Handbook of neurocritical care


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Handbook of neurocritical care

  1. 1. Handbook of Neurocritical Care
  2. 2. Anish Bhardwaj, MD, FAHA, FCCM, FAANMarek A. Mirski, MD, PhDEditorsHandbook ofNeurocritical CareSecond Edition
  3. 3. EditorsAnish Bhardwaj Marek A. MirskiChairman Vice-Chair, Department of AnesthesiologyDepartment of Neurology and Critical Care MedicineTufts University School of Medicine Director, Neurosciences Critical CareProfessor of Neurology DivisionNeurological Surgery, and Neuroscience Chief, Division of Neuro AnesthesiologyNeurologist-in-Chief Director, Anesthesia Perioperative ClinicalTufts Medical Center Research ProgramBoston, MA, USA Co-Director, Comprehensive Strokeabhardwaj1@tuftsmedicalcenter.org Program Professor of Anesthesiology, Neurology, Neurosurgery Johns Hopkins Medical Institutions Baltimore, MD, USA mmirski@jhmi.eduISBN 978-1-4419-6841-8 e-ISBN 978-1-4419-6842-5DOI 10.1007/978-1-4419-6842-5Springer New York Dordrecht Heidelberg LondonLibrary 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 writtenpermission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use inc­ onnection 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 arenot identified as such, is not to be taken as an expression of opinion as to whether or not they are subjectto proprietary rights.Printed on acid-free paperSpringer is part of Springer Science+Business Media (www.springer.com)
  4. 4. ForewordNeurocritical Care is a multi-specialty multi-disciplinary field dedicated to ­mproving ithe care and outcomes of critically ill patients with neurological conditions. It hasmoved 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 butignored in managing critically ill patients, but rather critical care management isfocused on optimizing brain function. This shift in focus has been driven as much byadvances in medical knowledge and techniques as by the vision of its practitionerssuch as the editors and contributors to this second edition of Handbook ofNeurocritical 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 anddisciplines. This is clearly evident in this text with contributors from the specialtiesof neurology, vascular neurology, neurosurgery, interventional neuroradiology,anesthesiology, and medical critical care and the disciplines of nutrition andadvanced practice nursing. By bringing together this breadth of expertise to updatethis concise focused handbook the editors have created a tool useful to practitionersfrom 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 thepoint. While it is not meant to be comprehensive, it captures the most important keypoints that are necessary for thoughtful clinical decision making. The tables andfigures provide easy to use tools that facilitate rapid evaluation and decision makingboth for trainees in neurocritical care as well as for experienced practitioners inrelated fields. This text provides concise practical review of the current 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. v
  5. 5. PrefaceIn the preface to the first edition of Handbook of Neurocritical Care, we commentedthat neurocritical care as a subspecialty has grown rapidly over the last two decadesand 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 fellowshiptraining programs at various facilities, the recently instituted subspecialty certifica-tion examination by the United Council for Neurologic Subspecialties, and theincreasing number of critical care units around the world. These major strides in thesubspecialty that are commensurate with the goals of “decade of the brain,” coupledwith the emerging data from clinical series and translational research, occasionsanother edition of this handbook. The overarching goal of the handbook remains the same. The operative tenetcontinues to be that “time is brain,” and rapid diagnosis and therapeutic interven-tions in these challenging patients cannot be overemphasized. The care provided tothis subset of critically ill neurologic and neurosurgical patients continues to beinterdisciplinary and includes care rendered by colleagues in emergency medicalservices and emergency medicine, neurologists, neurosurgeons, anesthesiologists,critical care physicians, critical care nurses, nurse practitioners, and physicianassistants. The onus lies heavily on first-line physicians and other healthcare pro-viders for early recognition, timely therapeutic interventions, and proper referralsin patients experiencing acute neurologic deterioration. This handbook is not meantto substitute for a full-length text, rather it is intended to serve as a quick-referenceguide for those involved in the care of critically ill neurologic and neurosurgicalpatients. In response to feedback from the readership and colleagues regarding theprevious 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 andconfirming 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, keypoints and references highlight essential elements and should serve as quick sum-maries of salient features. We hope that this second edition of the handbook vii
  6. 6. viii Prefacecontinues to provide a succinct and practical approach to the management of thecritically ill patient population that we serve. We are indebted to the authors for their valuable contributions and thank TziporaSofare, MA, for lending her exceptional editorial skills. We would also like to par-ticularly express our thanks to the Johns Hopkins Clinician Scientist Program, theAmerican Heart Association, the National Stroke Association, and the NationalInstitutes of Health extramural programs; their support has helped to advance ourinvestigative work, aided in the establishment of fellowship training programsin neurosciences critical care, and augmented the much needed advancement ofthis field. Anish Bhardwaj, MD, FAHA, FCCM, FAAN Marek A. Mirski, MD, PhD
  7. 7. Special IntroductionThis second edition of the Handbook of Neurocritical Care is a major revision of thefirst edition that appeared in 2004. As pointed out by the editors, since that time thisfield has grown and matured to include many more training fellowships as well asrecent sub-specialty certification by the United Council for Neurologic Subspecialties.This handbook has also progressed forward: an expanded yet handy and easy to usereference manual for the management of patients with life threatening neurologicand neurosurgical illnesses. As in the first edition, all of the chapters are made up ofbulleted teaching points followed by a list of Key Points and important referencesallowing 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 amyriad of important general principles such as electrolyte derangements, fever andinfection, cerebral blood flow, cerebral edema, brain and cardiovascular monitoring,ventilatory management, and sedation and analgesia to mention only a few. Thesecond section covers the major diagnostic categories of neurocritical care withseveral 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 makingprocess. Whereas most of the contributors to the first edition were colleagues of theeditors at the Johns Hopkins Hospitals, an impressive array of new authors has beenadded from all over the country reflecting the broad scope of this subspecialty. Thishandbook covers the current state of the art concisely and completely and shouldfind itself into critical care units everywhere. It serves as a useful complement toother monographs in the Humana Press Current Clinical Neurology series such asCritical Care Neurology and Neurosurgery by Jose Suarez, Seizures in Critical Careby Panayiotis Varelas, and Status Epilepticus by Frank Drislane. This second editionis published by Springer, the new parent company of Humana Press. All books inthe series can be found at www.springer.com. Daniel Tarsy, MD Professor Neurology Harvard Medical School Vice Chair, Department of Neurology Beth Israel Deaconess Medical Center ix
  8. 8. ContentsPart I  General Principles of Neurocritical Care  1 Establishing and Organizing a Neuroscience Critical Care Unit........ 3 Marek A. Mirski  2 Electrolyte and Metabolic Derangements. ............................................ . 13 Nikki Jaworski and Ansgar Brambrink  3 Fever and Infections................................................................................ . 37 Neeraj Badjatia  4 Cerebral Blood Flow and Metabolism: Physiology and Monitoring........................................................................................ 51 Jeremy Fields and Anish Bhardwaj  5 Multimodality Monitoring in Acute Brain Injury................................ 61 Kristine H. O’Phelan, Halinder S. Mangat, Stephen E. Olvey, and M. Ross Bullock  6 Cerebral Edema and Intracranial Hypertension.................................. 73 Matthew A. Koenig  7 Cardiac Dysfunction, Monitoring, and Management.......................... . 89 Andrew Naidech  8 Airway Management and Mechanical Ventilation in the NCCCU.......................................................................................... 99 Paul Nyquist  9 Blood Pressure Management.................................................................. 115 Ameer E. Hassan, Haralabos Zacharatos, and Adnan I. Qureshi10 Nutrition in Neurocritical Care.............................................................. 123 Tara Nealon xi
