OR

Equivocalb

AngiographyOR

CT angiography

Lumbar puncturea

No aneurysmAneurysm(s)SAH ruled out

Plan for prompttreatment

Repeat angiography in 1–2 weeks

Noncontrasthead CT

No aneurysm

Consider alternative etiologyc

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


Management

Preoperative management■

Assess airway, breathing, and circulation♦

Establish peripheral IV access♦

Place arterial line♦

Assess need for intubation♦

Indications for endotracheal intubation•

GCS ▲ £8Poor airway protection▲

Elevated ICP▲

Hemodynamically unstable▲

Poor oxygenation▲

Hypoventilation▲

Need for heavy sedation or paralysis▲

Use rapid-sequence intubation•

100 mg lidocaine IV▲

Blunts cough and gag response and subsequent rise in ICPN

10–40 mg etomidate IV▲

Minimal hemodynamic effectsN

Suppresses adrenal-pituitary axisN

Propofol (may be used for induction and/or maintenance sedation)▲

1–2 mg/kg bolus; and then, 2–10 mg/kg/hN

Neuromuscular blockade: 0.1 mg/kg vecuronium or 0.6 mg/kg rocuro-▲

nium; may double-dose for faster onset

Short actingN

NondepolarizingN

Ensure that patient bags easily before paralyzingN

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▲


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 loweredLower BP only if MAP >110 mmHg or end-organ damage▲

5 mg nicardipine IV bolus; then, 5–15 mg/h IVN

10 mg labetalol IV q 10–20 min; can double dose each time up to N

cumulative of 150 mg10 mg hydralazine IV q 10–20 min; can double dose each time up N

to cumulative of 150 mg0.625 mg enalaprilat 0.625 mg–1.25 mg IV q 6 hN

Avoid nitroprusside if possible▲

May elevate ICPN

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 pre-scribed in neuro ICUsUse 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 ▲

controversialSome advocate “watch and wait” strategy, while others recommend ▲

early CSF drainage via EVD


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 drainageIF EVD is placed, pressure-release setting (“pop-off”) is typically set at •15–20 cmH

2O 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•


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♦

H•2 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 hyper-tensive therapy, if indicatedOperative management includes either endovascular treatment or surgical ♦

clippingOptimal 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•


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 endovas-cular 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 encephalopathySymptomatic vasospasm may lead to ischemic stroke (delayed cerebral ▲

ischemia), the most important factor in determining long-term disabilityNo intervention is known to prevent vasospasm▲

Avoid hypotension and maintain euvolemia (CVP, 5–8 mmHg)▲

Normal saline IV bolus 250 mLN

Consider alternating with 25–50 g human albumin (25%) IVN

Clinical trial currently underway (ALISAH) to determine if human N

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

90–120 cm/s (mean) = elevated velocityN

120–160 cm/s = mild vasospasmN

160–200 cm/s = moderate vasospasmN

>200 cm/s = severe vasospasmN

For posterior circulation, a lower threshold of mean blood flow N

velocities (MCBFV) is considered abnormal compared to anterior circulation


TCD findings of severe vasospasm accurately predict severe N

angiographic vasospasm but correlate less well with symptomatic vasospasm or delayed cerebral ischemiaIncrease in MCBFV > 50 cm/s/24 h may better predict symptomatic N

vasospasm compared to MCBFV aloneLindegaard ratio (MCBFV of MCA:extracranial ICA) controls for N

global increased cerebral blood flow velocityMCBFV > 120 cm/s and Lindegaard ratio >3:1 = vasospasmN

MCBFV > 120 cm/s and Lindegaard ratio <3:1 = global hyperemiaN

CT perfusion was recently reported to be superior to TCD in predicting ▲

symptomatic vasospasmOther 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)▲

Reported to improve short-term neurologic status in 75% with N

symptomatic vasospasmHypertension induced with vasopressors such as phenylephrine N

or norepinephrine; increase SBP up to 200+ mmHg, mean BP, 110–140 mmHgHypervolemia with normal saline/albumin [(CVP 8–12 mmHg or N

pulmonary capillary wedge pressure (PCWP) 16–24 mmHg)]Hemodilution refers to decreased blood viscosity achieved by nor-N

mal saline infusionIn patients with refractory symptomatic vasospasm, augmentation N

of cardiac output with dobutamine may be considered

Role of endovascular treatment of refractory symptomatic vasospasm ▲

has yet to be determinedEndovascular 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 ran-domized 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 phenomenaMost 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


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 intravas-▲

cular 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▲

Evaluate with echocardiography, troponinsN

Must weigh risk/benefit ratio regarding antiplatelets/ anticoagulation N

use in postoperative period12.5–100 mg metoprolol b.i.d.N

Dysrhythmias▲

Correct underlying electrolyte disturbances (magnesium, potassium, ▲

calcium)12.5–100 mg metoprolol b.i.d.▲

Pulmonary•

Pneumonia▲


Use standard ventilator precautions to avoid risk of ventilator associated ▲

pneumonia

Hand washingN

Head of bed at 30–45°N

Avoid frequent circuit changesN

Continuous subglottic suctioningN

Chlorhexadine oral rinse (0.12 or 0.2%) 15 mL b.i.d.N

Acute respiratory distress syndrome▲

Use low-tidal volume ventilation 6 mL/kg/ideal body weight and keep ▲

plateau pressure <30 mmHg to avoid barotrauma5 cmH▲

2O 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 depletionIncrease 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▲

Replete potassiumN

Early feeding▲

Enteral route preferredN

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


Hyponatremia•

Distinguish between SIADH and cerebral salt wasting by assessing ▲

fluid balanceIf treatment is necessary, options include:▲

Increase normal saline infusion, or institute hypertonic saline (3%)N

Consider fludrocortisone 0.1–0.4 mg daily and oral salt tabletsN

Key Points

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 negativeEarly definitive treatment of the aneurysm by surgical clipping or endovascular coil-■

ing is considered the standard of care to both prevent rebleeding and allow for aggres-sive supportive management to help attenuate the devastating effects of vasospasmPostoperative care requires a multimodality approach that anticipates and treats ■

the neurologic and medical complications of SAH to optimize the patient’s long-term 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):928–939Broderick JP, Viscoli CM, Brott T et al (2003) Major risk factors for aneurysmal subarachnoid

hemorrhage in the young are modifiable. Stroke 34:1375–1381Claassen 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 hemor-rhage: 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 intracra-nial 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


Introduction

Neurologic injury resulting from global cerebral ischemia secondary to cardiac ■

arrest (CA) continues to be a major clinical problem that requires urgent neuro-critical care interventionEstimates 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 arrestsSurvival 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 levelsThe 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

Chapter 24Brain Injury Following Cardiac Arrest

Romergryko G. Geocadin

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]

390 R.G. Geocadin

Recent recognition of special needs of patients following CA has let to charac-■

terization 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 failureNeuronal injury starts rapidly and continues for hours to days after the initial ■

insultTypical neuronal injury cascade includes:■

Total circulatory arrest♦

Loss of ATP production and dysfunction of membrane ATP-dependent ♦

Na+–K+ pumpsLoss of cellular integrity, which triggers release of neurotransmitters that ♦

mediate excitotoxic injury such as glutamate, aspartate, and glycineReduction of inhibitory neurotransmitters such as ♦ g-aminobutyric acid (GABA)Influx of calcium into the intracellular space, with activation of second ♦

messengersReperfusion 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 cellsSubcortical areas, such as the brainstem, thalamus, and hypothalamus, are ♦

injured to a lesser degree due to relatively high tolerance to ischemia

Clinical manifestations of injuries are based on the areas involved and may be ■

divided into acute and chronicFrom 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 CAAreas that require urgent focus are the bilateral cortical regions and ascending ♦

arousal systems, which involved the subcortex, thalamus, and rostral brainstemHippocampal injury and its effect on memory and learning, while highly ♦

emphasized in the literature, have little impact on acute presentation and emergent care

Relative tolerance of brainstem to ischemic injury is manifested by the preserva-■

tion of cranial nerve and sensory motor reflexesOver the course of recovery, comatose survivors may transition to vegetative ■

state, where some aspects of arousal are regained but without the means to inter-act meaningfully to the environmentThe vulnerability of the cortex leads to high occurrence of seizures in survivors■

39124 Brain Injury Following Cardiac Arrest

Survivors with cortical hemispheric injury present with cognitive and neuropsy-■

chiatric disorders

Wide range, including myoclonic disorders, dyscoordination, and movement ♦

disorders, account for most of the functional impairments in long-term survivors

Numerous drugs believed to have neuroprotective actions (i.e., thiopental, corti-■

costeroids, nimodipine, lidoflazine, magnesium, diazepam, etc.) have failed to show treatment benefit in clinical trialsRecently, 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

Extent of neurologic injury is a major determinant in functional recovery of ■

patients resuscitated from CANeurologic injury is a major focus in resuscitation efforts as well as in post-■

resuscitation care; considering that most CA survivors are admitted to the cardiac or medical ICU, neurocritical care input in the care of these patients is criticalNeurologic care must involve a detailed clinical evaluation and stratification of ■

injury, direct involvement with acute neuroprotective care and strategies, manage-ment of acute neurologic problems and complications, prognostication of poor out-come 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

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 outcomeIt 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 deathIf 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

392 R.G. Geocadin

During the post-resuscitation period, it is important to ascertain the pre-cardiac-■

arrest function and neurologic condition of the patientsIt 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 ♦

obscure the neurologic examination, such as paralytic and sedative medications, illicit drug use before arrest, ongoing cerebral hypoperfusion, seizures or pos-tictal encephalopathy, electrolyte abnormalities, and metabolic derangementsNeurologic evaluation should assess mental status by documenting the ♦

patient’s ability to arouse and interact meaningfully with the examinerEvaluation of brainstem function includes the testing of cranial nerve function ♦

and reflexes, most importantly the pupillary light reflex, corneal reflex, gri-macing to noxious stimulation, oculocephalic reflexes, cough and gag reflexes, and the presence of spontaneous respirationsIn the unresponsive patient, the motor and sensory examination relies on the ♦

evaluation of the patient’s response to a noxious stimulus, which may be purpose-ful (warding off the stimulus), reflexive (extensor or flexor posturing), or absentIt is also helpful to note the autonomic responses, such as respiratory pattern, ♦

labile core temperature, and extreme swings of heart rate and blood pressureIt 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 GCSMissing evaluation of cranial nerve functions becomes problematic as prog-♦

nostication is soughtThe 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 validationIn patients who are able to arouse and interact meaningfully with the exam-♦

iner 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 care-ful 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

Focus of neurologic treatment is on patients who remain unresponsive or coma-■

tose after successful CPRUnfortunately no specific interventions have been studied in responsive or ■

noncomatose patients after CPR


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-of-♦

hospital arrest associated with an initial rhythm other than ventricular fibril-lation (Class IIb)

The basis for these recommendations on comatose survivors of out-of-hospital ■

CA with ventricular fibrillation is provided belowMore recent post-trial studies show beneficial effect of hypothermia in those ■

with asystole and pulseless electrical activityControlled clinical trials with therapeutic hypothermia on patients with in-hos-■

pital CA are still necessaryThe 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 sal-vage neurologic functions post-CAIt 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 hSome 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, over-whelming infections, and preexisting terminal conditionGuidelines are based on two landmark studies, one by the Hypothermia after ■

Cardiac Arrest (HACA) group in Europe, and the other by Bernard and col-leagues 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 thermometerPatients were rewarmed passively over a period of 8 h•Sedation with midazolam and paralysis with vecuronium were used to •prevent shiveringSeventy-five of the 136 patients (55%) in the hypothermia group had a favor-•able neurologic outcome (moderate disability but able to perform daily activ-ity 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)

394 R.G. Geocadin

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 tempera-ture to 33°CPatients 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 pro-tocols were provided to patients assigned to the normothermic group, tar-geting a temperature of 37°CPassive rewarming was used in these patients if they had mild spontaneous •hypothermia on arrivalThe primary outcome measure was location of discharge: home, rehabilita-•tion facility, or long-term nursing facilityDischarge 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 outcomeThe study found that 21 of 43 patients (49%) who were treated with hypo-•thermia 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

Since the publication of the two landmark trials discussed above, results of sev-■

eral other studies have been published, demonstrating that the therapeutic impact of hypothermia is robustSystematic review (meta-analysis) of the literature shows that to attain the ben-■

eficial 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 ~5–7These 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 con-versely, the benefits waned as treatment was delayed


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 hThe European study rewarmed patients passively over 8 h after 24 h of hypo-■

thermia, whereas the Australian study reported active rewarming for 6 h with a heated-air blanket, beginning 18 h after ROSCThe delivery of therapeutic hypothermia can be divided into three phases: induc-■

tion, maintenance, and rewarmingThe 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 coolingBefore 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 ♦

normal saline or Ringer lactate); studies showed no hemodynamic, pulmo-nary, renal, or acid–base complicationsThis intervention was safe and effective in decreasing body temperature rap-♦

idly from normothermia to therapeutic range in 30 min to 1 hThe 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 systemsA 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 belowOnce the target temperature (32–34°C) is achieved, the maintenance phase ♦

followsThe 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 mannerWhile the optimal rewarming rate is not known, current consensus provides a ♦

rewarming rate of ~0.25–0.5°C/hBecause 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

396 R.G. Geocadin

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


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

Shivering in response to hypothermia leads to generation of heat that is associ-■

ated with increase in oxygen consumption and worse neurologic outcome; in generating heat, shivering delays attainment of therapeutic temperatureAll of these are likely to lessen the benefits of hypothermia; shivering may be ■

pronounced during the induction of hypothermiaAt 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 agentSome changes have been institute in practice, from continuous sedation and ■

pharmacologic paralysis to noncontinuous and as-needed pharmacologic paraly-sis, with sedation based on presence of shiveringConsidering 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 injuriesOf 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 prognosticationOther drugs, such as IV magnesium, meperidine, buspirone, and dexmedetomi-■

dine, may control shiveringNonpharmacologic strategies such as counter-warming of face and extremities ■

may be tried

Complications of Hypothermia

Potential complications of therapeutic hypothermia include renal insufficiency, ■

bleeding, sepsis, and pancreatitisIn clinical trials, the incidence of these conditions was similar in both hypo-■

thermia and normothermia groupsSome 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 hyperglyce-mia in the study by Bernard and colleagues

398 R.G. Geocadin

Other possible complications include hypokalemia, metabolic acidosis, and car-■

diac 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 complicationsFrom a neurologic perspective, acute complications such as seizures have been ■

noted in patients treated with normothermia and hypothermiaIt is advisable to have a low threshold to perform EEG on patients who are sus-■

pected to have seizures, especially those who are paralyzed or heavily sedated, as these conditions can mask the clinical manifestation

Managing Neurologic Complications Post-CPR

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 injuryCerebral perfusion and oxygenation■

Early hemodynamic optimization is an important goal post-CPR♦

Systemic hypotension and hypoxemia worsen cerebral ischemia, and they ♦

should be avoidedOptimal 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 flowHowever, definitive studies are necessary to fully understand the role of •augmented cerebral perfusionA 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 avoidedA 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 outcomeAttempts to augment MAP must be made with caution, considering the •cardiovascular injury that is primarily associated with CAOxygenation 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 treatmentRisk of poor neurologic outcome increases for each degree of body tempera-♦

ture higher than 37°C


The reported worse outcome includes severe disability, coma, or persistent ♦

vegetative state; in managing temperature elevation, etiology must be worked up aggressivelyAssociated 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 aggres-sive 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 ♦

injury, increased cerebral metabolic demand, and elevated intracranial pres-sure (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 timeIf a patient develops a seizure, it should be worked up as a new-onset seizure ♦

and treated with standard anticonvulsant medicationsMyoclonus may occur independently or in association with seizures; the ♦

treatment of myoclonus may be difficult, and agents that have been used suc-cessfully include clonazepam, sodium valproate and levetiracetamEEG should be performed on any patient who is suspected of having seizures ♦

or in those with myoclonus to rule out associated seizuresIncidence of seizures associated with hypothermia or seizures masked by ♦

paralysis with hypothermia has been increasingExcept 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 hypothermiaIn cases where nonconvulsive seizures are suspected, continuous EEG moni-♦

toring is necessary to establish the diagnosisPresence of myoclonic status epilepticus as well as intractable status epilepti-♦

cus has been highly associated with poor outcome; impact of the two condi-tions 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 observedIf it occurs, ICP elevation can compromise cerebral blood flow, and cerebral ♦

edema may lead to cerebral herniation syndromes, leading to severe impair-ment or death

400 R.G. Geocadin

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 pressureHypoxia, 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 injuryIn general care in the post-CA period, the goal of mechanical ventilation is to ♦

achieve normocapniaIn cases in which worsening cerebral edema and mass effect are noted, stan-♦

dard brain edema management may also be undertaken (see Chap.)

