Interpersonal communication and cognitive behavior require sufficient wakefulness, arousal, or alertness. Patients in the persistent vegetative state appear conscious or awake at times, but have little to no communicative or cognitive ability. Coma is the unconscious, sleep-like state of patients who are unresponsive to stimuli. Coma may be due to severe, even lethal, brain damage, or to potentially treatable or reversible causes. Comatose patients thus require prompt evaluation, followed by appropriate therapeutic intervention.
Arousal is a function of the ascending reticular activating system (ARAS), a complex pathway from pons to midbrain to intralaminar thalamic nuclei and basal forebrain, with diffuse cortical connections. Single structural lesions, such as an ischemic infarct or tumor, may produce coma by directly disrupting this pathway in the upper brainstem. However, a unilateral cerebral hemispheral lesion does not produce coma unless it creates enough edema and midline shift to adversely affect the ARAS bilaterally, typically at the thalamic level. Coma may also occur from extensive, severe, bilateral cortical lesions, such as multiple hemorrhages, or from metabolic processes suppressing cortical function in a global way, such as drug intoxication or hypoglycemia. If treated immediately, hypoglycemic coma may resolve completely, as may other toximetabolic etiologies. Certain causes of coma, such as fulminant encephalitis, are progressively fatal, and the patient never wakens. In other situations, such as anoxic encephalopathy, the patient may “wake up” after several days of coma, yet remain in a persistent vegetative state with poor or no cognitive recovery.
I. EVALUATION
A. History.
1. Sudden onset of coma is suggestive of the following:
a. Intracranial hemorrhage (prodromal severe headache may accompany subarachnoid hemorrhage [SAH] from a ruptured intracranial aneurysm, or occur with cerebral hemorrhage).
b. Critical brainstem infarction or multiple embolic cerebral infarcts.
c. Significant cerebral hypoperfusion after cardiopulmonary arrest.
d. Observed or unwitnessed head trauma.
2. Confusion or delirium preceding coma is suggestive of a toximetabolic etiology (organ dysfunction or infection, electrolyte disorder, medicinal or drug toxicity).
3. Important information to obtain immediately consists of the following:
a. Current medications, especially any diabetic, anticonvulsant, cardiac drugs, or warfarin.
b. Any history of adverse or allergic medicinal reactions.
c. Any history of recent head trauma, febrile or other illness, or previous neurological symptoms.
d. Any use of recreational drugs.
B. Physical examination.
1. A rapid general or systemic examination may provide important clues for the etiology of coma.
a. Hypertension to an extreme degree may point to causes other than an acute cerebral hemorrhage or infarction, including hypertensive encephalopathy, cocaine abuse, or eclampsia.
b. Hypotension reflects hypovolemia, cardiogenic or septic shock.
c. Fever accompanies systemic or CNS infections, as well as malignant hyperthermia, neuroleptic malignant syndrome, or serotonin syndrome.
d. Hypothermia after cold exposure may even mimic brain death.
e. Cutaneous bleeding around the eyes or mastoid area accompanies skull fractures. More diffuse hematomas suggest a systemic bleeding disorder. Infective endocarditis may cause “splinter” nailbed or palmar/plantar hemorrhages, producing coma by means of cerebral infarcts or abscesses.
f. Jaundice and ascites may be noted in hepatic coma patients, as well as hepatosplenomegaly.
g. An arrhythmia or heart murmur may be clues for cardiogenic shock, cerebral cardioemboli, or infective endocarditis.
h. Once cervical spine stability is assured, the finding of nuchal rigidity suggests infective meningitis or SAH, but may disappear in deeper stages of coma.
i. Papilledema evolves a few hours after severe elevation in intracranial pressure. The funduscopic examination may also reveal preretinal “fluid level” hemorrhages from subarachnoid bleeding or retinal hemorrhages from infective endocarditis.
C. Although the neurological examination in coma is limited, it offers not only a means of localizing the level of neurological deficit, but also serves as a serial measurement of improvement or deterioration. Developed initially for use in trauma patients, the Glasgow Coma Scale is an easy and reproducible scoring system for all medical personnel, as is the more recently developed FOUR Score (see Table 5.1), which also assesses brainstem reflexes and breathing patterns.
