DESCRIPTION

Cocaine is a widespread drug of abuse as well as a pharmaceutical product used to produce vasoconstriction of the nasal mucosa.

FORMS AND USES

• Pharmaceutical cocaine is available in aqueous solutions of 4% to 10% for use as a topical anesthetic and vasoconstrictor and is often combined with tetracaine and adrenaline to form Tetracaine Adrenaline Cocaine (TAC), a topical anesthetic.
• The coca plant, Erythroxylan coca, is the source of cocaine. Dried coca leaves contain approximately 2% cocaine
• "Crack" cocaine is the crystalline base form of cocaine that is heat stable and may be smoked.
• Slang terms include coke, crack, snow, rock, and white girl, among many others.

TOXIC DOSE

Individual toxic response to cocaine varies widely; in patients who are not chronic users, nasal application of 25 mg (less than 1 ml of 4% solution) has resulted in death.

PATHOPHYSIOLOGY

Cocaine increases the concentration of norepinephrine in the synapse by increasing release of norepinephrine from neurons in both the CNS and peripheral nervous systems and blocking its reuptake at the presynaptic membranes of the sympathetic nervous system.

EPIDEMIOLOGY

• Cocaine is one of the most frequently used illicit drugs, and poisoning is common.
• Death occurs in patients with severe toxic effects, such as seizure, dysrhythmia, or hyperthermia.

CAUSES

• Cocaine poisoning usually results from recreational cocaine abuse.
• Severe toxicity may develop in "body-packers" or "body-stuffers."
• Child neglect should be considered in pediatric patients.

DRUG AND DISEASE INTERACTIONS

• Cocaine has a synergistic effect with other sympathomimetic agents (e.g., amphetamines).
• Cocaine may interact with monoamine oxidase inhibitor antidepressants (e.g., phenelzine or tranylcypromine) to cause severe hypertension, hyperthermia, and death.

PREGNANCY AND LACTACTION

• US FDA Pregnancy Classification X. Studies in animals or humans have demonstrated fetal abnormalities, or there is evidence of fetal risk based on human experience, or both, and the risk clearly outweighs any possible benefit.
• Maternal cocaine use during pregnancy is associated with spontaneous abortion, placenta previa, abruptio placentae, fetal prematurity, low birth weight, multiple intestinal atresia, and necrotizing enterocolitis.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTACTION

DIFFERENTIAL DIAGNOSIS

• Other toxicologic causes of adrenergic excess include other sympathomimetic agents (e.g., amphetamine, methamphetamine), neuroleptic malignant syndrome, and serotonin syndrome.
• Nontoxicologic causes of adrenergic excess include hyperthyroidism, manic episode, alcohol or sedative withdrawal, and pheochromocytoma.

SIGNS AND SYMPTOMS

Vital Signs

• Hypertension, tachycardia, and mild hyperthermia are common.
• Severe hyperthermia and hypotension may develop in overdose.
• Shock may result from severe overdose.

HEENT

Mydriasis may occur, along with nasal mucosal ischemia or septal perforation (with chronic abuse)

Dermatologic

Pallor and diaphoresis are common.

Cardiovascular

• Acute toxic effects may include myocardial ischemia and infarction, aortic dissection, cardiac sudden death, and dysrhythmias.
• Chronic cocaine abuse may cause myocarditis and cardiomyopathy.

Pulmonary

• Pneumomediastinum, pneumothorax, and pulmonary hemorrhage may be seen in freebase and crack cocaine smokers.
• Pulmonary hypertension and pulmonary edema may develop.

Gastrointestinal

• Bowel ischemia and infarction due to splanchnic vasospasm may occur in patients of all ages.
• Necrotizing enterocolitis may occur in neonates.

Hepatic

Hepatic necrosis may develop in patients with severe hyperthermia.

Renal

Acute renal failure may occur as a complication of rhabdomyolysis.

Fluids and Electrolytes

Lactic acidosis may occur.

Musculoskeletal

Rhabdomyolysis may occur due to hyperthermia, agitation, and seizures.

Neurologic

• Agitation and seizures are common.
• Intracranial hemorrhage, ischemic infarcts, and cerebral vasculitis occur in rare cases.

Vascular

Peripheral ischemia may follow intraarterial injection.

Psychiatric

Psychosis, paranoid delusions, and mania are common.

PROCEDURES AND LABORATORY TESTS

Essential Tests

Laboratory testing may not be needed in asymptomatic or minimally symptomatic patients.

Recommended Tests

• ECG and cardiac monitoring should be performed in symptomatic patients.
  • Sinus tachycardia is common; other dysrhythmias (supraventricular and ventricular) suggest severe toxicity.
  • Acute ischemia and infarction may occur.
• Serum electrolytes, BUN, creatinine, glucose, and urinalysis should be obtained to assess renal injury and effects.
• Complete blood count, liver function tests, coagulation studies, and serum creatine kinase should be obtained in patients with hyperthermia or marked agitation.
• Serum acetaminophen and aspirin levels in an overdose setting may detect occult ingestion; the urinary cocaine screen may detect cocaine metabolites several days after exposure.
• Head CT, lumbar puncture, pulse oximetry, and toxicology studies are used to evaluate other causes of seizure and altered mental status.
• Chest radiography should be performed in patients with chest pain, pulmonary symptoms, or hypoxia.
• Abdominal radiographs should be performed in patients suspected of ingesting packets of cocaine.