  9. 9. xii Contents11 Sedation, Analgesia, and Neuromuscular Paralysis............................. 145 Marek A. Mirski12 Postoperative Care................................................................................... 173 W. Andrew Kofke and Robert J. Brown13 Care Following Neurointerventional Procedures. ................................ 217 . Yahia M. Lodi, Julius Gene Latorre, Jesse Corry, and Mohammed Rehman14 Ethical Issues and Withdrawal of Life-Sustaining Therapies............. 247 Wendy L. Wright15 Collaborative Nursing Practice in the Neurosciences Critical Care Unit.................................................................................... 265 Filissa M. CasertaPart II  Specific Problems in Neurocritical Care16 Coma and Disorders of Consciousness.................................................. 277 Edward M. Manno17 Acute Encephalopathy............................................................................. 287 Robert D. Stevens, Aliaksei Pustavoitau, and Tarek Sharshar18 Traumatic Brain Injury. ......................................................................... 307 . Geoffrey S.F. Ling and Scott A. Marshall19 Acute Myelopathy.................................................................................... 323 Angela Hays and Julio A. Chalela20 Ischemic Stroke........................................................................................ 341 Neeraj S. Naval and Anish Bhardwaj21 Intracerebral Hemorrhage. .................................................................... 353 . Neeraj S. Naval and J. Ricardo Carhuapoma22 Intraventricular Hemorrhage................................................................. 365 Kristi Tucker and J. Ricardo Carhuapoma23 Subarachnoid Hemorrhage..................................................................... 371 Eric M. Bershad and Jose I. Suarez24 Brain Injury Following Cardiac Arrest................................................. 389 Romergryko G. Geocadin
  10. 10. Contents xiii25 Meningitis and Encephalitis.................................................................... 409 Barnett R. Nathan26 Cerebral Venous Sinus Thrombosis....................................................... 421 Agnieszka A. Ardelt27 Neuroleptic Malignant Syndrome, Malignant Hyperthermia, and Serotonin Syndrome......................................................................... 435 Panayiotis N. Varelas and Tamer Abdelhak28 Brain Tumors .......................................................................................... 445 Sherry Hsiang-Yi Chou29 Hydrocephalus......................................................................................... 469 . Michel T. Torbey30 Neuromuscular Disorders....................................................................... 475 Jeremy D. Fields and Anish Bhardwaj31 Status Epilepticus..................................................................................... 489 Marek A. Mirski32 Deep Venous Thrombosis and Pulmonary Embolism.......................... 505 Wendy C. Ziai33 Neurocritical Illness During Pregnancy and Puerperium................... 523 . Chere Monique Chase and Cindy Sullivan34 Brain Death and Organ Donation.......................................................... 533 Alexander Y. Zubkov and Eelco F.M. WijdicksIndex.................................................................................................................. 541
  11. 11. ContributorsTamer Abdelhak Departments of Neurology and Neurosurgery, Henry Ford Hospital,Detroit, MI, USAAgnieszka A. ArdeltUniversity of Chicago, Departments of Neurology and Surgery (Neurosurgery),Division of Neurocritical Care, 5841 South Maryland Ave MC2030,Chicago, IL 60637, USANeeraj BadjatiaDepartments of Neurology and Neurosurgery,Columbia University, New York, NY 10032, USAEric M. BershadDepartment of Neurology, Baylor College of Medicine,One Baylor Plaza, MS NB302, Houston,TX 77030, USAAnish BhardwajDepartment of Neurology, Tufts UniversitySchool of Medicine, Tufts Medical Center, Box 314,800 Washington Street, Boston, MA 02111, USAAnsgar BrambrinkDepartment of Anesthesiolgy, Oregon Health and Science University,3181 SW Sam Jackson Park Road,Portland, OR 97239, USARobert J. BrownDepartment of Neurology, Hospital of the University of Pennsylvania,Philadelphia, PA, USAM. Ross BullockDepartment of Neurological Surgery,University of Miami Miller School of Medicine, Miami, FL, USA xv
  12. 12. xvi ContributorsJ. Ricardo CarhuapomaNeurosciences Critical Care Division, Johns Hopkins University School ofMedicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore,MD 21287, USAFilissa M. CasertaNeurosciences Critical Care Unit,Johns Hopkins University School of Medicine, 600 N. Wolfe Street - Meyer8-140, Baltimore, MD 21287-7840, USAJulio A. ChalelaMedical University of South Carolina, PO BOX 250606, Charleston,SC 29425, USAChere Monique ChaseForsyth Comprehensive Neurology, 2025 Frontis Plaza Boulevard,Greystone Professional Center, Suite 102, Winston-Salem, NC 27103, USASherry 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, USAJesse CorryUpstate Medical University, Syracuse, NY, USAJeremy D. FieldsDepartment of Neurology, Oregon Health and Science University,Portland, OR, USARomergryko G. GeocadinDivision of Neuroscience Critical Care, Johns Hopkins University Schoolof Medicine, 600 North Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USAAmeer E. HassanZeenat Qureshi Stroke Research Center, Department of Neurology,University of Minnesota, Minneapolis, MNAngela HaysMedical University of South Carolina, Charleston, SC, USANikki JaworskiDepartment of Anesthesia and Peri-operative Medicine,Oregon Health and Science University, Portland ORMatthew A. KoenigAssociate Medical Director of Neurocritical Care,The Queen’s Medical Center, Neuroscience Institute–QET5,1301 Punchbowl Street, Honolulu, HI 96813, USA
  13. 13. Contributors xviiW. Andrew KofkeDepartments of Anesthesiology and Critical Care, Department of Neurosurgery,Hospital of the University of Pennsylvania, 3400 Spruce Street - 7 Dulles,Philadelphia, PA 19104, USAJulius Gene LatorreNeurosciences Critical Care Unit and Neurocritical Care Fellowship Program,Upstate Medical University, Syracuse, NY, USAGeoffrey S.F. LingCritical Care Medicine for Anesthesiology and Surgery,Uniformed Services University of the Health Sciences,4301 Jones Bridge Rd. Bethesda, MD 20814, USAYahia M. LodiDivision of Cerebrovascular Program and Services,Vascular/Neurological Critical Care Neurology and Envovascular SurgicalNeuroradiology, Upstate Medical University and University Hospital, SUNY, NYand Department of Neurology, 813 Jacobsen Hall, 750 East Adams Street,Syracuse, NY 13210, USAHalinder S. MangatDepartment of Neurology, University of Miami Miller School of Medicine,Miami, FL, USAEdward M. MannoMayo Clinic School of Medicine,200 First St. SW, Rochester, MN 55905, USAScott A. MarshallUniformed Services University of the Health Science, Bethesda, MD, USAMarek A. MirskiDepartment of Anesthesiology and Critical Care Medicine,Johns Hopkins University School of Medicine, 600 N. Wolfe Street,Meyer 8-140, Baltimore, MD 21287, USAAndrew NaidechDepartment of Neurology, Northwestern University, FeinbergSchool of Medicine, Neuro/Spine ICU, Northwestern Memorial Hospital,Chicago, IL 60611-3078, USABarnett R. NathanDepartment of Neurology and Internal Medicine, University of Virginia Schoolof Medicine, PO Box 800394, Charlottesville, VA 22908, USANeeraj S. NavalNeurosciences Critical Care Fellowship Program,Oregon Health and Science University, Portland, OR, USA
