DESCRIPTION

Coma is defined as markedly depressed mental status, generally without appropriate response to verbal stimuli.

PATHOPHYSIOLOGY

• Depressed mental status may be produced by hundreds of agents.
• General causes of coma include substrate insufficiency (hypoxia, ischemia, or hypoglycemia), effect of a chemical agent (e.g., gamma hydroxybutyrate acid [GHB] or opioid agonist), electrolyte abnormality (e.g., hyper- or hyponatremia), environmental disturbance (hyper- or hypothermia), or systemic infection.

EPIDEMIOLOGY

• Coma is common in poisonings and usually results from intentional ingestion or substance abuse.
• Elderly patients may develop CNS depression at therapeutic doses of some drugs, especially if more than one drug with a sedative effect is ingested.
• Death usually occurs only if adequate airway is not maintained.

Section Outline:

• DESCRIPTION
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY

DIFFERENTIAL DIAGNOSIS

Associated findings in the presence of coma assist in determining its cause.

Toxicologic Causes

Numerous commonly used toxicologic agents can cause coma. Further information on each poison is available in SECTION IV, CHEMICAL AND BIOLOGICAL AGENTS.

• Opioids also cause miosis, decreased bowel sounds, and respiratory depression.
• Cholinergic agonist drugs, such as pilocarpine, bethanechol, organophosphate, or carbamate insecticide, are associated with bradycardia, salivation, lacrimation, urination, defecation, and muscle weakness.
• Benzodiazepine drug overdose is usually associated with mid-position pupils and respiratory depression; coma is unusual in these cases unless the benzodiazepine is combined with other sedative agents or administered parenterally.
• Neuroleptic or other dopamine agonist or serotonin agonist ingestion, either chronic or recent, may suggest neuroleptic malignant syndrome (NMS) or serotonin syndrome, two similar entities that result in altered mental status, hyperthermia, muscle rigidity, and autonomic instability.
• Barbiturate overdose is usually associated with mid-position pupils and respiratory depression.
• Sedative-hypnotic agent overdose, such as with chloral hydrate, GHB, and rohypnol ("roofies"), is usually associated with mid-position pupils and respiratory depression.
• Clonidine and tetrahydrozoline produce respiratory depression with small pupils, bradycardia, and hypotension.
• Tricyclic antidepressant (TCA) overdose is usually associated with cardiac dysrhythmia, often with seizures; a QRS complex width of >= 0.10 seconds may be present, as may anticholinergic effects.
• Anticonvulsants commonly cause nystagmus, ataxia, and slurred speech prior to the onset of coma; carbamazepine may cause hallucinations, hyponatremia, and seizures.
• Carbon monoxide, cyanide, or hydrogen sulfide cause nausea, headache, and rapid onset of coma; metabolic acidosis is common. Multiple victims may be involved.
• Methanol is associated with nausea, ataxia, and slurred speech, followed by metabolic acidosis, visual complaints, or blindness.
• Ethylene glycol causes nausea, ataxia, and slurred speech, followed by metabolic acidosis, proteinuria, hematuria, calcium oxalate crystalluria, and renal failure.
• Isopropyl alcohol causes marked mental status depression and occasionally hemorrhagic gastritis without metabolic acidosis.
• Hydrocarbons such as toluene may cause metabolic acidosis and renal tubular acidosis.

A few less common agents also may cause coma:

• Nearly any toxic agent may cause CNS depression or coma as a preterminal event.
• Diphenoxylate/atropine (Lomotil) can cause anticholinergic effects initially, followed by narcotic effect.
• Ethchlorvynol (Placidyl) causes profound coma that may persist for days.

Nontoxicologic Causes

• Coma is nondiagnostic in itself; it is important to determine whether localizing neurologic signs are present. Localizing signs often indicate a focal intracranial infection, bleed, or other structural abnormality; lack of lateralization, however, does not exclude an intracranial process.
• All nontoxic causes of hypotension, hypoxia, or hypoglycemia may lead to coma.
• Specific nontoxic causes of mental status depression include severe electrolyte abnormalities, hypo- or hypernatremia, hypoglycemia, or intracranial events (infection, bleed, embolus).

SIGNS AND SYMPTOMS

Physical signs that occur in the patient with coma may help reveal the poison involved.