Glucose management■

Hyperglycemia after ischemic brain injury has been associated with worse ♦

outcomeHyperglycemia is common after CA♦

Recent studies have shown that tight glucose control in some populations of ♦

critically ill patients can lead to better outcomeA 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•

Post 24 h: Prognostication

Despite the advances in resuscitation medicine, most CA survivors continue to ■

have poor outcomesPrognostication after CA resuscitation was once the main reason that neurologic ■

consultation was sought in these patientsWith success of therapeutic hypothermia, prognostication in CA survivors should ■

be refocusedProcess of prognostication is based on the determination of the extent and the ■

irreversibility of neurologic injury and its impact on the functional outcome of survivorsFactors used to predict outcome after CPR are divided into pre-CA parameters, ■

intra-CA parameters, and post-CA factorsWith an evidence-based review, the American Academy of Neurology (AAN) ■

published practice parameters on the prediction of poor outcome in comatose


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 hypothermiaThe AAN prognostication guidelines provide the prediction of poor outcome ♦

in comatose survivors of CA only; therefore, the opposite observation does not necessarily predict favorable outcomeNo definitive studies have been undertaken to predict functional recovery in ♦

noncomatose survivorsThe clinical parameters used in prognostication may be affected by physio-♦

logic 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 correctedPre-CA factors♦

Numerous studies have investigated patients’ pre-CA characteristics, but •no pre-arrest characteristic has been established as a reliable predictor of outcomeSome of the patient characteristics studied are age, race, activity level, •and preexisting health conditions such as diabetes, cancer, and renal failureThe 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 outcomeMost notable of these factors are prolonged duration of pulselesness (CA •time), prolonged CPR duration, lack of adherence to CPR guidelines, non-cardiac 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 outcomeThese 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 neuroimagingNumerous 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

402 R.G. Geocadin

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


Sudden interruption of blood flow to the brain and brainstem leads to ▲

widespread neurologic failureAbsence of neurologic function immediately after ROSC is not a reli-▲

able predictor of poor outcome; however, the retention of any neuro-logic function during or immediately after CPR portends a good neurologic outcome; in the era of effective intervention with therapeu-tic hypothermia, prognosticating poor outcome, thereby possibly lead-ing to withdrawal of life support on day 1, is not advisedReliability and validity of neurologic examination as a predictor of poor ▲

outcome depends on the presence of neurologic deficits at specific time points after ROSCFindings 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 outcomeAnother important bedside observation is the occurrence of seizures ▲

and myoclonus, which if prolonged and repetitive, may carry their own grave prognosisAlthough 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 casesBecause 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 derangementsThe N20 component (representing the primary cortical response) of the ▲

SSEP with median nerve stimulation is the best studied evoked-potential waveform in prognosticationIn 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 sur-vivors did not reliably predict a good outcome

404 R.G. Geocadin

• 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 general-ized suppression to <20 mV, burst suppression pattern with generalized epi-leptiform 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 disordersConsidering all of these, EEG is insufficient to reliably prognosticate ▲

futility

• Biochemical markers derived from cerebrospinal fluid (creatine phospho-kinase 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 markersOf these, the most reliable, per the AAN practice parameters, is NSE, ▲

a cytoplasmic glycolytic enzyme found in neurons, cells, and tumors of neuroendocrine originSerum 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 vari-ability of threshold values to predict poor outcome, and differing mea-surement techniquesThe other biochemical marker, S100▲ b, a calcium-binding protein from astroglial and Schwann cells, is less favoredAn S100▲ b 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 sensi-tivity 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 CASeveral studies using CT scans of the brain showed that widespread ▲

injury and changes in edema characteristics are associated with poor outcome


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 neuroim-aging such as MR spectroscopy or positron-emission tomography (PET) may show cellular dysfunction that is associated with poor outcomeAt this time, the practical utility of neuroimaging, especially CT scan-▲

ning, is limited to excluding intracranial pathologies such as hemor-rhage or strokeThe detection of structural and functional abnormality may be used to ▲

help support the other clinical findings

Neurologic Prognostication After Therapeutic Hypothermia

The recent practice parameters issued by the AAN focused only on predictors of ■

poor outcome in patients who were not treated with hypothermiaAs a therapy, hypothermia has the ability to alter both survival and functional ■

outcomeFurthermore, hypothermia is known to alter some physiologic processes, e.g., ■

clearing of paralytic agents and causing some delay in the return of motor functionIt 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 prac-tice parameters should be modified to account for these additional confoundersAt 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 observedFor patients treated with hypothermia, two substudies of the HACA trial provide ■

some limited insight into the use of evoked potentials and biochemical markers as prognosticatorsA substudy of the HACA trial examined the prognostic accuracy of SSEPs in 57 ■

patients 24–28 h after CAThirty patients were treated with hypothermia, and the N20 latency was pro-■

longed in all of themEleven patients had absent N20 responses (three hypothermic and eight normo-■

thermic 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 patientsAnother HACA substudy compared NSE and S100■ b 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 patientsSurvival, recovery of consciousness, and good outcome seemed to correlate with ■

decreasing levels of NSE between 24 and 48 h

406 R.G. Geocadin

Although the investigators identified cut-off values for NSE concentrations that ■

were predictive of poor outcomes, these values differed between the hypo-thermia and normothermia groups

Key Points

Brain injury continues to be the leading cause of disability after CA, despite ■

significant advances in resuscitation and critical care over several decadesCare of these patients can be challenging, and it requires a great deal of medical ■

resources and expendituresTherapeutic hypothermia, in demonstrating benefit in survival and functional ■

outcome measures, has renewed the enthusiasm for the amelioration of brain injury in post-CA patientsImplementation 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 centersAs the specialists whose primary focus it is to enhance recovery from neurology ■

injuries, neurointensivists should take a lead in the implementation of this therapySeveral 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 hypothermiaOnce the best efforts have been undertaken to provide the appropriate interven-■

tions to protect the brain from further injury post-CA, the focus of neurologic care shifts to prognostication, especially in those survivors who remain comatoseOutcome 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 CASeveral 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


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.


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 spaceInflammation may be infectious (bacterial, viral, fungal), chemical (blood, ♦

anesthetics), or idiopathic

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 hospitalizationFungal 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 influ-enzae type b (Hib) vaccine

Chapter 25Meningitis and Encephalitis

Barnett R. Nathan

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]

410 B.R. Nathan

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 decreasedAdults 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

Predominant causative pathogens in community-acquired adult bacterial menin-■

gitis 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 immunityIn neonates, gram-negative bacilli and streptococci are most common. In older ■

children, with the reduction of H. influenzae, pneumococcus and meningococ-cus are now the most commonMost common organisms following neurosurgical procedures are gram-negative ■

bacilli and staphylococci (including Pseudomonas and methicillin-resistant Staphylococcus aureus)


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 statusClassic 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 featuresMost 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 benefitFungal meningitis may present with nonspecific symptoms (malaise, weight ■

loss), but it may also present with signs and symptoms similar to those of bacte-rial meningitis; while bacterial meningitis is typically a fulminant disease, fun-gal meningitis may present subacutely or as a chronic presentation

41125 Meningitis and Encephalitis

Diagnosis

In patients with acute meningitis, CT is used mainly to assess the safety of lum-■

bar puncture (LP), rather than to make a diagnosisA 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 subse-quent LP predict herniationAccording to the ■ Practice Guidelines for the Management of Bacterial Meningitis, a CT scan should be performed prior to an LP if the patient has:

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

Table 25.1 Symptoms and signs on presentation from 352 consecutive cases of community-acquired bacterial meningitis

Symptoms and signs on presentationSeizures 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 fea-tures, complications, and outcome in adults with pneumococcal meningitis: a prospective case series. Lancet Neurol 5(2):123–129

412 B.R. Nathan

Blood cultures are likely to be helpful in the following (descending order): ♦

H. influenzae, S. pneumoniae, N. meningitides, beta-hemolytic streptococci, and S. aureusAnalysis of CSF is the gold standard for diagnosing bacterial meningitis♦

Typical ranges of CSF parameters in bacterial meningitis♦

Opening pressure: >15 cmH•2O

CSF WBC: 1,000–10,000 cells/mm• 3; predominantly neutrophilsCSF 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 patientSeverely 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

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 highGram stain has 92% sensitivity and >99% specificity in diagnosing bacterial or ■

fungal meningitis in those who have received no treatmentDiagnosing 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 organ-isms (gram stain or culture) difficultThe 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 cul-ture, as evidence for infection

Management (Fig. 25.1)

Treatment, particularly antibiotics in bacterial meningitis, should never be ■

delayed once the diagnosis is suspected


Most patients should still have positive CSF cultures after 1–2 h subsequent ♦

to parenteral antibiotic treatment. Therefore in most cases, antibiotics can be administered prior to the CT and LPThe literature does not support a consistent relationship between time to pre-♦

sentation and morbidity/mortality; it is clear, however, that meningitis and other CNS infections can be rapidly progressive entities for which urgent antibiotic administration is necessaryBecause 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 focusedRecommendations for empiric therapy are summarized in Table ♦ 25.2, and those for specific etiologic agent are summarized in Table 25.3Duration of treatment is dependant on the organism identified. Meningococcus ♦

can typically be treated for 7 days, pneumococcus for 14 days, and gram-negative 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 BAdjunctive treatment (Fig. ■ 25.1)

Five randomized, controlled studies have evaluated the use of adjunctive ste-♦

roids in the treatment of community-acquired bacterial meningitis

Fig. 25.1 Diagnosis and treatment algorithm for suspected community-acquired bacterial menin-gitis. From Tunkel AR, Hartman BJ, Kaplan SL et al (2004) Practice guidelines for the manage-ment of bacterial meningitis. Clin Infect Dis 39(9):1267–1284

414 B.R. Nathan

Significant survival and sequela improvement was demonstrated in adults •when dexamethasone was administered prior to the administration of antibioticsImprovement was most dominant in • S. pneumoniae meningitisDosing of dexamethasone prior to antibiotics reduces the subsequent •intrathecal inflammatory response that occurs with the bacterial lysisDexamethasone should be dosed at 10 mg (IV) q 6 h for 4 days•

Table 25.2 Recommendations for empiric treatment regimens for community-acquired bacterial meningitis

Predisposing factor Common bacterial pathogens Antimicrobial therapy

Age<1 month Streptococcus agalactiae, Escherichia

coli, Listeria monocytogenes, Klebsiella species

Ampicillin plus cefotaxime or ampicillin plus an aminoglycoside

1–23 months Streptococcus pneumoniae, Neisseria meningitides, S. agalactiae, Haemophilus influenzae, E. coli

Vancomycin plus a third-generation cephalosporina,b

2–50 years N. meningitidis, S. pneumoniae Vancomycin plus a third-generation cephalosporina,b

>50 years S. pneumoniae, N. meningitidis, L. monocytogenes

Vancomycin plus ampicillin plus a third-generation cephalosporinab

Head traumaBasilar

skull fractureS. pneumoniae, H. influenzae, group

A b-hemolytic StreptococciVancomycin plus a third-

generation cephalosporina

Penetrating trauma Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic gram-negative bacilli (including Pseudomonas aeruginosa)

Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem

Postneurosurgery Aerobic gram-negative bacilli (including P. aeruginosa), S. aureus, coagulase-negative staphylococci (especially S. epidermidis)

Vancomycin plus cefepime, vancomycin plus ceftazidime, or vancomycin plus meropenem

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):1267–1284a Ceftriaxone or cefotaximeb Some experts would add rifampin if dexamethasone is also givenc In infants and children, vancomycin alone is reasonable unless Gram stains reveal the presence of gram-negative bacilli


Acute Viral Encephalitis

Definitions and Epidemiology

Encephalitis implies direct inflammation of the brain; most infectious encepha-■

litides affect the cortical structures, though many also cause inflammation of the deeper structuresVariety of different organisms, such as herpes simplex, arbovirus, and rabies, ■

can cause encephalitisMost common cause of sporadic fatal encephalitis in the US are the herpes sim-■

plex 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♦

Table 25.3 Recommendations for specific treatment regimens for community-acquired bacterial meningitis

Microorganism Recommended therapy Alternative therapies

Streptococcus pneumoniae

Vancomycin plus a third-generation cephalosporina,b

Meropenem, fluoroquinolone

Neisseria meningitidis Third-generation cephalosporina

Penicillin G, ampicillin, chloramphenicol, 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

Escherichia coli Third-generation cephalosporina Cefepime, meropenem, aztreonam, fluoroquinolonec, trimethoprim-sulfamethoxazole

Note. In children, ampicillin is added to the standard therapeutic regimen of cefotaxime or ceftri-axone plus vancomycin when L. monocytogenes is considered and to an aminoglycoside if a gram-negative enteric pathogen is of concernFrom: Tunkel AR, Hartman BJ, Kaplan SL et al (2004) Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39(9):1267–1284a Ceftriaxone or cefotaximeb Some experts would add rifampin if dexamethasone is also givenc Gatifloxaxin or moxifloxacind Addition of an aminoglycoside should be considered

416 B.R. Nathan

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 prognosisHSV spreads from cell to cell, infecting both neurons and glia♦

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 virusSerologic cross-reactions with these viruses♦

Thought to have originated in Uganda, though genetic lineage of US WNV ♦

comes from Middle EastOnly 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 area2003 – 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 transmis-sion in third trimester, and via breast milk


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♦


WNV encephalitis■

“Flu-like” syndrome (fever, malaise, myalgias, etc.) during the summer in ♦

nonencephalitic patientsEncephalitis♦

Fever, fatigue, headache, altered mental status, weakness, movement dis-•orders/parkinsonismRisk 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% PMNsRBC <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 •encephalitisProtein – 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

418 B.R. Nathan

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 cortexGadolinium enhancement around the periphery of the infection▲

No study conducted yet to determine the sensitivity and specificity, but ▲

both are most likely highAbnormality 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 treatmentDependent 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 infectionCross-reaction with yellow fever (vaccine), Japanese encephalitis (vac-•cine), St. Louis encephalitis, or Dengue feverIgM 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


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 reversibleEven 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 ventilation4% mortality (overall), with 10% mortality in patients with encephalitis♦

At least 50% of survivors of encephalitis will have neurologic sequelae♦

Key Points

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 treatmentsIn suspected bacterial meningitis, empiric antibiotics should be chosen based on ■

the patient’s risk factors and should be started immediately; choices for antibi-otic coverage should be refined based on culture and sensitivity resultsIn 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; anti-biotics should not be held for the sake of these proceduresDepending on the resistance patterns of the institution, ■ S. pneumoniae may be resistant to penicillins and cephalosporins

420 B.R. Nathan

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 ventricu-lostomy: a randomised study. Acta Neurochir Suppl 71:146–148

Tunkel AR, Hartman BJ et al (2004) Practice guidelines for the management of bacterial menin-gitis. Clin Infect Dis 39:1267–1284

van de Beek D, Gans J de et al (2004) Clinical features and prognostic factors in adults with bacte-rial 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


Epidemiology

Cerebral venous sinus thrombosis (CVST) constitutes ~1% of all stroke ■

presentationsOccurs at any age, but incidence peaks in the neonatal period and in the third ■

decadeEstimated annual incidence: adults, three to four cases per million; children or ■

neonates, seven cases per millionFemale-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

Chapter 26Cerebral Venous Sinus Thrombosis

Agnieszka A. Ardelt

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]

422 A.A. Ardelt

Pregnancy/puerperium – 20% of cases of CVST in women <50 years old•

CVST is more likely during puerperium, especially within 3 weeks of ▲

deliveryAssociated 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, otitisSystemic 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•

42326 Cerebral Venous Sinus Thrombosis

Anatomy

Normal anatomy■

Cerebral venous system♦

Components – dural sinuses, superficial cortical veins, deep cerebral veins, •posterior fossa veinsAnatomy 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 spacesReceive 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

424 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 narrow-•ing 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

Sinus/vein

Frequency, percent of casesa

Adult Pediatric

n = 624 n = 160

Superior sagittal sinus 50 55Lateral sinus 45 (left), 41 (right) 51Straight sinus 18 24Superficial cortical veins 17 6Jugular veins 12 9Deep cerebral veins 11 19Cavernous sinus 1.3Cerebellar veins 0.4a Multiple sinuses and veins are involved in ~30% of adult patients and 50% of pediatric patients


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•


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 thrombusTiming 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 CVSTThe 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•

426 A.A. Ardelt

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▲


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 casesHyperdensity due to intraparenchymal hemorrhage – 30% of CVST cases•

May be in a speckled, multifocal, petechial pattern within a hypodense ▲

areaMay 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 ▲

usedContrast 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 thrombusLoss of intravascular signal on time-of-flight angiography suggests throm-•bus but may be artifactual or reflective of congenital hypoplasia or stenosisAppearance of thrombus on MRI•

428 A.A. Ardelt

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 claustrophobiaContraindicated 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 casesPossibility 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•

Table 26.2 Signs of CVST on MRI

Age of thrombus (time from onset)

MRI sequence

CommentsT1-weighted T2-weighted

Acute (days) Isointense Hypointense Deoxyhemoglobin in intact red blood cells

Subacute (weeks to a month)

Hyperintense Hyperintense Methemoglobin in lysed red blood cells

Chronic (>1 month) Isointense Hyperintense Varies depending on recanalization


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 H•2O – 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 admis-sion 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 contraindicationSpecific goals of therapy♦

430 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 reversalLow-molecular-weight heparin can be used, but efficacy/safety compared •to unfractionated heparin in CVST is unknownWarfarin 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 publishedRisk-benefit compared, or as an adjunct, to systemic anticoagulation can-•not be calculated due to paucity of trial dataDecision 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 tissue-plasminogen 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


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 pro-■

thrombotic drugsTreatment 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 suppressionDecompressive surgery in selected intractable cases▲

Steroids are not beneficial and should be avoided▲

432 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 intrac-•erebral 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%♦


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 con-•ditions, 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 puerpe-■

rium) is the most common risk factor in adultsHeadache 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 patientsRandomized controlled trials of thrombolysis for CVST are lacking, thus risks/■

benefits cannot be determined at this timeOutcomes 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 adultsRate of CVST recurrence is low in adults, even in cases of pregnancy/puerpe-■

rium-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, MOPaciaroni M, Palmerini F, Bogousslavsky J (2008) Clinical presentations of cerebral vein and

sinus thrombosis. Front Neurol Neurosci 23:77–88Renowden S (2004) Cerebral venous sinus thrombosis. Eur Radiol 14:215–226


Neuroleptic Malignant Syndrome

Epidemiology■

Neuroleptic malignant syndrome (NMS) is rare, diagnosed annually in 2,000 ♦

hospitalized patients in the USRecent studies suggest an incidence of 0.01–0.02% in patients treated with ♦

antipsychotic medicationsRisk 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 risperidoneRisk with quetiapine, apiprazole, or ziprasidone may be even lower▲

Low potency D2-receptor antagonists, such as metoclopramide or ▲

tricyclic antidepressants, have also been implicatedAn 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

Chapter 27Neuroleptic Malignant Syndrome, Malignant Hyperthermia, and Serotonin Syndrome

Panayiotis N. Varelas and Tamer Abdelhak

P.N. Varelas, MD, PhD (*) and T. Abdelhak, MD Departments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, MI, USA e-mail: [email protected]

436 P.N. Varelas and T. Abdelhak

Two associated signs or symptoms (mental status change, tremors, dysau-•tonomia with tachycardia or bradycardia and labile blood pressure, tachyp-nea or hypoxia, diaphoresis, incontinence or sialorrhea), ORLaboratory abnormalities (rhabdomyolysis, metabolic acidosis, leukocyto-•sis, 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 monthAfter the antipsychotic is discontinued, symptoms and signs regress within ♦

1 week in 63% of patients; persistent signs of extrapyramidal rigidity or cata-tonia may last for weeks in a few patientsDifferential 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 (methylenedioxymetham-•phetamine, “ecstasy”), amphetamines, or phenylcyclidineWithdrawal syndrome (alcohol, sedatives, amantadine, • l-dopa, baclofen)Neuroleptic hypersensitivity syndrome in dementia with Lewy bodies•Nervous system infections (meningitis, encephalitis, abscess, tetanus) or •sepsisNonconvulsive 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 adequateMonitor for signs of disseminated intravascular coagulation (DIC), follow ♦

electrolytes, creatine phosphokinase, and renal function closelyVolume resuscitation (if rhabdomyolysis present, at least 150–200 mL/h IV ♦

fluids), with central venous pressure goal of 6–10 mmHgSystemic 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

43727 Neuroleptic Malignant Syndrome, Malignant Hyperthermia, and Serotonin Syndrome

in divided doses is an alternative); monitor for excessive muscle weakness or hepatotoxicityElectroconvulsive 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 anesthesiasAlthough it can occur with the first exposure, patients may require three anes-♦

thesias on the average to develop symptomsMore 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 individualsTriggering factors♦

Halogenated inhalational anesthetics•Succinylcholine. Non-depolarizing paralytics, propofol or ketamine have •not been implicatedExtreme 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 muta-•tion 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 CO

2 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, auto-•somal-recessive disease with a mutation in the RYR1 implicated in most cases)Multiminicore disease•Some sodium-channel forms of myotonia•