  14. 14. xviii ContributorsTara NealonJohns Hopkins University School of Medicine, Baltimore, MD, USAPaul NyquistDepartment of Neurology, Anesthesiology and Neurological Surgery,Johns Hopkins University School of Medicine,600 North Wolfe Street – Phipps 126, Baltimore,MD 21287, USAStephen E. OlveyDepartment of Neurology, University of Miami Miller School of Medicine,Miami, FL, USAKristine H. O’PhelanAssistant Professor Director of Neurocritical CareDepartment of Neurology, University of Miami Miller School of Medicine,Miami, FLTarek SharsharHospital Raymond Poincare, University of Versailles, Versailles, FranceRobert D. StevensNeurosciences Critical Care Division, Johns Hopkins University Schoolof Medicine, Department of Anesthesiology and Critical Care Medicine,Division of Neurosciences Critical Care, 600 North Wolfe Street - Meyer 8-140,Baltimore, MD 21287, USAJose I. SuarezDepartment of Neurology, Baylor College of Medicine, One Baylor Plaza,MS NB302, Houston, TX 77030, USAKristine H. O’PhelanDepartment of Neurology, University of Miller School of Medicine,Miami, FL, USAKristi TuckerDepartments of Neurology and Anesthesiology/Critical Care,Wake Forest University Health Sciences, Winston-Salem, NC, USAPanayiotis N. VarelasDepartments of Neurology and Neurosurgery, Henry Ford Hospital,Detroit, MI, USAAliaksei PustavoitauJohns Hopkins University School of Medicine,Baltimore, MD, USA
  15. 15. Contributors xixAdnan I. QureshiZeenat Qureshi Stroke Research Center, Department of Neurology,University of Minnesota, Minneapolis, MNMohammed RehmanDepartment of Neurology, Upstate Medical University, Syracuse, NY, USACindy SullivanNeurocritical Care Program, Novant Health Systems,Forsyth Medical Center, Winston-Salem, NC, USAM.T. TorbeyDepartment of Neurological Surgery and Neurology, Medical Collegeof Wisconsin, Department of Neurology, 9200 W.Wisconsin Avenue,Milwaukee, WI 53226, USAEelco F.M. WijdicksDepartment of Neurology and Neurological Surgery, Mayo Clinic School ofMedicine, 200 First Street SW, Rochester, MN 55905, USAElco A. WidjicksProfessor of NeurologyChair, Division or Critical Care NeurologyMayo Clinic and Mayo College of Medicine, Rochester, MNWendy L. WrightEmory University School of Medicine, 1365B Clifton Rd.,NE, Ste. 6200, Atlanta, GA 30322, USAHaralabos ZacharatosZeenat Qureshi Stroke Research Center, Department of Neurology,University of Minnesota, Minneapolis, MNWendy C. ZiaiDepartment of Neurology and Neurological Surgery,Johns Hopkins University School of Medicine, 600 N. Wolfe Street – Meyer8-140, Baltimore, MD 21287, USAAlexander Y. ZukbovStroke Center, Fairview Southdale Hospital, Minneapolis Clinic of Neurology,Rochester, MN, USA
  16. 16. Part IGeneral Principles of Neurocritical Care
  17. 17. Chapter 1Establishing and Organizing a NeuroscienceCritical Care UnitMarek A. Mirski■ 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 ♦ background ♦ Greater case efficiency of neurosurgical and neurointerventional cases♦ ♦ Efficient ICU management♦ ♦ Hub of clinical neuroscience communication♦ ♦ Academic clinical neuroscience concentration♦ ♦ Hospital hub for stroke, acute brain, and spinal cord injury centers♦ ♦ Neurocritical-trained nursing♦ ♦ Cohesive and comprehensive rounds♦ ♦ Neurologic monitoring – capable and savvy♦ ♦ Sensitive neurologic evaluations♦ ♦ Precisely match therapeutics to neurologic pathophysiology♦ ♦ Shorter lengths of stay (LOS) for patient in both the ICU and hospital♦ ♦ Improved patient outcomes♦ ♦ Increased regional referral network♦ ♦ Enhanced marketing strategy♦■ NCCU requires consensus-driven support from medical center ♦ Medical center administration♦ ♦ Neurology♦ ♦ Neurosurgery♦ ♦ Radiology♦ ♦ Anesthesiology♦M.A. Mirski, MD, PhD (*)Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University Schoolof Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USAe-mail: mmirski@jhmi.eduA. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, 3DOI 10.1007/978-1-4419-6842-5_1, © Springer Science+Business Media, LLC 2011
  18. 18. 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 populations • Neurology – for intracranial hemorrhage (ICH), data has been published that compared general ICU care versus NCCU; Cumulative survival enhanced in NCCU (Fig. 1.1) • Patients with ischemic stroke – data demonstrates reduced ICU and hospi- tal LOS and improved the disposition of patients • Patients 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 neurosciencespeciality critical care unit. There is approximately an additional 10 percent survival benefit aftera 10 day ICU length of stay. Data from Diringer 2001
  19. 19. 1  Establishing and Organizing a Neuroscience Critical Care Unit 5Fig. 1.2  Comparative hospital outcome data from patients with intracerebral hemorrhage (ICH)treated in general medical-surgery intensive care unit (ICU) versus a neuroscience subspecialtyICU (NSICU). GCS = Glasgow Coma Scale score; Rehab = rehabilitation; LOS = total hospitallength of stay; SEM = standard error of the mean. Data from Mirski 2001 ♦ Improvement in ICU efficiency of care and ICU LOS♦ • Shorter ICULOS leads to reduction in cost and increased case-load profitability • For neurology patients, reduction of LOS from 4.2 ± 4.0 to 3.7 ± 3.4 following development of an NCCU; another series reports a reduction in LOS to 2.0 ± 0.9 NCCU days compared to 3.0 ± 0.2 for comparable patients in MICU • For neurosurgery patients, LOS post-craniotomy for tumor and traumatic brain injury reduced post-implementation of specialty NCCU compared to general surgical ICU model of care: (DRG 001-craniotomy; DRG 002-; DRG 027-; DRG 028-) (Fig. 1.3)■ Hospital argument for NCCU ♦ Improvement in ICU efficiency of care and cost of care♦ • Subspecialty intensivist can minimize cost of services due to recognition of patient condition and diagnoses based on precise and focused 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
  20. 20. 6 M.A. MirskiFig. 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 neurosurgeryseverity 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 withor without intracerebral hemorrhage or coma; A-DRGs 027 and 028 = skull fracture with andwithout hemorrhage or coma; SEM = standard error of the mean. Data from Mirski, 2001 ♦ 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 neurointensivist • Documentation improved from 32.5 to 57.5% [Odds Ratio 2.8; 95% Confidence Interval (CI), 1.9–4.2] in the after period; documentation using Glasgow Coma Scale, clot volume, Hunt & Hess scale, and Fisher grade also improved significantly in each of the diagnoses examined in the after period■ Nationally – Studies by Leapfrog Group support neurointensivists ♦ ICU data clearly demonstrate decreased mortality in intensivist-run ICU ♦ model • Leapfrog group examined nine published studies on intensivist-driven ICU care and found that relative reductions in mortality rates associated with intensivist-model ICUs ranged from 15 to 60% • Leapfrog Group conclusion – using a conservative estimate of effective- ness (15% reduction), full implementation of intensivist-model ICUs would save ~53,850 lives each year in the US
  21. 21. 1  Establishing and Organizing a Neuroscience Critical Care Unit 7Fig.  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 principalneurosurgery 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-DRGs027 and 028 = skull fracture with and without hemorrhage or coma; SEM = standard error of themean. Data from Mirski, 2001 ♦ Further evidence♦ • A meta-analysis of 26 relevant observational studies of alternative staffing strategies revealed that high-intensity staffing was associated with a lower ICU mortality, with a pooled estimate of the relative risk for ICU mortality of 0.61 (95% CI, 0.50–0.75) • High-intensity staffing reduced hospital LOS in 10 of 13 studies and reduced ICU LOS in 14 of 18 studies without case-mix adjustment ♦ Neurointensivists – Support of staffing models and Leapfrog key standards ♦ (http://www.leapfroggroup.org/media/file/Leapfrog) • Intensivists are present in the ICU during daytime hours 7 days/week, with no other clinical duties during this time • Return >95% of pages within 5 min • Rely on a physician (e.g., fellow or resident) or nonphysician extender who is in the hospital and able to reach ICU patients in <5 min during non-daylight hours
  22. 22. 8 M.A. MirskiFig. 1.5  Hospital savings from implementation of The Leapfrog Groups Intensive Care UnitPhysician 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 netcosts are demonstrated for the worst-case scenario (diamonds) sensitivity analysis. Data fromPronovost 2006 ♦ Cost savings of intensivist coverage♦ • Data demonstrate intensivist coverage renders considerable savings to medi- cal center • Neurointensivists offer additional ICU staffing options for hospital in pro- viding necessary expertise to critical care • Survey and analysis suggest savings across 6-, 12-, and 18-bed ICU designs (Fig. 1.5) ♦ Leapfrog ramification: Further need for additional intensivists♦ • US hospitals manage 5,980 US ICUs; ~55,000 patients/day p Non-teaching, community hospitals (pn = 4,245; 71% of hospitals) p Hospitals of <300 beds (pn = 3,710; 62%) p Combined medical-surgical ICUs (pn = 3,865; 65%) p One in four ICUs are described as “high-intensity” (pn = 1,578; 26%) p Half have no intensivist coverage (pn = 3,183; 53%) p Remainder have some intensivist presence (pn = 1,219; 20%)■ Key components to NCCU successful staffing model ♦ Specialty-trained neurointensivists♦ • 2-Year accredited fellowship
