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NEUROLOGIC COMPLICATIONS
OF CRITICAL ILLNESS
SERIES EDITOR
Eva Feldman, MD, PhD, FAAN, FANA
Russell N. DeJong Professor of Neurology
University of Michigan
Contemporary Neurology Series
74 NEUROLOGIC COMPLICATIONS
OF CRITICAL ILLNESS
Third Edition
Eelco F.M. Wijdicks, MD, PhD
75 CLINICAL NEUROPHYSIOLOGY
Third Edition
Jasper R. Daube, MD, and
Devon I. Rubin, MD, Editors
76 PERIPHERAL NEUROPATHIES IN
CLINICAL PRACTICE
Steven Herskovitz, MD, Stephen N. Scelsa,
MD, and Herbert H. Schaumburg, MD
77 CLINICAL NEUROPHYSIOLIOGY OF
THE VESTIBULAR SYSTEM
Fourth Edition
Robert W. Baloh, MD, and
Kevin A. Kerber, MD
78 THE NEURONAL CEROID
LIPOFUSCINOSES (BATTEN DISEASE)
Second Edition
Sara E. Mole, PhD, Ruth D. Williams, MD,
and Hans H. Goebel, MD, Editors
79 PARANEOPLASTIC SYNDROMES
Robert B. Darnell, MD, PhD, and
Jerome B. Posner, MD
80 JASPER’S BASIC MECHANISMS OF
THE EPILEPSIES
Jeffrey L. Noebels, MD, PhD,
Massimo Avoli, MD, PhD,
Michael A. Rogawski, MD, PhD,
Richard W. Olsen, PhD, and
Antonio V. Delgado-Escueta, MD
81 MYASTHENIA GRAVIS AND
MYASTHENIC DISORDERS
Second Edition
Andrew G. Engel, MD
82 MOLECULAR PHYSIOLOGY
AND METABOLISM OF THE
NERVOUS SYSTEM
Gary A. Rosenberg, MD
83 SEIZURES AND EPILEPSY
Second Edition
Jerome Engel, Jr., MD, PhD
84 MULTIPLE SCLEROSIS
Moses Rodriguez, MD, Orhun H. Kantarci, MD,
and Istvan Pirko, MD
85 FRONTOTEMPORAL DEMENTIA
Bruce L. Miller, MD
86 AUTONOMIC NEUROLOGY
Eduardo E. Benarroch, MD
87 EVALUATION AND TREATMENT
OF MYOPATHIES
Second Edition
Emma Ciafaloni, MD, Patrick F. Chinnery,
FRCP, FMedSci, and
Robert C. Griggs, MD, Editors
88 MOTOR NEURON DISEASE IN ADULTS
Mark Bromberg, MD
89 HYPERKINETIC MOVEMENT
DISORDERS
Roger M. Kurlan, MD, Paul E. Green, MD,
and Kevin M. Biglan, MD, MPH
90 THE NEUROLOGY OF EYE MOVEMENTS
Fifth Edition
R. John Leigh, MD, FRCP, and
David S. Zee, MD
91 MIGRAINE
Third Edition
David W. Dodick, MD, and Stephen D.
Silberstein, MD
92 CLINICAL NEUROPHYSIOLOGY
Fourth Edition
Devon Rubin, MD and
Jasper Daube, MD, Editors
93 NEUROIMMUNOLOGY
Bibiana Bielekova, MD, Gary Birnbaum, MD,
and Robert P. Lisak, MD
94 PLUM AND POSNER’S DIAGNOSIS AND
TREATMENT OF STUPOR AND COMA
Fifth Edition
Jerome B. Posner, MD, Clifford B. Saper,
MD, PhD, Nicholas D. Schiff, MD,
and Jan Claassen, MD, PhD
95 CLINICAL NEUROPHYSIOLOGY
Fifth Edition
Devon I. Rubin, MD, Editor
96 PARKINSON DISEASE
Roger L. Albin, MD
97 NEUROLOGIC COMPLICATIONS
OF CRITICAL ILLNESS
Fourth Edition
Eelco F. M. Wijdicks, MD, PhD
NEUROLOGIC COMPLICATIONS
OF CRITICAL ILLNESS
Fourth Edition

Eelco F. M. Wijdicks, MD, PhD, FACP, FNCS

Professor of Neurology
Neurocritical Care Services
Department of Neurology, Mayo Clinic
Rochester, Minnesota
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Library of Congress Cataloging-in-Publication Data

Names: Wijdicks, Eelco F. M., 1954– author. |
Mayo Foundation for Medical Education and Research, sponsoring body.
Title: Neurologic complications of critical illness / Eelco F.M. Wijdicks.
Other titles: Contemporary neurology series.
Description: 4. | New York, NY : Oxford University Press, [2023] |
Series: Contemporary neurology series | Includes bibliographical references and index.
Identifiers: LCCN 2022040676 (print) | LCCN 2022040677 (ebook) |
ISBN 9780197585016 (hardback) | ISBN 9780197585030 (epub) |
ISBN 9780197585047 (online)
Subjects: MESH: Critical Illness | Neurologic Manifestations | Critical Care
Classification: LCC RC350 .N49 (print) | LCC RC350 .N49 (ebook) |
NLM W1 CO769N | DDC 616.8/0428—dc23/eng/20230315
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DOI: 10.1093/med/9780197585016.001.0001

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Contents

Preface xiii

PART I CRITERIA, URGENCY, AND IMPORTANCE

1. INDICATIONS FOR A NEUROLOGIC CONSULT IN

THE INTENSIVE CARE UNIT 3
CATEGORIES OF CONSULTS 4
BENEFITS OF A CONSULTATION 6

2. CONSULTING IN THE INTENSIVE CARE UNIT 9

PREPARATION AND HISTORY-TAKING 9
COMMON REQUESTS FOR CONSULTS IN THE ICU 10

PART II GENERAL CLINICAL NEUROLOGIC PROBLEMS IN

THE INTENSIVE CARE UNIT

3. ACUTE CONFUSIONAL STATE IN THE INTENSIVE CARE UNIT 19

TERMINOLOGY 20
ASSESSMENT OF DELIRIUM 21
NEUROLOGIC EXAMINATION OF THE ACUTELY CONFUSED PATIENT 23
MANAGEMENT OF DELIRIUM 24

4. COMA AND OTHER STATES OF ALTERED AWARENESS IN THE

INTENSIVE CARE UNIT 27
DEFINITIONS OF ALTERED STATES OF CONSCIOUSNESS 27
NEUROLOGIC EXAMINATION OF THE COMATOSE PATIENT 32
CAUSES OF COMA 39
NEUROLOGIC EXAMINATION IN BRAIN DEATH 39

v
vi Contents

5. NEUROLOGIC MANIFESTATIONS OF MUSCLE RELAXANTS AND

DRUGS USED FOR ANALGESIA AND ANESTHESIA IN THE
INTENSIVE CARE UNIT 47
PRINCIPLES OF PHARMACODYNAMICS AND PHARMACOKINETICS IN
CRITICAL ILLNESS 48
EFFECT OF DRUGS ON NEUROMUSCULAR JUNCTION 51
EFFECT OF DRUGS ON LEVEL OF CONSCIOUSNESS 55

6. SEIZURES IN THE INTENSIVE CARE UNIT 63

GENERALIZED TONIC–CLONIC SEIZURES 64
DRUG-INDUCED AND DRUG-WITHDRAWAL SEIZURES 64
SEIZURES AND ACUTE METABOLIC DERANGEMENTS 67
SEIZURES AND STRUCTURAL CENTRAL NERVOUS SYSTEM
ABNORMALITIES 68
CONVULSIVE STATUS EPILEPTICUS 68
NONCONVULSIVE STATUS EPILEPTICUS 72
MANAGEMENT OF SEIZURES AND STATUS EPILEPTICUS 73
OUTCOME 79

7. GENERALIZED WEAKNESS IN THE INTENSIVE CARE UNIT 85

GENERAL CONSIDERATIONS 86
DISORDERS OF THE SPINAL CORD 86
DISORDERS OF PERIPHERAL NERVES 88
DISORDERS OF THE NEUROMUSCULAR JUNCTION 92
DISORDERS OF SKELETAL MUSCLE 93

8. ACUTE FOCAL NEUROLOGIC FINDINGS AND ASYMMETRIES IN

THE INTENSIVE CARE UNIT 103
GENERAL CONSIDERATIONS IN LESION LOCALIZATION 103
BRAIN INJURY PATTERNS 108

9. ACUTE MOVEMENT ABNORMALITIES IN THE INTENSIVE CARE UNIT 111

SEMIOLOGY 112
EMERGENT AND URGENT MOVEMENT ABNORMALITIES 115
 Contents vii

PART III NEUROLOGIC COMPLICATIONS IN MEDICAL AND SURGICAL

INTENSIVE CARE UNITS AND TRANSPLANTATION UNITS

10. NEUROLOGIC COMPLICATIONS OF INVASIVE PROCEDURES IN

THE INTENSIVE CARE UNIT 123
NEUROTOXICITY OF RADIOLOGIC CONTRAST AGENTS 124
CHOLESTEROL EMBOLIZATION 124
AIR EMBOLISM 126
NEUROLOGIC COMPLICATIONS ASSOCIATED WITH SPECIFIC
PROCEDURES 127

11. NEUROLOGIC MANIFESTATIONS OF ACUTE BACTERIAL INFECTIONS

AND SEPSIS 147
BACTERIAL MENINGITIS 147
SPINAL EPIDURAL ABSCESS 151
INFECTIVE ENDOCARDITIS 154
CLOSTRIDIAL SYNDROMES 161
SEPSIS 164

12. NEUROLOGIC MANIFESTATIONS OF VIRAL OUTBREAKS 175

WEST NILE VIRUS NEUROINVASIVE DISEASE 176
TICK- AND MOSQUITO-BORNE ENCEPHALITIS 179
ENDEMIC INFLUENZA 180
SARS-COV-2 (COVID-19) PANDEMIC 183

13. NEUROLOGIC COMPLICATIONS OF CARDIAC ARREST 189

GENERAL CONSIDERATIONS IN RESUSCITATION MEDICINE 190
POSTRESUSCITATION ENCEPHALOPATHY 193
SUPPORTIVE CARE 203
SPECIFIC TREATMENT AND TARGETED TEMPERATURE MANAGEMENT 204

14. NEUROLOGIC MANIFESTATIONS OF ACID–BASE DERANGEMENTS,

ELECTROLYTE DISORDERS, AND ENDOCRINE CRISES 215
ACID–BASE DISORDERS 215
ELECTROLYTE DISORDERS 219
ENDOCRINE EMERGENCIES 232
viii Contents

15. NEUROLOGIC COMPLICATIONS OF ACUTE RENAL DISEASE 249

UREMIC ENCEPHALOPATHY 249
DIALYSIS DYSEQUILIBRIUM SYNDROME 253
POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME 255
NEUROMUSCULAR DISORDERS 260

16. NEUROLOGIC MANIFESTATIONS OF ACUTE HEPATIC FAILURE 269

GENERAL CONSIDERATIONS 270
HEPATIC ENCEPHALOPATHY 270
BRAIN EDEMA IN FULMINANT HEPATIC FAILURE 275

17. NEUROLOGIC COMPLICATIONS ASSOCIATED WITH DISORDERS

OF THROMBOSIS AND HEMOSTASIS 289
GENERAL CONSIDERATIONS 289
DISSEMINATED INTRAVASCULAR COAGULATION 290
THROMBOLYSIS AND ANTICOAGULATION 291
NEOPLASTIC COAGULOPATHIES 295
THROMBOTIC THROMBOCYTOPENIC PURPURA 297

18. NEUROLOGIC COMPLICATIONS OF ACUTE VASCULITIS SYNDROMES 305

GENERAL CONSIDERATIONS 305
LARGE-VESSEL VASCULITIS 307
POLYARTERITIS NODOSA 308
CHURG-STRAUSS SYNDROME 312
GRANULOMATOSIS WITH POLYANGIITIS 313
DRUG-INDUCED VASCULITIS 315

19. NEUROLOGIC COMPLICATIONS IN THE CRITICALLY ILL

PREGNANT PATIENT 321
NEUROLOGY OF PREGNANCY 321
ECLAMPSIA 323
HELLP SYNDROME 326
AMNIOTIC FLUID EMBOLISM 328
NEUROLOGIC COMPLICATIONS OF TOCOLYTIC AGENTS 328
 Contents ix

20. NEUROLOGIC COMPLICATIONS OF CANCER IN THE ICU 333

GOALS OF CARE IN CRITICAL ILLNESS AND ADVANCED CANCER 334
NEURO-ONCOLOGIC EMERGENCIES 334
PARANEOPLASTIC ENCEPHALITIS 336
COMPLICATIONS OF RADIATION AND CHEMOTHERAPY 338
COMPLICATIONS OF CANCER IMMUNOTHERAPY 340

21. NEUROLOGIC COMPLICATIONS OF AORTIC SURGERY 343

SCOPE OF THE PROBLEM 344
VASCULAR ANATOMY OF THE SPINAL CORD 346
NEUROLOGIC FEATURES OF SPINAL CORD INFARCTION 348
DIAGNOSTIC EVALUATION OF SPINAL CORD INFARCTION 350
THERAPEUTIC OPTIONS 353
PLEXOPATHIES 354
AORTIC DISSECTION 354

22. NEUROLOGIC COMPLICATIONS OF CARDIAC SURGERY 361

GENERAL CONSIDERATIONS 362
ISCHEMIC STROKE 366
NEUROPSYCHOLOGIC IMPAIRMENT 373
SEIZURES 374
RETINAL DAMAGE 374
PERIPHERAL NERVE DAMAGE 375

23. NEUROLOGIC COMPLICATIONS OF ACUTE ENVIRONMENTAL

INJURIES 385
THERMAL BURNS 385
SMOKE INHALATION 389
ELECTRICAL BURNS 392
LIGHTNING INJURY 393
ACCIDENTAL HYPOTHERMIA 395
HEAT STROKE 397
NEAR-DROWNING 399
x Contents

24. NEUROLOGIC COMPLICATIONS OF DRUG OVERDOSE, POISONING,

AND TERRORISM 407
THE PRESENTING EMERGENCY AND PRINCIPLES OF TREATMENT 408
SPECIFIC POISONINGS 410
BIOLOGICAL AND CHEMICAL WARFARE 419

25. NEUROLOGIC COMPLICATIONS OF TRAUMATIC BRAIN INJURY 429

CLINICAL SPECTRUM OF HEAD INJURY 430
NEURORADIOLOGIC FINDINGS IN HEAD INJURY 430
GENERAL PRINCIPLES OF MANAGEMENT 440
MANAGEMENT OF INCREASED INTRACRANIAL PRESSURE 442
MANAGEMENT OF TRAUMATIC INTRACRANIAL HEMATOMAS 444
WAR-RELATED BRAIN INJURY 446
MANAGEMENT OF TRAUMATIC CEREBRAL ANEURYSM 446

26. NEUROLOGIC COMPLICATIONS OF TRAUMA TO THE SPINE,

SPINAL CORD, AND NERVES 455
TRAUMA OF SPINE AND SPINAL CORD 455
ACUTE SPINAL CORD INJURY 464
POSTTRAUMATIC NEUROPATHIES ASSOCIATED WITH FRACTURES 467
FAT EMBOLISM SYNDROME 468

27. NEUROLOGIC COMPLICATIONS OF ORGAN TRANSPLANTATION 473

SURGICAL TECHNIQUES OF ORGAN TRANSPLANTATION 474
NEUROLOGIC COMPLICATIONS IN TRANSPLANT RECIPIENTS 479
NEUROLOGIC COMPLICATIONS OF GRAFT-VERSUS-HOST DISEASE 501

PART IV OUTCOME IN CENTRAL NERVOUS SYSTEM CATASTROPHES

28. OUTCOME OF ACUTE INJURY TO THE CENTRAL NERVOUS SYSTEM 513

DESCRIPTION OF OUTCOME CATEGORIES 514
OUTCOME IN ENCEPHALOPATHIES 516
OUTCOME IN STROKE 522
OUTCOME IN HEAD INJURY 524
 Contents xi