Hypokalemic periodic paralysis•King Denborough syndrome (very rare)•

Mortality from MH is <5% with modern anesthesia techniques♦


MH occurs during anesthesia or immediately after; symptoms and signs ♦

include:

Unexpected increase in end-tidal CO•2 > 55 mmHg or PaCO

2 > 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 failureMetabolic acidosis (base deficit >8 mEq/L, pH < 7.25) with elevated ▲

lactateAltered 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 syndromeAcute renal failure▲

Hyperkalemia▲

Hyperthermia (in dramatic cases, up to 1–2°C q 5 min, sometimes up ▲

to 44°C), usually a later signDIC, 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 caffeineGenetic 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 per-formed to identify the mutation

Differential diagnoses♦

Sepsis (usually responds to antipyretics) or tetanus•Thyrotoxicosis or pheochromocytoma•Iatrogenic overheating•Rebreathing of CO•

2 from faulty anesthesia equipment


Intrathecal injection of high-ionic, water-soluble contrast – myoclonic •jerks start from the lower body and progress rostrally, ending in seizures and hyperthermiaNMS 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 succinyl-choline administration

■ Management

Immediate cessation of all inhalation agents or succinylcholine♦

Admission to an ICU for monitoring and supportive treatment♦

Increased minute ventilation to normalize PaCO♦2

Body cooling – nasogastric lavage with icy solutions, fans, ice packs in ♦

groins, axillae or neck, surface or invasive cooling systems; goal is tempera-ture of 38.5°CDandrolene (directly antagonizes RYR1-mediated Ca♦ 2+ release) – 2.5 mg/kg IV bolus and repeat q 15 min up to 10 mg/kg/day if tachycardia or hypercar-bia 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 hepatotoxicityHyperkalemia♦

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 diureticsMonitor 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 reactionFactors associated with recrudescence♦

Muscular body type•MH grading score >35•Temperature increase•Period between induction to adverse reaction >150 min•


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 usedSuch 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 anti-depressant drug nefazodoneAffects 14–16% of patients overdosing on SSRIs (selective serotonin reuptake ♦

inhibitors)SS is believed to result from overstimulation of the 5-HT♦

1A or 5-HT

2A recep-

tors from various medications, including:

Excess of serotonin or serotonin agonists – buspirone, LSD, Lithium, •sumatriptan, l-tryptophan, trazodoneIncreased serotonin release – amphetamines, MDMA, cocaine, fenflu-•ramine, reserpineDecreased serotonin breakdown – MAO (monoamine oxidase) inhibitors, •linezolid (a weak MAO inhibitor), ritonavirDecreased serotonin reuptake – SSRIs, tricyclics, trazodone, venlafaxine, •meperidine, dextromethorphan, fentanyl, tramadol


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, hyper-•thermia (up to 40°C), diaphoresis, mydriasis, hyperactive bowel, hypere-flexia and clonus (characteristically seen in lower extremities and seen much less in upper extremities), horizontal ocular clonus, agitation/ hypervigilance, and rotatory head turning movements


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 patientsAdmission 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 mmHgIf 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 MAPIn severe hypertension, short-acting IV agents such as nitroprusside or ♦

esmolol should be used; if intracranial pressure is elevated, nicardipine infu-sion may be an alternative

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

MajorMental symptoms: confusion, elevated mood, comaAutonomic symptoms: fever, diaphoresisNeurologic symptoms: myoclonus, tremors, hypereflexia, chills, muscle rigidityMinorMental symptoms: agitation, nervousness, insomniaAutonomic symptoms: tachycardia, tachypnea, diarrhea, low or high blood pressureNeurologic symptoms: impaired coordination, akathisia, mydriasis


For moderate cases, 5-HT♦2A

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 sedationOlanzapine 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

Table 27.2 Differential diagnosis of SS, MH, NMS and anticholinergic intoxication

SS NMS MH Anticholinergics

Drug Serotoninergic agent

Dopamine antagonist

Succinylcholine, inhalational anesthetics

Anticholinergic agent

Lag time 6–12 h 1–7 days 30 min to few hours

6–12 h

Vitals ↑ HR, ↑ BP, ↑ RR ↑ HR, ↑ BP, ↑ RR

↑ HR, ↑ BP, ↑ RR

↑ HR, ↑ or ↔ BP, ↑ RR

Fever £40°C in moderate, >41°C in severe

>41.1°C Up to 46°C £38.5°C

Pupils ↑↑ ↔ ↔ ↑↑Mucosa Sialorrhea Sialorrhea Normal DrySkin Diaphoresis Pallor,

diaphoresisMottled,

diaphoresisHot and dry

Bowel ↑sounds, diarrhea Normal or ↓ sounds

↓ sounds ↓ sounds

Muscle tone

↑in LE ↑↑ Lead-pipe ↑↑, Masseter Normal

Reflexes ↑↑, Clonus in LE, ocular clonus

Bradyreflexia ↓ Normal

Mental status

Agitation, coma Stupor, akinetic mutism, coma

Agitation Agitated 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


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 352:1112–1120Burkman 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 2:21Strawn JR, Keck PE Jr, Caroff SN (2007) Neuroleptic malignant syndrome. Am J Psychiatry

164:870–876


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 populationOverall 5-year survival of all brain tumors is estimated to be 33%■

The only well-validated risk factor for developing primary brain tumor is ion-■

izing radiation exposure, typically from prior treatment of cancerGliomas 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 28.1Certain inherited syndromes are associated with tumors that involve the ner-♦

vous system; these are summarized in Table 28.2

Chapter 28Brain Tumors

Sherry Hsiang-Yi Chou

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]

446 S.H.-Y. Chou

Metastatic brain tumors are the most common brain neoplasms in the adult ♦

populationThe 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•

44728 Brain Tumors

Table 28.1 Primary brain tumors (2007 WHO Classification)

TumorWHO grade Epidemiology Prognosis

Tumors of neuroepithelial tissue

Astrocytic Tumors

Pilocytic astrocytoma I More common in children

Common locations: cerebellum, hypothalamus, and optic nerve

Usually slow growing, and prognosis is typically better than that of astrocytoma

Outcome depends on surgical accessibility of tumor

Pilomyxoid astrocytoma

II Onset in infancy (median age of onset is 10 months)

Prognosis worse than that of pilocytic astrocytoma

Occur in hypothalamus or optic chasm

Subependymal giant cell astrocytoma

I More common in children

Benign

Associated with tuberous sclerosis

Pleomorphic xanthoastrocytoma

II RareAverage age of onset

is 10 years

Postoperative survival ranges from 2 to 17 years

Slow growing but may undergo malignant transformation

Diffuse astrocytoma (fibrillary astrocytoma; gemistocytic astrocytoma; protoplastic astrocytoma)

II Age of onset is 30–40 years

Survival is 6–8 years after surgical resection

Mostly supratentorial in location

Gross total resection associated with better prognosis

Can occur in spinal cord and brainstem

Anaplastic astrocytoma

III Mean age of onset is 41 years

5-Year survival rate is 30%Presence of oligodendroglial

component improves survivalMale predominanceGross total resection is

associated with better prognosis

Glioblastoma (giant cell glioblastoma; gliosarcoma)

IV Peak age of onset is 40–60 years

Median survival on treatment is 12 months

Arise either as primary tumor or transformation from anaplastic astrocytoma

5-Year survival rate is 3.3%

Gliomatosis cerebri IV Diffusely infiltrating glioma involving more than two lobes of the brain

Very poor prognosisMedian survival is 12 months

May extend into posterior fossa and spinal cord

(continued)

448 S.H.-Y. Chou


Oligodendroglial Tumors

Oligodendroglioma II Slow growing Median survival is 11.6 yearsLack of contrast enhancement

on imaging is associated with better survival

Often calcifiedMean age of onset is

42.6 yearsAccount for <5% of all

brain tumorsAnaplastic

oligodendrogliomaIII Mean age of onset is

48.7 yearsMedian survival is 3.5 yearsChromosome 1p and 19q

deletion is associated with better prognosis

Oligoastrocytic Tumors

Oligoastrocytoma II 2.3% of all brain tumorsLargely located

supratentoriallyOccur in adults

Recurrence post resection is common

Younger age and lower grade at initial diagnosis are associated with better prognosis

Anaplastic oligoastrocytoma

III–IV Rare Prognosis depends on histologic grade

Ependymal Tumors

Subependymoma I 90% occur in adults Often asymptomatic and found incidentally on autopsyAssociated with tuberous

sclerosisMyxopapillary

ependymomaI Male:Female = 2.2:1 Survival >10 years

Almost exclusively located in cauda equina

More common in adults than in children

Ependymoma (cellular; papillary, clear cell, tanycytic)

II Comprise 4% of all brain tumors

10-Year survival is 45% in adults

Third most common CNS tumor in children

Total resection associated with better prognosis

90% are in brain, and 10% in spinal cord

Seeding of CSF space is associated with poor prognosis

Anaplastic ependymoma

III Rare Prognosis worse with higher grade

Choroid Plexus Tumors

Choroid plexus papilloma

I Comprise 0.5% of intracranial tumors

Benign; surgery is curative

Males affected more often than females

Onset usually in first decade of life

May cause hydrocephalus due to excess CSF production

(continued)


44928 Brain Tumors



Atypical choroid plexus papilloma

II Choroid plexus papilloma with increased mitotic activity

Surgery can be curativeRecurrence rate higher than that

of choroid plexus papillomaChoroid plexus

carcinomaIII Tends to arise in the

lateral ventricle and invade adjacent brain

5-Year survival rate is 26–50%

Systemic metastases may occur

Diagnosis is made only after exclusion of metastatic lung adenocarcinoma in adults

Other Neuroepithelial Tumors

Astroblastoma I Rare glial neoplasm of uncertain histogenesis

Unknown

Mostly occurs in young adults but have been reported in children

Chordoid glioma of the third ventricle

II Occurs exclusively within the rostral third ventricle

Surgical excision is treatment of choice

Angiocentric glioma I Occur mainly in children and young adults

Benign; Surgery is curative

Leading symptom is refractory epilepsy

(continued)

Neuronal and Mixed Neuronal-Glial Tumors

Dysplastic gangliocytoma of cerebellum (Lhermitte–Duclos)

I Rare syndrome VariableCNS manifestation of

Cowden diseaseDesmoplastic Infantile

astrocytoma/ganglioglioma

I Variant of ganglioglioma; occur up to age 2 years

Surgery can be curative

Dysembryoplastic neuroepithelial tumor

I Mean age of onset is 9 years

Associated with intractable childhood epilepsy

Temporal lobe is the most common location

Favorable outcome after surgical resection

Associated with cortical dysplasia

Gangliocytoma I Occurs mostly in children and young adults

5-Year survival is 80%Associated with seizures

0.4% of all brain tumorsTemporal lobe is the most

common site

450 S.H.-Y. Chou


(continued)


Ganglioglioma II–III Most occur before age 214–8% of all pediatric

brain tumors

Temporal lobe is the most common site

Excellent prognosis after complete resection

Brainstem location is associated with worse prognosis

Associated with seizuresAnaplastic ganglioglioma IV Rare malignant

transformation of ganglioglioma

Poor

Central neurocytoma II Usually located in lateral or third ventricle near foramen of Monro, frequently within septum pellucidum

Excellent prognosis after surgical resection

Onset in second or third decade

Extraventricular neurocytoma

II Similar to central neurocytoma but located outside of ventricular system

Favorable outcome with maximal resection

Cerebellar liponeurocytoma

II Arise in cerebellum of adults

Favorable outcome following surgery

Papillary glioneuronal tumor

I Wide age range; mean age of onset is 27 years

Benign

Temporal lobe is the preferential location

Rosette-forming glioneuronal tumor of the fourth ventricle

I Rare Benign; surgery is curativePrimarily in young adults

(mean age of onset is 33)

Paraganglioma I Analogous to pheochromocytoma

Variable

Most often located in filum terminale

Rarely produces catechola-mines

Tumors of the Pineal Region

Pineocytoma I <1% of all brain tumors Slow growing, usually favorable prognosisOccur in middle-aged or

older adultsPineal parenchymal

tumor of intermediate differentiation

II, III Rare 5-Year event-free survival is ~60–69%

Pineoblastoma IV <1% of all brain tumors Poor prognosis

Metastasize via CSF pathways

45128 Brain Tumors


(continued)


Papillary tumor of the pineal region

II, III RareAffect children and young

adults (mean age of onset is 32 years)

5-Year event-free survival is 27–73%

Recurrences are common

Embryonal Tumors

Medulloblastoma (desmoplastic/nodular medulloblastoma; medulloblastoma with extensive nodularity, anaplastic medulloblastoma; large cell medulloblastoma)

IV Over 50% occur in children younger than 10 years of age

Recurrence is common, and most recurrences occur within 2 years of initial resection

5-Year progression-free survival is 60–80%

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

CNS primitive neuroectodermal tumor (PNET) (CNS neuroblastoma; CNS ganglioneuroblastoma; medulloepithelioma, ependymoblastoma)

IV Occurs mostly in children and young adults

Death occurs within 8–24 months of diagnosis

Metastases to lungs and other systemic organs can occur

Atypical teratoid/rhabdoid tumor

IV Childhood disease>60% occurs in the

posterior fossa

Survival rate in children under 3 years old is <10%

2-Year survival is <20%

Tumors of cranial and paraspinal nerves

Schwannoma (cellular, plexiform, melanotic)

I 8% of all intracranial and 29% of all spinal tumors

Prognosis is excellent post resection

Malignant transformation is exceedingly rare

Female:Male = 2:1Peak incidence in the

fourth and fifth decades

Most common site is the vestibular nerve

Neurofibroma I Arises from nerve terminal in the dermis and large nerve trunks

Prognosis depends on the prognosis of NF1

Associated with neurofibromatosis (NF) I

Perineurioma (perineurioma, NOS; malignant perineurioma)

I–III Rare Variable

452 S.H.-Y. Chou


(continued)


Malignant peripheral nerve sheath tumor (MPNST) (epithelioid MPNST; MPNST with mesenchymal differentiation, melanotic MPNST; MPNST with glandular differentiation)

II–IV >50% occur in patients with NF1

5-Year survival is 34%; 10-year survival is 23%

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)

I–III Majority are benign More aggressive subtypes include atypical, clear cell, choroid, rhabdoid, papillary, and anaplastic

Female:Male = 3:2Common sites: cerebral

convexities, falx cerebri, olfactory groove, tentorium cerebelli, sphenoid ridge, and parasellar region

Mesenchymal Tumors

Lipoma n/a Favors midline locations BenignLumbosacral lipomas are

associated with spinal dysraphism

Angiolipoma n/a Rare BenignContains adipose tissue

and blood vesselsInvasion of surrounding

tissue is rareHibernoma n/a Derived from brown fat Benign

Very rareLiposarcoma n/a Very rare VariableSolitary fibrous tumor n/a Rare Benign

Occurs in adultsMimics meningioma

Fibrosarcoma n/a Rare, <1% of all intracranial tumors

May invade neural parenchyma

Malignant fibrous histiocytoma

n/a Tumor containing pleomorphic atypical histiocyte and fibroblast-like cells

Variable

Very rareLeiomyoma n/a Rare BenignLeiomyosarcoma n/a Rare Variable

Tumor cells express EBV in AIDS patients

Rhabdomyoma n/a Rare Variable

45328 Brain Tumors


(continued)


Rhabdomyosarcoma n/a Rare VariableResembles neuroepithelial

neoplasmChondroma n/a Commonly arises from

skull base or spineBenign

Chondrosarcoma n/a Preferentially located in petrosal, occipital, or sphenoid bones

Variable

Osteoma n/a Commonly arises from skull base or spine

Benign

Osteosarcoma n/a May occur in Paget disease VariableOsteochondroma n/a Commonly arises from

skull base or spineBenign

Hemangioma n/a Vascular malformations Benign unless they hemorrhage

Epithelioid hemangioendothelioma

n/a Very rare Variable

Hemangiopericytoma II Most CNS hemangiopericytomas occur in the meninges

Recurrence post surgery is 80%

20% have systemic metastasesOccurs in all ages; peak in

fourth to sixth decade 5-Year survival rate is slightly less than 50%

Anaplastic hemangiopericytoma

III Very rare Variable

Angiosarcoma n/a Very rare VariableKaposi sarcoma n/a Very rare Variable

Associated with AIDSEwing Sarcoma – PNET n/a

Primary Melanocytic Lesions

Diffuse melanocytosis n/a Rare VariableFrom leptomeningeal

melanocytesMelanocytoma n/a Rare BenignMalignant melanocytoma n/a Rare Malignant tumor

Must exclude metastatic disease from cutaneous melanoma

Total resection appears to improve prognosis

Meningeal melanocytosis n/a Rare Variable

Other Neoplasms Related to the Meninges

Hemangioblastoma I 1–2.5% of all intracranial tumors

Prognosis worse with post-operative recurrence or multiple hemangioblastoma

Frequently occurs in young and middle-aged persons

Commonly occurs in the cerebellum

Associated with von Hippel–Lindau disease

454 S.H.-Y. Chou


(continued)


Lymphomas and haemopoietic neoplasmsMalignant lymphoma n/a Account for <1% of

primary CNS tumor; lesions may be multiple in immunocompromised patients

Median survival is 17–45 months in immunocompetent patients and 2–6 months in immunocompromised patients

98% are B-cell lymphomas Solitary mass is associated with better prognosis

EBV virus is present in 95% of tumors in immunocompromised patients

10% of AIDS patients develop CNS lymphoma

Plasmacytoma n/a Majority evolve into systemic multiple myeloma

Not known

Granulocytic sarcoma n/a Exceedingly rare Not knownTumors of malignant white

blood cells

Germ cell tumors

Germinoma n/a CNS is second most common site for germinomas

5- and 10-year survival rates are 75–95%

10–15% have spinal cord metastasesAccounts for 60% of

pineal region tumors2–5% of all CNS

malignanciesMale:Female = 2.5:1Occurs primarily in children

and adolescentsEmbryonal carcinoma n/a Most undifferentiated

germ cell tumorPoor prognosis3-Year survival is 27.3%

a-Fetoprotein is elevated in CSF

MalignantYolk sac tumor n/a Rare Poor prognosis

Malignant 3-Year survival is 27.3%Choriocarcinoma n/a Presents with CNS

hemorrhagesPoor prognosis3-Year survival is 27.3%

MalignantTeratoma n/a Rare 10-Year survival is

70–92%Mixed germ cell tumors n/a Rare Variable, depends on the

components of the mixed cell lines

45528 Brain Tumors



Tumors of the sellar regionCraniopharyngioma

(adamantinomatous; papillary)

I Second most common neoplasm of sellar region

Recurrence is common10-Year survival rate is

68%Granular cell tumor I Most are asymptomatic BenignPituicytoma I Rare Unknown

Glial neoplasms that originate in the neurohypophysis or infundibulum

Spindle cell oncocytoma of the adenohypophysis

I Oncocytic, nonendocrine neoplasm of the anterior pituitary

Benign

Affects adults (mean age of onset is 56 years)

(continued)

