Douglas W. Scharre, MD

DESCRIPTION

• Coma is a state of unconsciousness with complete absence of awareness of the environment even when externally stimulated; the most severe form of unresponsiveness.
  • Patient unarousable to verbal or noxious stimuli; eyes closed
  • No spontaneous eye opening, facial movements, utterances or body movements
  • Painful stimuli may produce non-directed reflexive movements from spinal cord or brainstem pathways but do not result in any conscious responsiveness
• Results from severe diffuse bilateral cerebral dysfunction or significant brainstem impairment
• Structural, metabolic, hypoxic, and infectious causes are typical
• Clinical presentation, examination, and laboratory and neuroimaging evaluations determine the specific cause and guide treatment options

EPIDEMIOLOGY

No typical age or gender predilection due to multiple potential causes for coma.

Incidence

Incidence varies with the cause of coma. Overall coma occurs in 6/100,000 general population and 31/100,000 in children <16 years (1).

Prevalence

Prevalence varies with the cause of coma.

RISK FACTORS

The risk factors comprise any condition causing diffuse bilateral cerebral dysfunction or brainstem impairment.

Genetics

No reports available.

GENERAL PREVENTION

As there are multiple potential causes for coma there are no general prevention guidelines.

PATHOPHYSIOLOGY

• Conscious behavior requires both arousal and cognitive processing
  • The brainstem reticular activating system (RAS) extending from the midpons to the hypothalamus is responsible for arousal
  • The cerebral hemispheres are responsible for cognitive abilities and processing
• Coma results only from conditions disrupting both cerebral hemispheres diffusely or the brainstem ascending reticular activating system
• The locked-in syndrome is not coma; it results from lesions below the midpons that preserves the RAS for arousal and the brain for consciousness

ETIOLOGY

• Diffuse encephalopathies
  • Cerebral anoxia/ischemia
  • Encephalitis/Meningitis
  • Subarachnoid hemorrhage
  • Vasculitis
  • Cerebral shower of emboli
  • Hepatic/uremic encephalopathy
  • Metabolic encephalopathy (e.g., hyponatremia)
  • Diabetes (ketoacidosis, hypoglycemia, nonketotic hyperosmolar coma)
  • Nutritional deficiency (thiamine)
  • Alcohol/narcotic abuse
  • Drug overdose/intoxication
  • Hypothyroidism
  • Sepsis
  • Seizures (nonconvulsive status epilepticus)
  • Hypothermia/hyperthermia
  • Hypertensive encephalopathy
• Structural lesions
  • Brain herniation syndromes
  • Brain or brainstem tumor or abscess
  • Epidural/subdural hematoma or empyema
  • Intracerebral/brainstem/cerebellar infarction or hemorrhage
  • Basilar artery thrombosis
  • Head trauma (cerebral contusion)

COMMONLY ASSOCIATED CONDITIONS

Structural, metabolic, hypoxic, infectious, and drug toxicity are most commonly associated.

HISTORY

• Ask about onset and time course of the coma
  • Sudden onset with rapid progression suggests stroke or hemorrhage; subacute courses may indicate tumor or abscess
• Coma proceeded by acute confusion without focal deficits suggest diffuse encephalopathies
• Ask about recent head trauma, progressive neurologic deficits (brain tumor), fever, infection, severe headache, stroke risk factors, seizures, current medications, drug or alcohol abuse, nutritional deficiencies, depression, diabetes, and organ failure (heart, lung, liver, and kidney)

