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LEARNING OBJECTIVES
On completion of this article, the reader should be able to:
1. Describe changes in the level of consciousness.
2. Identify the indicators of prognosis in comatose patients.
3. Use this information in a clinical setting.
Dr. Stevens has disclosed that he is the recipient of direct grant/research funds from the National Institutes of Health, Public
Health Service; Dr. Bhardwaj has disclosed that he was the recipient of direct grant/research funds from the American Heart
Association and that he is/was the recipient of grant/research funds from the National Institutes of Health, Public Health
Service.
Wolters Kluwer Health has identified and resolved all faculty conflicts of interests regarding this educational activity.
Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information in obtaining continuing medical education
credit.
Background: Coma is a medical emergency and may constitute and are associated with a substantial risk of death and disability.
a diagnostic and therapeutic challenge for the intensivist. Management of impaired consciousness includes prompt stabili-
Objective: To review currently available data on the etiology, zation of vital physiologic functions to prevent secondary neuro-
diagnosis, and outcome of coma. To propose an evidence-based logic injury, etiological diagnosis, and the institution of brain-
approach for the clinical management of the comatose patient. directed therapeutic or preventive measures. Neurologic
Data Source: Search of Medline and Cochrane databases; prognosis is determined by the underlying etiology and may be
manual review of bibliographies from selected articles and mono- predicted by the combination of clinical signs and electrophysi-
graphs. ological tests. (Crit Care Med 2006; 34:3141)
Data Synthesis and Conclusions: Coma and other states of KEY WORDS: coma; vegetative state; hypoxic-ischemic enceph-
impaired consciousness are signs of extensive dysfunction or alopathy; traumatic brain injury; neurologic diagnosis; outcome
injury involving the brainstem, diencephalon, or cerebral cortex prediction
C
oma and other states of im- potentially reversible with the timely in- tive function, and motivation (2). The re-
paired consciousness repre- stitution of medical or surgical therapy. lationship between wakefulness and
sent a severe derangement in Physicians in the emergency and inten- awareness is hierarchical: Awareness can-
cerebral function that may be sive care arena have a central role in not occur without wakefulness, but wake-
structural or nonstructural (toxic-meta- diagnosing and treating comatose pa- fulness may be observed in the absence of
bolic, pharmacologic, seizures) in origin. tients, the principles of which are out- awareness (e.g., the vegetative state; dis-
Many of the underlying processes leading lined in this review. cussed subsequently).
to coma can be both life-threatening and Although many aspects of conscious-
Disorders of Consciousness ness remain unexplained, its neuroana-
Assistant Professor, Division of Neurosciences
tomical underpinnings have been studied
From a clinical perspective, con-
Critical Care, Department of Anesthesiology/Critical extensively. Wakefulness is linked to the
sciousness may be schematized as the
Care Medicine, Neurology and Neurosurgery (RDS), ascending reticular activating system
Vice Chairman, Department of Neurology, Co-Director, product of two closely related cerebral
functions: wakefulness (i.e., arousal, vig- (ARAS), a network of neurons originating
Division of Neurosciences Critical Care, Associate Pro-
fessor of Neurology, Neurological Surgery, Anesthesi- ilance, alertness), and awareness of self or in the tegmentum of the pons and mid-
ology/Critical Care Medicine (AB), The Johns Hopkins of the environment, often referred to as brain and projecting to diencephalic and
University School of Medicine, Baltimore, MD. cortical structures (3, 4). Awareness is
Supported, in part, by grant NS 046379 from the the content of consciousness (1). The
U.S. Public Health Service National Institutes of Health. content of consciousness encompasses, dependent on the integrity of the cerebral
Copyright 2005 by the Society of Critical Care in turn, several other overlapping brain cortex and its subcortical connections
Medicine and Lippincott Williams & Wilkins functions including attention, sensation (5). Biochemical analysis of the ARAS re-
DOI: 10.1097/01.CCM.0000194534.42661.9F and perception, explicit memory, execu- veals cholinergic and glutamatergic (pon-
Sleep/Wake
Pattern of Cerebral
Cyclic Respiratory Metabolism
Arousal Awareness Arousal Motor Function Function EEG Activity (% Normal)a
EEG, electroencephalograph.
a
As assessed by fluoro-deoxyglucose positron emission tomography.