OUTCOME IN TRAUMATIC SPINE INJURY 525

OUTCOME IN CENTRAL NERVOUS SYSTEM INFECTIONS 525

PART V CONSULTATIVE NEUROLOGY AND END-OF-LIFE CARE IN

THE INTENSIVE CARE UNIT

29. THE NEUROLOGIST AND END-OF-LIFE CARE IN THE INTENSIVE

CARE UNIT 533
GENERAL CONSIDERATIONS 534
LEGAL ASPECTS OF WITHDRAWAL OF TREATMENT 534
DECISIONS IN WITHDRAWAL OF TREATMENT 535
WITHDRAWAL OF TREATMENT 536
WITHDRAWAL OF TREATMENT IN SPECIAL NEUROLOGIC
CIRCUMSTANCES 537
BRAIN DEATH AND ORGAN DONATION 538
CARDIAC DEATH AND ORGAN DONATION 539

30. THE NEUROLOGIST AND ICU ETHICAL DILEMMAS 545

PRINCIPLES OF COMMUNICATION WITH FAMILIES 546
HOPE 547
FUTILITY 548
GUIDING A FAMILY CONFERENCE 548
THE ETHICS OF COMPASSIONATE SEDATION 550
THE COURTS 550

Index 553
Preface

Writ large in this book is the premise that the evaluation of a critically ill patient with a neurologic
manifestation or complication is the most demanding neurology consultation. This book, when
first published in 1995, provided a practical guide for every disquieted neurologist who entered
the intensive care unit (ICU). Just about what, as a young neurologist, I would have liked to have
known. Keeping this book up to date requires multiple editions because intensive care is one of
the fastest growing and changing specialties. Now, more than 25 years later, we can look back at
the extraordinary expansion in knowledge of critical illness and better understanding of this field
of neurology. Intensivists understand the issues involved and appreciate that a neurologic com-
plication in any medical or surgically critically ill patient is a major cause of mortality and later
morbidity. If recognized in time, treatment of a neurologic complication may greatly improve the
outcome. But neurocritical care in all its forms is also at times informed uncertainty, and many
clinical observations are not understood.
The framework of consults has also changed. New diseases have appeared, such as neurologic
complications of cancer immunotherapy, and older diseases, such as cyclosporine neurotoxicity
in transplant patients, have become rare occurrences. Neurotoxicities of drugs are better under-
stood (e.g., serotonin syndrome and cefepime neurotoxicity). Recent mosquito- and tick-borne
illness (e.g., Zika virus, Chikungunya, and Eastern equine encephalitis) in the United States has
resulted in intensive care admissions. The world since 2019 has been shaken by the SARS-CoV-2
pandemic with its multiple surges and no ICU spared. The pandemic has been a revelation,
certainly since the end of 2021, when ICUs (and morale) were at a breaking point as a result of
treating an unacceptably large number of unvaccinated patients who became infected with the
delta variant. Neurologic complications of SARS-CoV-2 infection have emerged, and this damaging
respiratory virus became the most common reason to consult neurologists, who, like their colleagues
in other specialties, had the disadvantage of dealing with a new disease. It is a prime example of how
suddenly ICU populations can change and have changed again in 2023.
The new edition has responded to changes in ICU care and changes in the ICU population and
is now thoroughly updated. I have added criteria for consultation and how to co-manage patients.
A consultation is often contingent on the following five perceptions: (1) an evolving situation that
requires neurologic expertise; (2) “something” might not be recognized; (3) an unusual CT scan
that does not appear to explain the condition; (4) movements that could indicate seizures requiring
expert evaluation and electroencephalography (EEG); and (5) the patient’s condition looks grim
but needs corroboration, and the family may request a neurologic opinion. All this is addressed.
Neurologic consultations are often requested when patients remain comatose after CPR, and the
neurologist is asked to have the last word. Failure to awaken after surgery or after extended seda-
tion has been discontinued are other typical examples that trigger a request. We have an obligation
to provide the best evaluation and management when the outcome can go either way. We also
have an obligation to evaluate for futility. Neurologic consultation not only provides diagnostic,
therapeutic, and prognostic advice but may also change the approach to the patient. This is a major
responsibility and not one to be taken lightly.
This edition also has new chapters on the interpretation of focal findings, acute movement
disorders in critical illness, cancer immunotherapy, and ethical dilemmas. A separate section
on interpretation of EEG requests (and how to use it in critically ill patients) is added. Several
new drugs (direct oral anticoagulants [DOACs] and chimeric antigen receptor T-cell therapy
[CAR-T]) have made their way into the ICU and are discussed in detail because their side effects
require specific intervention. There is a wealth of new tables, algorithms, and neuroimaging. I
have added a new section of advice for practical management to each chapter to reconcile theory
and practice.

xiii
xiv Preface

ICUs are challenged with an increasingly growing (and aging) population, and admissions are
increasing. Neurologic complications will increase, too. This clinical text will be helpful to a very
wide audience of healthcare providers and, in particular, for any intensivist and general neurologist
who must manage these patients with extremely complex medical disorders, surgeries, comorbid-
ity, and with different clinical trajectories. The book is also aimed at neurointensivists who consult
in ICUs other than their own. This book reaches beyond neurology and additionally targets emer-
gency physicians, neurosurgeons, transplant and vascular surgeons, internal medicine hospitalists,
pharmacists, allied healthcare providers, and ICU nursing staff.
I appreciate the help of so many. Lea Dacy not only dutifully edited the full manuscript, but
she has always been absolutely necessary to improve the prose. I am grateful for the work by the
illustrators of Mayo Clinic Media Support service and, in particular, David Factor, who predictably
provided beautiful and informative drawings. I appreciate my long-time working relationship with
Oxford University Press, and they are peerless when it comes to academic work.
The interest in the acute neurosciences in practice is the unexpected. I have lived the subject
matter for several decades, and our neurocritical care group sees several hundred patients in ICUs
other than our own Neurosciences ICU each year. I hope the book I set out to write reflects that
experience. The diagnosis and management of neurologic complications in critical illness, in my view,
has always been one of the major pillars of neurocritical care.
March 2023
Eelco Wijdicks
PART I

Criteria, Urgency, and

Importance
Chapter 1
Indications for a Neurologic Consult
in the Intensive Care Unit
CATEGORIES OF CONSULTS
BENEFITS OF A CONSULTATION
Teams working in intensive care units (ICUs) may
bring in a neurologist and for all kinds of reasons.1
When called to action, most neurologists enter-
ing an ICU are immediately confronted with the
complexity of critical illness. The modern ICU is
a unique place, with patients presenting with an
array of different conditions and with consultants
having specific expertise in handling critical ill-
ness. Patients enter the ICU in a life-threatening
state with failing organ systems and become
hypotensive, hypoxemic, hypercapnic, and tachy-
cardic; the initial resuscitation generally does not
concentrate on neurologic manifestations. Most
intensivists briefly check for pupil responses or
major asymmetries, but they accept an altered
level of consciousness as a common consequence
of an evolving critical illness. Some manifesta-
tions may not be considered atypical enough
for an urgent neurologic consult. This logically
implies that neurologists will see a selection of
neurologic manifestations in critical illness.
ICU consultative neurology focuses on those
patients admitted to medical and surgical ICUs
presenting with a de novo neurological prob-
lem related to their illness—questions . . . and
issues concerning the effects of antiseizure and
antiparkinson medication for prior diagnosed
illness are entirely different. These patients
are seen in consultation for diagnosis and
management—often expediently—but remain
under the care of intensivists and surgeons.
The complications observed may be quite spe-
cific (or mundane), but intensivists may intui-
tively feel uncomfortable in overseeing these
new neurologic conditions themselves. They
request not only assistance in identifying the
neurologic disorder but also help in manage-
ment. This is particularly pertinent with recur-
rent seizures or progressive neurologic decline.
Once the patient is seen, continuous attention
is necessary, which may involve prolonged bed-
side care and, later, calls at night from nursing
staff or attending intensivists and, ultimately,
direct management. Interpretation of electro-
encephalograms and neuroimaging is often
repeatedly required.2
3
4 Part I Criteria, Urgency, and Importance
More than in any place in the hospital, ICU
consultations involve questions about de-escalating
care. The attending team and family may consider
withdrawing intensive care or, at least, consider
a do-not-resuscitate status and thus need a neu-
rologist’s input. This involvement partly reflects
the high prevalence of neurologic catastrophes
in patients with a critical illness. Frequently, the
clinical situation is clear, as in persistently coma-
tose survivors after prolonged cardiopulmonary
arrest and in elderly patients with polytrauma
and severe traumatic brain injury; in other situ-
ations, the degree of brain injury may be more
difficult to ascertain. Neurologists are asked
to participate in family conferences, and they
can be helpful in clarifying the bigger picture.
Sometimes, the neurologic complication is a
defining moment, and little more can be done for
the patient. Neurologists can be conclusive and
advise the managing ICU team against treating
a patient in a futile situation. In other situations
the neurologic situation could be misjudged as
irrecoverably poor while there is a possibility for
another more favorable trajectory. This is not an
uncommon scenario, and neurologists can shed
more light on why they think that way. Another
fundamental rule of ICU consultation is to prog-
nosticate decisively when certain but to hold back
when information is incomplete or the clinical
situation is not fully understood.
Critical illness increases the probability of
a neurologic complication, and, according to
current best estimates and excluding perva-
sive delirious states, approximately 10–20% of
patients will develop some sort of neurologic
manifestation. The neurology of critical illness
is an important field that requires more pro-
spective research. The rationale for neurologic
Table 1.1 The field of neurology of
critical illness
Neurologic consultation in the ICU requires a
broad base of medical knowledge
Neurologic consultation provides diagnostic,
therapeutic, and prognostic advice
Neurologic consultation often involves assessment
of abnormalities of responsiveness or seizures
Neurologic consultation may detect an unsuspected
neurologic disorder
Neurologic consultation in the ICU may change
approach to the patient
Neurologic consultation involves end-of-life
decisions for patients
consultation is summarized in Table 1.1 and
shows common clinical neurologic problems
facing the intensive care specialist and consult-
ing neurologist in everyday decisions.
CATEGORIES OF CONSULTS
We must assume that ICU consults are urgent
or emergent. The urgency is often determined
by an inability to understand the full clinical pic-
ture and particularly when the initial presenta-
tion is disturbing. Examples are ICU consults for
acutely impaired consciousness, which require
a quick but comprehensive assessment of the
cause of coma and whether it can be immediately
reversed. Upon receiving a call to consult in the
ICU, we typically expect three clinical scenarios:
acute loss of consciousness, failure of patients
to awaken fully after recuperation from a major
surgical procedure, and occasionally, coma in a
developing but undiagnosed critical illness. We
are often consulted to evaluate and treat delirium,
and we now have a better sense of what this acute
brain dysfunction could entail.3–6
Any consult in a critically ill neurologic
patient must proceed through the steps out-
lined in Table 1.2. Any consult in a critically
ill patient may lead to a diagnosis not initially
considered by the managing team; in our expe-
rience, this occurs rather frequently.7 These
recognized neurologic disorders may all have
major consequences diagnostically, prognosti-
cally, and therapeutically.
Consultations may have a varying degree of
complexity and may involve management of
major acute neurologic injury. Consultation
may evolve from a simple question, to being
physically present, to continuously managing
Table 1.2 Essentials of a neurology
consult in the intensive care unit
Assess details on severity of critical illness
Assess blood pressure and extent of blood pressure
support
Assess drug administration over 5–7 days
Verify onset of symptoms with nursing staff
Assess major confounders
Assess for focal localizing sign
Assess for movements, twitching, new rigidity
Assess for drugs strongly related to movement
disorders

Table 1.3 Reasons for a consult in the
intensive care unit
Acutely comatose
Failure to awaken after resuscitation
Acute focal deficit
Acute agitation
New seizure(s)
Acute repetitive movements
Generalized weakness
Abnormal neuroimaging
Abnormal EEG
an acute injury to the brain or spine and, as
such, may even involve palliation and end-of-
life discussions (Table 1.3).
There is a spectrum of close participation
with the consulting neurologist (Figure 1.1).
In some cases, a consult consists of picking up
the phone and asking an expert, and in many
Figure 1.1. Types of consultations.
1 Indications for a Neurologic Consult 5
intensive care practices, it is often easier to call
a consultant rather than to ask for a formal con-
sult. Both parties often agree that some type of
advice will pragmatically direct testing or treat-
ment. For the intensivist, there may be other
immediately pressing priorities in the complex
care of the patient, and a new neurologic prob-
lem is best solved quickly. Many of the neurology
“curbsides” in the ICU are indeed simple phone
calls to ask a simple question, but some ques-
tions should probably generate a formal consult.
Consultants should generally and deliberately
avoid a practice of mostly taking phone calls for
curbsides, which are a set of quick questions that
pertain to critical illness. These include interpre-
tation of a CT scan of the brain, a question about
electroencephalograph (EEG) interpretation, or
the need for EEG monitoring. Other common
questions are how to manage neurologic medi-
cation such as antiepileptic drugs, assess the risk
of anticoagulation, or interpret specific neuro-
logic manifestations of acute neurologic disease.
It is often better to see the patient briefly and
then determine if a formal consult can be helpful.
The consulting neurologists will also have
to consider the following questions. How can
I best ask pointed questions? Am I able to
provide advice with limited information and
without having the opportunity to examine
the patient in detail? Am I confident enough
to dismiss or diagnose certain CT scan abnor-
malities? Does this clinical problem require a
close follow-up and thus a formal consultation?
Acute (STAT) consults in the ICU are the
most challenging in the hospital because (1)
decisions may have to be made in an evolving
situation; (2) the primary diagnosis may be
unclear and puzzling; (3) neurologic exami-
nation can be compromised when patients
are markedly swollen, jaundiced, immobile,
bruised, or have major operation sites or an
open chest; and (4) none of the neuroimaging
and electrophysiology results may be particu-
larly helpful. Any consulting neurologist will
ask him- or herself the following additional
questions: Are the neurologic findings com-
mensurate with the cause and degree of criti-
cal illness? Are the focal findings significant
or difficult to judge? How is neuroimaging or
electrophysiology best interpreted in the set-
ting of critical illness?2,8–10 Are there urgent
treatment options or treatment adjustments
that have not been considered? Will this neu-
rologic manifestation set the patient back
6 Part I Criteria, Urgency, and Importance
permanently? Can I provide a reliable opin-
ion on the future likelihood of full depen-
dence for the patient, and could this opinion
put an end to the aggressive, constantly esca-
lating care?
BENEFITS OF A CONSULTATION
The need for broad knowledge of critical care
could argue for a separate hospital service
staffed by experienced neurohospitalists or
neurointensivists. It goes to the heart of a long-
standing academic and clinical question (and,
in some centers, a charged debate): Who is
best qualified to see these patients? Many of
us are caught unaware by a variety of presenta-
tions, and as long as experience is gained, it is
better gained by a specialized group. We have
seen several conditions emerge more clearly
as a result of covering all ICU consults with
our neurocritical care services in both Mayo-
affiliated hospitals.
Telemedicine could be ideal for these con-
sults,11–16 but accurate metrics will need to be
developed to show benefit. These could include
(1) seizure control, (2) acute stroke care, (3)
neurosurgical intervention, (4) control of intra-
cranial pressure, and (5) limiting potent seda-
tive drugs and avoiding drug-drug interactions.
Ultimately, a full neurologic examination
leads to new tests (EEG, somatosensory evoked
potential [SSEP], CT scan, MRI, and CSF). All
these tests are highly neurospecific, and recom-
mendations of what to test or add to routine
orders require good communication and, most
importantly, accurate interpretation.
PRACTICAL ADVICE
• A major principle of consultation in the
ICU is to see the patient immediately rather
than paying a belated visit. A serious neuro-
logic illness requiring immediate interven-
tion might go unrecognized. Moreover, the
entire clinical picture may be unclear and
evolving, and neurologic expertise may point
toward the right direction.
• Treatments may be inappropriate, incom-
plete, and incorrect. Errors happen easily
even in the best-equipped, well-staffed ICUs.
• Neurologists should appreciate the pharma-
cology of sedative drugs and use of analgesic
drugs to provide a better assessment.
• Direct communication with the intensivist
might provide a comprehensive clinical course
and timeline of when events occurred.
• Direct communication with the surgeon on
the surgical procedure and possible intra-
operative events can decrease evaluation time
and capture important intraoperative compli-
cations such as hypotension or even CPR.
• The circumstances surrounding critical ill-
ness could make the patient vulnerable to
seizures. However, few patients in the ICU
have seizures; many more undergo EEGs.
Proportionality is necessary.
• A universal question is whether failure to
wean from a ventilator is due to a previously
unappreciated and undiagnosed neurologic
disorder. Early diffuse weakness in ICU may
be undiagnosed amyotrophic lateral sclero-
sis. Late diffuse weakness in ICU is often
sepsis-related or critical illness–associated
polyneuromyopathy.
REFERENCES
1. Wijdicks EFM. Why you may need a neurologist to
see a comatose patient in the ICU. Crit Care. 2016
Jun 20;20(1):193.
2. Rabinstein AA. Continuous electroencephalog-
raphy in the medical ICU. Neurocrit Care. Dec
2009;11(3):445–6. doi:10.1007/s12028-009-9260-6
3. Brown CH. Delirium in the cardiac surgical ICU.
Curr Opin Anaesthesiol. Apr 2014;27(2):117–22.
doi:10.1097/ACO.0000000000000061
4. Ely EW, Shintani A, Truman B, et al. Delirium
as a predictor of mortality in mechanically venti-
lated patients in the intensive care unit. JAMA. Apr
2004;291(14):1753–62. doi:10.1001/jama.291.14.1753
5. Hughes CG, Patel MB, Pandharipande PP.
Pathophysiology of acute brain dysfunction:
What’s the cause of all this confusion? Curr Opin
Crit Care. Oct 2012;18(5):518–26. doi:10.1097/
MCC.0b013e328357effa
6. Pandharipande PP, Girard TD, Jackson JC, et al.
Long-term cognitive impairment after critical ill-
ness. N Engl J Med. Oct 2013;369(14):1306–16.
doi:10.1056/NEJMoa1301372
7. Mittal MK, Kashyap R, Herasevich V, Rabinstein
AA, Wijdicks EF. Do patients in a medical or sur-
gical ICU benefit from a neurologic consultation?
Int J Neurosci. 2015;125(7):512–20. doi:10.3109/
00207454.2014.950374
8. Claassen J, Taccone FS, Horn P, et al. Recommendations
on the use of EEG monitoring in critically ill patients:
Consensus statement from the neurointensive care