1. Motor responsiveness.
a. Record your observations of the verbal and motor responses from the patient, rather than using brief terms (stuporous, obtunded) with variable meaning.
b. Verbal responses include oriented conversation, disoriented communication, meaningless words or sounds, to unresponsiveness.
c. Motor responses include spontaneous limb movements, limb movements on command, limb withdrawal to noxious stimuli, to unresponsiveness.
TABLE 5.1 Coma Scales
|
Glasgow Coma Scale |
Full Outline of UnResponsiveness (FOUR) |
|
Eye response |
Eye response |
|
4, eyes open spontaneously |
4, eyelids open or opened, tracking, or blinking to command |
|
3, eyes open to command |
3, eyelids open but not tracking |
|
2, eyes open to pain |
2, eyelids closed but open to loud voice |
|
1, no eye opening |
1, eyelids closed but open to pain |
|
0, eyelids remain closed with pain |
|
|
Motor response |
Motor response |
|
6, follows commands |
4, thumbs up, fist or peace sign |
|
5, localizes pain |
3, localizing to pain |
|
4, withdraws from pain (flexion) |
2, flexion response to pain |
|
3, decorticate posturing to pain |
1, extension response to pain |
|
2, decerebrate posturing to pain |
0, no response to pain or generalized myoclonus status |
|
1, no motor response |
|
|
Brainstem reflexes |
|
|
Verbal response |
4, pupil and corneal reflexes present |
|
5, oriented and converses |
3, one pupil wide and fixed |
|
4, disoriented and converses |
2, pupil or corneal reflexes absent |
|
3, uses inappropriate words |
1, pupil and corneal reflexes absent |
|
2, incomprehensible sounds |
0, absent pupil, corneal and cough reflex |
|
1, no verbal response |
|
|
Respiration |
|
|
4, not intubated, regular breathing pattern |
|
|
3, not intubated, Cheyne–Stokes breathing pattern |
|
|
2, not intubated, irregular breathing |
|
|
1, breathes above ventilator rate |
|
|
0, breathes at ventilator rate or apnea |
(1) Decorticate posturing (upper limb flexion with lower limb extension, uni- or bilateral) localizes to the cerebral hemispheres or thalamus.
(2) Decerebrate posturing (upper and lower limb extension, uni- or bilateral) localizes to the midbrain (red nucleus).
(3) If required, noxious stimuli include rubbing the sternum, or applying firm but gentle pressure to the forehead or nailbeds.
(4) Asymmetrical limb movements or hypertonia occur with structural brain lesions, whereas symmetrical motor responses are typical with toximetabolic conditions.
(5) Bilateral myoclonic jerks, asterixis, or tremulousness strongly suggest toximetabolic causes of coma.
(6) Asymmetrical or focal, rhythmical movements may be subtle clues when nonconvulsive status epilepticus causes coma.
2. Respiratory patterns do not strictly correlate with the level of brain dysfunction as once thought and may be obscured if the patient is mechanically ventilated.
a. Cheyne–Stokes’ breathing is observed as periods of increasing, then decreasing, tidal volumes and respiratory rate, followed by seconds of apnea.
(1) It occurs more commonly in elderly patients, with or without systemic medical problems or congestive heart failure.
(2) It may occur from bilateral cerebral lesions or a unilateral lesion with brain shift.
b. Persistent hyperventilation occurs more often from pulmonary causes like pneumonitis, and rarely from midbrain lesions.
c. Arrhythmical, irregular respirations accompany dysfunction at the medulla, where critical cardiorespiratory centers are located.
3. The pupils are typically small but reactive to light in the elderly, as well as those in toximetabolic coma, where other cranial nerve reflexes may be absent.
a. A unilaterally large pupil unreactive to light (“fixed or blown pupil”) in an unresponsive patient represents dysfunction of third cranial nerve pupilloconstrictive fibers.
(1) Most commonly found with ipsilateral temporal lobe compression of the third cranial nerve (uncal herniation) from hemorrhage or edema.
(2) Rarely due to a ruptured intracranial aneurysm at the junction of the internal carotid-posterior communicating artery.
(3) Asymmetrical pupils reflect a structural cause of coma.
b. Bilaterally midposition to large, unreactive pupils may occur with midbrain lesions or terminal anoxic brain injury.
c. Pinpoint, reactive pupils are caused by extensive pontine lesions interrupting the descending sympathetic pupillodilator fibers; however,
(1) pinpoint pupils can also be caused in older patients by cholinergic eyedrops for glaucoma, and
(2) narcotic overdose can also produce small pupils.