  23. 23. 1  Establishing and Organizing a Neuroscience Critical Care Unit 9 • Ideal: three intensivists for 8–12-bed NCCU; intensivists perform aca- demic activity or other non-ICU clinical duty 2 of 3 weeks • On-service 1–2 weeks per shift; 24/7 responsibility most common current format • If one neurointensivist: typical model is as hospital/ICU consultant • Two neurointensivists: minimum to establish functional unit and offer 24/7 schedule • >3 Neurointensivists – provide opportunities for advanced academics or expanded clinical function – stroke unit, intermediate care unit coverage, neurology or neurosurgery hospitalist function ♦ Closed unit design♦ • Using several metrics of staffing and outcomes (see below), closed ICU model has been demonstrated to be more effective • 10–14 ICU beds considered ideal range for ICU physician management ♦ Specialty-trained NCCU nursing♦ • Expertise with neurologic examination • Detect subtle neurologic findings consistent with deteriorating exam • Comprehend and administer neurologically specialized therapeutics • Familiar with long-term functional outcomes, accept patience in clinical management • Intelligent patient and family interaction; allay concerns and fears of 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) p Literature does not clearly support one model of critical care delivery p over another p Dedicated ICU personnel, specifically the intensivist, the ICU nurse, p respiratory care practitioner, and pharmacist, all work as a team p Multidisciplinary 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) p While leading the critical care service, the intensivist physician should p have no competing clinical responsibilities (Grade E recommendation) p ICUs with an exclusive critical care service and operating in the closed p format, as described previously, may have improved outcomes; when
  24. 24. 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) p 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). p 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
  25. 25. 1  Establishing and Organizing a Neuroscience Critical Care Unit 11■ 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 DRG • Income from surgical and interventional procedures • Complexity of admissions – APR-DRG-based coding ♦ Hospital improves revenue to cost ratio by:♦ • Lower LOS per each DRG; hence, from improved ICU efficiency • Lower cost per patient day • Fewer medical complications • Solid referral pattern for high reimbursement DRGs and procedures • Increase in high complexity procedures (operations, etc.) per ICU bed due to higher turnover potential by specialty neurointensivist-managed ICUKey Points■ Neurointensivist-managed NCCU offers expertise to provide improved outcome with lower cost/patient and ICU LOS■ This model has historically been financially beneficial to hospital administra- tion, despite increase in medical center ICU physician poolSuggested ReadingAngus 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 34:1016–1024Diringer 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
  26. 26. 12 M.A. MirskiMirski 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 13:83–92Pronovost PJ, Angus DC, Dorman T et al. (2002) Physician staffing patterns and clinical outcomes in critically ill patients: a systematic review. JAMA 288:2151–2162Pronovost 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–S24Suarez 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 32:2311–2317Varelas PN, Spanaki MV, Hacein-Bey L (2005) Documentation in medical records improves after a neurointensivist’s appointment. Neurocrit Care 3:234–236Varelas 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 9:293-299Young MP, Birkmeyer JD (2000) Potential reduction in mortality rates using an intensivist model to manage intensive care units. Eff Clin Pract 3:284–289
  27. 27. Chapter 2Electrolyte and Metabolic DerangementsNikki Jaworski and Ansgar BrambrinkAcid – 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 <7.35■ pH is a measure of the hydrogen ion concentration in the extracellular fluids and is determined by the pCO2 and HCO3 concentration ♦ [H♦2] (meq/L) = 24 × (PCO2/HCO3)■ The initial change in PCO2 or HCO3 is called the primary disorder; the subse- quent change is called the compensatory or secondary disorder■ Compensatory changes frequently will not return the pH to the normal range but will serve to limit the effect of the primary derangement■ Acid – base disorders are of particular concern in neurophysiology because of their effects on cerebral blood flow (CBF)■ Acidosis (decrease in pH) results in cerebral vasodilation, whereas alkalosis (increase in pH) results in cerebral vasoconstriction ♦ As pH increases, cerebral vasoconstriction also increases, resulting in ♦ decreased CBF and therefore decreased cerebral blood volume and ICP■ Changes in acid – base status within the blood are transmitted across the 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 CO2 + H2O to H+ and HCO3 by carbonic anhydraseN. Jaworski, MDDepartment of Anesthesia and Peri-operative Medicine,Oregon Health and Science University, Portland ORA. Brambrink, MD (*)Department of Anesthesiolgy, Oregon Health and Science University,3181 SW Sam Jackson Park Road, Portland, OR 97239, USAe-mail: brambrin@ohsu.eduA. Bhardwaj and M.A. Mirski (eds.), Handbook of Neurocritical Care: Second Edition, 13DOI 10.1007/978-1-4419-6842-5_2, © Springer Science+Business Media, LLC 2011
  28. 28. 14 N. Jaworski and A. Brambrink■ The pH of the CSF returns to normal after 6–8 h, as HCO3 is either retained or extruded across the BBB despite ongoing hyper- or hypocapnia, respectively■ As the CSF pH returns to normal, CBF also trends toward normalPrimary Acid: Base Disorders■ Respiratory acidosis – increased PaCO2 ♦ Compensation – subsequent increase in HCO♦3 ♦ Neurologic consequence♦ • CBF increases 1–2 mL/100 g/min for each 1 mmHg change in PaCO2 within the PaCO2 range of 20–80 mmHg • Hypoventilation and hypercapnia can exacerbate an already elevated intracranial pressure in a patient with cerebral edema ♦ Etiology♦ • Hypoventilation • Increased CO2 production from hypermetabolic state such as hyperthermia, fever, or seizures • Decreased cardiac output, resulting in accumulation of CO2 in blood and tissues■ Respiratory alkalosis – decreased PCO2 ♦ Compensation – subsequent decrease in HCO♦3 ♦ Neurologic consequence♦ • CBF decreases 1–2 mL/100 gm/min for each 1 mmHg change in PaCO2 within the PaCO2 range of 20–80 mmHg • Decreased CBF due to hypocapnia/hyperventilation can be detrimental to brain tissue that is already suffering from ischemia ♦ Hyperventilation can be a useful method for temporarily decreasing CBF and ♦ ICP in patients at risk for impending herniation ♦ Etiology♦ • Hyperventilation■ Metabolic acidosis – decreased HCO3 ♦ Compensation – subsequent decrease in PaCO♦2 (hyperventilation) ♦ Neurologic consequence♦ • Primarily a result of the compensatory change in PaCO2 • Hypoxia (PaO2 <60 mmHg) rapidly increases CBF most likely due to cere- bral vasodilation induced by lactic acid ♦ Differential includes anion gap vs. non-anion gap♦
  29. 29. 2  Electrolyte and Metabolic Derangements 15 ♦ Anion gap = Na – (Cl♦− + HCO3) = 12 (±4) • Most of the normal anion excess is due to albumin ♦ An elevated anion gap is due to the addition of fixed anions♦ • Lactic acid, ketoacidosis, end-stage renal failure, methanol, ethanol, 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 HCO3 ♦ Compensation – subsequent increase in PCO♦2 (hypoventilation) ♦ Neurologic consequence♦ • Again, this is primarily due to the compensatory change in PaCO2, result- ing in increased CBF ♦ Etiology♦ • Administration of NaHCO3 • Contraction alkalosis from overdiuresis (kidney retains HCO3 ions to maintain electrical neutrality while losing Cl- ions) • Any time the loss of chloride ions exceeds the loss of sodium ions (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 disturbances■ They may occur as a part of the disease process, or they may be iatrogenic■ If unrecognized or persistently severe, the consequences of electrolyte derange- ment may become life threatening■ Sodium ♦ Sodium cannot move freely across cell membranes and is the primary deter-♦ minant of tonicity or effective osmolarity ♦ Isosmotic solutions have the same number of dissolved particles, regardless ♦ of the amount of water that would flow across a given membrane barrier • In contrast, solutions are isotonic when they would not cause water to move across a membrane barrier, regardless of the number of particles dissolved • Example – 150 mM NaCL added to plasma is approximately isosmotic & isotonic to brain, and little water is therefore passed between plasma and brain.