section of the ESICM. Intensive Care Med. Aug
2013;39(8):1337–51. doi:10.1007/s00134-013-2938-4
9. Oddo M, Carrera E, Claassen J, Mayer SA, Hirsch LJ.
Continuous electroencephalography in the medical
intensive care unit. Crit Care Med. Jun 2009;37(6):2051–
6. doi:10.1097/CCM.0b013e3181a00604
10. Young GB. Continuous EEG monitoring in the ICU:
Challenges and opportunities. Can J Neurol Sci. Aug
2009;36 Suppl 2:S89–91.
11. Guinemer C, Boeker M, Furstenau D, et al. Telemedicine
in intensive care units: Scoping review. J Med Internet
Res. Nov 2021;23(11):e32264. doi:10.2196/32264
12. Lilly CM, McLaughlin JM, Zhao H, et al. A multi-
center study of ICU telemedicine reengineering of
adult critical care. Chest. Mar 2014;145(3):500–507.
doi:10.1378/chest.13-1973
1 Indications for a Neurologic Consult 7
13. Lilly CM, Zubrow MT, Kempner KM, et al. Critical
care telemedicine: Evolution and state of the art. Crit
Care Med. Nov 2014;42(11):2429–36. doi:10.1097/
CCM.0000000000000539
14. Weiss B, Paul N, Balzer F, Noritomi DT, Spies
CD. Telemedicine in the intensive care unit: A
vehicle to improve quality of care? J Crit Care. Feb
2021;61:241–6. doi:10.1016/j.jcrc.2020.09.036
15. Welsh C, Rincon T, Berman I, et al. TeleICU inter-
disciplinary teams. Crit Care Nurs Clin N Am.
2021;33:459–70.
16. O’Shea AM, Reisinger HS, Panos R, et al.
Association of interactions between Tele-critical
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tality. J Telemed Telecare. 2022 Jun 29. doi:
10.1177/1357633X221107993
Chapter 2
Consulting in the Intensive Care Unit
PREPARATION AND HISTORY-TAKING
As implied earlier, consults in the intensive
care unit (ICU) to evaluate and manage an
acute neurologic clinical problem are in stark
contrast to other requested hospital con-
sults. As this book demonstrates, neurologic
complications of critical illness are usually
of considerable complexity.1–11 Even enter-
ing the ICU can make one feel unsettled,
especially when patients have major trauma,
open chest or abdominal wounds, multiple
ongoing medical complications, and certainly
when patients are connected to an extra-
corporeal membrane oxygenation machine.
Some comatose patients are markedly swol-
len, jaundiced, and immobile. And then there
is polypharmacy with many potent sedatives.
In these situations, an adequate neurologic
assessment may seem a worthless undertak-
ing (Figure 2.1).
The clinical interpretation of a vexing neu-
rologic problem in the ICU requires skill and
full understanding of its immediacy. Before
we dive into the nitty-gritty of neurological
consultation in the medical and surgical ICU,
this chapter paints the larger picture of what
a neurologic consult in the ICU could entail.
COMMON REQUESTS FOR CONSULTS
IN THE ICU
PREPARATION AND
HISTORY-TAKING
First and foremost, gathering essential infor-
mation may be difficult, with some of this
information hidden in not easily accessible
drop-down menus on the patient’s monitor.
In other cases, particularly in recently trans-
ferred patients with long ICU stays, informa-
tion must be abstracted from an excessive
number of notes of variable granularity.
The second step is to gain an understanding
of the severity of the patient’s critical illness.
Two main factors must be taken into consider-
ation: history and recent clinical course. In the
ICU, the history is often reconstructed from
fragments of observations by the patient’s fam-
ily, nursing observations, attending consultant
notes, and, less often, from communication
with the patient. Therefore, the patient’s his-
tory could be potentially inaccurate, seriously
limiting a full assessment of neurologic com-
plications. A simple matter-of-fact question
such as “When were these signs first noted?”
may be difficult to answer reliably. In such
complex cases, direct communication with the
9
10 Part I Criteria, Urgency, and Importance
Figure 2.1. Critically ill 77-year-old man in a cardiovascular intensive care unit. The complexity of care (mechanical ventila-
tion, dialysis, and multipharmacy) can seriously hinder the neurologic examination for consulting physicians.
attending intensivist or surgeon is required and
could decrease evaluation time substantially.
As a rule, consultants evaluating patients
with a postoperative complication also need
to have a good understanding of the opera-
tive technique and surgical decisions (e.g.,
avoidance measures, anesthetic interventions).
Consultants evaluating patients with neuro-
logic manifestations of the CNS in the setting
of a major medical illness must be aware of the
patient’s prior hemodynamic instability, degree
of organ dysfunction, coagulation status, and
pharmacy regimen. For patients with general-
ized weakness, consultants must determine the
patient’s prior use of neuromuscular blockers
and intravenous corticosteroids and should be
able to correctly interpret electrodiagnostic
studies.
COMMON REQUESTS FOR
CONSULTS IN THE ICU
Most consults are prompted by very specific
neurologic signs that have been detected by
the nursing staff or attending physician during
rounds. Obviously, the threshold for consulting
a neurologist is variable and depends on the
recognition of neurologic signs and the comfort
level of some intensivists—less familiar with
disorders of the nervous system—in handling
these complications. In other circumstances,
the patient’s failure to improve medically (e.g.,
inability to be liberated from the ventilator),
acute coma, or failure to become fully coher-
ent and alert over a matter of days after surgery
may trigger a consultation.1,3,7 There may also
be a convincing need to transfer the patient to
a more specialized neurosciences ICU.
These situations are challenging for both
the neurologist approaching the bedside and
the intensivist trying to grasp the full clinical
picture. The quality and amount of informa-
tion available to the consulting neurologist can
be disconcerting. The consult request may be
summarized in only a few words (“new neu-
rologic event,” “periodic twitching,” or “unre-
sponsive”). Several consults are about pupil
asymmetries (because the eyes are exam-
ined frequently), and most are not concern-
ing. Another common but potentially urgent
category is the patient with “altered mental
status.” The term “altered mental status” has
achieved classic standing, although not for
its accuracy because it may mean anything.
This category of neurologic deficits—patients
who are agitated and less responsive—may

appear less worrisome. Patients are confused
and may not respond quickly, rarely fixate on
objects, and cannot follow simple commands.
Some can speak; others are unable to respond.
We assume that, in most situations, these
patients have an acute brain dysfunction from
sepsis-associated encephalopathy, new-onset
acute renal or liver failure, or a combination.
Posterior reversible encephalopathy syndrome
(PRES) is so prevalent that it is often listed at
the top of the differential diagnosis and, if the
circumstances are right, should be investigated
with MRI. Unfortunately, for many years, neu-
rologists had a tendency to describe any patient
with an encephalopathy as having “multifacto-
rial metabolic encephalopathy” and would list
the abnormalities that make up the patient’s
critical illness. None of this advanced an
understanding of these complicated patients.
More experience in examining and following
these patients has resulted in better efforts
to understand the true nature of acute brain
dysfunction. One principle is to set apart the
major driver of neurologic manifestations, but
it is equally accepted now to consider other
possible explanations such as structural injury.
Acute confusional state or delirium may trig-
ger a consult, but many intensivists recognize
this entity and treat it appropriately.3–6 Without
a doubt, the most difficult situation is to assess
a patient with decreased or increased arousal,
abnormal perception, abnormal attention, and
incoherent language. Within this category of
patients are those with apraxia and aphasia
(Chapter 3). Many ICU patients have agitated
delirium or “sundowning” due to preexisting
dementia or alcohol withdrawal. An unex-
plained observation is that delirium correlates
with prolonged ICU stay (and increased mor-
tality), but none of the clinical trials that have
aggressively treated patients in delirium have
shown an improved mortality rate.
There are some other urgent consults.
Consults for new-onset seizures or new move-
ment abnormalities are comparatively fre-
quent. A new focal finding (e.g., hemiparesis or
marked asymmetry) is less common. Consults
are often for newly perceived asymmetries. It is
a major challenge to recognize an acute stroke
during a critical illness or after a major vascular
procedure. Patients may have a delayed pre-
sentation or delayed recognition, particularly
when anesthetic drugs have been used and
are still washing out in the postoperative phase
2 Consulting in the ICU 11
of surgery. The challenge here is early recog-
nition to allow an endovascular intervention
because IV thrombolysis is contraindicated.
Acute ischemic stroke may warrant endovascu-
lar treatment if the situation allows. (CT scan
may already show a matured infarct.) Consults
in surgical and trauma ICUs are often related
to diagnostic evaluation of new spinal cord
injury and traumatic brain injury, but in most
instances, other specialties are involved (i.e.,
neurosurgery).
A special category is consultation for a trans-
plant recipient. This may have already started
before transplantation (e.g., fulminant hepatic
failure) because the attending intensivist or
surgeon values the presence of a neurologist.
Another special category is the patient admit-
ted with a left ventricular assist device (LVAD)
and new neurologic symptoms. Discussions
on discontinuing or improving anticoagulation
often involve a neurologist.
In the surgical ICU, consults may involve
the sudden appearance of paraplegia after
awakening from anesthesia. Acute spinal cord
infarction might indicate immediate placement
of a lumbar drain to reduce CSF spinal pres-
sure and improve residual spinal blood flow. In
each of these scenarios, prompt decisions are
warranted and can improve outcome if proper
measures are taken. Urgent consultation for a
possible complication of carotid artery surgery
involves assessment for possible ischemic stroke
or management of blood pressure and heart
rate instability. (The latter is mostly managed
by a neurointensivist, but a general neurolo-
gist should be aware of this major complication
involving damage to the baroreceptors.)
Generalized weakness in the ICU is very
common and nearly always prompts a neuro-
logic consult. Most neurologists expect (and
diagnose) critical illness polyneuropathy, criti-
cal illness myopathy, or both. One could argue
that, in fact, this myopathy is the most com-
mon cause of weakness in the ICU. The preva-
lence of ICU-acquired weakness is high in
survivors of critical illness and will increase as
more patients survive multiorgan failure, sep-
sis, and other fulminant infections. Failure to
wean off the ventilator (or unexplained reintu-
bations) is another trigger for a comprehensive
neurologic assessment, and a neurologic disor-
der other than critical illness polyneuropathy
may be found. Finally, consults may involve
an explanation of neuroimaging findings or the
12 Part I Criteria, Urgency, and Importance
interpretation of an ordered electroencepha-
lograph (EEG) in a patient with an undefined
repetitive movement).
Failure to awaken or prolonged unconscious-
ness is a very common consult, and requests
may be vague and not immediately alarming
(“altered mental status”). Such a consult needs
an immediate response; the neurologist must
see and examine the patient.
Several issues are pertinent. (More details
on examination and classification are found in
Chapter 4.)
First, a patient’s failure to awaken after
urgent cardiovascular repair is an ominous
sign. A devastating ischemic stroke involving
multiple arterial territories is a frequent cause
of failure to awaken.7 Its mechanism may be
hypotension or multiple emboli. Hypotension
can be implicated only if it persists for a con-
siderable period. In addition to perioperative
hypotension and cardiac resuscitation during
surgery, multiple embolic events are possible
reasons for multiple cerebral infarctions. In
some patients, the surgical approach and anes-
thetic support were without obvious distress to
the patient, and the cause for multiple cerebral
infarctions may remain unresolved. However,
the risk of embolization is significant for
patients with severe atherosclerotic disease of
the ascending aorta, and embolization almost
certainly occurs at the time of clamping.
Second, evaluation of impaired consciousness
in patients requiring intensive care for acute
medical illness starts with a series of important
questions (Table 2.1). The answers could narrow
down the list of causes of impaired conscious-
ness by a simple process of elimination.
Because triggers such as hypotension and
coagulopathies are common, neurologists
should focus on finding structural causes even if a
Table 2.1 Questions to family members and nursing staff concerning patients in
the intensive care unit with impaired consciousness
Family
• Illicit drug use?
• Alcohol abuse?
• Circumstance in which patient was found
(apneic, cyanotic, seizing)?
• Prior illness or constitutional symptoms?
• Recent medication adjustments or newly
started drugs?
• Prior, comorbid conditions?
pharmacologic cause of coma is likely. Therefore,
after location is determined, neuroimaging fol-
lows, and the combination of clinical and neuro-
imaging results can lead to specific actions. CT
of the brain (or CT angiogram in cases suggest-
ing an embolus to a major cerebral artery) is a
mandatory diagnostic test and currently has an
acquisition time of less than 10 min. A CT can
document generalized cerebral edema, cerebral
hemorrhage, and ischemic stroke with swelling,
but its diagnostic yield is low for anoxic–ischemic
brain injury and in the period early after trau-
matic head injury. If structural damage is pres-
ent, it should be correlated to the depth of coma.
A significant shift of the midline structures (sep-
tum pellucidum, calcified pineal gland) due to
a new mass, hydrocephalus, or intraventricular
hemorrhage must be recognized in patients with
rapidly deepening coma.
A normal CT scan in a patient with a meta-
bolic derangement or organ dysfunction does
not exclude a structural cause and, if feasible,
should be followed by MRI. Causes of coma
in patients with initially normal CT results are
presented in Table 2.2 for easy reference.
MRI has come to the fore as a diagnostic tool
in ICUs, and if anesthesia support is available,
it may be used to identify or exclude struc-
tural damage for comatose patients. However,
transport to the MRI suite takes the critically
ill patient out of the critical care environment,
and, once there, necessary support (vasopres-
sors, mechanical ventilator) is inadequate and,
in some instances, can jeopardize the patient’s
safety. In our experience, fewer than half of
comatose patients can be transported to the
MRI suite without difficulties. Therefore, the
yield of abnormalities and consequences for
management should be high before ordering
an MRI.
Nursing staff or attending consultant
• Intraoperative cardiopulmonary resuscitation?
• Intraoperative hypotension?
• Presence of asymptomatic interval after surgery?
• Hypotension requiring vasopressors?
• Hypoxemia requiring high level of positive
end-expiratory pressure?
• Myoclonus, eye deviation, eyelid blinking?