Table 28.2 Genetic syndromes with associated brain tumors

Syndrome Gene Clinical manifestation Chromosome location

Neurofibromatosis I NF1 = neurofibromin

Schwannomas, astrocytomas, optic nerve gliomas, meningiomas, neurofibromas, neurofibrosarcomas

17

Neurofibromatosis II NF2 = merlin Bilateral vestibular schwannomas, astrocytomas, multiple meningiomas, ependymomas

22

Von Hippel–Lindau VHL/VHL tumor suppressor

Hemangioblastomas, pancreatic cysts, retinal angiomas, renal cell carcinomas, pheochromocytomas

3

Li-Fraumeni TP53/p53 Gliomas, sarcomas, breast cancer, leukemia

17

Turcot syndrome APC/adenomatous polyposis coli

Gliomas, medulloblastomas, adenomatous colon polyps, adenocarcinoma

5

Basal cell nevus (Gorlin) syndrome

PTCH/patched Basal cell carcinomas, medulloblastomas

9

456 S.H.-Y. Chou

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 ♦

headachesCharacteristics 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•

Syndrome Gene Clinical manifestation Chromosome location

Tuberous sclerosis TSC1; TSC2 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

9q34; 16p13.3


45728 Brain Tumors

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 prophy-•laxis 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 tissueTumors 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 processingTumors 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 dysfunctionTumors 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:

▲ AtaxiaDiplopia▲

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 hydrocephalusBrain 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 hydrocephalusUnilateral or bilateral papilloedema are signs of ICP elevation♦

Unilateral or bilateral abducens (VI) nerve palsy may represent global ICP ♦

elevation and hydrocephalusFocal 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 compres-sion of motor fibers due to elevated ICP from tumor

45928 Brain Tumors

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, pros-tate, 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 CTCT may be superior for detecting tumors that involve bone or tumors that can ♦

calcify, such as meningiomas and oligodendrogliomasMRI 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 MRSDecreased NAA signal is attributed to neuronal loss due to infiltrating •mass, and elevated choline signal is attributed to increased turnover of cell membranePET 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 ♦

meningitisCSF studies may also show elevated protein, decreased glucose, and increased ♦

opening pressure at lumbar puncture in carcinomatous meningitis

460 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 immunocom-promised 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 symptomsThough brain tumors typically cause slow progressive increase in intracranial ♦

pressure and/or cerebral edema, sudden acute ICP spikes and cerebral hernia-tion can occurSymptoms that should raise concern for rapid deterioration include those of ♦

acute ICP elevation, such as altered mental status, nausea and vomiting, papil-loedema, and cranial nerve palsiesIn particular, tumors in the posterior fossa can cause acute life-threatening ♦

deterioration from acute hydrocephalusIn 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 ♦

edemaTo 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 intakeCorticosteroids, 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 intervalsCorticosteroids 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

46128 Brain Tumors

Osmotic therapy such as mannitol and hypertonic saline solutions can be used ♦

as rescue therapy for refractory mass effect and impending cerebral herniationSurgery 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 recommendedLong-term AED are appropriate for patients with brain tumor who have suf-♦

fered an unprovoked seizureMany traditional AEDs such as phenytoin, carbamazepine, and phenobarbital ♦

have significant interaction with chemotherapeutic agentsNon-enzyme-inducing AEDs such as levetiracetam and valproic acid are ♦

preferred in patients with brain tumor who are undergoing or expected to start chemotherapyAcute-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 drainageChronic hydrocephalus may be treated with various mechanisms of perma-♦

nent CSF shunting, typically with ventriculoperitoneal, ventriculopleural, or ventriculo-atrial shuntsPermanent 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 stalkMultiple 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 osmolalityCentral 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

462 S.H.-Y. Chou

Tabl

e 28

.3

Com

mon

ant

icon

vuls

ants

Med

icat

ion

Loa

ding

dos

eC

hron

ic d

ose

The

rape

utic

leve

lM

ajor

sid

e ef

fect

s

Phen

ytoi

n15

–20

mg/

kg I

V o

r 50

0 m

g PO

× 2

–3 d

oses

100

mg

tid; t

hen

adju

st

acco

rdin

g to

ser

um

leve

l

10–2

0 mg

/mL

(co

rrec

ted

for

albu

min

and

ren

al

func

tion)

Ras

h, S

teve

ns–J

ohns

on

synd

rom

eC

ardi

ac d

ysrh

ythm

ias

Inte

ract

s w

ith m

any

drug

sH

ypot

ensi

on, e

spec

ially

dur

ing

bolu

sE

pide

rmal

nec

rosi

s if

IV

infi

ltrat

esM

yelo

supp

ress

ion

Oph

thal

mop

legi

aA

taxi

aFo

s-ph

enyt

oin

15–2

0 ph

enyt

oin-

equi

vale

nt

units

/kg

IVn/

a10

–20 mg

/mL

(co

rrec

ted

for

albu

min

and

ren

al

func

tion)

Ras

h, S

teve

ns–J

ohns

on s

yndr

ome

Mye

losu

ppre

ssio

nO

phth

alm

ople

gia

Ata

xia

Lev

etir

acet

am1,

000–

2,00

0 m

g IV

× 1

500–

1,50

0 m

g bi

dN

ot d

efin

edA

gita

tion

Val

proi

c ac

id15

–20

mg/

kg I

V o

r

500

mg

PO ×

2–3

dos

es25

0–1,

000

mg

PO/I

V b

id/ti

d50

–100

mg/

mL

Hyp

eram

mon

emia

Plat

elet

dys

func

tion

Enc

epha

lopa

thy

Tre

mor

Panc

reat

itis

Low

est r

isk

for

rash

Thr

ombo

cyto

peni

aPh

enob

arbi

tal

15–2

0 m

g/kg

IV

50–1

00 m

g PO

bid

or

tid25

–40 mg

/mL

Seda

tion

Enz

yme

indu

ctio

nH

epat

itis

Hyp

oten

sion

Res

pira

tory

dep

ress

ion

46328 Brain Tumors

Car

bam

azep

ine

Non

eSt

art 2

00 m

g bi

d; m

ay

titra

te u

p to

600

mg

bi

d

8–12

mg/

mL

Mye

losu

ppre

ssio

nR

ash

Hyp

onat

rem

iaE

nzym

e in

duce

rA

taxi

a SI

AD

H/h

ypon

atre

mia

Lam

otri

gine

(no

t ap

prop

riat

e fo

r ac

ute

use;

mus

t tit

rate

upw

ard

slow

ly o

ver

6

wee

ks)

Can

not l

oad

this

dru

g!D

epen

ds o

n ot

her

co

ncom

itant

m

edic

atio

ns

Not

def

ined

Ris

k of

ras

h is

hig

her

in p

atie

nts

with

bra

in tu

mor

, par

ticul

arly

af

ter

wea

ning

off

of

ster

oids

po

st-r

adia

tion.

Int

erac

ts w

ith

valp

roic

aci

d, w

hich

inhi

bits

la

mot

rigi

neTo

pira

mat

eno

neSt

art 5

0 m

g bi

d; ti

trat

e

up to

400

mg

bid

Not

def

ined

Wea

k en

zym

e in

duce

rK

idne

y st

ones

Aci

dosi

sE

ncep

halo

path

yG

abap

entin

No

load

Star

t 300

mg

tid; t

itrat

e

up to

1,5

00 m

g–

2,40

0 m

g di

vide

d tid

Not

def

ined

Seda

tion

Myo

clon

us

Preg

abal

inN

o lo

adSt

art 7

5–30

0 m

g bi

d; m

ay

titra

te u

pwar

dN

ot d

efin

edA

ngio

edem

aSe

datio

nM

yocl

onus

Tri

lept

alN

o lo

adSt

art 3

00 m

g bi

d; m

ay

titra

te u

pwar

d to

90

0 m

g bi

d

Not

def

ined

Wea

k en

zym

e in

duce

rM

ay d

isqu

alif

y pa

tient

s fr

om s

ome

chem

othe

rape

utic

tria

lsH

ypon

atre

mia

Zon

isam

ide

No

load

Star

t 100

mg

q d;

may

tit

rate

upw

ard

to

300

mg

q d

Not

def

ined

Aci

dosi

sE

ncep

halo

path

ySt

even

s–Jo

hnso

n sy

ndro

me

Lac

osam

ide

No

load

Star

t 50

mg

po o

r IV

bid

, tit

rate

up

to 1

00–2

00 m

g bi

d

Not

def

ined

Firs

t deg

ree

A-V

blo

ck –

nee

d to

m

onito

r PR

inte

rval

on

EK

G;

Atr

ial f

ibri

llatio

n.

464 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 fatalMalignant 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) injectionDiagnostics for VTE include compression duplex ultrasonography for deep ♦

venous thrombosis, pulmonary VQ scan, and high-resolution chest CT angiography for pulmonary emboliMost patients with brain tumor with VTE can be treated with long-term sys-♦

temic anticoagulation therapyLow molecular weight heparin (LMWH) is twice as effective as warfarin in ♦

preventing recurrent VTE in brain tumor patients without any difference in hemorrhagic riskContraindications to systemic anticoagulation may include recent neurosur-♦

gery, chemotherapy-induced thrombocytopenia, hemorrhagic brain tumor, and other systemic or intra-cerebral hemorrhagic conditionsPlacement 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 resectionDecision regarding maximal resection vs. biopsy depends on tumor location, ♦

size, type, and patient’s medical condition

46528 Brain Tumors

For metastatic brain tumors♦

Surgical resection should be considered for patients with single metastasis •in an acceptable location who have a reasonable life expectancyRole 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 syndromesTemozolomide is a common chemotherapeutic agent in glioma patients; it ♦

causes mild myelosuppression and gastrointestinal distressSome 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 weeksWhole 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 associ-•ated 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 fatiguePeritumor cerebral edema may worsen during and following XRT♦

Incidence of radiation necrosis is 3–5% and increases with patient survival ♦

after XRTLong-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

466 S.H.-Y. Chou

Table 28.4 Chemotherapeutic agents and common side effects

Agent Treatment Side effects

Nitrosoureas: carmustine (BCNU); lomustine (CCNU)

Primary brain tumors, multiple myeloma, lymphoma

Subacute or chronic encephalopathy

SeizureLethargyLeukoencephalopathyRetinopathy and blindnessWorsening focal neurological

deficitsProcarbazine Primary brain tumors,

Hodgkin disease, systemic lymphoma

MAO inhibitor; CNS depression and acute hypertension may occur with tyramine-rich foods

Lethargy, depression, confusion, hallucinations, agitation, and psychosis

Peripheral neuropathy (20%)Thiotepa Leptomeningeal disease Encephalopathy and cognitive

impairmentMyelopathy (rare)

Cisplatin CNS tumors, testicular, lung, ovarian, head and neck, and many other tumors

NephrotoxicityPeripheral sensory

neuropathyAutonomic neuropathyDorsal root ganglionopathyEncephalopathyRetrobulbar neuritis and

retinopathySeizuresTransient cortical blindnessOtotoxicityStrokeMyasthenic syndrome

Carboplatinum Similar to cisplatin Least neurotoxicRare ototoxicity and

blindnessSensory neuropathy

Cyclophosphamide Lymphoma; leukemia, breast, ovarian, lung, and bladder cancers, and others

ConfusionSIADHHemorrhagic cystitis

Cytarabine liposome injection Lymphomatous meningitis

ArachnoiditisConfusion

Temozolomide Recurrent glioma; melanoma

SeizuresEncephalopathyMyelosuppression

(continued)

46728 Brain Tumors

Key Points

Clinical presentation of brain tumors depends on tumor location, presence of ■

ICP elevation from tumor bulk, associated cerebral edema and/or hydrocepha-lus, endocrine dysfunction, cranial nerve palsies, and seizuresMain treatment modalities for brain tumors include surgical resection, steroids, ■

chemotherapy, and XRTTreatment is individualized, taking into account the location, type, and histo-■

logic grade of tumor, as well as general patient characteristicsPrognosis 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):13–160Norden 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):1–16Smith 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


Agent Treatment Side effects

Thalidomide Primary brain tumors, breast cancer, Kaposi sarcoma, renal carcinoma, melanoma, multiple myeloma, and others

Peripheral neuropathyEncephalopathy and somnolence

Vincristine Primary brain tumors, leukemia, lymphoma, Kaposi sarcoma


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 developedDefined as ■ dilation of cerebral ventricles

Epidemiology

Hydrocephalus affects one in every 500 live births, making it one of the most ■

common birth defectsIs 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, reab-■

sorption, 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

Chapter 29Hydrocephalus

Michel T. Torbey

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]

470 M.T. Torbey

subarachnoid 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 hydrocephalusCaused 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 granu-•lations, 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 pressureDiagnosis 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 valuesDynamic compliance studies may also be helpful♦

Noncommunicating hydrocephalus■

Also known as ♦ obstructive hydrocephalusCaused 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 ventriclesAqueduct 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 ventricleFourth ventricle obstruction will lead to dilatation of the aqueduct, as well •as the lateral and third ventricles

47129 Hydrocephalus

Subarachnoid space surrounding the brainstem may also be obstructed due •to inflammatory or hemorrhagic fibrosing meningitis, leading to wide-spread 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 NPHFocal 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▲

Dilated cerebral ventriclesN

Bowing of third ventricle if under pressureN

Fourth ventricle is dilated in communicating hydrocephalusN

Absence of fourth ventricular dilation is suggestive of noncommu-N

nicating hydrocephalus

MRI findings▲

Dilated ventriclesN

Increased T2-weighted signal in periventricular area, signifying N

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▲

472 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. 29.1If 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 monitoringDrainage trial

10 mL/hr

B-waves, plateau wavesNear plateau waves

Yes No

Responded to CSFdrainage trial

NoYes

Shunt surgery

No surgeryContinue medical RxConsider repeat monitoring

in few months

Fig. 29.1 Algorithm for shunt placement in suspected NPH patients. CSF cerebrospinal fluid; Rx prescription

47329 Hydrocephalus

advised to keep pop-off at 15–20 mmHg and only drain if ICP is elevatedAs 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 consideredSystems are generally either ventricle to peritoneal (VP) or lumbar to peri-•toneal (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

474 M.T. Torbey

Key Points

Hydrocephalus is a common accompaniment of acute brain injury■

Communicating vs. noncommunicating hydrocephalus must be distinguished by ■

neuroimaging techniquesIn noncommunicating hydrocephalus, an external ventricular drain, rather than ■

a lumbar drain, should be placedIt 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 12:661–684Maramarou 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 22:2–3Pattisapu J (2001) Etiology and clinical course of hydrocephalus. Neurosurg Clin N Am

12:651–659Relkin N, Marmarou A, Klinge P et al (2005) Diagnosing idiopathic normal pressure hydrocephalus.

Neurosurgery 57:S4–S16Suarez-Rivera O (1998) Acute hydrocephalus after subarachnoid hemorrhage. Surg Neurol

49:563–565

475

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 neuro-muscular weakness may benefitAvoid 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 fea-♦

tures [Guillain–Barré Syndrome (GBS), Lambert–Eaton, botulism], be prepared for excessive heart rate and blood pressure response to induction agentsConsider early tracheostomy in patients with prolonged expected recovery ♦

(GBS, tetanus, botulism)

Chapter 30Neuromuscular Disorders

Jeremy D. Fields and Anish Bhardwaj

J.D. Fields, MD Department of Neurology, Oregon Health & Science University, Portland, OR, USA



476 J.D. Fields and A. Bhardwaj

Diagnostic studies that may be helpful■

Blood work – basic chemistries, CK, lactate, auto-antibodies associated with ♦

muscle disease, myasthenia gravis, or paraneoplastic syndromesLumbar puncture♦

Electromyogram (EMG)/nerve conduction studies; specialized testing may ♦

include nerve conduction studies of the phrenic nerve and EMG of the dia-phragm, repetitive nerve stimulationMuscle biopsy or nerve biopsy♦

Comprehensive ICU care■

Prophylaxis for deep vein thrombosis (DVT)♦

Bowel prophylaxis (antacids, H♦2 antagonists)

Control of hyperglycemia♦

Adequate fluid balance (insensible losses increased in diseases with auto-♦

nomic 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 cmH♦

2O;

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♦

47730 Neuromuscular Disorders

Assessment of autonomic function■

Systemic/cutaneous – absent sweating or lacrimation, unreactive pupils, con-♦

stipation, urinary retentionHemodynamic – orthostatic hypotension, blood pressure lability, heart rate ♦

either labile or abnormally constant, dysrhythmia


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 casesSymmetric quadriparesis, classically beginning in legs, affecting both proxi-♦

mal and distal musclesCorrelation with ♦ CampylobacterParesthesias 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•


Table 30.1 Neuromuscular causes of acute generalized weakness

Localization Disease

CNS Diseases with bilateral hemispheric injuryDiseases of the brainstemDiseases of the spinal cord

Motor neuron Motor neuron diseaseWest Nile virus infectionPoliomyelitisOther enteroviruses

Neuromuscular junction Myasthenia gravisLambert–Eaton myasthenic syndromeOrganophosphate poisoningBotulismTick paralysisHypermagnesemiaSnake/insect/marine toxins

Neuropathies Guillain–Barré syndromeCritical illness polyneuropathyChronic idiopathic demyelinating polyneuropathyToxic neuropathiesVasculitic neuropathyPorphyric neuropathyDiphtheriaLymphomaCarcinomatous meningitisAcute uremic polyneuropathyEosinophilia-myalgia syndrome

Myopathies Critical illness myopathyDermatomyositisPolymyositisPeriodic paralysis/hypokalemic myopathyMyotonic dystrophyAcid maltase deficiencyMuscular dystrophiesMitochondrial myopathiesCorticosteroid-induced myopathy

Table 30.2 Neuromuscular causes of acute respiratory muscle weakness


CNS Diseases of high cervical cord or medullaMotor neuron Motor neuron diseaseNeuromuscular junction Myasthenia gravis

Lambert–Eaton myasthenic syndromeNeuropathies Idiopathic bilateral phrenic nerve paresis

Guillain–Barré syndrome (rare)Neuralgic amyotrophyLarge artery vasculitisMultifocal motor neuropathy

Myopathies Acid maltase deficiency


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 sig-•nificant motor or sensory deficit in the limbsAccurate anatomic lesion sites and pathogenesis are still unknown•Associated with GQ1b or GT1a•

Table 30.3 Causes of acute predominantly bulbar weakness


CNS Brainstem diseasesBilateral white matter diseasesSyrinx

Motor neuron Amyotrophic lateral sclerosisKennedy disease

Neuromuscular junction Myasthenia gravisLambert–Eaton myasthenic syndromeBotulism

Neuropathies Guillain–Barré syndrome (rare)Carcinomatous meningitisSkull base tumor or metastasesMiller–Fisher diseaseSarcoidosisBasilar meningitis

Myopathies DermatomyositisPolymyositisOculopharyngeal muscular dystrophyMyotonic dystrophyDistal myopathy with vocal cord paralysis