PHYSICAL EXAM

• Observe for signs of head trauma
• Evaluate for stiff neck (meningitis or subarachnoid hemorrhage)
• Check vital signs and temperature
  • Elevated blood pressure (hemorrhage, stroke, or hypertensive encephalopathy)
  • Hypothermia (drug intoxication, hepatic encephalopathy, hypothyroid, hypoglycemia)
  • Hyperthermia (anticholinergic intoxication, heat stroke, status, hypothalamic lesions)
• Fundi
  • Papilledema and retinal hemorrhages suggest increased intracranial pressure
• Pupils
  • Normal to smaller and reactive (diffuse encephalopathies or hypothalamic compression)
  • Bilateral dilated and fixed (midbrain lesion, anoxia, drug intoxication: Anticholinergic, sympathomimetic, barbiturates, glutethimide)
  • Unilateral dilated and fixed (third nerve palsy)
  • Pinpoint reactive (pontine lesion, narcotic intoxication, organophosphate poisoning, and miotic eye drops)
• Extraocular movements
  • Check primary gaze for skews or deviations, roving eye movements; test oculocephalic (doll's) and oculovestibular (calorics) reflexes
  • Normal primary gaze with intact doll's and calorics (diffuse encephalopathies)
  • Normal primary gaze with impaired doll's and calorics (some drug intoxications: Tricyclics, barbiturates, antibiotics, benzodiazepines, succinylcholine, phenytoin; or preexisting vestibular dysfunction)
  • Dysconjugate gaze (structural lesions)
  • Deviated eyes toward lesion with intact doll's and calorics (supratentorial structural lesion)
  • Single downward deviated eye at rest that fails to adduct with doll's or calorics (third nerve palsy)
  • Skewed, deviated at rest (away from lesion) or normal primary gaze with absent doll's and calorics (pontine lesion)
• Brainstem reflexes
  • Corneal reflexes: Normal responses, direct and consensual (intact midbrain and pons)
  • Gag responses: If present (intact medulla)
• Motor examination
  • Look for spontaneous movements, check posture (laterally rotated legs, facial droop), tone, reflexes, response to noxious stimuli to extremity or face to detect hemiparesis, facial weakness, or other focal deficits
  • Repetitive movements: Limb or face (seizures)
  • Tremors, myoclonus, or asterixis (diffuse encephalopathies)
  • Flaccid tone (diffuse encephalopathies, pontine or medulla lesions)
  • Decorticate posturing to noxious stimuli: Arm flexion, leg extension (supratentorial or thalamic lesions, diffuse encephalopathies)
  • Decerebrate posturing to noxious stimuli: Arm and leg extension (subtentorial or brainstem)
• Transtentorial brain herniation
  • Progressive downward pressure on thalamus and brainstem due to supratentorial structural lesions or edema
  • Pupils: Progressing from small to mid-sized and nonreactive
  • Extraocular movements: Doll's and calorics progressively impaired until absent
  • Motor examination: Progressing to decorticate, then decerebrate posturing and finally flaccid
• Uncal brain herniation
  • Progressive lateral pressure on thalamus and upper brainstem due to lateral masses
  • Pupils: Dilated and fixed ipsilateral to lesion
  • Extraocular movements: Eye ipsilateral to lesion deviated laterally and fails to adduct
  • Motor examination: Hemiplegia ipsilateral to lesion due to cerebral peduncle compressed on the incisura of the tentorium (Kernohan's notch)
• Respiratory breathing patterns
  • Cheyne–Stokes: Periodic episodes of apnea alternating with hyperpnea (diffuse encephalopathies or structural lesions)
  • Central neurogenic hyperventilation: Rapid, sustained hyperpnea (midbrain to upper pons damage, diffuse encephalopathies or structural lesions)
  • Apneustic: Pausing at full inspiration (pontine damage, anoxia, meningitis, hypoglycemia)
  • Ataxic: Irregular (medullary damage)

DIAGNOSTIC TESTS AND INTERPRETATION

Lab

Lab tests: To identify specific causes of coma.

Initial Lab Tests

• Arterial blood gas, electrolytes, BUN, glucose, creatinine, calcium, magnesium, liver function tests, ammonia, CBC, PT, PTT, sedimentation rate, thyroid function tests, and toxicology screen
• Cervical spine films if trauma suspected
• Electrocardiogram to evaluate the heart
• Lumbar puncture for meningitis/encephalitis; avoid with mass lesions to prevent herniation
• Electroencephalogram if seizures suspected

Follow-Up & Special Considerations

ICU required for monitoring and intubation.

Imaging

Initial Approach

CT and MRI scans show structural lesions; MRI is better for visualizing the brainstem.