Table 2.2 Probable causes of coma in
critically ill patients with normal initial
CT findings
Anoxic–ischemic encephalopathy
Drug overdose
Neurotoxicity from chemotherapeutic agents or
immunosuppressive agents
Diffuse axonal brain injury
Acute central nervous system infection
Fat embolization
Acute basilar artery occlusion
Cholesterol embolization
Central pontine myelinolysis
Diffuse intravascular coagulation
Thrombotic thrombocytopenic purpura
Central nervous system vasculitis
Prolonged hypoglycemia
Acute severe hyponatremia
Acute severe hypercalcemia
Acute nonketotic hyperglycemia
Metabolic acidosis
Acute hypercapnia with hypoxemia
Adrenal crisis
Acute hypothyroidism
Acute hyperthyroidism
Acute uremia
Acute hyperammonemia
Recent laboratory values should be obtained,
and the medical records should be scrutinized
for trends. CSF examination is needed when
meningitis is suspected and should be consid-
ered in critically ill patients with spinal anes-
thesia, traumatic brain injury, trauma, and
evidence of paranasal sinusitis.
The role of EEG, including its place in the
detection of nonconvulsive status epilepticus, is
discussed in other chapters, but all too often,
only dysrhythmic slowing and triphasic waves
are seen.7 Except for documentation of subtle
seizures, EEG has generally lost its practical
value in these situations, relinquishing useful-
ness to neuroimaging, particularly diffusion-
weighted MRI. Whether nonconvulsive status
epilepticus is underdiagnosed in critically ill
patients remains debatable, and we have docu-
mented only a few verifiable instances of non-
convulsive status epilepticus in the medical or
surgical ICU over the past decades.
Third, another reason for consultation is a
request to explain failure of patients to awaken
after discontinuation of sedation, and this may,
despite everything, be a common cause of
impaired consciousness. A prolonged, lingering
2 Consulting in the ICU 13
Table 2.3 Information gathering for
a critically ill patient with impaired
consciousness and prior use of
sedation
• Chart drugs, doses, and serum levels (if available)
• Review drug toxicology screen, serum-urine (if
available)
• Assess factors that delay washout of drugs (e.g.,
liver or kidney function)
• Assess and reconstruct any plausible
pharmacodynamic and pharmacokinetic effects;
calculate 5 × half-life period
• Review possible neurotoxic drugs
• Consider antagonists (e.g., flumazenil, naloxone)
sedative effect is an obvious consideration but
could be difficult to quantify, let alone prove
(Table 2.3). Reconstruction of the pharmaco-
dynamics and pharmacokinetics is useful.
Often alkalosis, drug interactions, and large
doses of sedative drugs change elimination to
zero-order kinetics, which directly contributes
to prolonged sedation (Chapter 2). Drug levels
should be measured if possible. For any drug,
the consultant should obtain the metabolic
half-life and calculate the time remaining to
clearance, assuming full elimination. Patients
who do not fully awaken after withdrawal of
sedatives, narcotic agents, or combinations
of these agents are frequently jaundiced and
often have recently been given a benzodiaze-
pine (midazolam) or a narcotic drug (fentanyl).
Both drugs are designed to clear through the
liver and therefore may accumulate. Prolonged
sedation occurs after many days of accumulated
metabolites, and further observation over time
may be required.
Fourth, consults are requested for patients
who become acutely comatose while they are
critically ill, and these patients commonly have
a catastrophic neurologic illness. A large propor-
tion of patients in our experience have a devas-
tating intracerebral hematoma or subarachnoid
hemorrhage. These disorders, which may be
the inaugural presentation, typically occur in
patients with systemic fungemia, coagulopathies,
or a ruptured mycotic aneurysm from endocar-
ditis. Acute basilar artery occlusion due to an
embolus can complicate dissection of the thoracic
aorta, valve repair, and cardiac transplantation.
Rapidly deepening loss of consciousness in
patients with multiple traumatic injuries should
point to fat embolization, evolving epidural or
14 Part I Criteria, Urgency, and Importance
subdural hematoma, or enlarging hemorrhagic
contusions with mass effect and edema. Acute
coma can occur after correction of hyponatre-
mia, cardiac resuscitation, and carbon monox-
ide poisoning, all of which are manifestations of
extensive demyelination of both hemispheres.
Typically, patients who seem to be doing very
well suddenly and unexpectedly lapse into a
deep coma and succumb.
If failure to awaken occurs after traumatic
brain injury and the patient has been admit-
ted directly to the operating room from the
emergency department, intracranial contusion
or extraparenchymal hematoma should be con-
sidered. Patients taken directly to the operating
room with life-threatening, blunt abdominal
trauma may have additional head injury, sub-
dural hematoma, or epidural hematoma that
was not apparent on initial examination. A uni-
lateral, fixed pupil may suddenly occur during
surgical repair of a vascular injury or abdomi-
nal exploration for trauma. (Pupillary light
reflexes are the only brainstem reflexes that
can be monitored during general anesthesia.)
Extraparenchymal hematomas may become
evident on CT after 24 hr.
Acute electrolyte imbalance is a relatively
frequent cause of postoperative confusion,
progressive drowsiness, or coma. Increased
levels of antidiuretic hormone associated
with decreased serum osmolality and hyper-
osmolar urine are typical during the first few
postoperative days. When hypotonic fluids are
used, renal handling of free water is impaired
because renal function decreases after the use
of inhalational anesthetics, barbiturates, and
opioids. Hyponatremia can occur rapidly and
typically results in seizures, apnea, and cardiac
arrhythmias, often at sodium levels below 110
mEq/L. Other common causes of acute post-
operative hyponatremia are administration
of large doses of hypotonic fluids to patients
with impaired ability to excrete water after
transurethral prostatectomy and administra-
tion of oxytocin to patients during obstetric
procedures.
Fifth, failure to awaken after transplanta-
tion requires a separate discussion. Neurologic
complications in the early postoperative phase
of cardiac transplantation have decreased in
recent years. Much of the decrease is due to
meticulous attention to removing all residual
atrial tissues or thrombi. Also, the use of a
more precise everting anastomosis may have
decreased intracardiac thrombus formation on
the suture interface and thereby the resultant
massive embolic showers and cerebral infarc-
tions. Therefore, impaired consciousness after
heart transplantation is infrequently due to a
structural lesion in the CNS. Without local-
izing neurologic findings, the most common
cause of unresponsiveness is drug-induced
coma. Narcotic agents are often used liber-
ally in cardiac transplant recipients to decrease
pain and overcome postoperative hypertension.
These agents (usually morphine and fentanyl)
may cause significant postoperative sedation.
Typically, high doses of narcotic agents are
given intraoperatively such as fentanyl (with
diazepam) or sufentanil (with lorazepam).
Naloxone (0.04–0.08 mg) reverses the effects
of narcotic agents. However, failure to awaken
may originate with the marked hypotension
that occurs intraoperatively, with episodes
of significant hypoxemia, or more often, with
cardiac resuscitation for asystole or ventricu-
lar fibrillation. Cardiac arrest can occur in the
immediate postoperative phase and can be
devastating. In these patients, the most common
clinical problems associated with perioperative
cardiac arrest are hypovolemia, tamponade,
and overdose of potent vasodilators.
Neurologic evaluation in the first several days
after a lung transplant is difficult because most
patients are sedated, paralyzed, and mechani-
cally ventilated. Some programs dictate con-
tinuing mechanical ventilation to decrease
stress on the critical tracheal anastomosis,
but most patients are rapidly weaned within
36 hr. Pulmonary hemorrhage and infection
may dominate the early postoperative course.
Impaired consciousness, therefore, may reflect
the hypoxemia associated with pulmonary
edema from reperfusion injury to the graft.
Impaired consciousness and acute con-
fusional state occur in a large proportion of
patients with liver transplantation. Many
metabolic abnormalities are present, but none
significantly contributes to the diminished
alertness of the patients. With a new function-
ing liver, the level of alertness should improve
rapidly.
Patients with fulminant hepatic failure
are prone to increased intracranial pressure
because of brain edema, and liver transplanta-
tion is their only hope for survival. Return of
consciousness to baseline level takes days, and
these patients typically have more prolonged
 2 Consulting in the ICU 15

awakening in the postoperative phase. In addi-
tion, the use of barbiturates perioperatively
to control increased intracranial pressure
may contribute substantially to postoperative
altered consciousness.
Treatment of comatose patients involves
management of increased intracranial pres-
sure, neurosurgical evacuation of a new mass,
treatment of seizures, and correction of labora-
tory abnormalities. Patients who remain coma-
tose need careful examination to determine
the chances of awakening and to prognosticate
later disability if they improve. Supportive care
can be provided if prognosis is uncertain and
should include placement of a tracheostomy
and percutaneous gastrostomy, meticulous skin
and eye care, and physiotherapy measures to
prevent contractions. A comprehensive discus-
sion on care can be found in another text.5
Finally, another common issue is whether the
patient has an undiagnosed neurologic disease
of the peripheral nervous system. Acute exac-
erbation of chronic obstructive pulmonary dis-
ease often leads to mechanical ventilation and,
frequently, a tracheostomy, and these patients,
if not already in a poor nutritional state before
admission, will have an emaciated appear-
ance. It is therefore not unthinkable that the
combination of CO2 retention before endo-
tracheal intubation, difficulty with liberating
from the ventilator, and abnormal pulmonary
function tests (inspiratory and expiratory pres-
sures) points toward a neuromuscular disorder.
Clinical distinction between a myopathy, a poly-
neuropathy, or a neuromuscular disorder is dif-
ficult if all four limbs are flaccid and other signs
are lacking.
Electrodiagnostic testing is often a part of the
evaluation, but interpretation requires exper-
tise, and muscle or nerve biopsy may bring a
more definitive classification. Quantitative anal-
ysis of motor unit potentials, which requires
cooperation by the patient, may be difficult in
very weak, confused, and agitated patients. At
least three motor nerves (distal latency, ampli-
tude, and conduction velocity) and three sen-
sory nerves (amplitude and conduction velocity)
should be studied and followed by needle inser-
tion in multiple muscles. The most common
electrophysiologic abnormalities are listed in
Table 2.4, and more details on the differential
diagnosis can be found in Chapter 7.
Phrenic nerve stimulation in a patient with
diffuse muscle weakness strongly points to a
critical illness polyneuropathy if both sides are
abnormal.6 Abnormal blink reflexes are found

Table 2.4 Electrophysiological features of major neuromuscular disorders

associated with critical illness
Disorder NCV and EMG findings Special considerations
Critical illness Reduced CMAP amplitude, short Lack of direct stimulation of muscle
myopathy duration, early recruitment may be diagnostic
Critical illness Reduced CMAP and SNAP Reduced sensory potentials may be
polyneuropathy amplitudes, decreased recruitment, due to ankle edema or underlying
fibrillation potentials, positive systemic illness, such as diabetes
sharp waves mellitus; phrenic nerve stimulation
abnormalities are diagnostic
Myasthenia gravis or Reduced CMAP amplitude, Higher diagnostic yield with proximal
prolonged NMBA decremental response with muscles than with distal muscles,
effect 3-Hz repetitive stimulation higher yield with facial stimulator
Acute polyradiculopathy Prolonged distal latency, reduced Absence of blink responses and
(GBS or CIDP) motor velocities, conduction block prolonged F-wave latency may be
diagnostic
Motor neuron disease Polyphasic waveforms with late Typical asymmetrical distributions,
components, poor recruitment, early abnormal phrenic nerve CMAP
widespread fibrillation and diaphragm denervation
potentials, normal SNAP
CIDP, chronic inflammatory demyelinating polyneuropathy; CMAP, compound muscle action potential; EMG, electromyography; GBS,
Guillain-Barré syndrome; MG, myasthenia gravis; NCV, nerve conduction velocity; NMBA, neuromuscular blocking agent; SNAP, sensory
nerve action potential.
16 Part I Criteria, Urgency, and Importance
only in inflammatory polyneuropathies and thus
may be helpful in ambiguous cases. F-wave
responses may also be useful if they document
delayed responses disproportionate to abnor-
malities in nerve conduction, suggesting abnor-
mal conduction in the proximal segments of
peripheral motor nerves.
PRACTICAL ADVICE
We can conclude that “participatory” and
“well-informed” are two adjectives that ideally
sum up the neurologist’s demeanor in the ICU
while pondering over the presenting problem.
• Consultations in the medical and surgical
ICUs can be divided into separate catego-
ries, each with different complexity. Failure
to awaken, acute agitation, new focal find-
ings, a movement disorder, seizure, and
severe muscle weakness are reasons to con-
sult a neurologist. These consults—by their
nature—require immediate attention and
prompt evaluation.
• Treatment could decrease morbidity
(e.g., drainage of an epidural abscess in
a febrile patient, early treatment of sei-
zures in immunosuppression-associated
neurotoxicity).
• The impact of these consults on outcome in
the current ICU environment remains to be
studied prospectively.
REFERENCES
1. Bleck TP. Neurological disorders in the intensive care
unit. Semin Respir Crit Care Med. Jun 2006;27(3):201–
9. doi:10.1055/s-2006-945531
2. Gustafson OD, Williams MA, McKechnie S, Dawes
H, Rowland MJ. Musculoskeletal complications fol-
lowing critical illness: A scoping review. J Crit Care.
Dec 2021;66:60–66. doi:10.1016/j.jcrc.2021.08.002
3. Howard RS. Neurological problems on the ICU. Clin
Med (Lond). Apr 2007;7(2):148–53. doi:10.7861/
clinmedicine.7-2.148
4. Mittal MK, Kashyap R, Herasevich V, Rabinstein
AA, Wijdicks EF. Do patients in a medical or surgi-
cal ICU benefit from a neurologic consultation?
Int J Neurosci. 2015;125(7):512–20. doi:10.3109/
00207454.2014.950374
5. Pizzi M, Ng L. Neurologic complications of solid organ
transplantation. Neurol Clin. Nov 2017;35(4):809–23.
doi:10.1016/j.ncl.2017.06.013
6. Sanap MN, Worthley LI. Neurologic complications of
critical illness. Part II: Polyneuropathies and myopa-
thies. Crit Care Resusc. Jun 2002;4(2):133–40.
7. Sanap MN, Worthley LI. Neurologic complications of
critical illness. Part I: Altered states of consciousness
and metabolic encephalopathies. Crit Care Resusc.
Jun 2002;4(2):119–32.
8. Wijdicks EF. Why you may need a neurologist to
see a comatose patient in the ICU. Crit Care. Jun
2016;20(1):193. doi:10.1186/s13054-016-1372.8
9. Wijdicks EF. The scope of neurology of critical illness.
Handb Clin Neurol. 2017;141:443–7. doi:10.1016/
B978-0-444-63599-0.00024-7
10. Wijdicks EF. The neurologic consultation:
Pointers and takeaways for intensivists. Intensive
Care Med. Jun 2020;46(6):1267–70. doi:10.1007/
s00134-020-06055-w
11. Wijdicks EF. Identifying encephalopathies from
acute metabolic derangements. J Intern Med. 2022
Dec;292(6):846-857.
PART II

