Cocaine Overdose

• Sajeev Handa, M.D.

 Basic Information

Definition

Cocaine is an alkaloid derived from the coca plant Erythroxylum coca, native to South America, which contains approximately 0.5% to 1% cocaine. The drug produces physiologic and behavioral effects when administered orally, intranasally, intravenously, or by inhalation after smoking. Cocaine has potent pharmacologic effects on dopamine, norepinephrine, and serotonin neurons in the central nervous system (CNS) involving alteration and blockade of cellular membrane transport and prevention of reuptake. Cocaine’s second action involves the blockage of voltage-gated sodium ion membrane channels, which is responsible for its anesthetic effect. Table 1 describes the pharmacokinetics of cocaine according to route of administration. The mechanism by which cocaine alters sympathetic tone is illustrated in Fig. 1.

Synonyms

1. Cocaine hydrochloride: topical solution (FDA approved as a topical anesthetic)

2. Crack: this is produced when the hydrochloride molecule is removed by ether extraction, which frees the basic cocaine molecule or “free base.” Heating does not destroy the free base; rather, it melts at 98° F and vaporizes at higher temperatures, allowing it to be smoked.

3. Freebase: aqueous solution of cocaine hydrochloride converted to a more volatile base state by the addition of alkali, thereby extracting the cocaine base in a residue or precipitate.

4. Street names include Bernice, Blow, C, Carrie, Cecil, Charlie, Coke, Dust, Dynamite, Flake, Gin, Girl, Gold dust, Green gold, Jet, Powder, Star dust, Paradise, Pimp’s drug, Snow, Stardust, White girl, Yay, Yayo

5. Liquid lady: alcohol + cocaine

6. Speedball: heroin + cocaine

7. Street measures: hit (2-200 mg), snort, line, dose, spoon (approximately 1 g)

ICD-10CM CODES
T40.5	Poisoning, cocaine
F14.20	Cocaine dependence, uncomplicated

Epidemiology & Demographics

1. •

   The National Survey on Drug Use and Health (NSDUH) reported in 2012 that there were 1.6 million individuals ages 12 yr or older who had dependence on or had abused cocaine in the preceding year compared with 1.4 million in 2011.

2. •

   Table 2 summarizes characteristics of patients with cocaine-induced myocardial infarction.

   TABLE2 Characteristics of Patients with Cocaine-Induced Myocardial InfarctionFrom Mann DL, et al.: Braunwald’s heart disease, ed 10, Philadelphia, 2015, Elsevier.

   Dose of Cocaine

   5-6 lines (150 mg) to as much as 2 g Serum concentration, 0.01-1.02 mg/L

   Frequency of Use

   Reported in chronic, recreational, and first-time users

   Route of Administration

   Occurs with all routes of administration 75% of reported MIs occurred after intranasal use

   Age

   Mean, 34 (range, 17-71) yr 20% younger than 25 yr

   Sex

   80%-90% male

   Timing

   Often within minutes of cocaine use Reported as late as 5-15 hr after use

Physical Findings & Clinical Presentation

Phase I

1. •

   CNS: euphoria, agitation, headache, vertigo, twitching, bruxism, unintentional tremor

2. •

   Nausea, vomiting, fever, hypertension, tachycardia

Phase II

1. •

   CNS: lethargy, hyperreactive deep tendon reflexes, seizures (status epilepticus)

2. •

   Sympathetic overdrive: tachycardia, hypertension, hyperthermia

3. •

   Incontinence

Phase III

1. •

   CNS: flaccid paralysis, coma, fixed dilated pupils, loss of reflexes

2. •

   Pulmonary edema

3. •

   Cardiopulmonary arrest

Psychological dependence manifests with habituation, paranoia, and hallucinations (cocaine “bugs”).

1. CNS: Cerebral ischemia and infarction, cerebral arterial spasm, cerebral vasculitis, cerebral vascular thrombosis, subarachnoid hemorrhage, intraparenchymal hemorrhage, seizures, cerebral atrophy, movement disorders, and hyperthermia

2. Cardiac: Acute myocardial ischemia and infarction (Fig. 2), arrhythmias (Table 3), and sudden death, dilated cardiomyopathy and myocarditis, infective endocarditis, aortic rupture, acceleration of coronary atherosclerosis

   

   TABLE3 Cardiac Dysrhythmias and Conduction Disturbances Reported with Cocaine UseFrom Mann DL, et al.: Braunwald’s heart disease, ed 10, Philadelphia, 2015, Elsevier.