Table 30.4 Causes of acute failure of the autonomic nervous system


CNS Diseases affecting the hypothalamus, brainstem/medulla/high cervical cord

R insular strokeNeuromuscular junction Lambert–Eaton myasthenic syndrome

BotulismNeuropathies Diabetic autonomic neuropathy

Amyloid neuropathyGuillain–Barré with predominant dysautonomiaParaneoplastic dysautonomiaAssociated with connective tissue disorders

SjogrensSLEInfectiousChagasHIVLeprosyDiphtheria


Electrophysiology■

Early – F waves are normal very early; then, prolonged♦

Later – prolonged distal motor latencies and increased duration/polyphasia of ♦

distal compound muscle action potentialsIn 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 cmH•2O; decline in FVC or NIF >30%

in 24 hClinical 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 cmH•2O; PaO

2 <70; decrease >50% in 24 h

Hypoventilation (PaCO•2 >45 or significantly increasing) or hypoxia (PaO

2

<70 on room air)

Dysphagia♦

Aspiration•Severe bulbar dysfunction/bilateral facial weakness•


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 preferredHypotension – treat with fluids before considering pressors; phenylephrine •is pressor of choice, as primary problem is peripheral vasodilationHypertension – treat only extremes of blood pressure; consider nicardipine •or sodium nitroprusside (peripheral vasodilators)Maintain positive fluid balance, as insensible losses are often markedly •increasedMonitor 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 cmH•

2O

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 extubationSecretions 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)


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 diagnosisSuggestions 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)

Table 30.5 Drugs that inhibit transmission across neuromuscular junction


Antibiotics AminoglycosidesTrimethoprim/sulfamethoxazoleTetracyclinesClindamycinCarbapenemsNeomycin/colistin

Cardiovascular QuinidineProcainamideDiltiazemVerapamilb Blockers

CNS PhenytoinCarbamazepineDiazepamMorphine

Other d-PenicillamineInterferon aNeuromuscular blockersCorticosteroidsMagnesiumLithium


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, bradycardiaIf 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 cmH♦2O; rapid decline in PFTs

Hypoventilation (pCO♦2 >45 or significantly increasing) or hypoxia (pO

2 <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 dis-ease; in patients either intubated or at risk for intubation, these medications increase secretions, have variable oral absorption, increase weakness in over-dose, and are therefore usually withheld in myasthenic crisisCorticosteroids (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 therapyPlasma exchange (five 1-volume exchanges q day or qod) is equivalent to ♦

IVIG (0.4 mg/kg q day × 5 days) but may work fasterObtain chest CT to rule out thymoma♦

Weaning criteria■

FVC >10 mL/kg or NIF >–20 cmH♦2O

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 failureCritical illness neuropathy and myopathy frequently overlap; therefore, the ♦

term ICU-acquired weakness is sometimes used


Risk factors♦

Vastly increased risk of critical illness myopathy with combination of corti-•costeroids (usually high dose and prolonged) and neuromuscular blockersIncreased risk of critical illness myopathy and neuropathy in sepsis/sys-•temic inflammatory response syndrome, trauma, and multiorgan failureHyperglycemia•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 myopathyRecovery may be prolonged and incomplete♦

Clinical features of critical illness myopathy■

Persistent moderate or severe generalized weakness, with decreased tone and ♦

eventual atrophyProximal ♦ 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 latenciesMuscle biopsy is myopathic, with findings of muscle fiber atrophy (predomi-♦

nantly type II), occasional fiber necrosis, and decreased myofibrillar adenos-ine triphosphatase staining (corresponding to loss of myosin filaments) with a relative absence of inflammatory cellsRecovery 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 holi-days, and optimal nutrition


Intensive glucose control may decrease the incidence of these diseases; there-♦

fore, aggressive glucose control is likely warranted in affected patientsAssociated with prolonged ventilation time♦

Complete recovery in ~2/3 of patients♦

Prolonged Neuromuscular Blockade

Defined as prolonged neuromuscular blockade after administration of neuro-■

muscular blocking agents; may be prolonged for hours to as much as 40 daysPrimarily 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 CNSIncubation period typically ~1 week♦

Physical exam♦

Trismus (lockjaw) is initial symptom in 50–75%•Risus sardonicus (facial muscle contraction) common•


Nuchal rigidity, board-like abdomen, periods of apnea and dysphagia•As disease spreads, generalized muscle spasms occur either spontaneously •or triggered by sensory stimuliCranial nerve palsies only in cephalic tetanus: VII >> VI > III > IV > XII•Hyperadrenergic state with sweating, tachycardia, and hypertension are •commonSpatula test (94% sensitivity, 100% specificity)•

Insert spatula into oropharynx▲

Patient gags/tries to expel spatula ▲ → normalPatient 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 infec-•tion suspected

Antitoxin and immunization♦

Human tetanus immune globulin 3,000–6,000 U given as soon as disease •suspectedTetanus diphtheria toxoid administered q 2 weeks for three total doses•

Muscle spasms♦

Sedatives – benzodiazepines (midazolam, lorazepam, diazepam) often •effectiveBaclofen 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 dys-•autonomia, inability to protect airwayEarly tracheostomy decreases laryngospasm compared with endotracheal •tube


Botulism

Pathophysiology and clinical features■

Caused by neurotoxin of ♦ Clostridium botulinum, which blocks presynaptic release of acetylcholine at the neuromuscular junctionStereotypical 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 foodsWound botulism – most common in heroin users who “skin pop”; also •present in dusty areas such as construction sitesInfant 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•

Normal sensory studies and motor conduction velocities▲

Decremental response to repetitive nerve stimulation▲

Post-tetanic facilitation▲

Increased brief polyphasic motor unit action potentials and spontane-▲

ous denervation potentials

Treatment■

Primarily supportive♦


Antitoxin sometimes used if disease is detected early♦

Administer test dose subcutaneously•Decreased anaphylaxis (<1%) in patients given only one vial•

Key Points

Neuromuscular diseases frequently present with respiratory failure requiring ■

cardiopulmonary supportDiagnosis is made following careful elicitation of history of illness, pattern of ■

weakness, physical examination and ancillary laboratory diagnostic testsDysautonomia is a common accompaniment of neuromuscular disorders■

Treatment in ICU involves immunomodulatory therapies, cardiopulmonary sup-■

port, and prevention of systemic infectionEarly 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;1541–1549Sobel J (2005) Botulism. Clin Inf Dis 41:1167–1173

489

Definition

■ A seizure that persists for a sufficient length of time or is repeated frequently enough to produce a fixed and enduring epileptic conditionDistinct seizure phenomenon – not simply a prolonged seizure; status epilepti-■

cus (SE) represents a reconfiguration of excitatory and inhibitory networks within the brainHistorically, experts in the field arbitrarily defined SE as unremitting seizures for ■

a specific duration of 30 minSubsequently, 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

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 non-■

convulsive type, which are only diagnosed by concurrent EEGSE represents only 0.2% of ICU admission diagnoses; most hospital cases occur ■

post-admissionIn 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

Chapter 31Status Epilepticus

Marek A. Mirski

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]


490 M.A. Mirski

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 ♦

prolongedBy 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♦

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 featuresOther terms within NCSE: complex-partial SE, subtle SE, non–tonic-clonic ♦

SE, subclinical SEHallmark 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 under-recognizedRecent trend is to assign label of NCSE to severe anoxic/ischemic encephal-♦

opathy when EEG spikes are present

Anatomy of SE

Partial or focal SE■

Single focus with local spread; often occur in brain regions with previous ♦

injuryEEG 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” generalizationSuch seizures spread via cortical networks or cortical–subcortical circuits•“Primary” generalized seizures (e.g., absence) probably utilize brainstem/•subcortical structures in mediation and propagation

49131 Status Epilepticus

Etiologies of Seizures and SE

Neurologic (cortical) injury■

Possible causes of seizures include primary pathology in the patient or iatro-♦

genic causesRegarding etiology of SE on admission to hospital, ♦ anticonvulsant non-compliance, alcohol withdrawal, and other drug toxicity are most com-mon precipitants per data obtained during the 1980s and more recently (Table 31.1)Primary neurologic disorders that have cortical involvement carry an appre-♦

ciable 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 Non-primary pathologyNeurovascular Hypoxia/ischemia

Stroke Drug/substance toxicityArteriovenous malformations AntibioticsHemorrhage Antidepressants

Tumor AntipsychoticsPrimary BronchodilatorsMetastatic Local anesthetics

CNS infection ImmunosuppressivesAbscess CocaineMeningitis AmphetaminesEncephalitis Phencyclidine

Inflammatory disease Drug/substance withdrawalVasculitis BarbituratesAcute disseminated encephalomyelitis Benzodiazepines

Traumatic head injury OpioidsContusion AlcoholHemorrhage Infection fever (febrile seizures)

Primary epilepsyPrimary CNS metabolic disturbance (inherited)

Metabolic abnormalitiesHyponatremiaHypophosphatemiaHypoglycemiaRenal/hepatic dysfunctionSurgical 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

492 M.A. Mirski

Such incidence likely under-reports true risk; with EEG monitoring, true ♦

incidence of NCSE may be doubledHighest reported incidence of seizures/SE following TBI is associated with ♦

depressed skull fracture, intracerebral hematoma, or subdural hematomaPoorer 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 ageFollowing 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 ageEarly 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 treatedOverall risk of seizures post-stroke is 2–3 times higher following intracere-♦

bral hemorrhage (ICH) than following ischemic stroke; some reports suggest >25% risk of EEG-detected seizures after ICHAs expected, cortical (lobar) localization of ICH is associated with much ♦

higher seizure risk than is hemorrhage in basal ganglia or thalamic or poste-rior fossa

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

Table 31.2 Risk of seizures from specific neuropathologies

Pathology Risk Conditions that exacerbate risk

Stroke 6–12% HemorrhagicLarge cortical involvementAcute confusional state

Intracranial tumor >25% Cortical – primaryCortical – metastatic

Traumatic head injury ³4% Cerebral contusionAcute SDHDepressed skull fracturePenetrating missile injuryEvacuation/chronic SDH

Adapted from Mirski MA, Varelas PN (2008) Seizures and status epilepticus in the critically ill. Crit Care Clin 24(1):115–47, ixSDH subdural hematoma


Commonly, re-rupture of the aneurysm may manifest by an early post-SAH ♦

seizureCoiling 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 ♦

manifestationRecurrent 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) dependentSlower growing, lower grade neoplasms (astrocytomas, meningiomas) have ♦

higher reported risk (50–70%); 90% reported for oligodendrogliomas in patient seriesHigh-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 conditionParticular 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

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 sodiumUp to 15% of hospital-based seizures are linked to alcohol or medication toxic-■

ity, and such seizures can commonly transition to SEIncidence 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 glutamater-gic systemAlcohol-withdrawal seizures are typically generalized tonic-clonic convulsions, ■

often leading to SE; they occur within first 48 h, preceding development of delirium tremens

494 M.A. Mirski

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 SEAntibiotics are most common group associated with seizures, especially the ■

penicillins and cephalosporins, due to b-lactam group (1–6% overall risk, high-est for imipenam)Proconvulsants – aztreonam, fluoroquinolones, isoniazid, metronidazole – all ■

antagonize the action of GABANext highest risk for seizures – psychotropic group, especially the antidepres-■

sants (0.1–4%)Serotonin selective re-uptake inhibitors have lowest incidence, as do trazodone, ■

doxepin, and monoamine oxidase inhibitorsMedium-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 disinhibitionAs a consequence, ■ the longer the duration of SE, the more difficult it is to terminate


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 ♦

evidence suggests that permanent morbidity has been attributed to this form of SEThus, 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 reportedIn hospitalized patients – certainly in the ICU – the diagnosis of NCSE is ♦

usually associated with moderate to severe cerebral injury, similar to follow-ing an anoxic-ischemic event or traumaAssociating the effects of NCSE with direct neuronal injury is difficult in this ♦

setting, although most epileptologists agree that in such scenarios, the pres-ence of continuous paroxysmal activity may accentuate injury incurred by the primary insultTherefore, it is prudent to attempt therapy as rapidly as is feasible♦

Monitoring

■ EEG is critical in correctly diagnosing SE and in monitoring therapeutic response; EEG seizures often persist following effective termination of convul-sive 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

Table 31.3 Associated complications of GCSE

SystemicAcidosisHyperthermiaRhabdomyolysisRenal failureDysrhythmiasTraumaImpaired V/Q matchingPneumonia

NeurologicDirect excitotoxic injuryEpileptogenic fociSynaptic reorganizationImpaired protein synthesis

496 M.A. Mirski

Typical EEG Presentation of GCSE and NCSE (Table 31.4)

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 seizureSuch a perspective would necessitate treating PLEDs, even if not coincident ■

with recognizable classic EEG ictal periodsRegardless, 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

Fig. 31.1 Example of complex-partial SE (CPSE) over left hemisphere, predominantly temporal-parietal region, with large amplitude, rhythmic discharges. (From Kaplan PW. The EEG of Status Epilepticus, with permission)


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 moni-toring is enabledSimilarly, residual epileptiform activity may be evidence for NCSE■

■ For ongoing SE, EEG (preferably continuous) is mandatory to ensure effective treatment

Fig. 31.2 Example of NCSE, displaying generalized rhythmic sharp-wave discharges; the pat-terns 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

498 M.A. Mirski

Commonly, convulsive SE is incompletely treated and is associated with residual ♦

subtle convulsive SE or NCSE, despite cessation of motor ictal activitySome 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

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 criteria3. 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 frequency3. Post-discharge slowing or voltage attenuation4. 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 gen-eralized nature of dysfunction (From Kaplan PW. The EEG of Status Epilepticus, with permission)


Treatment

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 investigatedNevertheless, 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 ♦

the rational first-line agent for the treatment of seizures that can be classi-fied as SEAlthough one well-conducted study supports the drug lorazepam as most ♦

efficacious, the three commonly used BDZ – lorazepam, midazolam, diaze-pam – all are effective in appropriate dosesAdvantage of lorazepam is its long clinical duration of plasma concentra-♦

tion and action (t½, 15 h) secondary to its high water solubility and slow eliminationDiazepam 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 administeredMidazolam is also lipophilic, very brief in action, yet rapidly metabolized, ♦

yielding more consistent correlation between dosage and clearanceHence, 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 existsIV 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 Elimination time (t½, h)Recommended dosage range (mg/kg)

Lorazepam 15 0.05–0.1Midazolam 2–4 0.05–0.2Diazepam 20 0.1–0.4

500 M.A. Mirski

Phenytoin (PHT), fosphenytoin (fPHT), and sodium valproate (VPA) are ♦

common selectionsAlthough similar in parent compound, fPHT is a phosphate ester pro-drug ♦

of PHTfPHT 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 compoundWhen 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)

As new anticonvulsants become available, their utility in treating refractory ■

seizures and possibly SE is evaluated, if only superficiallyLevetiracetam (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 managementDue 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 suppressionBecause 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 antagonismHence, BDZ remain the first-line therapy, and PHT and other agents may offer ■

little added benefit

Table 31.7 Second-line therapy for SE

Anticonvulsant Dosage Target serum level (mg/mL)

Phenytoin 15–20 mg/kg 15–20Fosphenytoin 15–20 mg/kg PE 15–20Valproate 15–20 mg/kg 50–100


Table 31.8 Medical and pharmacologic treatment of SE

Initial management

Preserve airway and oxygenation by intubation; order EEG to be available during therapyMeasure finger-stick blood glucose and administer IV glucose if <40–60 mg/100 dLImmediate benzodiazepines: 5–10 mg lorazepam IV, 20–40 mg diazepam, or 5–20 mg

midazolam over 5 minPHT 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/dLContinuous EEG if availableIf seizures continue, PHT or fPHT (additional 5–10 mg/kg or 5–10 mg/kg PE); goal serum

level, 20–25 mg/dLOption: 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 tried5–10 mg/kg pentobarbital, followed by 1–10 mg/kg/h is common recipe for long-term burst-

suppression requirementRecommend 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 attemptNot 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 YesGabapentin YesFelbamatea Yes YesTopiramate YesTiagabine YesVigabatrinb Yes YesLevetiracetam Yes Yesa Restricted use due to aplastic anemiab Not available in US

502 M.A. Mirski

In refractory cases or in other drug overdose states, hemodialysis is a viable ■

therapeutic optionSeveral more common drug offenders and potential treatment strategies are ■

listed in Table 31.10

Drug Interactions

Anticonvulsant drug interactions may complicate therapy for refractory SE when ■

no single agent is able to control the seizures and poly-pharmacy is requiredUsually this occurs when weaning from EEG-suppressive therapy (barbiturates, ■

propofol, etc.) is undertakenThe 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 sys-■

tems or alter serum protein binding, thereby disturbing the kinetics of other agentsThe common known cross-effects of anticonvulsants are listed in Table ■ 31.11Similarly, anticonvulsants may interact with common drugs used in the ICU ■

setting, where patients treated for SE are commonly managedThe 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

Antibiotics – penicillins, b-lactams, fluoroquinolones

Benzodiazepines, hemodialysis

Theophylline Midazolam, hemodialysisIsoniazid IV Pyridoxine

Table 31.11 Alterations in drug plasma levels with combination anticonvulsants

Added drug

Effect on plasma levels of primary agents

% 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; ~, variablea↑ Free DPH levelbEpoxide


Key Points

GCSE is rapidly assessed and treated to prevent further primary and secondary ■

brain injury, systemic manifestations of muscle convulsive activity, and risk of cardiopulmonary complicationsIntubation is suggested, as nearly all AEDs have sedative effects, compounding ■

coma from SETreatable causes of SE should be identified early■

An algorithm should be followed with sequential drug administration for persis-■

tent SENCSE 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 11:117–120Bleck TP (2007) Intensive care unit management of patients with status epilepticus. Epilepsia

48(Suppl 8):59–60Brenner RP (2002) Is it status? Epilepsia 43(S3):S103–S113Brenner RP (2004) EEG in convulsive and non-convulsive status epilepticus. J Clin Neurophysiol

21:319–331Coulter DA, DeLorenzo RJ (1999) Basic mechanisms of status epilepticus. Adv Neurol

79:725–733Kaplan 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 23:221–229Lowenstein DH (2006) The management of refractory status epilepticus: an update. Epilepsia

47(Suppl 1):35–40Nuwer M (2007) ICU EEG monitoring: non-convulsive seizures, nomenclature, and pathophysiology.