  30. 30. 16 N. Jaworski and A. Brambrink • 150 mM alcohol in water, however, is isosmotic but hardly isotonic (it is quite hypotonic), as it readily passes into brain, with water also following, thus promoting edema ♦ Tonicity is the primary determinant of total body water as well as the distribu-♦ tion of body water between the intracellular and extracellular compartments • Hypernatremia and hyponatremia are disorders of water balance rather than disorders of sodium balance because it is the movement of water between the intra- and extracellular compartments that results in the change in serum sodium concentration • For any given serum sodium concentration (hypo-, eu-, hypernatremia), the actual amount of total body sodium may be low, normal, or high, which means that each state can actually be a hypo-, iso-, or hypertonic state, respectively ♦ During normal homeostasis, total body water is tightly coupled to total body ♦ sodium; for example, an excess of total body sodium (eating a really salty meal) results in the kidneys retaining more free water, and thus eunatremia is maintained; however, in some disease states, the body’s compensatory 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 state ▲ Azotemia – excess urea can result in an increase in total body water, ▲ leading to hyponatremia; however, as urea moves freely across cellular membranes this is actually an isotonic state ▲ Psychogenic polydipsia▲ ▲ Syndrome of inappropriate antidiuretic hormone secretion (SIADH)▲
  31. 31. 2  Electrolyte and Metabolic Derangements 17 N ADH is normally secreted when an increase in plasma osmolarity is detected by the hypothalamus or a decrease in plasma volume is detected by the peripheral and central baroreceptors N ADH secretion is considered inappropriate when the above criteria are not present or when it is secreted in the setting of low serum osmolarity N Findings include ° Urine is inappropriately concentrated (>100 mOsm/kg 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/L ° Extracelluar fluid volume remains normal or slightly elevated° N Etiology ° Exact etiology is unclear° ° SIADH may be associated with brain tumors, subarachnoid hemor-° rhage (SAH), traumatic brain injury, stroke, meningitis or encepha- litis, or may be drug induced (e.g., carbamazapine) N Other reasons for excessive ADH secretion must be ruled out; e.g., hypothyroidism, mineralocorticoid insufficiency, hypotension, 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 water ▲ Adrenal 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▲ N Characterized by excessive sodium loss accompanied by excess water loss; most likely due to impaired sodium reabsorption in the proximal renal tubule ° Theories are plentiful, but the impaired sodium reabsorption may ° be due to decreased sympathetic input to the kidneys or due to the release of natriuretic peptides, such as brain natriuretic peptide, by injured brain N Laboratory evaluation is similar to that for SIADH, with exception of extracellular fluid volume ° Urine volume will be normal or high° ° Plasma is hypotonic (<280 mOsm/kg H°2O) ° Urine sodium excretion remains >20 meq/L° ° Extracellular fluid volume becomes increasingly depleted°
  32. 32. 18 N. Jaworski and A. Brambrink N Primary distinguishing features between CSW and SIADH are pres- ence of hypovolemia and a negative sodium and fluid balance N CSW shares many of the same associated disease states as SIADH; recent evidence suggests that many conditions previously thought to be associated with SIADH such as meningitis, SAH, TBI, and pitu- itary surgery are more likely to be associated with CSW due to the presence of hypovolemia N Restoration of a positive sodium balance requires the infusion of hypertonic saline and may require the use of fludrocortisone, a syn- thetic mineralocorticoid N SAH ° Hyponatremia is the most common and severe electrolyte abnor-° mality after SAH ° Hypovolemia and hyponatremia are likely due to CSW and occur ° 2–10 days after aneurysm rupture; they are frequently associated with cerebral vasospasm and are particularly concerning, as they further increase the risk of delayed cerebral ischemia • High sodium stores – excess of sodium and water, with the water gain exceeding the sodium gain ▲ Cardiac, renal, or hepatic failure▲ ♦ Neurologic manifestations♦ • Symptoms usually do not develop until serum sodium drops to <120 meq/ dL; however, a rapid decrease in serum sodium concentration is more likely to be symptomatic than chronic hyponatremia • Symptoms include headache, anorexia, nausea, vomiting, malaise, confusion, or lethargy • If untreated, symptoms may progress to metabolic encephalopathy associ- ated with cerebral edema, elevated ICP, and tonic-clonic seizures • As 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 volume • The sodium deficit may then be calculated to guide further therapy ▲ Na▲+ deficit (meq) = Normal TBW x (130 – Current Na+)
  33. 33. 2  Electrolyte and Metabolic Derangements 19 • In patients with isovolemia or hypervolemia, infusion of furosemide with isotonic fluids may be helpful • Euvolemic patients with asymptomatic hyponatremia may be treated with free water restriction alone or in combination with oral sodium supplementation • Severely symptomatic patients may require the use of hypertonic saline • Fludrocortisone ▲ A synthetic mineralocorticoid▲ ▲ May be used for mineralocorticoid replacement in patients with pri-▲ mary adrenal insufficiency ▲ May be considered in refractory CSW with ongoing losses of sodium ▲ and free water (0.1–0.2 mg daily) • Important risk – osmotic demyelination syndrome ▲ Results from a too-rapid correction of serum sodium that triggers ▲ demyelination of susceptible neurons, particularly the pons ▲ Symptoms progress over hours to days and include spastic paralysis, ▲ pseudobulbar palsy, and decreased level of consciousness ▲ Correction of serum sodium should be limited to 0.5 meq/L/h and no ▲ more than 8–10 mmol/L over 24 h to limit risk ♦ Hypernatremia♦ • Defined as a serum sodium >145 meq/L • Hypernatremia always represents a deficiency in water relative to total body sodium ▲ Normal sodium stores – loss of free water with minimal or no loss ▲ of sodium N Diabetes insipidus (DI) ° Most frequently occurs after pituitary or diencephalic surgery° ° May occur with brain neoplasms, anoxic brain injury, meningitis, ° or cerebral edema ° Injury to the hypothalamus results in insufficient secretion of ADH, ° rendering the kidneys unable to concentrate urine in the face of a rising serum osmolarity ° Diagnosis° — High urine output — Serum Osm >290 mOsm/kg — Urine specific gravity <1.010 ° Associated with loss of other electrolytes due to high urine ° output ° Is often temporary, lasting 3–5 days° ° Treatment includes vasopressin (DDAVP); sodium and serum ° osmolarity should be checked frequently, as the use of vasopres- sin in the setting of resolving DI may result in hypervolemia and hyponatremia
  34. 34. 20 N. Jaworski and A. Brambrink ° DI may be nephrogenic or neurogenic; however, nephrogenic DI ° rarely occurs in the neuro ICU ▲ Low sodium stores – loss of water greater than the loss sodium (loss of ▲ hypotonic fluid) N Excessive sweating, vomiting, or diarrhea without volume replacement N Iatrogenic ° Mannitol is frequently used in the NCCU for treatment of acutely ° elevated ICP and results in free water loss greater than sodium loss; serum osmolality and sodium should be monitored ▲ High sodium stores – gain of more sodium than water (gain of hyper-▲ tonic fluid) N Frequently iatrogenic in the NCCU; hypertonic saline is used for treatment of cerebral edema due to stroke or TBI as well as to replace sodium losses during CSW N To avoid development of symptoms, an upper limit to treatment must be set and the sodium levels must be frequently checked to ensure that levels are not rising too rapidly ♦ Neurologic manifestations♦ • Symptoms usually do not develop until Na >160 mmol/L, but a rapid increase in sodium concentration may cause symptoms at lower levels • Symptoms primarily include a decreased level of consciousness and confu- sion that may progress to tonic-clonic seizures • Intracellular 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 restored • Chronic 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