General Clinical Neurologic

Problems in the Intensive
Care Unit
Chapter 3
Acute Confusional State in the
Intensive Care Unit
TERMINOLOGY
INITIAL ASSESSMENT OF DELIRIUM
Patients who are confused and less responsive
may, in comparison to the unconscious patient,
appear less concerning. Patients in a confusional
state may not respond quickly, rarely fixate on
objects, and cannot understand simple tasks
or nursing requests. Some can speak; others
are unable to voice anything intelligible. Some
exhibit extremely wild behaviors; others are
more subdued when hallucinating. Delirium
has several similarly disturbed components
(arousal, language, perception, orientation,
mood, sleep), which make clinical classification
difficult. Restlessness can be associated with
pallor, sweating, tachycardia, and wide pupils.
Most patients are hyper-aroused, with incoher-
ent, rambling speech, and little comprehensible
verbal output. Orientation to time is impaired
first, followed by place.
Management of delirium may increase length
of stay, often due to related complications (e.g.,
aspiration), and these could be iatrogenic (over-
sedation).2–5 Agitated or delirious patients are
NEUROLOGIC EXAMINATION OF THE
ACUTELY CONFUSED PATIENT
MANAGEMENT
frequently seen after a major surgical procedure,
and cardiac surgery with long extracorporeal cir-
culation times is a notorious cause.6–8 Delirium
often occurs in patients with Parkinson’s disease
undergoing surgery.9 Recently, unusually high
dose requirements for sedation, analgesics, and
neuromuscular blockade have been reported in
patients with SARS-CoV-2 (COVID-19; see
Chapter 12), and the treatment of resulting
delirium contributed to prolonged mechanical
ventilation and delayed awakening.
Consults are triggered when agitation
becomes uncontrollable. The liaison psychiatrist
is asked to assist with adjustments to treatment
and to consider long-term care, the neurologist
is asked to exclude serious structural neurologic
disease, and both are asked to suggest medica-
tion. Consulting neurologists may continue to
assist in management.
Delirium can accompany acute neurologic
disease: for example, a lesion in the limbic
cortex or frontal regions or in the caudate
19
20 Part II General Clinical Neurologic Problems
nucleus may cause severe agitation (but also
periods of extreme quietness) because of
interruption of connecting fibers to the frontal
lobes. But although DSM-5 criteria for delir-
ium include numerous other acute neurologic
conditions, most cases of delirium in medical
or surgical ICUs are not a result of a new struc-
tural injury.
Acute confusional state and delirium
commonly affect elderly patients, who may
be notably susceptible because of an underly-
ing (and not previously recognized) dementia.
In these instances, family members confirm a
gradual decline in performance and produc-
tivity before being admitted for other reasons.
Taking the time to explore the patient’s prior
functioning with family often reveals earlier
episodes of disconcerting behavior in demand-
ing circumstances. Delirium of the elderly in
intensive care settings might be more common
than appreciated, and recent studies have found
that it may occur in up to 50% of ICU patients;
this figure increases to 80% when patients are
on a mechanical ventilator. ICU delirium sub-
stantially impacts costs and is directly related to
protracted ICU stay for management.
We must distinguish delirium from acute ill-
ness or withdrawal from prior used alcohol or
illicit drugs, although our clinical ability to dis-
cern differences remains provisional. This chap-
ter summarizes the evolving terminology and
management of delirium in the ICU.
TERMINOLOGY
For centuries, delirium was a settled diagnosis,
but there was an interest in renaming the disor-
der. “Clouding of consciousness” was used in the
DSM–III. “Delirium” returned later. In DSM-5,
delirium is defined as “disturbance of conscious-
ness with reduced ability to focus, sustain, or shift
attention. Dementia must be excluded as a reason
to explain change in cognition or perceptual dis-
turbance. The disorder develops over time, and
there must be evidence that delirium is caused
by medical disorder.” For most neurologists,
“delirium” was seen as a hyper-alert state with
hyperactive autonomic nervous system and total
disorientation. A hypo-alert state would be clas-
sified as “encephalopathy.” Later, this workable
terminology was followed by many synonyms
and then a more recent serious attempt to
reduce the number of designations of types of
delirium to simply hyperactive, hypoactive,
and mixed. Others have added subsyndromal
delirium, a state between no delirium and
clinical delirium.10,11 The proposed definition of
hypoactive delirium describes a patient charac-
terized by reduced attention and a paucity of
movement, as opposed to hyperactive delirium,
which is characterized by increased attention and
agility and an exaggerated response to a simple
stimulus. Some have inaccurately suggested this
state be called catatonic retardation.12 Mixed
forms are a combination of hypoactive and hyper-
active delirium. Studies have found hyperactive
delirium to be far less common than hypoactive
delirium or a mixed form. Others have suggested
the term “delirium disorder,” but this new term
does not further clarify the disorder.13
In the ICU, hypoactive delirium is the most
difficult to detect, and unless a validated screen-
ing tool is developed and tested, it will remain
one of the most problematic designations for
any neurologist. It is difficult to determine
how much obtundation or how little respon-
siveness qualifies as hypoactive delirium. Any
drowsy patient lacks concentration and atten-
tion and is unable to think clearly. The term
“encephalopathy” may not be ideal but is much
better understood than “hypoactive delirium.”
Moreover, and more importantly, introducing
the word “delirium” may dramatically increase
the prevalence and perhaps lead to unneces-
sary treatment.
Phenotypes, subphenotypes, and even endo-
types are being introduced.11 Recently, clini-
cal phenotypes of delirium were defined as
hypoxic, septic, sedative-associated, or meta-
bolic (renal or liver dysfunction) delirium, add-
ing further to the melee of terminology.10,11
Generally, terminology evolves with further
understanding of the disorder at hand; the over-
whelming concern here is that with attempts at
new terminology and poorly defined boundar-
ies, this is not the case. This new terminology
has received little approbation from neurolo-
gists. Throughout history, delirium was linked
with agitation. In fact, the word “delirium”
derives from the Latin delirio- or delirare,
which means to deviate from a straight line, to
be crazy, deranged, out of one’s wits, to dote, to
rave. There is nothing silent about it.
Thus, we can only conclude that the current
terminology of delirium is equivocal. Once we
change the terminology and accept “quiet delir-
ium” (or its halfway station term “subsyndromic
delirium”), we struggle to distinguish it from
 3 Acute Confusional State 21

acute encephalopathy, and neurologists may ASSESSMENT OF DELIRIUM

feel forced to integrate it into yet another term
such as “delirium disorder.” As with any poorly
understood disorder and unclassifiable patho-
physiology, there is a range of opinions. But to
simplify matters and to develop a practical plan
of action, here we call it “delirium” if there is
agitation or another manifestation of bewilder-
ment, and we call it “acute encephalopathy” in
other cases. We must, however, acknowledge
that we have little understanding of the patho-
physiologic mechanisms of the acute confu-
sional state and delirium (Box 3.1).
Consults are rarely introduced as delirium.
The more typical phrase is “altered mental sta-
tus,” and it quickly becomes clear that there
is ongoing delirium. If we take acute agitation
as a starting point, we can look at a number of
diagnostic possibilities and initial approaches
for management (Figure 3.1).
In the overwhelming proportion of cases,
either critical illness or ICU pharmacology is a
major factor.19 Commonly used drugs that can
cause or worsen delirium are benzodiazepines,

Box 3.1 Pathophysiologic Mechanisms of Delirium

The pathogenesis of the acute confused state that we call “delirium” is unknown.
We have identified risk factors, which could provide a window into neuronal dys-
function and functional disconnection, but we cannot escape the conclusion that
there is little understanding, striking differences of interpretation, and excessive
speculation. The bottom line is that a solid framework does not exist. For years,
there was a search for structural changes in delirium tremens—the archetype of
delirium—and nothing was found. Some studies have shown that ethanol selec-
tively inhibits N-methyl-D-aspartate (NMDA) receptors that transmit the excit-
atory effects of the neurotransmitter glutamate. The depressive effect of alcohol on
NMDA receptors (NMDARs) results in compensatory up-regulation of these recep-
tors and consequent brain hyperexcitability that emerges upon the withdrawal of
alcohol.14–16
The known association between cognitive disorders and delirium has created
interest in pathways of cholinergic deficiency that have been associated with
several types of dementias. When examined as potential pathogenesis of delirium,
again nothing definitive is found. Virtually all neurotransmitters (and combina-
tions) have been implicated, and this has led to the modern idea of pharmacologic
manipulation (e.g., dopamine antagonists, acetylcholinerase inhibitors, and mela-
tonin substitution). Cholinergic deficiency is one emerging pathway to treatment
when delirium is associated with sepsis syndrome.17 There are other associations
between peripheral levels of insulin-like growth factor-1 (IGF-1), C-reactive pro-
tein (C-RP), interleukin-6 (IL-6), and postoperative delirium.18 Their significance is
unknown.
There is a clear understanding that these patients have a major global brain dys-
function, but many decades of research have not improved our understanding of
the pathophysiologic processes or the transient effect of a major illness on neuronal
circuitry. Truthfully, there is only indirect evidence implicating neurotransmitters,
based on the fact that certain drugs improve agitation either through stimulation or
toning down of these neurotransmitters. Examples are (1) quetiapine or olanzapine
and serotonin; (2) dexmedetomidine and noradrenaline; (3) propofol, ketamine,
and NMDA; and (4) haloperidol and dopamine. Also, because critical illness in
trauma or sepsis is associated with inflammation, cytokine signal substances like
IL-1 or IL-6 and tumor necrosis factor could potentially cross the blood–brain bar-
rier or enter elsewhere to cause microglial dysfunction.
22 Part II General Clinical Neurologic Problems

Figure 3.1. Algorithm for evaluation and management of agitation in the intensive care unit.
D/C, discontinue.

opioids, corticosteroids, aluminum-containing how to ameliorate the manifestation of delir-

antacids, beta-adrenergic blockers, tacrolimus, ium by removing these triggers.
cyclosporin, and histamine-receptor antagonists Postoperative delirium may occur in 25–50%
with high doses administered (Table 3.1). of elderly patients, frequently in orthopedic sur-
Prediction of delirium, contrary to what gery patients or with use of anticholinergics and
might be claimed, is not robust, and most barbiturates as anesthetic drugs.20 Postoperative
physicians can only categorize patients as pain may be a factor causing delirium, and pain
being in high- or low-vulnerability categories may increase the risk of delirium by early dis-
(Figure 3.2). There may be so many different turbance of the sleep–wake cycle. There is no
risk factors in the ICU that it becomes irrel- conclusive evidence for a significant association
evant to sort out which one predominates and of hypoxemia or hypocapnia with delirium.
Delirium after organ transplantation is most
related to cyclosporine or tacrolimus neuro-
toxicity and occurs in 20–30% of transplant
Table 3.1 Categories of drugs
associated with delirium
Adrenocorticosteroids Opioid agonistsa
α-Adrenergic agonists Penicillins
α-Adrenergic blockers Phenothiazines
Aluminum-containing Quinolone
antacidsa antibiotics
Aminoglycoside antibiotics Sulfonamides
β-Adrenergic blockersa Tacrolimusa
Benzodiazepinesa Tetracyclines
Butyrophenones Thiazide diuretics
Calcium-channel blockers Tricyclic and
Cephalosporins tetracyclic
Cyclosporinea antidepressants
Digoxine
Histamine receptor
antagonistsa
a
If delirium is present, administration of these drugs
should be discontinued first. Figure 3.2. Predisposing factors in delirium.

recipients. Delirium is more common in patients
who undergo a liver transplant for alcoholic dis-
ease. Alcohol withdrawal does not offer a good
explanation for this because serum alcohol lev-
els measured before transplant are normal in
these patients if they have been in a rehabilita-
tion program, and transplant surgeons require
sobriety. The pathogenesis of delirium requires
further study because agitation may jeopardize
safety through dislodgment of lines.
Delirium is more commonly associated with
cardiac surgery and intra-aortic balloon-pump
procedures and may occur in one-third of
these patients. However, incidence studies of
delirium after cardiac surgery are complicated,
and results are probably not reliable because of
small sample size, changing classification over
time, and heterogeneous patient diagnosis.
NEUROLOGIC EXAMINATION OF
THE ACUTELY CONFUSED PATIENT
Acute confusional state and delirium are
conceptually related but differ in severity.
Neurologic examination of cognition in ICU
patients is frustrating and often fragmentary.
Only patients with mild manifestations can give
reliable responses to the test questions. Acute
confusional states, however, can be graded by
testing recall (e.g., naming three unrelated
objects: “apple” “Mr. Johnson,” “tunnel”), atten-
tion (repeating a series of digits, telephone num-
ber), or calculation (counting down from 100 by
subtracting 7). Writing and reading a complete
sentence, copying a cube, and following complex
commands (e.g., take this paper, fold it in half,
and put it to the left of your body) test agraphia,
apraxia, and alexia as more specific neurobehav-
ioral disorders.
In any newly confused or delirious patient,
clues may suggest a structural lesion rather
than more common physiologic brain dysfunc-
tion. These may include neglect of the left side,
hemiparesis, and denial of blindness.
These confusional states are more typically
characterized by impairment of all mental
faculties and a condition of “being out of
touch” with surroundings. Thus, attention
and memory, logical thinking, orientation, and
mathematical skills are abnormal, with a cha-
otic perception of surroundings. The capacity
to recall parts of the day, procedures, discus-
sions with physicians, and visits by family is
3 Acute Confusional State 23
lost, and patients often look bewildered at their
restraints. Patients may yell and swear and are
generally noisy; they will try to get out of bed or
move into a diagonal position in bed dangling
their legs over the edge. Coherent conversation
is not possible, and directions are not followed.
Although sleep hygiene in ICUs is typically
fragmented, sleep-and-wake patterns for these
patients are disturbed and random. Snoring
during the day becomes excessive from seda-
tive drugs administered the night before for
nocturnal agitation.
As alluded to earlier, patients with a critical ill-
ness are at high risk for delirium, and triggers or
predisposing factors are consistent throughout
studies. These include advanced age, dementia,
Parkinson’s disease, surgery, fever, infections
(particularly in the urinary tract), visual impair-
ment, polypharmacy, and use of psychoactive
drugs. There are also risk factors induced by
critical illness. These include hypoxemia, acute
electrolyte imbalances, congestive heart failure,
sepsis, any acute infection, hyperthermia, and
the development of a new neurologic illness
such as an ischemic stroke or infection.
It is important to distinguish between
alcohol-related delirium and other causes, not
only because the manifestations might be dif-
ferent but also because there might be differ-
ent therapeutic approaches. Alcohol-related
delirium is characterized by profound percep-
tual disturbances, hallucinations. and tremor
(tremens). The level of awareness fluctuates, and
systemic manifestations emerge. Hallucinations
can be vivid and frightening.
Warning signs of delirium tremens have been
identified (Table 3.2). Delirium tremens poses
complex management issues and typically
begins on the third or fourth day after a patient
stops drinking alcohol. Delirium tremens is
characterized by involuntary tugging at sheets,
picking at imaginary objects, intensified tremor,
and severe confusion, often accompanied by
Table 3.2 Warning signs with delirium
tremens
Pulse ≥120/min
Systolic blood pressure >180 mm Hg
Respirations >30/min or <10/min
Temperature >38.5°C
Seizures
Difficult to arouse
Increasing use of benzodiazepines
24 Part II General Clinical Neurologic Problems

agitation and (typically visual) hallucinations MANAGEMENT OF DELIRIUM

or tactile tachycardia, sweating, and hyperten-
sive episodes. Extremely severe manifestations
are surprisingly uncommon (with estimates of
5% of patients withdrawing from alcohol), but
they are potentially life-threatening, especially
in critically ill patients. The syndrome typically
lasts for 5 days once it has begun, and duration
is probably not affected by treatment.
Identification of delirium has been stan-
dardized by the CAM–ICU score (Table 3.3)
used by nursing staff to alert physicians and
administer medication when certain thresh-
olds are reached. Concerns about its reliability
remains including how sedative infusions affect
nurses’ ability to evaluate delirium.3
Looking at the predictive factors of acute agita-
tion and delirium (Figure 3.2), one could argue
in favor of correcting these triggers. Although
delirium may be prevented by simple mea-
sures in already low-risk patients (Table 3.4),
it is unclear if the same measures will temper
delirium in critically ill patients. Most patients
will need multi-pharmacotherapy.
Management of patients with acute confusion
and delirium requires knowledge of the effects
of certain sedative drugs. It is common practice
to withdraw anticholinergic drugs such as meto-
clopramide, H2 blockers, promethazine, and
diphenhydramine.