tomesencephalic origin), adrenergic (lo- pharmacologic, physiologic, and meta- not speak or move spontaneously. They
cus ceruleus), serotonergic and bolic causes of coma should be excluded. do not follow commands, and when pro-
dopaminergic (brainstem), and histamin- Coma. Coma is characterized by the voked by a noxious stimulus their eyes
ergic (hypothalamic) pathways (5). Many total absence of arousal and of awareness. remain closed, vocalization is limited or
of these neurons converge on the thala- As opposed to states of transient uncon- absent, and motor activity is absent or
mus, which then sends projections to the sciousness such as syncope or concus- abnormal and reflexive rather than pur-
cerebral cortex. Additional neurons of the sion, coma must last 1 hr (10). Coma- poseful or defensive (1). Sleep-wake cy-
ARAS project directly to the cerebral cor- tose patients have no eye opening and do cles are lacking. Coma is typically a tran-
tex or to other diencephalic structures sitional state, evolving toward recovery of
such as the hypothalamus. consciousness, the vegetative state, the
Pathologic changes in consciousness Table 2. Glasgow Coma Scale minimally conscious state, or brain death
(Table 1) imply a significant alteration in (Fig. 1). Coma is associated with injury to
the awareness of self and of the environ- Motor response (M) or functional disruption of bilateral cor-
Follows commands 6
ment, with variable degrees of wakeful- Localizes pain 5 tical structures or of the ARAS. Lesions
ness (6). Descriptive terms such as som- Withdraws to pain 4 involving the brainstem portion of the
nolence, stupor, obtundation, and Flexion 3 ARAS frequently coexist with oculomotor
lethargy used to denote different levels of Extension 2 findings and pathologic breathing pat-
None 1
wakefulness are best avoided, given the terns.
Verbal response (V)
lack of uniformity in the way these states Oriented 5 Vegetative State. The vegetative state
are defined in the literature (1, 6) and the Confused speech 4 (VS) is notable for preserved arousal
availability of objective measures such as Inappropriate words 3 mechanisms associated with a complete
the Glasgow Coma Scale (Table 2) (1, 7, Incomprehensible 2 lack of self or environmental awareness
None 1
8). Eye opening (E) (10, 11). Patients in a VS open their eyes
Brain Death. Consciousness disorders Spontaneous 4 spontaneously; however, there is no evi-
must be distinguished from brain death, To command 3 dence of sustained visual pursuit (track-
which is the irreversible loss of all brain To pain 2 ing) or visual fixation. They do not follow
None 1
and brainstem function, clinically diag- commands and do not move in any mean-
nosed by demonstrating absence of con- When assessing record best motor and re- ingful or purposeful manner. They evolve
sciousness, lack of motor response to sponse. Endotracheal tube or tracheostomy in- through temporal cycles of increased and
noxious stimulus, and the disappearance validates the verbal component. Coma defined as decreased arousal akin to a sleep-wake
of brainstem reflexes and respiratory M 4, V 2, E 2 (Glasgow Coma Scale 8). pattern. Cardiovascular regulatory func-
drive (9). Before this determination, Adapted from Teasdale and Jennett (8). tion, breathing patterns, and cranial
zures or a resulting postictal state may enough to cause displacement of midline ide), alterations in neuronal excitability
also lead to altered consciousness. structures (shift) (1). Brainstem and dien- and signaling (seizures, acidosis, drug
cephalic lesions resulting in coma may be toxicity), or changes in brain volume (hy-
Etiology and Pathogenesis comparatively small; however, they must pernatremia, hyponatremia). The degree
also involve bilateral structures (4). Com- of neurologic impairment is related to
Common causes of coma are traumatic partmental shift of sufficient magnitude the time course of the underlying cere-
brain injury (TBI), hypoxic-ischemic en- will disrupt the structural integrity or func- bral pathology. Thus, an acute hemi-
cephalopathy (HIE), drug overdose, isch- tion of contralateral reticulothalamic or spheric or brainstem hemorrhage with
emic stroke, intracranial hemorrhage, cen- thalamocortical fibers, impairing the ARAS mass effect will be associated with de-
tral nervous system infections, and brain and its projections. Shift may also cause pressed consciousness, whereas a slowly
tumors. From a pathophysiologic stand- central or tentorial herniation with com- developing brain tumor of identical loca-
point, coma may be viewed as the expres- pression of the midbrain, compromising tion and volume may be asymptomatic. A
sion of a) primary insults to the cerebral more proximal elements of the ARAS (32). similar observation can be made for met-
cortex, diencephalic structures, midbrain The pathophysiology of toxic and met- abolic changes, such as acute vs. progres-
or rostral pons; and b) secondary cerebral abolic coma is specific to the underlying sive hyponatremia.
manifestations of systemic toxic, metabolic, cause and in many instances incom-
or endocrine derangements (Table 3) (1, pletely understood (33). In a simplified Approach to the Comatose
32). view, these conditions have been linked Patient
To affect consciousness, lesions of the to an interruption in the delivery or uti-
cerebral cortex must involve both hemi- lization of oxygen or substrate (hypoxia, Disorders of consciousness such as
spheres or must be unilateral lesions large ischemia, hypoglycemia, carbon monox- coma are potentially life threatening and
Examination Normal
Technique Response Afferent Pathway Brainstem Efferent Pathway
M
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