  35. 35. 2  Electrolyte and Metabolic Derangements 21 ♦ Treatment♦ • Volume status should be assessed, and hypovolemia should be treated with isotonic fluids to maintain hemodynamic stability • Free water deficit is then calculated using the following formula: ▲ TBW = total body water▲ ▲ TBW deficit = Normal TBW – Current TBW▲ ▲ Current TBW = Normal TBW x (Normal P▲Na/Current PNa) ▲ Replacement Volume = TBW deficit × (1/1 – X)▲ N X = concentration of sodium in the replacement fluid • As described above, acute hypernatremia may be corrected over a few hours as the brain is able to rapidly eliminate accumulated electrolytes • To avoid the risk of cerebral edema, chronic hypernatremia should be 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 osmolesPotassium■ Potassium is the major intracellular cation■ Only 2% of potassium stores are found extracellulary, and only 0.4% is found in plasma; therefore, serum potassium is a poor measure of total body potassium■ Total body potassium is ~50 meq/kg■ Large intracellular stores of potassium are very effective at replenishing 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 depleted■ Hypokalemia ♦ Defined as serum K < 3.5 meq/L♦ ♦ Etiology♦ • Transmembraneous shift ▲ Catecholamines (i.e., ▲b agonists) stimulate Na+/K+ ATPase activity ▲ Alkalosis – hydrogen ions are shifted extracellularly in exchange for ▲ potassium ions ▲ Hypothermia▲ ▲ Insulin enhances Na/K ATPase activity▲ ▲ Hypertonicity – the increase in electricochemical gradient favors the ▲ movement of ions out of cells ♦ Potassium depletion♦ • Renal losses
  36. 36. 22 N. Jaworski and A. Brambrink ▲ Diuretic therapy increases the distal tubular flow and sodium delivery ▲ to the distal tubule, stimulating the secretion of potassium via Na+/K+ ATPase N Mannitol is a frequently used diuretic to treat elevated ICP in the NCCU; because of its potassium wasting properties, serum K+ should be monitored and replaced as needed ▲ Mineralocorticoids▲ N Aldosterone stimulates the reabsorption of sodium and the secretion of potassium in the distal tubule N Fludrocortisone therapy is often employed in the NCCU in the treat- ment of hyponatremia in the context of CSW; serum potassium levels should be monitored and replaced to avoid associated hypokalemia ▲ ADH stimulates potassium secretion at the distal tubule independent ▲ from its water-retaining effects ▲ Magnesium depletion▲ N Impairs potassium reabsorption across the renal tubules ▲ High-dose steroids used to treat spinal cord injury and 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 conduction • Hypokalemia can be associated with nonspecific EKG changes, including U waves, flattening or inversion of T waves, and prolongation of the QT interval • Hypokalemia promotes cardiac dysrhythmia when combined with other pro-dysrhythmic conditions such as ischemia, digitalis toxicity, or 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 dysrhythmia ▲ Stroke patients frequently have coexisting cardiac disease; for example, ▲ the case of an embolic stroke due to atrial fibrilliation with a patient who not only has coexisting cardiac disease but also receives digoxin for adequate heart rate control
  37. 37. 2  Electrolyte and Metabolic Derangements 23■ Hyperkalemia ♦ Defined as serum K♦+ >5.5 meq/L ♦ Transmembraneous shift♦ • b antagonists/digitalis • Acidosis • Rhabdomyolysis ▲ Occasionally, patients with neurologic disease are found after being ▲ unconscious for an unknown period of time; a high level of suspicion for rhabdomyolysis is indicated in these patients, and serial creatinine kinase and potassium level checks are indicated ♦ Impaired renal excretion♦ • Renal insufficiency, renal failure • Adrenal insufficiency • Drugs ▲ ACE inhibitors/adrenergic receptor binders▲ ▲ K▲+-sparing diuretics ▲ NSAIDs▲ ▲ Heparin – e.g., patients with ischemic stroke may be placed on a hepa-▲ rin infusion ▲ Antibiotics – trimethoprim-sulfamethozaxole, potassium penicillin▲ • Blood transfusion ▲ Potassium leaks from erythrocytes in stored blood▲ ▲ The extra potassium is normally cleared by the kidneys, but in circula-▲ tory shock that requires transfusion greater than one blood volume, potassium can accumulate and result in hyperkalemia ♦ Clinical relevance♦ • Slowing of electrical conduction within the heart can begin at levels of 6.0 meq/L and is almost always present by 8.0 meq/L; progressive EKG changes occur ▲ Peaked T waves → flattened P waves → lengthened PR interval → loss ▲ of P waves with prolonged QRS → ventricular fibrillation → asystole • Hyperkalemia is a relatively uncommon electrolyte abnormality in NCCU patients; however, it can occur, particularly in those who have coexisting renal failureMagnesium■ 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
  38. 38. 24 N. Jaworski and A. Brambrink■ Magnesium acts as a cofactor for many enzymatic reactions involving ATP ♦ Regulates the movement of calcium into smooth muscle cells, rendering it ♦ important for cardiac contractility and vascular tone ♦ Regulates calcium influx into neuronal cells via glutamate receptor – associated ♦ ion channels; magnesium partially blocks the receptor and reduces calcium 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 ♦ Clinical relevance♦ • Symptoms include exacerbation of neurologic dysfunction, apathy, delir- ium, muscle weakness, hyperreflexia, muscle spasms, ataxia, nystagmus, and seizures • Associated electrolyte abnormalities ▲ Hypokalemia and hypocalcaemia can be refractory to replacement ▲ therapy in the setting of hypomagnesemia ▲ Low magnesium impairs the release of parathyroid hormone and 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 N Acts as an endogenous calcium-channel antagonist N Inhibition of release of excitatory neurotransmitters such as glutamate
  39. 39. 2  Electrolyte and Metabolic Derangements 25 N NMDA-receptor antagonism N Direct vascular smooth muscle relaxation ▲ 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 admission ▲ Relationship between low magnesium levels, SAH, and myocardial ▲ stunning remains unclear ▲ Combination of low magnesium with stunned myocardium represents ▲ a pro-dysrhythmic state, and magnesium should be replaced in these patients • Prevention of seizures – low magnesium levels reduce the seizure 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 preeclampsia • Hemolysis • Adrenal Insufficiency • Lithium intoxication • Hyperparathyroidism ♦ Clinical relevance♦ • Hypermagnesemia becomes symptomatic at levels >4 meq/L • Progress of symptoms – hyporeflexia → first degree AV Block → complete heart block → respiratory failure → cardiac arrest • Not a common problem in the NCCU but should be on the differential of patients with hyporeflexiaCalcium■ Primarily an extracellular cation that exists in protein-bound (inactive), anion- bound (inactive), and ionized (active) forms■ Tightly regulated by parathyroid hormone (PTH) and vitamin D; PTH secretion by the parathyroid gland results in increased reabsorption of calcium in the thick ascending limb and the distal tubule of the nephron