Vital Signs

• Tachycardia suggests poisoning by a TCA, phenothiazine, cyclobenzaprine, or sympathomimetic or anticholinergic drug.
• Bradycardia may indicate beta-receptor or calcium channel blocker, baclofen, clonidine, imidazoline, cholinergic agent, or decongestant.
• Hypotension suggests TCA, phenothiazines, beta-receptor or calcium channel blocker, clonidine, imidazolines, or late course of monoamine oxidase (MAO) inhibitor.
• Hypertension is typical early in the course of phenylpropanolamine, sympathomimetic, or anticholinergic poisoning.
• Hyperthermia is common in sympathomimetic or anticholinergic overdose, NMS, serotonin syndrome, overdose of salicylate or hallucinogen, and alcohol withdrawal.
• Environmental hypothermia may develop from any cause of prolonged coma.

HEENT

• Pinpoint pupils suggest opioid, clonidine, imidazoline, or cholinergic agent involvement.
• Mydriasis may indicate hypoxia or poisoning with sympathomimetic or anticholinergic agent, phenothiazine, TCA, or carbamazepine.
• Nystagmus suggests ethanol, carbamazepine, phenytoin, phencyclidine, phenobarbital, or sedative-hypnotic toxicity.

Dermatologic

• Dry, flushed skin suggests anticholinergic toxicity.
• Cyanosis suggests hypoxia or methemoglobinemia.
• "Track marks" may indicate heroin, cocaine, or amphetamine abuse.

Cardiovascular

• QRS widening or an R wave in the ECG lead aVR suggests TCA, phenothiazine, or severe carbamazepine overdose.
• beta-receptor blockers also produce hypotension, hyperglycemia, bradycardia atrioventricular (AV) block, ventricular dysrhythmia, and seizures.
• Calcium channel blockers may produce hypotension, CNS depression, bradycardia, AV block, and ventricular dysrhythmia.

Pulmonary

• Respiratory depression may indicate opioid, sedative-hypnotic, TCA, phenothiazines, beta-receptor or calcium channel blocker, clonidine, or imidazoline.
• Hyperpnea is typical with salicylates and agents that cause metabolic acidosis (e.g., isoniazid, ethylene glycol, or methanol), and with hypoxia or hyperthermia from any cause.

Gastrointestinal

• Increased bowel sounds and diarrhea may be present with cholinergic stimulant (organophosphate or carbamate insecticides) toxicity.
• Decreased bowel sounds are consistent with anticholinergic, opioid, or sedative-hypnotic agents.

Fluids and Electrolytes

• Increased anion gap metabolic acidosis suggests lactic acid, methanol, ethylene glycol, iron, isoniazid, salicylate, carbon monoxide, cyanide, metformin, paraldehyde, or toluene toxicity.
• Decreased anion gap suggest lithium or bromides.
• Hypoglycemia suggests hypoglycemic agents, ethanol (particularly in children), or severe hepatic injury from any cause.

Musculoskeletal

Rhabdomyolysis may develop from seizures or prolonged coma.

Neurologic

• Prolonged or recurrent seizures may develop with isoniazid, cocaine or other sympathomimetic agents, lithium, TCA, or carbamazepine toxicity among many others.
• Myoclonus and tremor may occur with lithium, methaqualone, carbamazepine, phenytoin, valproate, barbiturates, chloral hydrate, ethanol, glutethimide, ethanol, or phenothiazines.
• Myoclonus without tremor may occur with anticonvulsants, benzodiazepines, TCAs, ethanol, or sedative-hypnotics.
• Fasciculation may occur with lithium, amphetamines, cholinergic agents, cocaine, nicotine, and phencyclidine or hypoglycemia from any cause.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Oxygenation should be assessed (pulse oximetry or arterial blood gas); hypoxia and hypercarbia are treatable causes of CNS depression.
• Blood glucose should be measured.
  • Hyperglycemia is a reversible cause of coma that may cause permanent neurologic injury if not promptly treated.
  • Hypoglycemia should be treated presumptively with a bolus of D₅₀ if bedside testing is not immediately available.
• ECG and continuous cardiac monitoring should be performed; these tests may reveal evidence of TCA intoxication (tachycardia, QRS widening, R wave in lead aVR), beta-adrenergic antagonist (bradycardia, AV block), or calcium channel antagonist (bradycardia, AV block).
• Serum electrolytes, calcium, magnesium, BUN, and creatinine should be obtained to assess for anion gap metabolic acidosis and severe electrolyte abnormalities (hypo- or hypernatremia), and renal injury.