Table 3.3 Confusion Assessment Method for the Intensive Care Unit
(CAM-ICU)
Feature 1: Acute Onset or Fluctuating Course: Positive if you answer “yes” to either 1A or 1B.
1A: Is the patient different from his/her baseline mental status?
1B: Has the patient had any fluctuation in mental status in the past 24 hr as evidenced by fluctuation on
a sedation scale (e.g., RASS), GCS, or previous delirium assessment?
Feature 2: Inattention: Positive if either score for 2A or 2B is <8. Attempt the ASE letters first. If
patient can perform this test and the score is clear, record this score and move to Feature 3. If patient is
unable to perform this test or the score is unclear, then perform the ASE Pictures. If you perform both
tests, use the ASE Pictures’ results to score the Feature.
2A: ASE Letters: Record score (enter NT for not tested). Directions: Say to the patient, “I am going
to read you a series of 10 letters. Whenever you hear the letter ‘A’, indicate by squeezing my hand.”
Read letters from the following letter list in a normal tone. S A V E A H A A R T Scoring: Errors are
counted when patient fails to squeeze on the letter “A” and when the patient squeezes on any letter
other than “A.”
Score 2A (score out of 10)
2B: ASE Pictures: Record score (enter NT for not tested). Directions are included on the picture
packets.
Score 2 B (score out of 10)
Feature 3: Disorganized Thinking. Positive if the combined score is <4.
3A: Yes/No Questions (Use either Set A or Set B, alternate on consecutive days if necessary):
Set A Set B
1. Will a stone float on water? 1. Will a leaf float on water?
2. Are there fish in the sea? 2. Are there elephants in the sea?
3. Does one pound weigh more than 3. Do two pounds weigh more than
two pounds? one pound?
4. Can you use a hammer to pound a nail? 4. Can you use a hammer to cut wood?
Score____ (Patient earns 1 point for each correct answer out of 4)
3B: Command: Say to patient: Hold up this many fingers.” (Examiner holds two fingers in front of
patient.)
“Now do the same thing with the other hand.” (Not repeating the number of fingers.) *If patient
is unable to move both arms, for the second part of the command, ask patient, “Add one more
finger.”
Score____ (Patient earns 1 point if able to successfully complete the entire command)
Combined Score (3A + 3B):______ (out of 5)
Feature 4: Altered Level of Consciousness: Positive if the Actual RASS score is anything other than
“0” (zero)
Overall CAM-ICU: (Features 1 and 2 and either Feature 3 or 4 = CAM-ICU positive)

Table 3.4 Non-pharmacologic
measures to reduce delirium
prevalence
Early physical and occupational therapy
Sleep enhancement (reduction of light and noise)
Music therapy
Improved daylight exposure
Single-room ICU
Minimize disruptions to sleep
Hearing and vision aids for those with impairments
Pain control
Avoid physical restraints when able
Reorientation to environment
None of these intuitive measures are proven efficacious.
If a rapid effect is desired, IV lorazepam
is infused at 0.01–0.1 mg/kg/h intravenously.
Midazolam may be used at 0.02 mg/kg/h to ini-
tiate therapy.21 There is a consensus to avoid
benzodiazepines unless there is an alcohol-
withdrawal delirium or withdrawal from benzo-
diazepines. The evidence that benzodiazepines
are a risk factor for delirium is strong.
Haloperidol has been traditionally used.
Haloperidol is administered intravenously at
an initial dose of 0.5–1.0 mg for mildly agi-
tated patients and 5–10 mg for those who are
severely agitated. Onset of action is 30 min via
IV. If the patient’s condition remains unstable,
the initial dose is doubled every 30 min until
control is established. Once control of agita-
tion is achieved with the loading dose, 50% of
the total loading dose is given as a maintenance
dose divided into 6- to 8-hr intervals. Titration
is to the lowest dose that controls symptoms. IV
administration and higher doses carry a greater
risk of QTc prolongation and torsades de pointe.
Dosages need to be significantly decreased in
the elderly and in those with hepatic failure. A
recent prospective clinical trial found no better
outcome in treated patients and questionable
effectiveness. (Nearly all patients needed rescue
treatment.)22
Atypical antipsychotic drugs such as risperi-
done, olanzapine, or quetiapine, which show
anecdotal evidence of a good effect, can be
used but may take 2 hr for effect. We have far
more often used 5-10 mg IV olanzapine (up to
30 mg daily), which has a rapid effect and low
rates (<3%) of respiratory depression. There
is a lower risk of QTc prolongation compared
with haloperidol. A consensus found 100 mg of
quetiapine in divided doses up to 200 mg orally
every 12 hr for a maximum 10 days to be very
3 Acute Confusional State 25
helpful in patients with underlying dementia
and postoperative agitation. At a low dose of 1.7
mg/d, on average, risperidone is effective in the
majority of patients.
Dexmedetomidine has also emerged as a very
effective drug23 when loaded with 1 μg/kg IV
followed by continuous infusion starting at
0.2–0. 7 μg/kg. Unfortunately, hypotension and
bradycardia are common. Another effective agent
for the treatment of alcohol withdrawal syn-
drome is phenobarbital24 at 130 mg IV every
15 min until the patient’s symptoms are con-
trolled, not exceeding 15 mg/kg in the first day.
PRACTICAL ADVICE
What is it like to be delirious? We do not know
because patients do not know, and they can-
not recall much in detail.1 All they know is
what they have been told they did. They do not
remember a delirious state because they do not
register (awareness) and do not store memo-
ries, pointing to a major brain dysfunction most
certainly provoked by the amnestic properties
of anesthetic drugs. We do not understand
what underlies this global brain dysfunction.
Clinicians have expressed concern regarding a
possible association of delirium with long-term
cognitive impairment and dementia. This asso-
ciation may not be causal, and it is not known
if more aggressive treatment will reduce the
risk of later cognitive impairment. Recent stud-
ies found that acceleration of cognitive decline
is seen with any hospitalization in predisposed
patients.25–27 The decline is more pronounced
after nonelective compared to elective hospi-
talizations and after hospitalizations for medical
compared to surgical indications. Therefore, we
cannot exclude the possibility that patients who
experience delirium already had undiagnosed
cognitive impairment made worse following
treatment in the ICU. The main takeaways for
the clinician are:
• Drowsiness is not hypoactive delirium.
• Delirium has become a blanket term for what
most neurologists consider encephalopathy.
• Agitated delirium requires multiple treatment
approaches.
• ICU tools to recognize delirium for nursing
staff are available and questionably helpful.
• IV medication first; other measures (restraints,
reduced noise and visits) later.
26 Part II General Clinical Neurologic Problems
• IV dexmedetomidine is quickly becoming a
standard treatment.
• Olanzapine, risperidone, quetiapine, haloper-
idol, phenobarbital, and valproate acid28–30 are
good options.
This approach in assessment and management is
currently the most reasonable advice. It remains
to be seen if the pathogenesis of delirium can be
better understood.
REFERENCES
1. Wijdicks EFM, Rabinstein AA. What is it like to be
delirious? Neurocrit Care. 2022 Aug;37(1):1–5.
2. Ely EW, Gautam S, Margolin R, et al. The impact of
delirium in the intensive care unit on hospital length of
stay. Intensive Care Med. Dec 2001;27(12):1892–900.
doi:10.1007/s00134-001-1132-2
3. Ely EW, Margolin R, Francis J, et al. Evaluation of
delirium in critically ill patients: Validation of the
Confusion Assessment Method for the Intensive Care
Unit (CAM-ICU). Crit Care Med. Jul 2001;29(7):1370–
9. doi:10.1097/00003246-200107000-00012
4. Pandharipande P, Cotton BA, Shintani A, et al. Prevalence
and risk factors for development of delirium in surgical
and trauma intensive care unit patients. J Trauma. Jul
2008;65(1):34–41. doi:10.1097/TA.0b013e31814b2c4d
5. Pun BT, Ely EW. The importance of diagnosing and
managing ICU delirium. Chest. Aug 2007;132(2):624–
36. doi:10.1378/chest.06-1795
6. Dyer CB, Ashton CM, Teasdale TA. Postoperative
delirium: A review of 80 primary data-collection
studies. Arch Intern Med. Mar 1995;155(5):461–5.
doi:10.1001/archinte.155.5.461
7. Parikh SS, Chung F. Postoperative delirium in the
elderly. Anesth Analg. Jun 1995;80(6):1223–32.
doi:10.1097/00000539-199506000-00027
8. Robinson TN, Eiseman B. Postoperative delirium in
the elderly: Diagnosis and management. Clin Interv
Aging. 2008;3(2):351–5. doi:10.2147/cia.s2759
9. Golden WE, Lavender RC, Metzer WS. Acute post-
operative confusion and hallucinations in Parkinson
disease. Ann Intern Med. Aug 1989;111(3):218–22.
doi:10.7326/0003-4819-111-3-218
10. Stollings JL, Kotfis K, Chanques G, Pun BT,
Pandharipande PP, Ely EW. Delirium in critical ill-
ness: Clinical manifestations, outcomes, and manage-
ment. Intensive Care Med. Oct 2021;47(10):1089–103.
doi:10.1007/s00134-021-06503-1
11. Bowman EML, Cunningham EL, Page VJ, McAuley
DF. Phenotypes and subphenotypes of delirium: A
review of current categorisations and suggestions for
progression. Crit Care. Sep 2021;25(1):334. doi:10.1186/
s13054-021-03752-w
12. Maldonado JR. Acute brain failure: Pathophysiology,
diagnosis, management, and sequelae of delirium.
Crit Care Clin. Jul 2017;33(3):461–519. doi:10.1016/
j.ccc.2017.03.013
13. Oldham MA, Holloway RG. Delirium disorder:
Integrating delirium and acute encephalopathy.
Neurology. Jul 2020;95(4):173–8. doi:10.1212/
WNL.0000000000009949
14. Wijdicks EFM. The discovery of acute alcohol with-
drawal as a cause of delirium. Neurocrit Care. Mar
2021:1–4.doi:10.1007/s12028-021-01196-2
15. Nagy J. Alcohol related changes in regulation of NMDA
receptor functions. Curr Neuropharmacol. Mar
2008;6(1):39–54. doi:10.2174/157015908783769662
16. Lovinger DM, White G, Weight FF. Ethanol inhibits
NMDA-activated ion current in hippocampal neurons.
Science. Mar 1989;243(4899):1721–4. doi:10.1126/
science.2467382
17. Adamis D, van Gool WA, Eikelenboom P. Consistent
patterns in the inconsistent associations of Insulin-like
growth factor 1 (IGF-1), C-reactive protein (C-RP)
and interleukin 6 (IL-6) levels with delirium in surgi-
cal populations: A systematic review and meta-analysis.
Arch Gerontol Geriatr. 2021;97:104518. doi:10.1016/
j.archger.2021.104518
18. Noah AM, Almghairbi D, Evley R, Moppett IK. Pre-
operative inflammatory mediators and postoperative delir-
ium: Systematic review and meta-analysis. Br J Anaesth.
Sep 2021;127(3):424–34. doi:10.1016/j.bja.2021.04.033
19. Brown TM. Drug-induced delirium. Semin Clin
Neuropsychiatry. Apr 2000;5(2):113–24. doi:10.153/
SCNP00500113
20. Hughes CG, Boncyk CS, Culley DJ, et al. American
Society for Enhanced Recovery and Perioperative Quality
Initiative Joint Consensus Statement on postoperative
delirium prevention. Anesth Analg. Jun 2020;130(6):
1572–90. doi:10.1213/ANE.0000000000004641
21. Wijdicks EFM, Clark SL. Neurocritical Care
Pharmacotherapy: A Clinician’s Manual. 1st ed.
Oxford University Press; 2018.
22. Andersen-Ranberg NC, Poulsen LM, Perner A, et al.
Haloperidol for the treatment of delirium in ICU
patients. N Engl J Med. Dec 2022;387(26):2425–35.
doi:10.1056/NEJMoa2211868
23. Pandharipande PP, Sanders RD, Girard TD, et al.
Effect of dexmedetomidine versus lorazepam on out-
come in patients with sepsis: An a priori-designed anal-
ysis of the MENDS randomized controlled trial. Crit
Care. 2010;14(2):R38. doi:10.1186/cc8916
24. Oks M, Cleven KL, Healy L, et al. The safety and utility
of phenobarbital use for the treatment of severe alco-
hol withdrawal syndrome in the medical intensive care
unit. J Intensive Care Med. Sep 2020;35(9):844–50.
doi:10.1177/0885066618783947
25. James BD, Wilson RS, Capuano AW, et al. Cognitive
decline after elective and nonelective hospitalizations
in older adults. Neurology. Feb 2019;92(7):e690–9.
doi:10.1212/WNL.0000000000006918
26. Schulte PJ, Warner DO, Martin DP, et al. Association
between critical care admissions and cognitive trajectories
in older adults. Crit Care Med. Aug 2019;47(8):1116–24.
doi:10.1097/CCM.0000000000003829
27. Sprung J, Knopman DS, Petersen RC, et al.
Association of hospitalization with long-term cogni-
tive trajectories in older adults. J Am Geriatr Soc.
Mar 2021;69(3):660–8. doi:10.1111/jgs.16909
28. Quinn NJ, Hohlfelder B, Wanek MR, et al. Prescribing
practices of Valproic Acid for Agitation and delir-
ium in the Intensive Care Unit. Ann Pharmacother.
2021;55(3):311–17.
29. Herman JA, Urman RD, Urits I, Kaye AD, Viswanath
O. The effect of a dexmedetomidine infusion on delir-
ium in the ICU. J Clin Anesth. 2022 Aug;79:110351.
30. Tiberio PJ, Prendergast NT, Girard TD. Pharmacologic
management of delirium in the Intensive Care Unit.
Clin Chest Med. 2022 Sep;43(3):411–24.
Chapter 4
Coma and Other States of Altered
Awareness in the Intensive Care Unit
DEFINITIONS OF ALTERED STATES OF
CONSCIOUSNESS
NEUROLOGIC EXAMINATION OF THE
COMATOSE PATIENT
Critically ill patients are hardly ever sharp;
their attention tends to fade away, and they
may fall wearily asleep. The ability to stay
awake diminishes with a downward spiral in
organ function, and this precarious wake-
fulness may become even more affected by
sedative drugs. Impaired consciousness, not
to mention acute confusion and delirium,
emerges when the CNS becomes part of a
critical illness. The brain of a patient could
become permanently injured after enduring an
overwhelming systemic infection complicated
by marginal oxygenation and blood pressures
trending downward. The CNS can also sustain
damage from trauma, environmental injury, or
an intricate surgical procedure.
In this chapter, I discuss the clinical diagno-
sis of altered states of consciousness in critical
illness, but I also juxtapose coma with other
types of acute disturbances of consciousness
(excluding delirium, which was discussed in
CAUSES OF COMA
NEUROLOGIC EXAMINATION IN
BRAIN DEATH
the previous chapter). This chapter mainly
focuses on classification and recognition. The
first course of action is to determine whether
the patient is comatose from a lesion causing
mass effect in one hemisphere, in both hemi-
spheres, or in the posterior fossa. Next is to
determine whether structural brain injury, sei-
zures, a toxin, or acute metabolic or endocrine
derangement are responsible for persistent loss
of consciousness.
DEFINITIONS OF ALTERED STATES
OF CONSCIOUSNESS
Normal consciousness implies being awake and
aware of self and environment. It requires an
arousal stimulus (ascending reticular forma-
tion in the upper brainstem) and intact con-
tent, coherence of thought, and mental activity
27
28 Part II General Clinical Neurologic Problems
(cerebral hemispheres).1,2 Arousal disturbances
lead to diminished alertness. Content distur-
bances lead to diminished awareness and
inattention, disorientation, and lack of integra-
tion of perception and processing memory. In a
sense, altered arousal involves an altered state of
awareness, and these two components are inter-
related but sometimes dissociated. One can be
awake and aware, awake but not aware, or not
awake and not aware.
Consciousness is traditionally dichotomized
into two components in a conceptually useful
approach. The content of consciousness includes
all cognitive functions, emotions, and intuitions
of the brain. The level of consciousness refers
to global alertness and behavioral responsivity.
Several key anatomical structures control the
conscious state: the ascending reticular activat-
ing system (ARAS) in the midbrain and upper
pons, the diencephalon (thalamus and hypo-
thalamus), anterior cingulate cortex, associa-
tion cortices (precuneus and cuneus), and the
cortex proper (Figure 4.1). The neurochemistry
driving this complex system consists of several
important neurotransmitters: norepinephrine
(originating from the locus ceruleus and pontine
Figure 4.1. Brain regions critically involved in generating
and maintaining cortical activation and the waking state.
These areas, maximally active during waking, include the
ascending reticular activating system (ARAS) of the dorsal
brainstem, the midline-medial and intralaminar thalamo-
cortical projection system, and the basal forebrain.
lateral tegmentum), dopamine (ventral tegmen-
tum), serotonin (raphe nuclei), acetylcholine
(basal forebrain), histamine (posterior hypo-
thalamus), and orexin-hypocretin (lateral hypo-
thalamus). As the target of all incoming signals,
the thalamus is central in governing conscious-
ness and relays and gates information diffusely
to brain networks.
Major mechanisms of coma involve destruc-
tive lesions of the thalamus or diffuse connec-
tions to the cortex or ARAS. These structures
can be directly damaged or injured by com-
pression or shifts, and the changes often alter
consciousness permanently. More selective
lesions involving a unilateral hemisphere or
thalamus will not substantially impair long-term
consciousness.
It is often difficult to determine the state of
awareness in critically ill patients. They may
look about, seem distracted and detached, fidget
constantly, and fail to focus on anything until
they catch sight of the doctor or nurse entering
the room.
The impact of sedation on the state of
awareness of the critically ill patient varies
substantially. In some patients, a dreamlike
state exists, with temporary awakening occur-
ring during pain-causing procedures. Many
pharmacologic sedating agents produce a
calming effect, but some patients may feel
“closed in” when blanketed with sedative
agents, or they may lack any urge to signal
discomfort or fear. Some patients may experi-
ence invasive procedures as painless manip-
ulations, prodding, or sticking, which may
explain the patient’s easy compliance with the
attending staff; in other patients, because of
the perception of impending pain, any close
contact causes agitation.
It is practically useful to subject these patients
to neurologic scrutiny and to distinguish differ-
ent categories of unconsciousness and mimick-
ers. The disorders of consciousness are listed
here to facilitate conversations between neu-
rologists and intensivists in day-to-day practice.
Locked-in syndrome is a rare condition,
and patients have a normal awareness but
complete body paralysis except for voluntary
vertical eye movements. Structural lesions in
the base of the pons spare the pathways to
the oculomotor nuclei in the mesencepha-
lon, so that patients continue to communicate
through vertical eye movements and blinking.
They cannot move their limbs, grimace, or
 4 Coma and Other States of Altered Awareness
swallow. Hearing is intact, but later vocalizing
is not possible through a capped tracheostomy
cannula. The medulla oblongata is spared.
Central chemoreceptors in the ventral surface
of the medulla are intact, and thus there is nor-
mal respiratory drive. Consciousness may still
be reduced when the tegmentum or thalamus
(e.g., with a top of the basilar artery occlusion)
is involved. Variants of this classic syndrome
are common, with patients retaining some
motor movements and later regaining ability
to speak. Locked-in syndrome should be dif-
ferentiated from paralysis of all muscle (and
eye) movement by paralytic agents.
Hypersomnia is an increase in sleeping time
with normal sleep patterns, a situation often
caused by sleep deprivation, metabolites of
sedative drugs, or acute hepatic or renal failure.
Acute brainstem lesions involving the tegmen-
tum or bilateral lesions of the paramedian dorsal
thalamus may also dampen arousal.
Coma is a state of unresponsiveness in which
the patient lies with eyes closed and cannot be
aroused to stimuli. Self-awareness is absent. At
best, there is only eye opening to pain, or eyes
are open with no tracking or fixation. Brainstem
reflexes can be intact or variably absent.
Movements are pathologic motor responses
(decorticate or decerebrate) or no response at
all. In most patients, it is a transient state, recov-
ering into a minimally conscious state and better.
However, a devastating injury (often anoxic-
ischemic insult) causes persistent coma.3–6
Minimally conscious state (MCS) has been
identified as a separate category and is best
placed between severe disability and persistent
vegetative state (PVS). The boundaries of this
condition remain difficult to define, but currently
it is understood as patients who open eyes after
prodding, track a finger, or reach for an object
but with no higher level of communication,
intellectual thinking, or recall of prior events,
even simple ones.7 Verbalization of syllables
or brief sentences may occur. Responses are
very slow, inconsistent, and often unreliable.8
The long-term outcome of patients in a MCS—
often a result of major brain injury—is not
exactly known. Some rehabilitation physicians
have subclassified MCS into MCS with lan-
guage (MCS+) or without language (MCS−).
Additionally, functional MRI-based categoriza-
tion has revealed a patient subset fulfilling all
PVS criteria but showing command-following
response on functional MRI (cognitive motor
29
dissociation or CMD). Another patient sub-
set, higher-order cortex-motor dissociation
(HMD), exhibits cortical response to auditory
stimuli, again without evident awareness. (The
clinical relevance of these fMRI subsets are yet
unknown.)
Persistent vegetative state. The appearance
of intensive care units (ICUs) and mechanical
ventilation has allowed patients with devastating
brain injuries to survive. While deeply coma-
tose during the acute phase, some patients
transition to a different clinical state in which
they regain awake-and-sleep cycles but remain
unaware of their surroundings. This clini-
cal syndrome—named “persistent vegetative
state” in the early 1970s—describes patients
with no evidence of a functioning mind. This
state has also been referred to as “unrespon-
siveness wakefulness syndrome” because of
the alleged negative connotation of the word
“vegetative,” but this term is no improvement
and more confusing to family members.9 After
prolonged coma, patients begin to have periods
of spontaneous eye-opening but do not visually
fixate or track objects with their eyes and may
gradually emerge from coma due to exten-
sive injury to the brain. This complete lack
of awareness becomes associated with sleep–
wake cycles and opening of the eyes but with-
out any expression or recognition of external
stimuli. There are often roving eye movements
with nystagmoid jerks. Visual tracking to shown
objects is absent. Brainstem function, including
respiratory drive, is largely preserved, and the
damage is in multiple cortical areas. Injury may
be predominantly in both thalami, interrupting
the thalamocortical circuits. The diagnosis of
PVS is rarely made with certainty in the ICU,
and several weeks of close observation on the
ward are needed before even considering the
diagnosis. The condition is considered irrevers-
ible after a year in such a state, and recovery to
awareness is exceptional.
Brain death is a term used for irreversible loss
of all clinical brainstem function. The diagnosis is
based on a set of strict clinical criteria and signifies
the patient has died. After excluding confound-
ers, this implies documentation of permanently
lost consciousness, no motor response to pain
stimuli, absent brainstem reflexes, and absent
respiratory drive after the respiratory centers are
maximally stimulated with a CO2 challenge.10
The pathophysiologic mechanisms of altered
consciousness are discussed in Box 4.1.
30 Part II General Clinical Neurologic Problems