  40. 40. 26 N. Jaworski and A. Brambrink■ Calcium is the primary mediator of muscle contraction■ Calcium is of primary importance in the neurocritical care environment due to its central role in neuronal death after CNS injury ♦ Cytotoxic intracellular calcium movement is mediated via glutamate recep-♦ tors, voltage-gated calcium channels, and pH-dependent calcium channels ♦ Influx of calcium from the extracellular space and the endoplasmic reticulum ♦ results in the activation of cellular injury and death cascades■ Calcium-channel blockers ♦ The calcium-channel antagonist nimodipine has been shown to reduce the ♦ incidence of cerebral ischemia due to vasospasm following SAH and should be initiated as soon as possible following hemorrhage and continued for 21 days; a similar benefit has not been seen in stroke patients■ Hypocalcemia ♦ Defined as serum ionized Ca <1.1 mmol/L♦ ♦ Rather uncommon in the NCCU patient population♦ ♦ Relevant causes include phenytoin, phenobarbital, hypoparathyroidism after ♦ neck surgery, renal failure, and blood transfusion (citrate anticoagulant in packed red blood cells binds calcium) ♦ Respiratory alkalosis as a result of hyperventilation (i.e., for treatment of ♦ e ­ levated intracranial pressure) results in an increase in protein binding of calcium ♦ Clinical manifestations are related to cardiac and neuromuscular conduction ♦ and to depressed myocardial contractility • Cardiac findings include prolonged QT and ST intervals, decreased cardiac output, hypotension, and bradycardia, and can progress to ventricular dysrhythmias • Neuromuscular symptoms include tetany, parathesias, weakness, and seizures■ Hypercalcemia ♦ Defined as serum ionized Ca >1.3 mmol/L♦ ♦ Also relatively uncommon in the NCCU patients♦ ♦ Relevant causes include malignancies, renal failure, prolonged immobi-♦ lization, phosphorus depletion, hyperparathyroidism, lithium, and thiaz- ide diuretics ♦ Clinical manifestations involve the gastrointestinal, cardiovascular, renal, and ♦ neurologic systems • Cardiovascular – increased vascular resistance, QT shortening, occasional dysrhythmias • Neurologic – confusion, lethargy, memory impairment, weakness, h ­ ypotonia, and hyporeflexia leading to progressive obtundation and coma
  41. 41. 2  Electrolyte and Metabolic Derangements 27Phosphate■ The most abundant intracellular anion; phosphate is important for membrane structure, cellular energy, the production of ATP, cell transport, and intracellular signaling cascades■ Depletion of high-energy intracellular phosphates is considered crucial for the development of a delayed cerebral deficit in the context of cerebral vasospasm, as well as following acute cerebral ischemia■ Hypophosphatemia ♦ Defined as serum Phos <2.5 mg/dL or 0.8 mmol/L♦ ♦ Etiology♦ • TBI • Malnutrition • Hypomagnesemia or hypocalcemia • Phosphorus-binding antacids – sucralafate, aluminum salts • Drugs – diuretics, steroids, b agonists ♦ Clinical relevance♦ • Phosphate is a major component in the production of cellular energy (ATP); therefore, phosphate depletion is concerning but can be 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 alcoholics ▲ Hypophosphatemia can be profound and occurs as tissues begin to ▲ rebuild themselves upon the initiation of nutritional support N May lead to muscle weakness, including respiratory muscle weak- ness, and glucose intolerance N May be associated with other electrolyte abnormalities (hypocalce- mia, hypokalemia, or hypomagnesemia), further exacerbating muscle weakness
  42. 42. 28 N. Jaworski and A. Brambrink■ Hyperphosphatemia ♦ Defined as serum Phos >4.5 mg/dL or 1.45 mmol/L♦ ♦ Etiology♦ • Renal insufficiency • Cellular necrosis – rhabdomyolysis, sepsis, multiple trauma, tumor lysis ♦ Rapid increases in serum phosphate can lead to development of severe ♦ hypocalcemia; symptoms are related to the hypocalcemiaMetabolic 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 reasons■ Metabolic disorders and endocrinopathies should always remain in the differen- tial diagnosis of encephalopathy■ Metabolic disorders may occur as comorbidities in any patient, including neuro- surgical or neurologic patients■ Hyperglycemia ♦ Hyperglycemia (defined as blood glucose >150 mg/dL) in the setting of ischemic ♦ brain injury has been shown to be an independent predictor of poor outcome ♦ In animal studies, hyperglycemia before or during ischemic injury has been ♦ shown to increase severity of injury ♦ Elevation of blood glucose in the setting of severe ischemia or TBI is most ♦ likely due to the physiologic stress caused by the injury ♦ The exact blood glucose level at which insulin therapy should be initiated ♦ remains undefined; however, most practitioners aim to keep blood sugar l ­evels <150 mg/dL and >80 mg/dL in critically ill patients with CNS disease ♦ Two specific conditions that may result in severe hyperglycemia and may be ♦ the reason for admission to the ICU are nonketotic hypersmolar coma (NKHC) and diabetic ketoacidosis • NKHC ▲ A form of hypertonic encephalopathy similar to that of hypernatremia▲ ▲ Patients usually have enough endogenous insulin to prevent ketosis▲ ▲ Patient may or may not have a prior history of diabetes, but onset is ▲ u ­ sually precipitated by physiologic stress ▲ Encephalopathy usually presents as altered mental status but may ▲ p ­ rogress to focal deficits and seizures ▲ Findings▲ N Blood glucose usually >1,000 mg/dL N Persistent osmotic diuresis leads to profound hypovolemia ▲ Treatment▲ N Volume resuscitation with isotonic fluids or colloids
  43. 43. 2  Electrolyte and Metabolic Derangements 29 N Replacement of free water once intravascular volume has been 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 treatment N Restoration of brain cell volume may occur rapidly; therefore, vol- ume replacement should occur slowly N Insulin therapy can be initiated after volume status has been restored ° Insulin therapy via infusion: start at 0.1 unit/kg bolus + 0.1 unit/° kg/h with goal of decreasing blood glucose by 50–70 mg/dL/h; decrease infusion of insulin to 0.05 units/kg/h when a serum 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 diabetes ▲ May be seen in a previously well-controlled diabetic who is experienc-▲ ing acute physiologic stress such as infection or sepsis ▲ Findings▲ N Blood glucose usually > 250 mg/dL but <800 mg/dL N Serum bicarbonate <20 meq/L N Elevated anion gap N Ketones in blood and urine ▲ Treatment▲ N Volume resuscitation with isotonic fluids; fluid deficit is usually 100 mL/kg N Insulin therapy via infusion: start at 0.1 unit/kg bolus + 0.1 unit/kg/h with goal of decreasing blood glucose by 50–70 mg/dL/h; decrease infusion of insulin to 0.05 units/kg/h when serum glucose of 200 mg/dL has been reached N Replace potassium; correction of underlying acidosis in combina- 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 develop • Hypoglycemia increases CBF which may be detrimental to patients with elevated ICP