4. Ocular reflexes, when present in a comatose patient, indicate preserved brainstem function in the absence of over-riding cortical control.
a. The oculocephalic (“doll’s eyes”) reflex occurs when the examiner passively turns the head to one side, eliciting a normal lateral conjugate rolling of the eyes to the opposite side.
b. The oculovestibular (“cold caloric”) reflex occurs after sequential instillation of 50- to 200-cc ice water into one ear canal, with the head elevated 30˚, eliciting a slow, tonic deviation of both eyes toward the irrigated ear, after several seconds delay.
(1) Ensure that the tympanic membrane is intact, so nonsterile water and debris cannot enter the middle ear.
(2) Ensure there is no impacted cerumen in the ear canal, causing a false negative test.
(3) Lateral jerk nystagmus of the eyes toward the nonirrigated ear occurs in conscious patients, but not comatose patients where cortical function is depressed.
c. Ocular reflexes
(1) should not be checked in trauma patients until cervical spine stability is assured,
(2) may be absent because of previous labyrinthine trauma, mastoiditis or toxicity from benzodiazepines or barbiturates, and
(3) appear asymmetrical from a structural lesion affecting the brainstem, or from facial bone fractures restricting extraocular muscle function.
d. In coma,
(1) the eyes are slightly divergent at rest,
(2) conjugate lateral deviation of the eyes toward one side occurs from a lesion in the contralateral brainstem or ipsilateral cerebral hemisphere,
(3) persistent, rhythmical nystagmus may be a subtle finding of nonconvulsive status epilepticus, and
(4) “ocular bobbing” consists of repetitive downward jerks of the eyes, with slower updrift, due to pontine lesions with poor outcome.
e. Blinking
(1) occurs spontaneously if the pontine ARAS is intact and
(2) along with vertical eye movements may be the only motor functions (and means of communication) in a patient with the “locked-in syndrome” from basilar artery occlusion or severe neuromuscular paralysis.
II. ETIOLOGY
A. Toximetabolic coma accounts for almost two-thirds of unresponsive emergency room patients.
1. A confusional state or delirium occurs initially, followed by symmetrical motor or ocular reflex findings and preserved pupillary light reflex.
2. Exceptionally, hemiparesis or aphasia may be due to hyperglycemic, hypoglycemic, hyponatremic, or dysosmolar states.
3. Tremulousness, myoclonic jerks, and asterixis are typical.
4. Drug intoxication or overdose may also lead to subsequent traumatic brain injury and structural lesions leading to coma.
B. Structural coma accounts for about one-third of unresponsive emergency room patients.
1. Asymmetrical motor or ocular reflex findings occur early.
2. A unilaterally dilated pupil unresponsive to light indicates uncal herniation until proven otherwise.
III. DIFFERENTIAL DIAGNOSIS
A. Brain death.
1. Irreversible, severe loss of brain and brainstem function.
a. Comatose patient with absence of all brainstem reflexes, including spontaneous respiration (abnormal bedside apnea test: no observed breaths despite pCO2 ≥ 60 mm, while on 100% oxygen).
b. The cause of coma is known and sufficient to cause brain death, such as cardiopulmonary arrest.
2. No improvement occurs during observation and treatment.
a. Observation is at least 6 hours in adults, 12 hours to 2 days for children.
b. Hypothermia, hypotensive shock, and drug intoxication have been ruled out or treated.
c. Ancillary testing may help to confirm the clinical diagnosis (absent cerebral blood flow on radioisotope brain scan, or “flat-line” EEG).
B. Persistent vegetative state.
1. After several days of coma, the patient appears intermittently awake, breathes spontaneously, and exhibits primitive reflexes or eye-roving behavior.
2. Severe cerebral damage persists, however, and no meaningful communication or cortical responsiveness occurs.
C. “Locked-in syndrome.”
1. The patient may appear to be in a persistent vegetative state, and is unable to move the limbs and face, or gaze laterally (“de-efferented”).
2. Vertical gaze and eyeblinking are preserved, and serve as a means of proving that communication and cortical functions are preserved (the patient accurately blinks once for “yes,” or twice for “no” in response to the examiner).