Clin Neurophysiol 118:1653–1654Treiman DM et al (1998) A comparison of four treatments for generalized convulsive status

epilepticus. NEJM 339:792–798Varelas PN, Mirski MA (2004) Management of seizures in critically ill patients. Curr Neurol

Neurosci Rep 4:489–496Varelas PN, Mirski MA (2007) Treatment of seizures in the neurologic intensive care unit. Curr

Treat Options Neurol 9:136–145Wasterlain CG, Fujikawa DG, Penix L, Sankar R (1993) Pathophysiological mechanisms of brain

damage from status epilepticus. Epilepsia 34 (S1):S37–S53

Table 31.12 Effects of anticonvulsants on commonly used medications

Added drug

Effect on plasma levels or clinical effectiveness of primary agents

Warfarin Theophylline Steroids Haloperidol Lithium

PHT ↓ ↓ ↓PB ↓ ↓ ↓ ↓CBZ ↓ ↓ ↓ ↓ ↑PHT phenytoin; PB phenobarbital; CBZ carbamazepine; ↓ decrease; ↑ increase

505

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 ♦

extremitiesOverall 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 arrestMortality 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 diseaseRate of recurrent VTE on anticoagulation is <5% (30% after 10 years)♦

PE occurs in ~15% of patients with central venous catheter-related upper-♦

extremity 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♦

Chapter 32Deep Venous Thrombosis and Pulmonary Embolism

Wendy C. Ziai

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]


506 W.C. Ziai

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 onsetMost important risk factor is low Barthel Index score•Antiplatelet drugs decrease incidence of PE but do not affect risk of DVT•

0 10 20 30 40 50 60 70 80

Prevalence (%)

Critical Care Patients

Spinal Cord Injury

Major Trauma

Hip/Knee Surgery

Stroke

Neurosurgery

Urologic/Gyne Surgery

General Surgery

Medical Patients

Prevalence of VTE in Hospitalized Patients (%)

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

50732 Deep Venous Thrombosis and Pulmonary Embolism

♦ 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 VTEAntiphospholipid 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♦

508 W.C. Ziai

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)

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■


Diagnostic Tests

D-dimer■

Degradation products of cross-linked fibrin♦

D-dimer assays rely on monoclonal antibodies to bind to this specific protein ♦

fragmentQuantitative 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 ageCauses 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 veinNegative-predictive value (NPV) – 98% in a symptomatic patient with full ♦

compressibility of both sitesLess 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 casesNormal 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

Contrast venography■

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 work-♦

up if negative duplex US of lower extremitiesIntermediate 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 outcomesNegative 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 radiationMeasures 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♦


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 testsWells 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 comorbiditiesWells 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 optionLow 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

Clinical probabilityWells score for DVT diagnosis

Wells score for PE diagnosis

Low £0 0–1Intermediate 1–2 2–6High ³3 ³7

512 W.C. Ziai

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 treatmentIf CTA is positive (PPV 58%)•

Main or lobar PE (PPV 97%) ▲ → TreatSegmental PE (PPV 68%) or Subsegmental PE (PPV 25%) ▲ → Proceed to other options

Repeat CTA if poor qualityN

Doppler US (or MRI venography), serial USN

Table 32.2 Wells prediction rule for diagnosing DVT

Clinical feature Score

Active cancer 1Paralysis, paresis, recent immobilization 1Immobilized >3 days or surgery in past 4 weeks 1Tenderness along deep venous system 1Entire leg swollen 1Calf swelling >3 cm vs. other side 1Pitting edema of symptomatic leg 1Collateral superficial veins 1Alternative 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 3.0HR >100/min 1.5Immobilized ³3 days or surgery in past 4 weeks 1.5Prior PE or DVT 1.5Hemoptysis 1.0Cancer (6 months) 1.0PE 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 embo-lism. Am J Med 113:269–275


V/Q scanN

Pulmonary angiogramN

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%) • → TreatIf CTA is negative (NPV 60%)•

Proceed to other options▲

Repeat CTA if poor qualityN

Doppler US (or MRI venography), serial USN

V/Q scanN

Pulmonary angiogramN

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 ambulatoryLow-molecular-weight heparin (LMWH) or low-dose unfractionated heparin ♦

(UFH) should be used in combination with mechanical prophylaxisLMWH 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 dose-dependent bleeding risk existsUFH – (♦ £6,000 IU/day or weight-adjusted £86 IU/kg/day)

514 W.C. Ziai

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 bleedingAfter confirmed DVT (in patients with contraindication to anticoagulation), ♦

LMWH recommended as prophylaxis to prevent PE (in addition to consider-ation 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 ICHProphylaxis 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 dosingRandomized trials support use of LMWH or fondaparinux for symptomatic ♦

PE and for DVTIn patients with cardioembolic transient ischemic attack, ischemic stroke, ♦

anticoagulants increase risk of major ICH, especially in first 2 weeksDecision to start anticoagulant treatment should be determined on an ♦

individual basis in patients with intracranial vascular pathologySubsegmental 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 CNSIV heparin infusion – 18 IU/kg/h•


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 emboliLess 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 injectionOnce-daily subcutaneous dosing without anticoagulation monitoring•Potentially lower risk of heparin-induced thrombocytopenia than with •LMWHMore 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 therapyHeparin, 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

516 W.C. Ziai

In only one study (cancer patients with normal Cr), LMWH group had •lower recurrence rate of DVT than did those in warfarin group; other stud-ies showed no differenceBleeding rates in all LMWH groups were similar or below rates in oral •anticoagulant groupLMWH may be useful for patients in whom INR control is difficult and •may be more efficacious in patients with cancerFull 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 factorRecurrent DVT risk decreases stepwise as duration of anticoagulation •increases from 3 to >12 months with INR 2–3Incidence 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 •normalWarfarin 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)•


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 PERecommended 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 •therapyMassive PE (where additional emboli may be fatal)•

No randomized trials demonstrate clear benefit of IVC insertion in trauma ♦

patientsIVC 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 murmurSBP 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 shockSubmassive PE Hemodynamically stable patient with right ventricular dysfunctionNonmassive PE Hemodynamically stable patient with normal right ventricular function

518 W.C. Ziai

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 PaO•2 (<80 Torr)

Respiratory alkalosis (tachypnea); acidosis (dead space)•Higher median alveolar-arterial (A-a) oxygen difference seen as proportion •of lung perfusion defects increaseNormal A-a gradient and PaO•

2 >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 branchesCan be used to diagnose acute PE in hemodynamically unstable patient •and initiate thrombolysis/embolectomyCan 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 yearCumulative 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•


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 infarctionElevated BNP (brain natriuretic peptide) and NT-pro BNP are associated •with RV dysfunction in acute PE and are predictive of all-cause in-hospital mortalityNPV 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 failureEmbolic 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 PECurrent 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 onsetReduces risk of death or recurrent PE by 55% in massive PE (five ▲

RCTs)Thrombolysis can significantly reduce pulmonary vascular resistance ▲

and RV stress

520 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, percuta-•neous embolectomy, embolus fragmentation, pulmonary artery stent placementCatheter embolectomy – 83% (10/12) survival rate in one study•

Clinical success defined as improvement in hemodynamic parameters ▲

immediately after procedureReverses 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 escala-tion but did not reduce risk of death

Key Points

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 careFor massive PE, catheter-directed embolectomy with or without local lytic ■

therapy is preferred over systemic thrombolysis in centers with experienceCurrent evidence does not support use of thrombolytic agents in hemodynami-■

cally stable patients with right ventricular dysfunctionChoice of thromboprophylaxis in acute ischemic stroke patients depends on ■

individual risk assessment of VTE and bleeding complications


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 358:1037–1052Vergouwen 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

523

Introduction

Critical care support and admission to an ICU is a relatively infrequent occur-■

rence during pregnancy and the postpartum periodRetrospective analyses of hospital admissions and complication rates indicate ■

that 0.11–1.1% of deliveries are complicated by maternal ICU admissionPatient demographics and hospital type clearly vary and affect outcomes differ-■

ently; therefore, understanding the true risk of obstetric complications is some-what difficultLiterature 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 careIn one study, 71% of obstetric patients transferred to the ICU required ventila-■

tory 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 simultane-ously manage mother and pregnancy viabilitySurvival depends on care algorithms that allow for early detection of maternal ■

problems and prompt referral to tertiary centers with ICUsProactive and aggressive measures, including optimal cardiopulmonary manage-■

ment, minimize the incidence of multiorgan failure and mortality

Chapter 33Neurocritical Illness During Pregnancy and Puerperium

Chere Monique Chase and Cindy Sullivan

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


524 C.M. Chase and C. Sullivan

Admission criteria for appropriate triage are essential; decisions may be based ■

on several models (which utilize prioritization) or diagnostic and objective parametersThe 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 admissionGeneral 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

52533 Neurocritical Illness During Pregnancy and Puerperium

Neurologic Conditions in Pregnancy

Mental status, coma, and seizure■

General medical problems can complicate and, in some instances, exacerbate ♦

during pregnancy, resulting in neurologic complicationsICU 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 arterio-♦

venous malformation (AVM)) accounts for >50% of all cases of ICH during pregnancyICH from aneurysms is most commonly in the subarachnoid space and less ♦

commonly in intraparenchymal and intraventricular spacesAVMs 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 tumorsThe clinical features and presentation of ICH in the obstetric population are ♦

similar to those in the general populationSigns and symptoms are headache, nausea, vomiting, stiff neck, photophobia, ♦

seizures, and decreased level of consciousnessSeverity 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)

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 complicationsMedical 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


Preeclampsia and eclampsia■

Preeclampsia is a form of toxemia of pregnancy characterized by albuminuria ♦

and hypertensionIf convulsions occur before, during, or shortly after childbirth, the syndrome ♦

is classified as eclampsia

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 malariaIntracranial space-occupying

lesionsGliomas, meningiomas, acoustic neuromas, pituitary tumors,

tuberculomaMetabolic disorders Hypoglycemia, hepatic encephalopathy, hyponatremia and other

electrolyte abnormalities, acute intermittent porphyriaDrugs and toxins Magnesium sulfate, sedative overdose, ethanol, illicit drug

abuse, poisoningMiscellaneous 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 normal blood pressure

Mass lesions• Vascularmalformations• Benignandmalignanttumors• Cerebralabscess

Infectious disorders• Viral• Bacterial• Parasiticinfestations• HIV

Cerebrovascular complications• Cerebralinfarction• Cerebralhemorrhage• Subarachnoidhemorrhage• Cerebralvenousthrombosis• Cerebraledema

Metabolic disorders• Hypernatremiaandhyponatremia• Hypoglycemiaandhyperglycemia• Hypocalcemia• Hepaticfailure• Centralstimulants(e.g.,cocaine,theophylline)

New-onset seizures with hypertension

EclamsiaMalignant 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


Table 33.5 Common causes of paralysis in pregnancy other than cortical injury

Spinal cordTraumaDemyelination

Multiple sclerosisAcute transverse myelitis

Peripheral nerveGuillain–Barré syndromePorphyria

Neuromuscular junction disordersMyasthenia gravis exacerbation

Data from Karnad DR, Guntupalli KK (2005) Neurologic dis-orders in pregnancy. Crit Care Med 33(10 suppl):S362–S371

Eclampsia is the disorder most frequently confused with ICH from aneurysms ♦

and AVMs during pregnancy; however, hypertension and albuminuria are two cardinal features of eclampsiaImportant 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

Table 33.6 Differential diagnosis of intracranial hemorrhage

VascularAneurysmArteriovenous malformationsIntracranial venous or dural sinus thrombosisIntracranial arterial occlusionPituitary apoplexy

MassTumorsAbscessOther space-occupying lesions

Inflammatory/immuneMeningitisEncephalitisDemyelinating disease

ObstetricEclampsia


Table 33.8 Conditions that heighten the risk of HEELP

• Preeclampsia-eclampsiaearlyonset• Severegestationalhypertension• Early-onsethypertensionorsevereintrauterinegrowthrestriction• Thrombophilias• Abruptioplacentae• Nonspecificviralsyndromelikesymptoms• Rightupperquadrant,epigastric,orretrosternalpain• Persistentnauseaorvomitinginthirdtrimester• Bleedingfrommucosalsurfaces• Unexplainedhematuriaorproteinuria• Petechialhemorrhagesorecchymosis

Data from Sibai BM (April, 2005) A practical plan to detect and man-age HELLP syndrome. OBG Manag 52–69

Table 33.7 Hallmarks of HELLP syndrome

HemolysisDiagnosis requires at least two of the following:• Abnormalperipheralsmear(schistocytes,burrcells)• Elevatedserumbilirubin(³1.2mg/dL)• Lowserumhaptoglobin• Significantdropinhemoglobinlevels,unrelatedtobloodloss

Elevated liver enzymes• Aspartateaminotransferaseoralanineaminotransferaseatleasttheupperlevelofnormal• Lactatedehydrogenaseatleasttwicetheupperlevelofnormal;thisvalueisalsoelevatedin

severe hemolysisLow platelets• <100,000/mm3

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. sug-gest 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 paradigmConsideration 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


Uncontrolled tonic-clonic seizures are potentially hazardous to the mother ♦

and assumed to be more harmful to the fetus than are AEDsFetuses exposed to AEDs in utero are twice as likely to have congenital ♦

malformations than are the general populationData 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/dayIn the critically ill patient, especially those in status epilepticus, the use of ♦

polypharmacy and polytherapy is likelyPolytherapy with AEDs, compared to monotherapy, also appears to be ♦

associated with an increased risk of birth defectsMost women with epilepsy have no change in seizure frequency during ♦

pregnancy, despite a decline in plasma drug concentration with AEDsClinicians should note that patients who take lamotrigine and possibly oxcar-♦

bazepine can have break-through seizures; therefore, regular monitoring of drug concentrations during pregnancy is recommendedGeneral guidelines suggest monotherapy at lowest effective dosages to avoid ♦

generalized tonic-clonic seizures, risks to the fetus, and limited exposure through breast feedingThe 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 manage-♦

ment of seizures prior to conceptionSeizure freedom in 9–12 months before pregnancy is associated with seizure ♦

freedom during pregnancyOften delivery of the fetus is part of the solution for critically ill obstetric ♦

patientsClinicians 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 scantTo 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 pregnancyCT 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


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

Ultimately, the neurointensivist will have to prognosticate regarding morbidity ■

and mortality of obstetric patients in the ICUMaternal mortality rates vary widely, depending on the country, type of hospital, ■

available services, and personnelSeveral 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 scoresUnfortunately, none of these scoring systems adjust for normal obstetric ♦

physiologic changesIn that laboratory abnormalities in the obstetric population that may signal a ♦

sentinel event are not included in these scoring systems, their applicability may be limitedIn contrast, the scoring systems may also overestimate mortality risk in the ♦

critically ill pregnant patientAs the neurocritical care literature expands, future studies to provide reliable ♦

and reproducible severity scales in pregnancy should be conducted

Key Points

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 viabilityUp to 50% of critically ill obstetric patients have neurologic involvement, ■

including altered mental status, coma, seizures, and paralysisRupture of an intracranial vascular anomaly (e.g., aneurysm or AVM) accounts ■

for >50% of all cases of ICH during pregnancyTreatment of epilepsy during pregnancy requires careful consideration of mater-■

nal and fetal risks that are associated with uncontrolled seizures and of the potential teratogenic effects of AEDsEclampsia is the disorder most frequently confused with ICH from aneurysms ■

and AVMs during pregnancy; however, hypertension and albuminuria are two cardinal features of eclampsia


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):2727–2746Clardy PF, Reardon CC. Critical illness during pregnancy and the peripartum period. (2010) www.

uptodate.com 2010Dias MS (1994) Neurovascular emergencies in pregnancy. Clin Obstet Gynecol 37(2):337–354Germain S, Wyncoll D, Nelson-Piercy C (2006) Management of the critically ill obstetric patient.

Curr Obstet Gynecol 16:125–133Harden CL (2008) Antiepileptic drug teratogenesis: what are the risks for congenital malforma-

tions and adverse cognitive outcomes? Int Rev Neurobiol 83:205–213Harden CL, Sethi NK (2008) Epileptic disorders in pregnancy: an overview. Curr Opin Obstet

Gynecol 6:557–562Kaplan PW (1999) Neurological issues in eclampsia. Rev Neurol 155(5):335–341Karnad DR, Guntupalli KK (2005) Neurologic disorders in pregnancy. Crit Care Med

33(10 suppl):S362–S371Male DA, Stockwell M, Jandowski S (2000) Critical care in obstetric infections. Curr Obstet

Gynecol 10:196–201Martin SR, Foley MR (2006) Intensive care in obstetrics: an evidenced-based review. Am J Obstet

Gynecol 195(3):673–689Mallampalli A, Guy E (2005) Cardiac arrest in pregnancy and somatic support after brain death.

Crit Care Med 33(10):S325–S331Nasraway 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 preg-nancy/postpartum. Clin Perinatol 31:853–868

Williams J, Mozurkewich E, Chilimigras J et al (2008) Critical care in obstetrics: pregnancy-specific 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

533

Basic Principles

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 1981The UDDA reads: “An individual who has sustained either: (1) irreversible ces-■

sation 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 pro-posed 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 ♦

injuryExclusion of confounding factors ♦

Comprehensive assessment to evaluate the absence of any brain function♦

Chapter 34Brain Death and Organ Donation

Alexander Y. Zubkov and Eelco F.M. Wijdicks

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]


534 A.Y. Zubkov and E.F.M. Wijdicks

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 medica-•tions as lorazepam and fentanylA reasonable guideline is to calculate 5–7 times the elimination half-life in •hours and allow that time to pass before clinical examination is performedExamples 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 hThe legal alcohol limit for driving (blood alcohol content 0.08%) is a practi-•cal 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 deathBrain-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 hemor-•rhagic lesions, or diffuse cerebral edema with obliteration of basal cisternsCT scan can be initially normal if patient is imaged very early after cardio-•pulmonary 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 presentEven neuroimaging findings of severe brain injury do not exclude search •for potential confounders

53534 Brain Death and Organ Donation

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 compressionEye 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 reac-•tivity of pupilsAtropine 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 moni-tored for 2 min after testing to ensure no delayed responsesPen 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 suctioningGag reflex is very unreliable in the intubated patient•

Apnea test (passive oxygen-diffusion method)♦

No breathing drive with CO•2 challenge

Systolic blood pressure should be >90 mmHg or supported by vasopres-•sors above that levelPreoxygenation with 100% oxygen for at least 10 min•Obtain baseline ABG and confirm normal PaCO•

2 and increased PaO

2

(>150 mmHg)


Reduce positive end-expiratory pressure to 5 cmH•2O and observe for

deoxygenationDisconnect ventilator•Oxygenate patient with 100% oxygen at 6 L/min by placing catheter •through endotracheal tube to the level of the carinaMonitor for respiration movements by observation and palpation of the •chest and abdomenNormally, Pa increases at the rate of 3 mmHg/min; therefore, allow ~8 min •to increase PaCO

2 by 20 mmHg from baseline

Monitor oxygen saturation and blood pressure. Significant hypotension or •hypoxia may lead to early termination of apnea testRepeat ABG to confirm Pa increase•

PaCO▲2 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 requiredIf spontaneous respirations occur during test, test can be repeated in ▲

several hours

Ancilary Tests for Brain Death

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:■

Patient is unable to tolerate apnea test♦

Patient has high cervical injury, precluding apnea testing as useful♦

Patient is a known CO♦2 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 demonstratedA minimum of eight scalp electrodes should be used♦

Interelectrode impedance should be between 100 and 10,000 ♦ WIntegrity 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 minHigh-frequency filter settings should not be set below 30 Hz, and the low-•frequency setting should not be set above 1 Hz