Box 4.1 Pathophysiologic Mechanisms of Coma

The different clinical states of unconsciousness relate to different defects in neuro-
nal networks underlying consciousness, and some specific patterns are emerging.
Connections between thalamus, frontal cortex (particularly cingulate cortex), parietal
cortex (cuneus and precuneus cortex), and, ultimately, the brainstem play an important
role and, when damaged, result in abnormal awareness and wakefulness (Figure 4.1).2
The processes that govern normal consciousness are only partly understood.
More recent insight has emerged because of functional MRI and positron emission
tomography (PET) studies.2 One of the critical anatomical parts has been defined
under the term “ascending reticular activating system.” This system, located in the
rostral brainstem, targets the thalamus, which, in turn, disperses connections to
the cortex and vice versa, creating the thalamic–cortical circuitry.11 One column
of the system projects to the medial thalamic nuclei, interlaminar nuclei, and
ventromedial nuclei; another column remains ventral and courses through the
lateral hypothalamus to reach the basal forebrain neurons, which in turn modulate
cortical activity as well.11
The function discharged by the ascending reticular activating system is
arousal. Another major system, the limbic system, contributes not to arousal
but to mood, affect, motivation, and memory. Amnestic syndromes are mostly
a consequence of involvement of the hippocampus, an important component
that projects to the mamillary body and anterior thalamic nucleus.
Arousal is determined not only by intact connections but also by neuro-
transmitters (Figure 4.2). Excitatory glutaminergic neurons of the reticular formation
project to the nonspecific thalamocortical systems. The reticular retinal nucleus of
the thalamus may be a key component in gating interchange and in regulating
sleep–wake cycles and depth of sleep.12 The reticular retinal nucleus also contains
a large amount of inhibitory γ-aminobutyric acid (GABA) that can be recruited
to further modulate neuronal traffic and control excitability. Noradrenergic neu-
rons also modulate arousal. These cells are in the locus ceruleus, a small group
of pigmented cells localized in the lateral part of the upper pons. The role of this
structure is currently thought to be enhancement of vigilance, particularly with
unexpected stimuli. If damaged, it prevents the development of rapid eye move-
ment (REM) sleep and reduces total sleep time. Other monoamines, such as sero-
tonin and histamine, originating from raphe nuclei in the median brainstem and
from the hypothalamus, enhance wakefulness through ascending projections to
the thalamus, basal forebrain, and cortex.
The cholinergic system projects from the dorsal pontomesencephalic tegmentum
to subcortical relays and from the basal forebrain to the cerebral cortex. Its func-
tion is not only to enhance attention but also to retain recent memories and create
REM sleep.
This model, albeit oversimplified, can explain disorders of consciousness dis-
cussed in other chapters of this book. For example, benzodiazepines, barbitu-
rates, and propofol specifically enhance GABA activity and lower excitation,
inducing drowsiness, sleep, and coma. Benzodiazepines act on endogenous
receptors in the cortex and midbrain and on opioid target receptors throughout
the brain. In hepatic encephalopathy, GABA-mediated inhibition has been sug-
gested as a mechanism, as well as down-regulation of glutamate N-methyl-D-
aspartate receptors, both of which disrupt a sensible balance of excitation and
inhibition.
(continued)
Another random document with
no related content on Scribd:
LONG ago, soon after the Children of Israel came out of Egypt, they asked Aaron to make
a Golden Calf for them to worship, which could be carried in front of them, and would, they
hoped, lead them into the Promised Land. But we know how dreadfully they sinned in this.

And five hundred years after that, Jeroboam, King of Israel, made two Golden Calves, and
built two altars, one in Dan at the North of Palestine, and the other in Bethel at the South
of his Kingdom.

He told the people of Israel that it was too far for them to go to worship at Jerusalem,
three times in the year, and that they could go instead to worship his Golden Calf, and
could offer sacrifices upon the altars he had built.

Now God had told the Jews that Jerusalem was the place He had appointed for Worship;
and also that only God's Priests, the sons of Aaron, were to offer either Sacrifices or
Incense to Him.

One day, when King Jeroboam was himself offering incense on the altar he had made in
Bethel, a Prophet of the Lord was sent to him with a message from God.

And this was the message—That one day, on this; very altar, the priests whom Jeroboam
had made from the lowest of the people, should be offered, and their bones should be
burnt upon this altar.

God gave a Sign, by which King Jeroboam should know that the Prophet's words were
true, and that he had been sent by God.

This was the Sign. This altar of Jeroboam's should be rent—torn in pieces—and the ashes
should be scattered on the ground.

King Jeroboam was very angry at the message, and he tried to seize the Prophet, but his
hand dried up, and he could not use it.

And the Sign came to pass at once, for the altar fell to pieces and the ashes were
scattered.

Jeroboam was very frightened, and begged the Prophet to ask the Lord to restore his
hand.

And the Prophet did; and Jeroboam's hand was made quite well again.
 A Prophet of the Lord was sent to him with a message from God.

Then the King pressed the Prophet to come in to refresh himself, and to receive a reward.

But the Prophet answered that the Lord had strictly forbidden him to eat bread or drink
water in that place. So he turned away, to go back by another road, as the Lord
commanded him.

But now a great temptation met him.

For as the Prophet was turning away from Bethel, an old Prophet who lived there, thought
he would ask him to come back and rest at his house. He had heard how the Prophet had
cried against the Altar, and he longed to hear all about it.

But the Prophet again explained that the Lord had forbidden him to eat and drink in that
place.

Then the Old Prophet lied to him, and said that an Angel had told him he was to ask him
home to refresh him.

So the Prophet listened to his fellow-prophet, instead of obeying God, and he turned back
and went in, and ate and drank.

But when he had finished the meal, the Word of the Lord came to the Old Prophet, with a
terrible message to the disobedient man.

"Forasmuch as thou hast disobeyed the Lord, and hast not kept the Commandment which
the Lord thy God commanded thee . . . thy carcase shall not come to be buried in the
sepulchre of thy fathers."

So the Old Prophet gave the message, and he sorrowfully saddled the ass of the
disobedient Prophet, and sent him forth on his return journey. But very soon a lion met
him in the way, and slew him; and his body lay by the roadside, and the lion and the ass
stood by, but the lion did not eat either of them.

By and by people passed that way, and they hastened to the city to tell what they had
seen.

THE DISOBEDIENT PROPHET.

Then the Old Prophet told his sons to saddle his ass, and he hurried along the road until he
came to the spot where the dead Prophet lay. And he found all as he had been told, and
saw that the Lord had not allowed the lion to touch the dead man, or the ass.

Then the old man laid the body of the Prophet on his ass, and brought him back to bury
him in his own grave; and he mourned bitterly for him, for he knew he had tempted him,
and had been the cause of his death.

He charged his sons, that when he came to die, they were to bury him in the same grave
with the Prophet; and he added a solemn assurance that the words of God which the
Prophet had uttered against King Jeroboam's altar in Bethel, and against the other
idolatrous places which he had built, should surely come to pass.
All this was literally fulfilled three hundred years after, in the reign of Josiah, the good
young King. We read the account of it in three verses in 2 Kings 23.15-18.

But King Jeroboam, knowing of this Prophecy, remembering as he must that his withered
hand had been healed by God, did not set his heart to seek God and to find forgiveness.

He went on in his evil ways all his life, until at length we read in the Bible the name by
which he was known after his death, "Jeroboam, the son of Nebat, who made Israel to
sin."

This long ago story speaks an ever-living lesson.

The God who commands will enable us to obey. Let us seek Him with all our hearts: let us
learn His will in the Bible, and then the promise to each one of us will come true—

"To him that soweth righteousness, shall be a sure reward."

XXVI. THE LORD ANSWERS ELIJAH BY FIRE

1 KINGS 18, 19

THEN after a long time, the word of the Lord came to Elijah in the third year of the famine,
saying to him, "Go, show thyself to Ahab; and I will send rain upon the earth."

So Elijah went back from Zarephath, and came down to Samaria to show himself to Ahab;
and the famine was very sore there.

Ahab had a trusted servant called Obadiah, who was governor of his house; and this man
"feared the Lord greatly."

That meant, he did that which would please God, and earnestly obeyed Him in all things.
Once, when the wicked queen, Jezebel, tried to kill all the Prophets of the Lord, Obadiah
took fifty of them and hid them in a cave, and fed them with bread and water, and so
saved their lives.

So because the famine was very terrible in Samaria, Ahab called Obadiah, and told him
that they would both go out into the country with the horses and mules and find all the
brooks and streams that were left, where a little grass might be growing, to save the
horses alive.

Ahab went one way and Obadiah another, and as Obadiah was seeking for water, he met
Elijah, who was on his way to Ahab, as the Lord had told him. When Obadiah saw him, he
bowed himself to the earth before God's Prophet; and then Elijah said, "Go and tell thy
lord that Elijah is here."

Obadiah hesitated very much to carry this message, as he was afraid that the Spirit of the
Lord might carry Elijah away, so that he could not be found. He reminded Elijah that he
had "feared the Lord" since he was a child, but that Ahab would certainly slay him if he
carried such a message to him as that!

Then Elijah promised him, that he would surely show himself to Ahab that very day.

So Obadiah went and told Ahab, and the king came out to meet Elijah.

Then Ahab said to him, "Art thou he that troubleth Israel?"

And Elijah answered, "It is thou and thy father's house that have troubled Israel, because
ye have forsaken the Lord's commandments and have worshipped Baal!"

Then he told Ahab to gather together the people, and all the four hundred and fifty
prophets of Baal, and the four hundred prophets of the grove, who sat down daily at
Jezebel's table, and to take them to Mount Carmel, and meet him there.

So a number of the people, and all the prophets of Baal, came together to Mount Carmel.

And Elijah came to the people, and he said, "How long do you mean to halt between two
opinions? If the LORD be God, follow Him! but if Baal, then follow him."
 Then the fire of the Lord fell, and consumed the burnt sacrifice.

And the people did not answer a word.

Then Elijah said, "I am the only Prophet of the Lord, and Baal's prophets are four hundred
and fifty. Let them therefore give us two bullocks, and let them choose one for themselves
and slay it, and dress it, and put it on the altar, with no fire under."

"And I will slay and dress the other bullock, and put it on the altar, and put no fire under.
And the God that answereth by fire, let Him be God!"

So the priests of Baal took their bullock and did as Elijah had said; and they cried unto the
name of their god from morning until noon, saying, "O Baal, hear us!"

But there was no voice nor any that answered. And they leaped upon the Altar which was
made.

Then Elijah mocked them, and told them to cry aloud, as their god was talking, or on a
journey, or asleep, and must be awaked! And they cried aloud, and cut themselves with
knives. And thus they went on till the time of the evening sacrifice. But there was neither
voice, nor any to answer, nor any that regarded.

Then Elijah said to all the people, "Come near unto me."
And he repaired the Altar of the Lord that was broken down, and built it up with twelve
stones for the twelve tribes of Israel; and he cut a deep trench round the Altar, and put the
wood in order, and cut the bullock in pieces and laid him on the wood.

Then he told the men to fill four barrels with water, and to pour it on the burnt sacrifice
and on the wood; and this he ordered to be done three times, so that the water ran all
about the Altar; and he filled the trench with water.

Elijah knew what his God, Jehovah, was going to do, and what a glorious ending there
would be!

So at the time of the evening sacrifice Elijah drew near to the Altar and prayed: and he
said, "Lord God of Abraham, Isaac, and of Israel, let it be known this day that Thou art
God . . . and that I am Thy servant, and that I have done all these things at Thy word."

"Then the fire of the Lord fell, and consumed the burnt sacrifice, and the wood, and the
stones, and the dust, and licked up the water that was in the trench."

"And when all the people saw it, they fell on their faces: and they said, The Lord, He is the
God; the Lord, He is the God!"

"And Elijah said unto them, Take the prophets of Baal, let not one of them escape! And
they took them and brought them down to the brook Kishon." And they were all killed. The
children of Israel had acknowledged their God at last!