Follow-Up & Special Considerations

Repeat scans as clinically indicated.

Diagnostic Procedures/Other

Evaluation for brain death: Apnea testing (no spontaneous respirations observed with PCO₂ >59 mm Hg) and if indicated, confirmatory testing (cerebral angiography, electroencephalogram, nuclear scan) consistent with brain death.

Pathological Findings

Pathological findings depend on etiology.

DIFFERENTIAL DIAGNOSIS

• Persistent vegetative state: Unresponsiveness despite wakefulness and return of sleep–wake cycles; usually emerges after 2 weeks of coma
• Stupor: Can be aroused with noxious stimuli
• Lethargy: Arousable with verbal stimuli
• Acute confusional state: Represents attentional deficits between full responsiveness and lethargy
• Locked-in state: Mute, quadriplegic, conscious and blinks or vertically moves eyes on command
• Brain death: Irreversible cessation of all brain and brainstem function from an explainable cause

MEDICATION

First Line

Drug choices depend on causes of the coma.

ADDITIONAL TREATMENT

General Measures

Supportive care is critical.

Issues for Referral

Patients that survive often need rehabilitation or long-term care.

COMPLEMENTARY AND ALTERNATIVE THERAPIES

Complementary and alternative therapies depend on the specific etiology of coma.

SURGERY/OTHER PROCEDURES

Neurosurgical evaluation for neurosurgical causes of coma.

IN-PATIENT CONSIDERATIONS

Initial Stabilization

• Airway, breathing, and circulation
• Check and stabilize cervical spine fractures
• Give every coma patient 100 mg thiamine IV, 50 mL of 50% dextrose IV, 0.4–1.2 mg naloxone IV to treat for possible Wernicke's encephalopathy, hypoglycemic coma, and opiate overdose
• Treat seizures
• Diagnostic studies for causation of coma
• Wean off any sedative medications
• Stabilize vital signs and treat fever
• Correct metabolic and other treatable causes
• Treat meningitis, encephalitis, and brain abscess with antibiotics
• Treat hepatic encephalopathy if present
• Treat cerebral edema
  • Ischemic stroke edema is not helped by osmotic diuretics or steroids
  • Elevate head
  • Intubate and hyperventilate to PCO₂ 25 mm Hg
  • Administer mannitol 20% 1.5–2.0 g/kg IV over 30–60 minutes
  • Give normal saline two-thirds maintenance
  • For tumor, abscess, and maybe intracerebral hemorrhage, give dexamethasone 10 mg IV then 4 mg PO or IV every 6 hours with an H₂ blocker and monitor blood sugar

Admission Criteria

Admit to the intensive care unit for initial evaluation and treatment of coma.

IV Fluids

As needed depending on condition.

Nursing

• Adherence to medical orders
• Close monitoring to care for all basic activities of daily living and ensure patient comfort

Discharge Criteria

Discharge to rehabilitation or long-term care facilities once stabilized if recovery not complete.

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

Neurological checks required frequently for detecting changes in neurologic function.

DIET

Parenteral feeds initially, maximize nutrition.

PATIENT EDUCATION

Provide strategies to reduce reoccurrence of preventable, metabolic or other forms of coma.

PROGNOSIS

Mortality high in coma but depends on causation.

COMPLICATIONS

Complications will vary depending on the etiology of coma.

• Posner JB, Saper CB, Schiff ND, et al. Plum and Posner's diagnosis of stupor and coma, 4th ed. Contemporary Neurology Series. Oxford: Oxford University Press, 2007.

SEE-ALSO

• Brain herniation syndromes

ICD9

780.01 Coma

• Coma means unconsciousness with absence of awareness.
• Caused by diffuse cerebral dysfunction or brainstem reticular activating system impairment.
• Structural, metabolic, hypoxic, and infectious causes are typical.

1. Wong CP, Forsyth RJ, Kelly TP, et al. Incidence, aetiology, and outcome of non-traumatic coma: a population based study. Arch Dis Child 2001;84:193–199.