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 windowsShould 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♦

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. PaCO

2 partial pressure of arterial CO

2; EEG electroencephalogram. From Wijdicks EFM

(2010) The practice of emergency and critical care neuorology. Oxford University Press, Oxford


A static image of 500,000 counts should be obtained immediately after injec-♦

tion, at between 30 and 60 min laterA 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 ♦

circulationNo intracerebral filling at the level of the carotid bifurcation or circle of ♦

WillisExternal carotid circulation should be patent♦

Documentation

The time of death is determined by the time the arterial PaCO■2 reached the target

valueIf apnea test was aborted, brain death is the time at which the confirmatory test ■

has been completedComplete 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♦


Donation after cardiac death might be considered in patients with cata-•strophic injury who do not fulfill criteria for brain deathThe assumption is that the patient will develop circulatory arrest within •45–60 min after extubation and discontinuation of medical therapyThe diagnosis of cardiac arrest is determined in the operating room, fol-•lowed 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 ■

necessaryTime of death is determined by either time of completion of the apnea test or by ■

confirmatory testClinical examination should be documented carefully, and organ transplantation ■

agency should be notifiedA 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 6:88–89Robertson KM, Cook DR (1990) Perioperative management of the multiorgan donor. Anesth

Analg 70:546–556Wijdicks 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 344:1215–1221Wijdicks EFM (2002) The determination of brain death criteria worldwide: accepted fact but not

much of a global consensus in diagnostic criteria. Neurology 58:20–25Wijdicks EFM, Rabinstein AA, Manno EM, Atkinson J (2008) Pronouncing brain death: contem-

porary practice and safety of the apnea test. Neurology 71(16):1240–1244Zubkov AY, Wijdicks EFM (2008) Plantar flexion and flexion synergy in brain death. Neurology

70:E74 (includes a video of the response)

541

AAbdominal infections, 43–45Acid-base disorders, 13–15ACNP. See Acute care nurse practitionerAcromegaly, 182Acute adrenal insufficiency, 33–35Acute brain injury, multimodality monitoring

ICU, 62, 63monitoring techniques, 61–62neuromonitoring tools (see

Neuromonitoring tools, acute brain injury)

Acute care nurse practitioner (ACNP), 269–271

Acute coronary syndromes (ACS), 95, 96Acute disseminated encephalomyelitis

(ADEM), 303–304Acute encephalopathy

diagnosis, 292–293differential diagnosis, 293–295epidemiology, 288management, 295–297nomenclature and classification, 287–288pathophysiology

conscious awareness, 290etiologic classification, 289inflammatory mechanisms, 291–292injury pattern, 290metabolic alterations, 290neurotransmitter alterations, 290–291

selected syndromeADEM, 303–304alcohol withdrawal delirium, 302brain dysfunction, 299DDS, 299–300endocrine disorders, 300–301HE, 297–299nonendocrine disorders, 301PRES, 302–303

uremic encephalopathy, 299Wernicke encephalopathy, 302

Acute myelopathyclinical presentation, 328definitions, 323diagnosis, 332–333differential diagnosis, 331–332epidemiology, 325–326etiology, 324–325ICU management

autonomic dysreflexia, 337cardiocirculatory, 336corticosteroids, 337gastrointestinal and nutritional,

336–337respiratory, 334–336

pathophysiology, 326–327physical examination, 330–331prognosis, 337–339spinal cord syndromes, 328–330

Acute pulmonary edema, 387Acute respiratory distress syndrome

(ARDS), 106–107ADEM. See Acute disseminated

encephalomyelitisAdrenal crises. See Acute adrenal

insufficiencyAdvanced practial registered

nurse (APRN)ACNP, 269–270category, 268CRNP, 269education, 268neurocritical care, 271–272outcomes, 271practice scope, 268roles, 268–269safety, 271

AED. See Antiepileptic drugs

Index

542 Index

a2 agonistsaction mechanism, 161adverse reactions, 162dosage recommendations, 162–163drug-drug interactions, 162ICU use, 162pharmacokinetics and dynamics, 161–162

Airway management and mechanical ventilation

ARDS network protocol and permissive hypercapnia, 106–107

cervical cord injury, 112–113coma or brainstem injury, 113extubation strategies, 110–111gas exchange, 102ICP

and brain oxygenation, 106controlled to spontaneous ventilation,

105fiberoptic bronchoscopy, 106HFV effects, 105hyperventilation, 102–104ventilatory modes effect, 104

intubation criteria, 99–101NPE, 107–109stunned or neurogenic myocardium, 109ventilation control, 101–102ventilator liberation, 110weaning, type II respiratory failure,

111–112Alcohol withdrawal delirium (AWD), 302. See

also Delirium tremensAlexia without agraphia, 346Alzheimers disease, 142Analgesia

classes, 147–148pain assessment, 145–146pain etiology, 146

Anaphylaxis, 196Anesthesias, 437–438Aneurysmal subarachnoid hemorrhage

(aSAH), 492Anterior circulation stroke syndromes, 345Anticonvulsants, 461–463Antidopaminergic agent, 436Antiepileptic drugs (AEDs), 528Antipsychotic drugs, 435Anton syndrome, 345Anxiolysis, 147–148Apnea test, 535–536Apneustic breathing, 6102APRN. See Advanced practial

registered nurseARDS. See Acute respiratory distress

syndrome

Arteriovenous malformation (AVM) resection, 186–187

Aspiration pneumonia, 40, 111, 203, 283Ataxic breathing, 102Atelectasis, 334Atrial fibrillation, 342Autonomic dysreflexia, 337Autonomic nervous system, 477, 479

BBacterial meningitis

blood cultures, 411CNS infection, 45–46CSF analysis, 412definitions and epidemiology, 409predominant causative pathogens, 410symptoms and signs, 411treatment, 412–413

Bacterial ventriculitis, 47–48Balint syndrome, 345Benedikt syndrome, 346Benzodiazepines (BDZ)

action mechanism, 158adverse reactions, 159–160dosage recommendations, 160–161drug–drug interactions, 160ICU use, 159–160pharmacokinetics and dynamics, 158reversal, 159sedation, analgesia, and neuromuscular

paralysis, 499seizure therapy, 160

Bispectral index monitor (BIS), 68, 154Blood pressure (BP) management

AHA/ASA stroke treatment, 117CBF and CPP, 115ICH, 116–117ischemic stroke, 117–119pathophysiology, 116pharmacologic treatment,

hypertension control, 119–120Blood viscosity, 52Botulism, 487–488Bradycardia, 220Brain death, 262Brain death, organ donation

ancillary tests, 536–538confounding factors, 534–536documentation, 538neurologic criteria, 533procurement process, 538types, 538–539

Brain injury, cardiac arrestapproach, 391

543Index

CA estimation, 389neurologic complications management

cerebral edema and elevated ICP, 399–400

cerebral perfusion and oxygenation, 398

glucose control, 400seizure and myoclonus, 399temperature elevation, 398–399

neuronal injury, 389–391post-resuscitative period, 391–392prognostication

AAN guidelines, 400–401post-CA factors, 401–405pre-and intra-CA factors, 401

shivering management, 397therapeutic hypothermia

clinical impact and post-trail experience, 394

complications, 397–398delivery, 394–397neurologic prognostication, 405and neuroprotective strategies,

392–394Brain tumors

diagnosis and differential diagnosisMRI/CT imaging, 459MR spectroscopy (MRS), 459PET, 459progressive multifocal

leukoencephalopathy, 460epidemiology, 445etiology, 445–456management

cerebral edema, 460–461hydrocephalus, 461pituitary insufficiency, 461–464seizure treatment and prophylaxis,

461–463tumor-related complications, 460VTE, 464

symptoms and signsaltered mental status, 458headache, 456intracerebral hemorrhage, 458intracranial pressure elevation, 458progressive focal neurologic

deficits, 457seizure, 456–457

treatmentchemotherapy, 465–467radiation therapy (XRT), 465surgery, 464–465

Bronchospasm, 334–335Bulbar muscles, 477, 479

CCarbidopa/Levodopa, 140Carcinomatous meningitis, 446Cardiac dysfunction

diagnosis and differential diagnoses, 91–94

epidemiology, 89etiology, 90management, 94–96outcomes, 96–97signs and symptoms, 90–91

Cardiac ischemia, 222Cardiopulmonary stabilization, 285Cardiovascular dysfunction

postoperative hypertension, 207–208postoperative hypotension

dysrhythmias, 206–207hypovolemia, 205myocardial ischemia, 205vasodilation, 205

Carotid artery stenting (CAS)angiographic criteria, 219antiplatelet regimen, 223clinical characteristics, 219follow-up, 223intraoperative and postoperative

managementbradycardia, 220groin hematoma and retroperitoneal

hemorrhage, 222hypotension, 220–221ICH, 221–222instant thrombosis, 222–223ischemic stroke, 221seizure, 221

patient preparation, 220Carotid endarterectomy (CEA),

185–186, 219Carotid occlusive disease

carotid stenosis classification, 218CAS (see Carotid artery stenting)clinical presentation, 218etiology, 218incidence, 217–218management, 219recurrent events, 218

Carotid stenosis, 342–343Catheter-related infections, 48CEA. See Carotid endarterectomyCentral nervous system dysfunction

delayed awakening, 210–211delirium, 209–210perioperative stroke, 212

Central parenteral nutrition (CPN), 137, 139, 140

544 Index

Cerebral blood flow (CBF) and metabolismcerebral physiology, 51–53monitoring

cerebral microdialysis, 58–59EEG and CPP, 56imaging, 56–58SjVO2 and PbrO2, 56–59TCD, 56

pathophysiology, 53–55Cerebral edema. See also Intracranial

hypertensiondiagnosis and differential diagnoses,

77–79etiology

cytotoxic edema, 73–74hydrocephalic and hydrostatic

|edema, 74vasogenic edema, 73

managementcytotoxic edema, 80vasogenic edema, 79–80

sedation and analgesiadecompressive hemicraniectomy,

86–87hypertonic solutions, 83Lund concept, 87–88mannitol, 82

signs and symptoms, 75–77Cerebral herniation syndromes,

75–77, 80, 411Cerebral metabolism, 52–53Cerebral microdialysis, 58–59, 68–71Cerebral perfusion pressure (CPP),

56, 57, 87, 115, 316Cerebral salt wasting (CSW), 17–18Cerebral scintigraphy, 537–538Cerebral venous sinus thrombosis (CVST)

anatomyanatomic variations, 424normal anatomy, 423occlusion, frequency, 424

clinical differential diagnosis, 426complications

intracranial hypertension, 431–432persistent headache, 432seizures and epilepsy, 432

diagnostic testsbrain MRI, 427–428CCA, 428–429electroencephalography, 429head CT, 427lumbar puncture, 429

epidemiology, 421etiology, 421–422

managementmonitoring, 429systemic anticoagulation,

429–430therapy, 431thrombolysis, 430

outcomeadults, 432–433pediatric patients, 433

pathophysiology, 424–425symptoms and signs, 425–426

Cerebrospinal fluid (CSF), 469Certified registered nurse practitioner (CRNP),

268–270Cervical cord injury, 112–113Cervical corpectomy, 180Chemotherapeutic agent, 465–467Chest trauma, 335Cheynes–Stokes breathing, 101, 102Cholecystitis, 44Claude syndrome, 346Clinical diagnosis, 539Closed unit design, 9Clostridium tetani, 485Cluster breathing, 102CNS infections, 45–48Coagulopathy, 196Collaborative nursing practice

APRN (see Advanced practial registered nurse)

clinical nurse mentor, 267nurse manager, 267–268registered nurse, 265–266

Coma. See also Consciousness disordersassessment, 281–283cardiopulmonary stabilization, 285management, 283–284prognosis, 284–285

Communicating hydrocephalus, 470Community-acquired pneumonia, 39–40Consciousness disorders

definitions, 277–278etiology, 279–281terminology, 278–279

Contractures, 484Conventional cerebral angiography (CCA),

428–429CPN. See Central parenteral nutritionCPP. See Cerebral perfusion pressureCraniotomy

for aneurysm clipping, 178–180for ICH, 180for tumor, 177–178

CSW. See Cerebral salt wasting

545Index

DDandrolene, 436, 439Deep venous thrombosis (DVT)

clinical presentation, 508diagnostic approach

intermediate, high pretest probability, 511–512

Wells prediction rule, 511diagnostic tests

MRI venography, 510venous Doppler ultrasound, 509

managementacute ICH, 514AIS, 513–514VTE treatment (see VTE treatment)

Dejerine–Roussy syndrome, 346Delayed cerebral ischemia, 385Delirium

alcohol withdrawal, 302altered mental status algorithm, 296diagnosis, 148, 292–293differential diagnosis, 293–295epidemiology, 288etiology, 149injury pattern, 290neurotransmitter alterations, 290–291SPECT, 290

Delirium tremens, 302Diabetes insipidus (DI)

accurate fluid intake, 184after pituitary surgery, 182–183classic signs, 183and hypernatremia, 19–20postoperative, 183–184

Dialysis disequilibrium syndrome (DDS), 299–300

Dilated cardiomyopathy, 343Drowsy, 278Drug toxicity, 500–502DSM-IV-TR criteria, 435–436Dural sinuses, 423Dysautonomia, 486Dysphagia, 480Dyspnea and respiratory distress, 258–259Dysrhythmia, 91–92, 94–95, 206–207

EEarly endotracheal intubation, 285Eclampsia, 526–528Electroencephalography (EEG), 56, 66,

403–404, 429, 536Electrolyte and metabolic derangements

acid-base disorders, 13–14

adrenal crises, 33–35calcium, 25–26electrolyte disorders, 15–21Hashimoto encephalopathy, 31–32magnesium, 23–25metabolic disorders and endocrinopathies,

28–31phosphate, 27–28potassium, 21–23primary acid-base disorders, 14–15thyroid storm, 32–33

Electrolyte disorders, 15–21Elevated cTI, 95–96Embolectomy, 520Emergent endovascular revascularization

acute vessel occlusion, 225–226efficacy, 226end point and assessment, 226–227interventional treatment, 223–224intervention indications, 224–225intracranial AVMS, 243–245intraoperative and postoperative medical

management, 229–230nonpharmacologic techniques, 225–226outcome predictors, 228perioperative anesthetic consideration,

228–229preoperative medical management, 228procedural complications, 231–232Qureshi grading system, 227–228relative contraindications, 224–225stenotic artery/dissection, 225unruptured and ruptured intracranial

aneurysms (see Intracranial aneurysms)

Empyema, 42Encephalitis

definitions and epidemiology, 415–416diagnosis, 417–419management, 419signs and symptoms, 416–417

Endocrine disordersabsolute AI and diabetes mellitus, 301Hashimoto encephalopathy, 300–301myxedema, 300thyroid storm, 300

Endocrinopathies, 28–31Endovascular coiling, 234, 384Enteral nutrition (EN). See also Parenteral

nutrition (PN)aspiration, 135formula composition, 131–133formula selection, 131, 133–134initiation, 134

546 Index

Enteral nutrition (EN). See also Parenteral nutrition (PN) (cont.)

location, 130–131mechanical complications, 136neurologic impairment, 129oral intake, 136potential contraindications, 129–130timing, 130tolerance, 134–135

Ependymomas, 368

FFondaparinux, 514, 515Fosphenytoin (fPHT), 500

GGastric feeding, 134, 141Gastrointestinal ulcer prophylaxis, 383Generalized convulsive SE (GCSE)

EEG presentation, 496–498morbidity, 494–495subtype, 490

Genetic syndromes, 445, 455–456Groin hematoma, 222Guillain–Barré syndrome (GBS), 475

HHakim triad, 471Hashimoto encephalopathy, 31–32, 300–301Hemicraniectomy, 184–185Hemolysis, elevated liver enzyme concentra-

tions, and low platelet counts (HELLP) syndrome, 527–528

Hepatic encephalopathy (HE), 297–299Herpes encephalitis (HSE). See also West Nile

Virus (WNV) encephalitisdiagnosis, 417management, 419pathophysiology, 416signs and symptoms, 416

High-frequency ventilation (HFV), 105Hospital-acquired pneumonia, 40–43Hydralazine, 119, 120, 207, 208, 358Hydrocephalus

in brain tumor, 461classification

communicating hydrocephalus, 470CSF, 469diagnosis, 471–472noncommunicating hydrocephalus,

470–471

NPH, 470treatment, 472–473

epidemiology, 469Hypercalcemia, 26, 154Hypercapnia, 195Hypercarbia, 10, 28Hyperglycemia, 28–29, 139–140, 213–214,

400Hyperkalemia, 23, 169, 439Hypermagnesemia, 25, 478Hypernatremia, 16, 19–20, 526Hyperphosphatemia, 28Hypertension. See Blood pressure (BP)

managementHyperthermia, 32, 48, 213, 281, 440Hyperventilation, 81–82, 102–104, 316Hypocalcemia, 26, 526Hypoglycemia, 29, 154, 285, 491, 526Hypokalemia, 21–22, 24Hypomagnesemia, 23–24Hyponatremia, 16–21, 388Hypophosphatemia, 27, 125, 280Hypoplasia, 424Hypotension, 195–196, 220–221Hypothermia

clinical impact and post-trail experience, 394

complications, 397–398delivery, 394–397in metabolic suppression, 86neurologic prognostication, 405and neuroprotective strategies, 392–394shivering, 397temperature abnormalities, 212

Hypovolemia, 18, 92–93, 205Hypoxemia, 195Hypoxia, 284, 285

IICP elevation, 458ICP waveform analysis, 79Ideal body weight (IBW), 124Infective endocarditis, 42–43Inferior sagittal sinus, 423Instant thrombosis, 222–223Intracerebral hemorrhage (ICH)

BP management, 116–117clinical presentation, 355diagnosis, 355–356epidemiology, 353indication, 356–357management

emergent, 357

547Index

IV medication, 358–359primary injury, 358secondary injury, 359

pathophysiology, 353–355prognosis, 357recurrence prevention, 360–362surgical options, 359

Intracranial aneurysmsruptured

classification, 238epidemiology, 237follow-up, 242–243intraprocedural management, 239–240post-procedural management, 240–242pre-procedural care, 238risk factors, 237–238symptomology, 238

unrupturedepidemiology, 232follow-up, 235, 237intra-procedural management, 235patient preparation, 234patient selection, 233–234post-procedure care, 235, 236pre-procedure care/counseling, 233risk factors, 232–233symptomology, 233treatment risks, 234

Intracranial atherosclerosis, 343Intracranial AVMS

current treatments, 243endovascular embolization, 244follow-up, 245operative management, 244postoperative care, 244–245preoperative management care, 244

Intracranial hemorrhage (ICH), 146, 211, 318, 525–528

Intracranial hypertension. See also Cerebral edema

diagnosis and differential diagnoses, 77–79etiology, 74–75management, 80–81sedation and analgesia

hyperventilation, 81–82metabolic suppression, 84–86osmotic therapy (see Osmotic therapy)

signs and symptoms, 75Intracranial mass lesions, 101Intracranial neoplasm, 459Intracranial pathology, 28Intracranial pressure (ICP)

and brain oxygenation, 106controlled to spontaneous ventilation, 105

fiberoptic bronchoscopy, 106HFV effects, 105hyperventilation, 102–104ventilatory modes effect, 104