Then Elijah turned to Ahab the king, who, like the people, had cast himself in awe and
reverence upon the ground. And he said to Ahab, "Arise, and eat, for there is a sound of
abundance of rain!"

XXVII. JOSHUA'S COURAGE

JOSHUA 1.1-18
After the death of Moses, when the Lord, Himself, had buried His faithful servant, the Lord
came to Joshua and told him that he was to be the one who should lead the Children of
Israel into the Promised Land.

We hear of Joshua many times as we read the life of Moses.

He shared the glorious triumph when the Children of Israel were brought out of Egypt; and
soon after that, Moses chose Joshua to lead the people to fight against Amalek.

Next we hear of him as the trusted servant (or minister, as it is called in the Bible), who
went up with Moses to the Mountain called Sinai, when Moses received the Ten
Commandments from God.

Joshua did not go all the way with Moses, but waited somewhere on the mountain till
Moses should come down from talking with the Holy God.

And as they went down again, it was he who saw the Children of Israel worshipping the
golden calf below.

Next, Joshua was one of the twelve spies who were sent to search out the Land; and you
will doubtless remember that ten of these spies brought a bad report, and only two of
them, Caleb and Joshua, brought a good report.

We see Joshua's splendid courage through all these circumstances.

He trusted God with all his heart, and the Lord was his sure Refuge and constant Helper.

And it is very wonderful to remember, that among the Israelitish men who came out of
Egypt and wandered in the Wilderness for forty years, the only two who entered the
Promised Land were Caleb and Joshua, the two faithful spies! All the rest of the Israelitish
men who came out of Egypt died in the Wilderness for their disobedience, and only their
children entered the Promised Land.

It is a very solemn thing to be disobedient to God.

So as I said, the Lord came and spoke to Joshua, and told him he was to lead the people
into the Land of Canaan.

One day soon after this, Joshua sent two spies to bring back word what kind of a land it
was which he had to conquer. When they came to Jericho they came to the house of a
woman named Rahab, and lodged there.

But the King of Jericho heard of it, and sent to Rahab to give up the men to be killed.

But Rahab had heard of all the wonders that the Lord had done for His people, in bringing
them out of Egypt; how He had dried the Red Sea for the people to pass over, and of other
great victories; and instead of giving up those two Israelites to the King of Jericho, she
quickly hid them on the flat roof of her house, under a lot of flax stalks, and when the
messengers from the King came, they did not find them, and Rahab told the King's soldiers
that they had better seek the men on the road to Jordan, as quickly as they could.

So the King's men went away to look for them, and the City gates were shut, and all was
quiet again.
Then Rahab went up to the roof and told the spies that they must escape at once; and she
begged them to promise her faithfully, that when God had given them the Victory, which
she was sure He would do, that they would save her life.

So the men told her to bind a scarlet cord in her window which was on the outer wall, that
they might recognise the place; and she let them down in the night through this window,
and they got away.

All this the men faithfully carried out, and we read in the 11th of Hebrews, written nearly
1500 years after, that it was by faith that Rahab saved the spies, and by this saved her
own life too.

God loves for us to have faith in Him! And it was this faith in God which made Joshua
courageous all his life.

So Joshua and the people crossed the Jordan and entered into the Land, and came to
Jericho; and one day when Joshua was standing viewing the strength of the City, suddenly
he found Someone by him with a drawn sword in His hand.

So Joshua went to him at once, and asked "if he were going to fight for the Israelites or for
their enemies?"

And the Stranger said: "Nay, but as Captain of the Lord's Host am I now come."

Then Joshua fell on his face and worshipped, for he knew that this was the Lord Who was
speaking to him, and Who had taken the Supreme Command!

No wonder that when Joshua was old, and knew he was going to die, that he called all the
Israelites together, and rehearsed all the wonderful doings of the Lord; and that he begged
them with all his strength to serve and obey the Lord with all their hearts.

CHOOSE YE THIS DAY.

And Joshua set up a great Stone to be a Witness to them, that they had promised to love
and obey God; and he said the Stone would remind them, lest they should forget their
promise and turn back from serving God.

So the Israelites promised to be faithful, and while the elders who outlived Joshua were
alive, they did follow the Lord. But after a time they began to forget, and this brought a
great deal of sorrow upon them.

Perhaps you think within yourselves, "I should like to obey God, and follow Him! I wonder
how I could begin?"

Think of Joshua. He followed the Lord wholly—which meant with all his heart. That was the
first thing. So you can pray, "Take my heart, Lord Jesus, and help me to follow Thee!"

Then he obeyed whatever God told him to do. And whatever Command you find in the
Bible, as shewing you God's Will—do it!
 XXVIII. THE FIERY FURNACE

NEBUCHADNEZZAR'S dream of the Great Image had been explained to him by Daniel and
his three companions; but the king soon forgot the wonderful interpretation which God had
sent him, containing such an unfolding of the future which, in due time, has come to pass.

One great dynasty after another—Babylon, the Medes and Persians, Greece, and Rome,
have arisen and passed away, till at length, up to now, only the Feet of the Vision of the
Great Image wait to be accomplished.

And when history shows us that all has been fulfilled except the Feet of iron and clay, we
know that we must be very near to the coming of the Wonderful Stone, which by and by is
to fill the whole earth.

You will some of you understand what I mean when I say that this is Symbolical language.
That means, that it is a picture of Heavenly Things which is to teach us about earthly
things.

That Stone is a symbol of our Lord Jesus Christ when He comes back from Heaven to reign
over the whole earth. We read in the seventh chapter of Daniel these words: "I saw in the
night Visions, and behold one like the Son of man came with the clouds of Heaven . . . and
there was given Him dominion and glory and a kingdom, that all people, nations and
languages should serve Him: His dominion is an everlasting dominion which shall not pass
away, and His kingdom that which shall not be destroyed."

King Nebuchadnezzar remembered the part of his dream of the Great Image that applied
to himself—he knew he was the head of gold.

This probably made him think of making a real image, and setting it up in the plain of Dura
for every one to worship.

So the heralds went forth and told the people that at the sound of any musical instrument
they were instantly to fall down and worship the Golden Image that Nebuchadnezzar had
set up.

And in order to force compliance, this mighty king made a terrible threat, that whoever
refused to worship it, should be cast into a burning fiery furnace.
 The most mighty men in his army were to bind Shadrach, Meshach, and Abednego.

But the Chaldeans, who were very jealous that Shadrach, Meshach, and Abednego had
been set up over the affairs of the kingdom, came near and told Nebuchadnezzar that the
Jews refused to bow down and worship the Golden Image which he had set up.

Then Nebuchadnezzar in his rage and fury commanded to bring Shadrach, Meshach, and
Abednego before him.

So he asked them: "Is it true that you will not worship the Golden Image which I have set
up? If you are ready to worship, well; but if not, you shall be cast the same hour into the
midst of the fiery furnace. And who is that God that shall deliver you out of my hand?"

But the three young men were strong in the might of their God, and they answered—

"We are not careful to answer thee in this matter. If it be so, our God whom we serve is
able to deliver us from the burning fiery furnace, and He will deliver us out of thine hand,
O King. But if not, be it known unto thee, O King, that we will not serve thy gods, nor
worship the Golden Image which thou hast set up."

Then Nebuchadnezzar was full of fury, and he ordered that they should heat the furnace
seven times hotter than usual, and that the most mighty men in his army were to bind
Shadrach, Meshach, and Abednego, and to cast them into the fiery furnace.

And because the king's command was urgent and the furnace exceeding hot, the flames
killed the men who had to throw Shadrach, Meshach, and Abednego into the fire.

And the three young men fell down, bound, into the midst of the furnace.

The king was watching the dreadful scene; but suddenly a great fear shook him, and he
turned to his counsellors with the question, "Did not we cast three men, bound, into the
fire?"
And his counsellors said that it was true, they had.

Then King Nebuchadnezzar said: "Lo! I see four men, loose, walking in the midst of the
fire, and they have no hurt; and the form of the fourth is like the Son of God."

Then Nebuchadnezzar came near to the mouth of the furnace, and he said: "Shadrach,
Meshach, and Abednego, servants of the Most High God, come forth and come hither!"

Then Shadrach, Meshach, and Abednego came forth of the midst of the fire.

And the Princes, Governors, and Captains, and the King's Counsellors, who were gathered
together watching, saw these men upon whom the fire had no power; nor was a hair of
their heads singed, neither were their coats changed, nor the smell of fire had passed on
them.

Then Nebuchadnezzar spake and said: "Blessed be the God of Shadrach, Meshach, and
Abednego, Who hath sent His angel and delivered His servants who trusted in Him, and
have changed the king's word, and yielded their bodies, that they might not serve nor
worship any god except their own God."

So Nebuchadnezzar made another decree, that if any one said anything against the God of
these three young men, he should be cut in pieces and his house destroyed—"because
there is no other god that can deliver after this sort."

And the king promoted Shadrach, Meshach, and Abednego in the province of Babylon.

This is a glorious chapter of one of the greatest deliverances of the Bible; and there are
plenty more!

XXIX. QUEEN ESTHER'S REQUEST

ESTHER 8.3-6
ESTHER was a very beautiful girl, and Ahasuerus the great King of the Medes and Persians
chose her to be his Queen, and he loved her very much.

Esther was not only beautiful in face, but she had a very beautiful character.

She belonged to the people of God, called the Jews, who had been carried away captives
from Palestine, and were now living in Persia.

Among these Jews was a man called Mordecai, who was much respected for his goodness,
and he sat in the King's Gate.

When Esther's father and mother died, Mordecai took the little girl and brought her up as
his own daughter. He taught her about God, and Esther was very obedient, and loved
Mordecai very dearly.

Mordecai took the little girl and brought her up.

Then Esther was made Queen, and things went on peacefully; until one day Mordecai
heard that there was a plot forming to kill King Ahasuerus. He at once secretly told Esther,
and she told the King; and the two conspirators were both hanged. But the King forgot to
thank Mordecai, though it was written down in the Chronicles of the Kingdom.

About that time the King took a great fancy to a man called Haman, who hated the Jews,
and especially Mordecai, because he did not bow down to him when he passed.

So Haman obtained leave from the King to fix a day when all the Jews should be killed in
the whole Kingdom.

But the City Shushan was much perplexed; for they knew, though the King did not, that
his beloved Queen was a Jewess!
When Mordecai found out all that was happening, he was bitterly grieved, and sent an
urgent message to Esther, and implored her to go in and tell the King, and beg him to
spare her people.

But Queen Esther sent back a message to Mordecai, to remind him that if anyone ventured
to go in to the King's inner Court, that person would certainly be put to death unless the
King should hold out his Golden Sceptre.

So Mordecai sent another urgent message to tell Esther that perhaps she had come to be
Queen, to do this very thing. But if she did nothing, then she and all the Jews would
perish!

Then Queen Esther begged Mordecai to gather all the Jews together who were in Shushan,
and to bid them fast and pray for three days; and she and her maidens would fast too; and
at the end of that time, she said, "I will go in to the King, which is not according to the
law, and if I perish, I perish."

Esther was brave because she knew that she had God on her side; and she believed that
He would answer the prayers they were all offering up.

QUEEN ESTHER BEFORE AHASUERUS.

So on the third day Queen Esther put on her Royal robes, and went into the Inner Court
and stood before the King.

When King Ahasuerus saw his beautiful young Queen standing there so meekly, he held
out the Golden Sceptre which was in his hand. And she drew near and touched the top of
the sceptre.

And when he asked her what request she had to make, the King must have been
astonished at her reply, for she only asked that the King and Haman should come to a
banquet which she had prepared for them. So when they came to the Banquet, the King
asked the Queen again what her petition was? And she said if the King and Haman would
come to a Banquet with her, again to-morrow, she would then tell the King what her
request was.

So Haman went out from Queen Esther's Banquet very proud; and he told his wife and his
friends of his second invitation, but he said that nothing was any pleasure to him, so long
as Mordecai, the Jew, sat in the King's Gate.

Then his wife and his friends advised him to make a gallows fifty feet high, and to get the
King to let him hang Mordecai on it.

But that night the King could not sleep, and one of his servants fetched a roll of the
Chronicles of the Kingdom, and he read to him how Mordecai had once saved the King's
life.

And in the morning the King asked Haman what would be suitable to do to "the man that
the King delighted to honour?"

But Haman little thought that when he proposed to set the man on the King's own horse,
dressed in the King's Royal clothes, that it would be Mordecai who was to be honoured,
and not himself!

But the King told Haman to lead Mordecai round the town, and to proclaim: "Thus shall it
be done to the man whom the King delighteth to honour."

After this Haman went to the Banquet that Esther had prepared. He little knew what the
Queen's request was going to be! For Esther told the King that a great plot had been made
to destroy her and all her people, and that this wicked Haman was the one who had
planned it all!

Then Haman was afraid before the King and Queen.

You can picture the anger of the King, and when he was told of the gallows which Haman
had prepared for Mordecai, he ordered that Haman should be hanged there at once.

Then the Queen begged that letters might be sent to stop all the Jews being killed, and
Ahasuerus sent urgent posts on mules and horses and swift dromedaries to tell the Jews
that they might stand up for their lives, and destroy any enemies who rose up against
them.

Thus God answered the prayers of that young Queen and her maidens, and of the Jews
who joined with her in fasting and praying, and sent them a great deliverance, the
remembrance of which has been handed down from generation to generation ever since.
 XXX. A GREAT RAIN, AND A TIRED
PROPHET

So Ahab ate and drank—but Elijah went up to the top of

Carmel, and cast himself upon the earth with his face
between his knees, and he said to his servant: "Go up now
and look towards the sea."

And the servant returned, saying he could not see anything.

Then Elijah said: "Go—" seven times. And when he came

back the seventh time, he said he could see a little cloud in
the sky, no bigger than a man's hand.

So Elijah hurriedly sent a message to the king, to prepare

his chariot, and get to his home quickly, or the rain which
was coming would stop him!

And as he spoke, the heavens became black with clouds,

and there was a great rain. And Ahab rode and went to
Jezreel.

And the hand of the Lord was on Elijah, and he ran before
Ahab's chariot, right to the entrance of Jezreel.

But when Ahab told his wife, the wicked queen, Jezebel,
that all her prophets were dead, Jezebel sent a message to
Elijah that she would kill him, as he had done the prophets
of Baal, by that time the next day!
And now, Elijah, who had been so wonderfully strong and
full of faith for this great scene, fled for his life when he
heard the threat of Queen Jezebel!

Hungry, thirsty, tired-out, he fled till he had passed

Beersheba, and had gone a whole day's journey into the
desert, before he felt he might be safe from Jezebel! Here
he cast himself under a juniper tree, and asked the Lord to
let him die!

Poor Elijah! For one brief moment his faith failed him! If
God had answered his prayer, Elijah would have missed the
great honour of going up to Heaven in a Chariot of Fire
without death at all!

And let us pause here, just to think for a moment about our
own prayers.

It seems to me that we are encouraged to tell God

everything; and then we are wise to leave the choice with
Him: asking Him to do that which, in His wisdom and love,
He knows to be best for us.

So the poor wearied Prophet prayed that he might die; and

then overpowered with fatigue, he fell asleep. And
meanwhile God was preparing for him, while he slept—as
He does so often for His faithful, and sometimes faithless,
children—and behold! An angel touched him, and said to
him: "Arise and eat!"
And when he looked up, there was a little cake of bread,
freshly baked, and a cruse of water standing ready by his
pillow!

And he ate and drank; and then, still so weary that he could
hardly hold up his head, he slept again!

Then the angel of the Lord came the second time and
touched him, and said: "Arise and eat; because the journey
is too great for thee!"

Oh, the compassion of God, Who knows just how we feel!

So Elijah obeyed; and he went in the strength of that food,
for forty days and forty nights, till he reached Horeb, the
Mount of God, where he found a cave and lodged there.

By and by he heard a Voice from the Lord speaking to him,

and it said: "What doest thou here, Elijah?"

Then Elijah said: "I have been very jealous for the Lord, but
now the Children of Israel have forsaken my God, and I,
even I, am the only one left, and they are going to kill me!"

And the Lord said: "Go out and stand on the mount before
the Lord."

Then the Lord passed by, and a great wind tore the rocks
and the mountains, and there was a great earthquake; but
the Lord was not in the earthquake nor in the fire that came
afterwards; and then there was a still, low voice. And when
Elijah heard that voice, he wrapped his face in his mantle
and went out and stood by the mouth of the cave.

Then the voice spoke to him again: "What doest thou here,
Elijah?" And again Elijah said that he was the only Prophet
left!