3. Caused by an extensive pontine infarction or profound neuromuscular paralysis, such as Guillain–Barré syndrome.
D. Thalamic lesions.
1. Bilateral lesions interrupting the projections of the intralaminar thalamic nuclei of the ARAS to the frontal lobes can produce an inattentive, unresponsive, but still wakeful state.
2. Paramedian thalamic syndrome.
a. Lethargic patient with quadriparesis, impaired vertical gaze, and bilateral asterixis.
b. Caused by bilateral infarction of the dorsal midbrain and thalamus.
E. Nonconvulsive status epilepticus.
1. Occasionally, continual or persistent generalized seizures may occur in the absence of obvious clinical convulsive activity.
2. Subtle clinical manifestations include rhythmical nystagmus, or twitching of an eyelid or part of the face or limb.
3. Obtain an emergent EEG recording and assess the response to IV benzodiazepine boluses.
F. Psychiatric unresponsiveness.
1. Occurs rarely, and remains a diagnosis of exclusion.
2. In the absence of drug overdose, brainstem reflexes and spontaneous breathing should be preserved, and no focal neurological deficits are seen.
3. EEG brain wave frequencies are more similar to that of the awake state than the diffuse EEG slowing typical of toximetabolic coma.
4. Psychiatric patients may become comatose from other medical or neurological disorders as well, or from therapeutic drug therapy (neuroleptic malignant or serotonin syndromes).
IV. MANAGEMENT
A. Initial approach for a comatose patient.
1. Maintain airway, breathing and circulation, since any problems here may be the primary cause of coma, or as secondary complications, may lead to death.
2. Urgently correct any hypothermia, which, if profound, can mimic brain death.
3. If trauma has occurred or is strongly suspected, establish stability of the cervical spine (CT scan) before moving the head, as occurs with testing the oculocephalic (doll’s eyes) reflex.
4. Rule out hypoglycemia, especially in diabetic patients, with an immediate fingerstick glucose reading (or empirical infusion of 50% dextrose if immediate testing is not available).
5. Check basic bloodwork (blood count, electrolytes, glucose, renal and liver functions, protime, activated partial thromboplastin time, arterial blood gases, possibly carbon monoxide (CO) level if CO poisoning suspected) and urine drug screen.
B. Comatose patient with suspected hemorrhage.
1. After the initial approach above, perform a brain CT scan without contrast in a known or suspected trauma patient to rule out intracranial hemorrhage.
2. Nontraumatic SAH is suspected with prodromal headache and sudden loss of consciousness.
a. Rule out SAH with a brain CT scan without contrast.
b. Perform a lumbar puncture (LP) if SAH is still strongly suspected but not seen on brain CT scan.
c. If SAH is found, request neurosurgical consultation and urgent conventional cerebral angiogram or computed tomography angiogram.
C. Comatose patient with fever or septic syndrome.
1. After the initial approach above, examine the patient for any likely systemic focus (abscess and peritonitis) of infection.
2. Panculture blood and urine, obtain chest X-ray.
3. Perform LP to exclude meningitis (in absence of focal neurological findings, papilledema, bleeding disorder, or local infection over the lumbar spine) and begin initial broad-spectrum antibiotic coverage.
4. If LP is contraindicated, request emergent brain CT scan with and without contrast, and neurosurgery consultation.
5. Especially in the case of Herpes simplex encephalitis, a brain MRI scan may help reveal typical frontotemporal lesions.
D. Comatose patient with focal findings on neurological examination.
1. After the initial approach above, exclude hemorrhage with a brain CT scan without contrast.
2. Investigate and treat intracranial hemorrhage or other cause of brain edema or shift.
3. If brain CT scan is normal, obtain brain MRI with and without contrast, including diffusion-weighted sequences, if patient is stable.
4. If brain CT and MRI scans are normal, perform EEG to exclude electrical status epilepticus or postictal state.
E. Comatose patient without focal findings on neurological examination.
1. After the initial approach above, consider administration of IV naloxone or flumazenil, respectively, for possible narcotic or benzodiazepine overdose.
2. If no toximetabolic causes become obvious, obtain a brain CT scan or brain MRI scan if patient is stable.
3. If brain CT and MRI scans are normal, perform an EEG to exclude electrical status epilepticus or postictal state.
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