Intraoperative brain swelling, 193–194Intraoperative hemorrhage, 194Intraventricular hemorrhage (IVH)

clinical presentation, 367epidemiology, 365–366management, 368pathophysiology, 367

Ischemic strokeand BP, 117–119and CBF, 55complications, 350–351definitions, 341emergent endovascular procedures types,

225–226epidemiology, 341etiology, 342–344indications, 224interventional treatment, 223–224investigations, 347management, 349–350relative contraindications, 224–225risk factors, 342subsequent care, 351subtypes, 342

anterior circulation stroke syndromes, 345

brainstem syndromes, 346posterior circulation stroke

syndromes, 345–346symptoms, 344

treatment, 348–349

JJugular venous oxygen saturation (SjVO

2),

56–59, 68, 69

LLabetalol, 119, 120, 207Lacunar strokes, 343Lacunar syndromes, 346Laser-Doppler flowmetry (LDF), 70Leapfrog ramification, 8Leptomeninges, 446Life-sustaining therapies

advance directives, 250–251comfort measures goals, 255–256communicating prognosis

communicating obstacles, 252–253

548 Index

Life-sustaining therapies (cont.)ethics consultation, 253medical futility, 251prognostic information, 251self-fulfilling prophecy, 251

dosing and titration, medications, 261ethical issues, 247–248informed consent, 248–250managing symptoms

anxiety, 260delirium, 260dyspnea and respiratory distress,

258–259fever, 260hunger and thirst, 260nausea and vomiting, 260NMBAs, 260–261pain, 258

palliative care, 255specific situations, 262–263withdrawal, 254

pitfall, 256–258standardized order forms, 256ventilatory support, 261–262

Low-grade gliomas, 456Low-molecular-weight heparin (LMWH)

prophylaxis regimensdalteparin (fragmin), 514enoxaparin (lovenox), 514fondaparinux, 514

vs. vitamin K, 515–516VTE prevention

AIS, 513–514elective neurosurgery, 513traumatic brain injury, 513

warfarin, 515Lumbar catheter, 78–79Lumbar puncture, 377, 379, 429Lung abscess, 42

MMalignant hyperthermia (MH)

differential diagnoses, 438–439epidemiology, 437–438management, 439–440postoperative care, 196symptoms and signs, 438

Mannitol, 82–84, 192–193, 315, 461Mean arterial pressure (MAP), 52, 57, 115Meningitis

definitions and epidemiology, 409–410diagnosis, 411–412

etiology, 410management, 412–415signs and symptoms, 410–411

Meta-analysis, 7Metabolic disarray, 28. See also

Toxic disarrayMetabolic disorders, 28–31Metastatic tumor, 368Multimodality monitoring, acute brain injury

ICU, 62, 63monitoring techniques, 61–62neuromonitoring tools

BIS, 68brain temperature, 67cerebral microdialysis, 68–71continuous EEG (cEEG), 67–68EEG, 66ICP monitoring, 64, 65LDF and NIRS, 70PbtO

2, 66–67

pupillometry, 67serial neurologic exam, 62, 64SjVO

2, 68, 69

TCD, 64–66thermal dilution flowmetry, 70

Multimodality neuromonitoring, 60Multi-slice CT angiography, 426Myasthenia gravis (MG), 481–483Myocardial ischemia, 93, 146, 178,

205, 207Myxedema coma, 30–31, 300

NNarcotics

action mechanism, 155adverse reactions, 157ICU use, 157pharmacokinetics and dynamics, 155–156sedative-hypnotics, 154tolerant patients, 157

Near-infrared spectroscopy (NIRS), 70Neurocritical illness

criteria, obstetrical admission, 524–525critically ill obstetric patients, 525diagnosis model, admission, 524maternal death, prediction, 530maternal ICU admission, 523, 524pregnancy

epilepsy, 528–529ICH, 525–526mental status, coma, and seizure,

525–527

549Index

preeclampsia and eclampsia, 526–528Neurogenic myocardium. See Stunned

myocardiumNeurogenic pulmonary edema (NPE),

107–109Neurogenic stunned myocardium (NSM),

90, 95–96Neurointensivists, 7–9Neurointerventional procedures

carotid occlusive disease (see Carotid occlusive disease)

emergent endovascular revascularization (see Emergent endovascular revascularization)

Neuroleptic malignant syndrome (NMS)differential diagnosis, 436epidemiology, 435management, 436–437symptoms and signs, 435–436

Neurolepticsaction mechanism, 163adverse reactions, 164dosage recommendations, 164–165drug–drug interactions, 164ICU use, 163–164pharmacokinetics and dynamics, 163

Neurologic test, 535Neuromonitoring tools, acute brain injury

BIS, 68brain temperature, 67cerebral microdialysis, 68–71continuous EEG (cEEG), 67–68EEG, 66ICP monitoring, 64, 65LDF and NIRS, 70PbtO

2, 66–67

pupillometry, 67serial neurologic exam, 62, 64SjVO

2, 68, 69

TCD, 64–66thermal dilution flowmetry, 70

Neuromuscular blockade, 534Neuromuscular blocking agents (NMBAs),

260–261Neuromuscular disorders

bedside assessment, 476–477botulism

pathophysiology, 487treatment, 487–488

comprehensive ICU care, 476critical illness neuropathy/myopathy

epidemiology and risk factors, 483–484

presentation, 484treatment and prognosis, 484–485

differential diagnosis, 477GBS

acute motor and sensory axonal neuropathy (AMSAN), 479

admission, NCCU, 480electrophysiology, 480epidemiology, 477features, 477ICU management, 481intubation, 480Miller–Fisher syndrome, 479

MGcholinergic crisis, 483epidemiology, 481–482features, 482myasthenic crisis, 482–483treatment, 483

prolonged neuromuscular blockade, 485tetanus

pathophysiology, 485–486treatment, 486

ventilation mode/intubation sequence, 475Neuromuscular paralysis

common indications, 167–168complications, 168depolarizing agent, 168myopathic disorders, 169nondepolarizing agents, 168pharmacology, 168succinylcholine-induced

hyperkalemia, 169Neuroscience critical care unit (NCCU)

costs, 11goals and benefits, 3hospital argument, 5–7hospital financial analysis, 11key components

National Guideline Clearinghouse, 9–10

neurointensivists, 6specialty-trained NCCU nursing, 9

national, 6–8nutrition (see Nutrition, NCCU)postoperative care (see Postoperative care,

NCCU)physician argument, 4–5revenue sources, 10–11

Nicardipine, 119, 120, 207, 358Nitroprusside, 119, 120Nonaneurysmal SAH, 372Noncommunicating hydrocephalus, 470–471

550 Index

Nonconvulsive SE (NCSE)diagnosis, 495EEG presentation, 495–498effects, 495SE

Nonconvulsive SE (NCSE) (cont.)epidemiology, 489subtype, 490

TBI, 491–492Nonendocrine disorders

ADEM, 303–304AWD, 302PRES, 302–303septic encephalopathy, 301–302Wernicke encephalopathy, 302

Nonketotic hypersmolar coma (NKHC), 28–29

Nonobstructive hydrocephalus. See Communicating hydrocephalus

Normal-pressure hydrocephalus (NPH), 470Nutrition, NCCU

epidemiology and etiology, 123management

drug nutrient interactions, 140enteral nutrition, 129–136nutritional considerations, 140–142parenteral nutrition, 136–140

signs and symptomsnutritional assessment components, 124premorbid nutritional status, 124–129

OObstructive hydrocephalus. See

Noncommunicating hydrocephalusOculovestibular response, 535Organ donation, 263Osmotic demyelination syndrome, 19Osmotic therapy

hypertonic saline, 83–84mannitol, 82–83rebound cerebral edema, 82

Oxygen tension in brain tissue (PbrO2), 56–59

PParalytics, 169Parenchymal brain tissue oxygen (PbtO

2),

66–67Parenteral nutrition (PN). See also Enteral

nutrition (EN)additives, 138–139administration, 139complications, 139–140

CPN, 140formulations, 137–138indications, 136–137monitoring and initiation, 139

Parkinson disease, 142Passive oxygen-diffusion method.

See Apnea testPatent foramen ovale (PFO), 343Peduncular hallucinosis, 346Pentobarbital, 85Perimesencephalic nonaneurysmal

hemorrhage (PMNAH), 377Periodic lateralizing epileptic discharges

(PLEDs), 496Peritonitis, 43–44Permissive hypercapnia, 107PFO. See Patent foramen ovalePituitary surgery

acromegaly, 182CSF leak, 184diabetes insipidus (DI)

(see Diabetes insipidus (DI))PLEDs. See Periodic lateralizing epileptic

dischargesPMNAH. See Perimesencephalic

nonaneurysmal hemorrhagePneumonia, 334Polytherapy, 529Positive end-expiratory pressure (PEEP), 104, 107Positron emission tomography (PET), 459Post-concussive syndrome, 311Posterior circulation stroke syndromes,

345–346Posterior reversible encephalopathy syndrome

(PRES), 302–303Postoperative care, NCCU

airway issues, 199–200anaphylaxis, 196anesthetics and anesthetic techniques

fluid management, 192–193hypnotic drugs, 188–189neuromuscular blocking drugs, 189–190opioids, 187–188perioperative airway issues, 191–192regional awake, 190–191volatile anesthetic agents, 190

arteriovenous malformation (AVM) resection, 186–187

cardiovascular dysfunction (see Cardiovascular dysfunction)

carotid endarterectomy, 185–186CNS dysfunction (see Central nervous

system dysfunction)coagulopathy, 196

551Index

craniotomy, 185aneurysm clipping, 178–180cervical corpectomy, 180–181ICH, 180multilevel thoracic fusion, 181–182

diet order, 175epilepsy surgery, 185general medical care, 174hemicraniectomy, 184–185hypercapnia, 195hyperglycemia, 213–214hypertension, 196hypotension, 195–196hypoxemia, 195indwelling tubes, 175–176intraoperative brain ischemia, 193intraoperative brain swelling, 193–194intraoperative hemorrhage, 194intraoperative injury, 197–198intraoperative seizure, 194laboratory study, 176malignant hyperthermia (MH), 196medication reconciliation, 176OR to NCCU transport, 173–174pain medications, 175pituitary surgery

acromegaly, 182CSF leak, 16diabetes insipidus (DI)

(see Diabetes insipidus (DI))POCD, 214–215PONV, 198–199prophylaxis, 176–177pulmonary dysfunction (see Pulmonary

dysfunction)sedation, 175temperature abnormalities, 212–213urinary and renal dysfunction, 208–209VAE, 194–195

Postoperative cognitive dysfunction (POCD), 214–215

Postoperative nausea and vomiting (PONV), 198–199

Preeclampsia, 526–528Premorbid nutrition assessment

body mass index (BMI), 124–125energy requirements, 126–129fluid requirements, 128, 129hepatic protein, 125–126IBW, 124malnutrition, 125nitrogen balance and neurotrauma, 126protein requirements, 128weight loss, 125

PRES. See Posterior reversible encephalopathy syndrome

Primary and secondary (noninfectious) causes, 37–38

Primary brain tumors, 445–455Primary CNS vasculitis, 343Propofol

action mechanism, 165adverse reactions, 166cautionary note, 167dose-dependent respiratory

depression, 166drug–drug interactions, 167hypotension-vasodilation, 166ICU use, 166in metabolic suppression, 85–86pharmacokinetics and dynamics, 165–166potential anaphylactoid reactions, 166

Propofol-infusion syndrome, 93–94Prosopagnosia, 346Pseudomembranous colitis, 44Pulmonary dysfunction

gastric contents aspiration, 203–204hypercapnia, 202hypoxemia, 200–202pneumothorax, 205preexisting lung disease, 202–203pulmonary edema, 204pulmonary embolism, 204

Pulmonary edema, 204, 335Pulmonary embolism (PE), 204

clinical presentation, 508diagnostic approach

intermediate, high pretest probability, 511–512

Wells prediction rule, 511, 512diagnostic tests

CT pulmonary angiography, 510pulmonary angiography, 511V/Q scan, 509–510

differential diagnosis, 508management

AIS, VTE prevention, 513–514VTE treatment (see VTE treatment)

management algorithmshigh clinical probability, 513intermediate clinical probability, 513low clinical probability, 512–513

risk stratificationABG, 518cardiac biomarkers, 518–519categories, 517chest CT, 519clinical evaluation, 517

552 Index

echocardiogram, 518EKG, 517–518massive PE, treatment, 519–520submassive PE, treatment, 520

Pulmonary thromboembolism, 335–336

RRadiation therapy (XRT), 465Radiographic pulmonary edema, 91Radioisotope cisternography, 471Refractory hypotension, 91, 93, 96Renal failure encephalopathy

brain dysfunction, 299DDS, 299–300uremic encephalopathy, 299

Respiration patterns, 101–102Respiratory muscles, 477, 478Reticular activating system (RAS), 277Retroperitoneal hemorrhage, 222Revenue sources, 10–11Rhabdomyolysis, 439Ruptured intracranial aneurysms, 237–243Ryanodine receptor (RYR), 437

SSAH. See Subarachnoid hemorrhageSecondary brain injury, 285Second-impact syndrome (SIS), 311Sedation

anxiolysis, 14/–148classes

a2 agonists, 161–163

benzodiazepines (see Benzodiazepines)narcotics (see Narcotics)neuroleptics, 163–165neuromuscular paralysis (see

Neuromuscular paralysis)propofol, 165–167

delirium, 148–149general issues, 145need identification, 145physiologic and brain function monitor,

149, 154propofol (see Propofol)scoring systems, 149therapy

pharmacokinetics and dosing, 149, 152–153

pharmacologic profile, 149–151physiologic etiologies, 149, 154

Seizure prophylaxis, 382–383Septic encephalopathy, 301–302

Serotonin syndrome (SS)differential diagnoses, 441, 442epidemiology, 440management, 441–442symptoms and signs, 440

Serum sodium, 16, 19Shunt placement, algorithm, 472SIADH. See Syndrome of

inappropriate antidiuretic hormone secretion

Sinusitis, 45Somatosensory-evoked potential (SSEP),

403, 405Spinal cord infarction, 326, 331Spinal cord injury (SCI), 89, 94, 141–142SSEP. See Somatosensory-evoked potentialStaffing models, 8Status epilepticus (SE)

anatomy, 490definition, 489drug interactions, 502–503drug toxicity, 500–502EEG presentation, GCSE and NCSE,

496–498epidemiology, 489etiologies of seizures

aSAH, 492–493cerebral neoplasms, 493cerebrovenous sinus thrombosis, 493neurologic (cortical) injury, 491, 492non-neurologic injury, 491, 493stroke, 492traumatic brain injury (TBI), 491–492

in-hospital-based seizures, 493–494medical and pharmacologic treatment,

500, 501monitoring, 495–498morbidity, 494–495NCSE, 495subtypes, 490treatment

first-line therapy, 499second-line therapy, 499–500

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (STEAT). See Hashimoto encephalopathy

Stunned myocardium, 109Stupor, 278, 281–283Subarachnoid hemorrhage (SAH)

cerebral blood flow, 55definition, 371diagnosis

angiography, 378–379

553Index

head CT, 376–377lumbar puncture, 377

epidemiology, 371–374management

operative, 383–384postoperative, 384–388preoperative, 380–383

signs and symptomsgrading scales, 375, 376headache, 374–375mimics, 375

Surgical clipping, 383, 388Surgical resection, 467Sustained ICP elevation, 88Symptomatic vasospasm, 384, 385Syndrome of inappropriate

antidiuretic hormone secretion (SIADH), 17, 18

Systemic inflammatory response syndrome (SIRS), 291

Systolic blood pressure, 534

TTBI. See Traumatic brain injuryTCD. See Transcranial DopplerTelemetry monitoring, 91, 94, 231Tentorial sinuses, 423Tetanus, 485–486Thermal dilution flowmetry, 70Thoracic infections, 39–43Thrombolysis, 519–520Thyroid storm, 32–33, 300Total parenteral nutrition. See Central

parenteral nutrition (CPN)Toxic disarray, 170Transcranial Doppler (TCD), 56, 64–66Transcranial-Doppler ultrasonography, 537Transverse myelitis

epidemiology, 325–326pathophysiology, 327physical examination, 330prognosis, 337–338

Transverse (lateral) sinuses, 423Traumatic brain injury (TBI)

in CBF, 54–55clinical management

examination, 312focused neurologic, 312fundamental concept, 314imaging, 312, 314sedation, 318tissue oxygenation and metabolic

monitoring, 314–315

epidemiology, 307–308nutritional consideration, 140–141pathogenesis, 308–309prognosis, 319taxonomy, 309–311treatment

autonomic dysfunction, 319deep venous thrombosis, 318gastrointestinal prophylaxis, 318hemodynamics, 316medical interventions, 315–316nutrition, 317prophylaxis with anticonvulsants,

318sedation, 318surgical interventions, 316

Treitz, 135Tumor location, 467

UUniform Determination

of Death Act (UDDA), 533Unremitting seizure activity, 494, 495Unruptured aneurysms, 232–237, 374Uremic encephalopathy, 299Urinary and renal dysfunction, 208–209Urinary tract infections, 44–45

VVascular-metabolic coupling, 84Vasospasm, 178, 242, 384–385Veneus air embolism (VAE), 194–195Venous thromboembolism (VTE).

See also Deep venous thrombosis; Pulmonary embolism

diagnostic approach, 464, 511–512diagnostic tests

contrast venography, 509CT pulmonary angiography, 510D-dimer, 509MRI venography, 510pulmonary angiography, 511venous Doppler ultrasound, 509V/Q scan, 509–510

epidemiologyDVT, 505–506PE, 505

managementacute ICH, 514AIS, 513–514appropriate indications, 517elective neurosurgery, 513

554 Index

inferior vena cava (IVC) filters, 516–517

LMWH prophylaxis regimens, 514traumatic brain injury, 513VTE treatment (see VTE treatment)

prevention, 464Venous thromboembolism

prophylaxis, 383Ventilator associated pneumonia (VAP),

41–42, 230, 387Vertebral/carotid dissection, 343Viral encephalitis

and CNS infection, 46–47definitions and epidemiology, 415–416diagnosis, 417–419management, 419signs and symptoms, 416–417

VTE treatmentanticoagulation therapy, 464bleeding complication, 515catheter-directed thrombolysis, 516

fondaparinux, 515heparin-induced thrombocytopenia, 516IV heparin, 514LMWH, 515–516optimal duration, vitamin K, 516warfarin, 515

WWallenberg syndrome, 346Warfarin, 515Watershed infarcts, 343Weber syndrome, 346Wernicke encephalopathy, 302West Nile Virus (WNV) encephalitis.

See also Herpes encephalitis (HSE)diagnosis, 418–419epidemiology, 416management, 419signs and symptoms, 417

Wisconsin algorithm, 473

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