  44. 44. 30 N. Jaworski and A. Brambrink■ Thyroid disorders ♦ Thyroid-releasing hormone is secreted by the hypothalamus, which stimulates ♦ the anterior pituitary to release TSH (thyroid-stimulating hormone), which subsequently stimulates the thyroid gland to secrete T3, T4, and rT3 ♦ Free (non-protein bound) 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 treatment ♦ Most likely to present in elderly women, but overall, a rare disease♦ ♦ Most likely scenario is a patient with stable hypothyroidism who develops ♦ one of these precipitating factors • Hypothermia • Sepsis from any source • Stroke • Congestive heart failure • Pneumonia • Hyponatremia • Amiodarone exposure ♦ Findings♦ • Slowly declining mental status that progresses from lethargy to coma • Respiratory failure (carbon dioxide retention + hypoxemia) • Possible airway edema • Cardiac – nonspecific ST changes, bradycardia, decreased contractility, decreased cardiac output, and cardiomegaly • Hyponatremia – kidneys are unable to properly secrete free water due to decreased GFR and increased vasopressin secretion • Hypoglycemia, hypoxemia, and hyponatremia may result in reduced CBF and seizures • Findings of chronic hypothyroidism are also likely to be present – dry skin, sparse hair, periorbital and pretibial nonpitting edema, macroglossia, m ­ oderate hypothermia, and delayed deep tendon reflexes ♦ Diagnosis♦ • Diagnosis may be evident by physical findings consistent with hypo­ thyroidism in the presence of stupor or coma and concomitant hypothermia • Urinary sodium excretion is normal • Elevated TSH and low total and free T4 and T3 • Be wary of patients with suspected myxedema coma and normothermia; may actually represent a “fever” and may be a sign of associated sepsis, as these patients are usually hypothermic
  45. 45. 2  Electrolyte and Metabolic Derangements 31 ♦ Treatment♦ • Ventilatory support • Cautious warming – rapid rewarming may result in vasodilation and refractory hypotension • Glucocorticoid therapy (50–100 mg hydrocortisone q 6 h) • Circulatory support with isotonic saline and vasopressors as needed • Volume restriction versus hypertonic saline to treat the hyponatremia, depend- ing on severity; sodium levels <120 meq/L are considered more severe • Thyroid hormone therapy ▲ No optimal approach exists, although IV therapy is a common option▲ ▲ High mortality of untreated myxedema coma must be considered versus ▲ risk of high-dose thyroid hormone therapy, which includes tachyar- rhythmias and myocardial ischemiaHashimoto Encephalopathy■ Hashimoto encephalopathy is an autoimmune disorder that is related to Hashimoto thyroiditis■ Also 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 encephalopathy■ Disorder is uncommon and present more frequently in females■ Findings ♦ Initial presentation is usually that of a rapidly progressive dementia similar to ♦ prion disease; however, the encephalopathy may present as delirium or psy- chosis with a gradual or subacute onset ♦ Seizures, rigidity, movement disorders, and myoclonus may also be present, ♦ although these symptoms may develop months after initial presentation of dementia■ Diagnosis ♦ Antithyroid antibodies, including antithyroid peroxidase (also known as anti-♦ microsomal antibody) and antithyroglobulin antibody will be present ♦ TSH may be normal or elevated♦ ♦ Free 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
  46. 46. 32 N. Jaworski and A. Brambrink ♦ Pathology findings include widespread vasculitis of the CNS♦ ♦ MRI may show focal or diffuse nonenhancing abnormalities♦■ Treatment ♦ Corticosteroids are effective in 50% of cases♦ ♦ Immunosuppressants may be necessary for refractory cases♦Thyroid Storm■ A severe form of thyrotoxicosis; the distinction between severe thyrotoxicosis and thyroid storm is somewhat subjective■ Mortality approaches 20–30%■ Most common etiology is Grave disease but may also occurs with solitary toxic adenoma or toxic multinodular goiter; exposure to iodine such as iodinated c ­ ontrast or amiodarone may also precipitate thyroid storm■ Findings ♦ CNS dysfunction♦ • Agitation, delirium, lethargy, or psychosis • Progresses to seizures and coma ♦ Cardiovascular dysfunction♦ • Dysrhythmia – frequently atrial fibrillation • Congestive heart failure • Tachycardia • Hyperdynamic contractility • Decreased systemic vascular resistance due to smooth muscle relaxation and release of nitric oxide from the endothelium ♦ Hyperthermia♦ • Increased metabolic rate (increased CO2 production/O2 consumption) ♦ Gastrointestinal dysfunction♦ • Nausea/vomiting • Jaundice • Hyperglycemia may be present ♦ Adrenocortical dysfunction♦ • Thyrotoxicosis accelerates the metabolism of exogenous and endogenous cortisol • Given the degree of physiologic stress, a normal cortisol level may actually represent a relative adrenal insufficiency
  47. 47. 2  Electrolyte and Metabolic Derangements 33 ♦ Diagnosis♦ • Elevated free T4 and free T3 with decreased level of TSH (<0.05 mU/mL) ♦ Treatment♦ • Goal of management is to stop synthesis and release of thyroid hormone and to block peripheral effects of the hormone • A thionamide (propylthiouracil or methimazole) should be given first to inhibit thyroid gland synthesis • Iodine therapy (potassium iodine) should be initiated no sooner than 30–60 min after thionamide therapy; iodine therapy inhibits release of thyroid hormone; however, if it is administered prior to thionamide therapy, it will actually stimulate the synthesis of new hormone, thus aggravating the condition • Acetaminophen and active cooling to treat hyperthermia • b blockade effectively treats effects of T3 on myocardial contractility • Glucocorticoids (hydrocortisone 100 mg q 8 h) ▲ Treats relative adrenal insufficiency if present▲ ▲ Provides some inhibition of peripheral conversion of T▲4 to T3 • Avoid aspirin ▲ Salicylates decrease protein binding of thyroid hormone, thereby ▲ increasing the free fraction of circulating hormoneAdrenal 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 cortisol■ Basal daily cortisol requirements = 15–25 mg hydrocortisone■ Cortisol requirements increase substantially under stress, trauma, or illness■ Cortisol is vital for cellular metabolism, homeostasis, and for the maintenance of vascular tone; insufficiency results in hypoglycemia and hypotension that is refractory to volume resuscitation and inotropic support■ This refractory hypotension can lead to decreased cerebral perfusion pressure■ Causes of adrenal insufficiency ♦ Primary (Addison disease)♦ • Destruction of adrenal gland commonly by an autoimmune process • Absence of mineralocorticoid and glucocorticoid • If left untreated, patients present with profound adrenal insufficiency mani- festing as hypotension, hypovolemia, and shock
  48. 48. 34 N. Jaworski and A. Brambrink ♦ Secondary (inadequate production of CRH or ACTH)♦ • Iatrogenic ▲ Chronic suppression▲ N Cortisol naturally participates in a negative feedback loop with ACTH secretion N Chronic administration of exogenous glucocorticoids results in adrenal gland atrophy and chronic suppression of the hypothalamus- anterior pituitary axis N The adrenal gland is then unable to mount an appropriate response to stress, resulting in profound hypotension, muscle weakness, and hypoglycemia ▲ Etomidate▲ N Etomidate directly inhibits cortisol synthesis by the adrenal gland; a single dose results in suppression for up to 12 h • Chronic subclinical adrenal insufficiency ▲ Chronic disease that is asymptomatic or presents with nonspecific ▲ symptoms such as weakness, dizziness, lethargy, or GI complaints ▲ Manifests as refractory hypotension in the setting of physiologic stress ▲ or infection • Pituitary injury due to hemorrhage, ischemia, surgery, compression, or trauma■ Diagnosis ♦ Random serum cortisol level♦ • > 35 mg/dL is considered normal • <15 mg/dL is considered abnormal • 15–35 mg/dL may require corticotrophin stimulation test for further differentiation■ Treatment ♦ “Stress-dose steroids” should be considered in any patient at risk for adrenal ♦ insufficiency or any patient with refractory hypotension despite volume 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