Recommended Tests

• Urine toxicology screen should be ordered to assess persistent coma of undetermined etiology; the presence of acetaminophen, salicylate, opioid, or other drugs will help guide treatment.
• Serum or breath ethanol level should be obtained to assess for this common cause of mental status depression.
• Serum acetaminophen and aspirin levels should be obtained in overdose settings to detect occult ingestion.
• Lumbar puncture; blood, urine, spinal fluid cultures; and specific drug levels (e.g., anticonvulsant) should be obtained as needed to evaluate for differential diagnoses.
• Head CT may be needed to investigate the possibility of intracranial disease.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
  • Toxicologic Causes
  • Nontoxicologic Causes
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Fluids and Electrolytes
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• If serious respiratory depression or difficulty in protecting the airway is present, the patient should be intubated endotracheally until the cause can be determined and treated.
• Intravenous access should be established, cardiac monitor should be placed, and reversible causes of coma should be treated empirically with immediate administration of oxygen, 2 mg of naloxone, 50 ml of D₅₀W (unless immediate glucose determination is available), and 100 mg of thiamine.
• Reversible causes of coma must be treated empirically.
• The dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care provider should call poison control center when:

• the cause of the coma is unknown.
• coingestant, drug interaction, or underlying disease presents unusual problems.

Admission Considerations

Nearly all cases of coma require admission with exception of quickly reversible causes that have not caused permanent injury (e.g., transient hypoglycemia).

DECONTAMINATION

• Syrup of ipecac should never be administered to a patient with CNS depression.
• If toxic ingestion is possible, gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients with altered mental status; in the comatose patient, lavage should be performed even if the ingestion occurred several hours previously.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic.

ANTIDOTES

Naloxone

• Indications. Altered mental status of undetermined etiology.
• Contraindications. None.
• Method of administration
  • Adult or pediatric dose is 2 to 10 mg administered in 2-mg increments.
  • A cumulative dose of 10 to 20 mg may be needed for propoxyphene, nalbuphine, or butorphanol poisonings.
  • If more than 10 mg is needed or produces only partial response, suspect the influence of another toxicant.
• Potential adverse effects
  • Naloxone may induce withdrawal syndrome.
  • Reversal of opioid effects may unmask another coexistent toxicity, such as cocaine.

Dextrose

• Indications. Altered mental status.
• Contraindication. None.
• Method of administration
  • Adult dose is 50 to 100 ml (25-50 g) of D₅₀ administered by intravenous push.
  • Pediatric dose is 2 to 4 ml/kg (0.5-1 g/kg) of D₂₅ administered by intravenous push.

Flumazenil

• Indications. Depressed mental status requiring intubation and extensive diagnostic assessment.
• Contraindications. Patients with a history of seizures, history or ECG evidence of TCA overdose (QRS widening, R wave in ECG lead aVR), or known benzodiazepine dependence.
• Method of administration
  • Adult dose is 0.2 mg administered intravenously and repeated every 1 to 2 minutes up to 2 mg; if effective, the dosage may be repeated every 30 minutes or more as needed.
  • Pediatric dose is 10 µg/kg administered intravenously; if effective, the dose may be repeated every 30 minutes or more as needed.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
• ANTIDOTES
  • Naloxone
  • Dextrose
  • Flumazenil

Cardiovascular and respiratory functions should be monitored continuously.

DIAGNOSIS

Brain death cannot be diagnosed by EEG alone in comatose patients with drug intoxication (e.g., barbiturates).

TREATMENT

• Airway should be managed aggressively; many toxicologic deaths occur simply because endotracheal intubation was not performed early.
• If vomiting is present, it is important to ensure that aspiration has not occurred.

Section Outline:

• DIAGNOSIS
• TREATMENT

ICD-9-CM 780.01

Alterations of consciousness: coma.

RECOMMENDED READING

Galliger EJ. Neurologic principles. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Katherine M. Hurlbut

Reviewer: Luke Yip