Not Recommended Tests

Serum cocaine levels are not clinically useful.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Hepatic
  • Renal
  • Fluids and Electrolytes
  • Musculoskeletal
  • Neurologic
  • Vascular
  • Psychiatric
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Tests

• Initial treatment should focus on controlling agitation, seizures, and hyperthermia, and supporting hemodynamic function.
• Dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Signs and symptoms are not consistent with cocaine poisoning.
• Severe effects such as altered mental status, seizure, cardiac dysrhythmia or ischemia, hyperthermia, or other end-organ damage are present.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• The patient or caregiver seems unreliable.
• Any toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted when minor toxic effects do not resolve quickly or with ischemic chest pain, hyperthermia, or other end-organ injury.

DECONTAMINATION

Out of Hospital

Emesis should not be induced because of its potential for causing seizures.

In Hospital

• Gastric lavage is generally not indicated in cocaine poisoning because cocaine ingestion is uncommon.
• If ingestion has occurred, one dose of activated charcoal (1-2 g/kg) should be administered if the ingestion is substantial and has occurred within the previous few hours.
• Whole-bowel irrigation should be considered for patients suspected of ingesting packets of cocaine

ANTIDOTES

There is no specific antidote for cocaine poisoning.

ADJUNCTIVE TREATMENT

• Control of agitation. A benzodiazepine familiar to the provider should be administered.
  • Diazepam. Adult dose is 5 to 10 mg intravenously. Pediatric dose is 0.2 to 0.5 mg/kg intravenously, doses repeated at 10-minute intervals, titrating to effect.
  • Airway should be monitored closely.
  • Haloperidol should be avoided in treating cocaine toxicity because it may interact with cocaine to cause hyperthermia.
• Hypertension. If hypertension is not responsive to benzodiazepines, or end-organ damage develops (aortic dissection, CNS bleed, myocardial infarction), a short-acting, titratable antihypertensive agent, such as nitroprusside, should be administered.
• Hypotension. The patient should be treated with isotonic fluid infusion, the Trendelenburg position, and, if needed, vasopressors. Dopamine is preferred, and norepinephrine is added for refractory hypotension.
• Seizures
  • A patent airway must be ensured.
  • A benzodiazepine is administered for initial control. If seizures persist or recur, another anticonvulsant such as phenobarbital may be added.
• Ventricular dysrhythmia or conduction abnormality
  • The health-care provider must first control seizures and correct acidemia.
  • If QRS widening or dysrhythmia persists, sodium bicarbonate may be administered: 1 to 2 mEq/kg intravenous bolus, repeated as needed to narrow the QRS interval, but not to exceed an arterial pH of 7.55.
  • Bretylium. 5 mg/kg over 1 minute; if unsuccessful, 10 mg/kg over 1 minute is administered, repeated as necessary to total dose of 30 mg/kg.
• Rhabdomyolysis. Acidemia and hyperkalemia should be corrected, and adequate hydration and urine output (1-2 ml/kg/h) should be ensured.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

Symptomatic patients require continuous cardiac and hemodynamic monitoring and frequent temperature measurement.

EXPECTED COURSE AND PROGNOSIS

• Patients generally recover within hours from mild or moderate intoxication.
• Health-care providers must also be alert for signs and symptoms of complications of cocaine poisoning:
  • End-organ injury from hypertension
  • Cerebral injury from uncontrolled seizures, cerebrovascular accident, or cerebral vasculitis or hemorrhage
  • Acute renal failure due to rhabdomyolysis or hypotension
  • Cardiac dysfunction due to ischemia, cardiomyopathy, valvular disease, or aortic dissection
  • Peripheral vasculitis and cardiac valvular disease due to chronic intravenous abuse
  • Complications and long-term sequelae are more common in massive, or chronic, intravenous or inhalational abuse

DISCHARGE CRITERIA/INSTRUCTIONS

• From emergency department. Patients may be discharged after cocaine effects have resolved, vital signs and mental status have returned to baseline, and myocardial ischemia has been ruled out.
• From hospital. Patients may be discharged after cocaine effects have resolved or stabilized, vital signs and mental status have returned to baseline, and laboratory values have normalized.
• Refer patients for substance abuse treatment.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

DIAGNOSIS

• Mental status changes, seizures, hypertension, and hyperthermia should prompt evaluation for CNS bleed or infarction and infection.
• Chest pain should prompt evaluation for myocardial infarction, aortic dissection, or pneumomediastinum.

TREATMENT

• Hyperthermia requires early and aggressive treatment.
• Intravenous abusers are at risk for complications of intravenous drug abuse.

Section Outline:

• DIAGNOSIS
• TREATMENT

Poisoning by other central nervous system depressants and anesthetics: surface (topical) and infiltration anesthetics.

See Also: SECTION II, Body Packer/Body Stuffer, Coma, Hypertension, Hypotension, Seizures, Ventricular Dysrhythmias chapters; and SECTION III, Nitroprusside and Whole-Bowel Irrigation chapters.

RECOMMENDED READING

Cregler LL, Mark H. Medical complications of cocaine abuse. N Engl J Med 1986;315:1495-1500.

Goldfrank LR, Hoffman RS. The cardiovascular effects of cocaine. Ann Emerg Med 1991;20:165-175.

Hollander JE. The management of cocaine-associated myocardial ischemia. N Engl J Med 1995;333:1267-1272.

Author: Edward W. Cetaruk

Reviewer: Luke Yip