   Sinus tachycardia Sinus bradycardia Supraventricular tachycardia Bundle branch block Complete heart block Accelerated idioventricular rhythm Ventricular tachycardia Ventricular fibrillation Asystole Torsades de pointes Brugada pattern (right bundle branch block with ST-segment elevation in leads V1, V2, and V3)

3. Pulmonary: Inhalation injuries (secondary to smoking crack cocaine): cartilage and nasal septal perforation, oropharyngeal ulcers; immunologically mediated diseases: hypersensitivity pneumonitis, bronchiolitis obliterans; pulmonary vascular lesions and hemorrhage, pulmonary infarction, pulmonary edema secondary to left ventricular failure, pneumomediastinum, and pneumothorax

4. Gastrointestinal: Gastroduodenal ulceration and perforation; intestinal infarction or perforation, colitis

5. Renal: Acute renal failure secondary to rhabdomyolysis and myoglobinuria; renal infarction; focal segmental glomerulosclerosis

6. Obstetric: Placental abruption, low infant weight, prematurity, microcephaly

7. Psychiatric: Anxiety, depression, paranoia, delirium, psychosis, suicide

Adulterants such as levamisole (an immunomodulator) and clenbuterol (a beta-adrenergic agonist) have been found mixed with cocaine. Levamisole can cause agranulocytosis, leukoencephalopathy, and cutaneous vasculitis leading to necrosis of the skin. Clenbuterol may cause tachycardia, hyperglycemia, and hypokalemia.

Etiology

Cocaine may be absorbed through different routes with varying degrees of speed:

1. •

   Nasal insufflation/snorting: 2.5 min

2. •

   Smoking: <30 sec

3. •

   Oral: 2 to 5 min

4. •

   Mucosal: <20 min

5. •

   Intravenous injection: <30 sec

Diagnosis

Differential Diagnosis

1. •

   Methamphetamine (“speed”) abuse

2. •

   Methylenedioxyamphetamine (“ecstasy”) abuse

3. •

   Cathinone (“khat”) abuse

4. •

   Lysergic acid diethylamide (LSD) abuse

Workup

Physical examination and laboratory evaluation

Laboratory Tests

1. •

   Toxicology screen (urine): cocaine is metabolized within 2 hr by the liver to major metabolites, benzoylecgonine and ecgonine methyl ester, which are excreted in the urine. Metabolites can be identified in urine within 5 min of IV use and up to 48 hr after oral ingestion.

2. •

   Blood: CBC, electrolytes, glucose, BUN, creatinine, calcium

3. •

   Arterial blood gas analysis

4. •

   ECG

5. •

   Serum creatine kinase and troponin concentration

Treatment

There is no specific antidote, and at present, no drug therapy is uniquely effective in treating cocaine abuse and dependence. Modifying cocaine’s pharmacokinetic properties by sequestering or hydrolyzing it in serum and limiting its access to its sites of action may prove helpful by using a bacterial cocaine esterase, currently investigational. Adulterants (such as levamisole and clenbuterol, discussed earlier), contaminants, and other drugs may be admixed with street cocaine and should be kept in mind with patients presenting with unusual manifestations. Amantadine may provide effective treatment for cocaine-dependent patients with severe cocaine withdrawal symptoms, as well as the other dopamine agonist bromocriptine (1.5 mg PO tid), which may alleviate some of the symptoms of craving associated with acute cocaine withdrawal.

Acute General Rx

Acute cocaine toxicity requires following advanced poisoning treatment and life support. A suspected “body packer” should have an abdominal radiograph to detect the continued presence of cocaine-containing condoms in the intestinal tract. If present, gentle catharsis with charcoal and mineral oil should be performed with ICU admission and monitoring.

Specific Treatment

Inhalation

Wash nasal passages

Agitation

1. •

   Check STAT glucose

2. •

   Diazepam 15 to 20 mg PO or 2 to 10 mg IM or IV for severe agitation

Hyperthermia

1. •

   Check rectal temperature, creatine kinase, electrolytes

2. •

   Monitor with continuous rectal probe; bring temperature down to 101° F within 30 to 45 min

Rhabdomyolysis

1. •

   Vigorous hydration with urine output at least 2 ml/kg

2. •

   Mannitol or bicarbonate for rhabdomyolysis resistant to hydration

Seizure Management (Status Epilepticus)

1. •

   Diazepam 5 to 10 mg IV over 2 to 3 min; may be repeated every 10 to 15 min.

2. •

   Lorazepam 2 to 3 mg IV over 2 to 3 min; may be repeated.

3. •

   Phenytoin loading dose 15 to 18 mg/kg IV at a rate not to exceed 25 to 50 mg/min under cardiac monitoring.

4. •

   Phenobarbital loading dose 10 to 15 mg/kg IV at a rate of 25 mg/min; an additional 5 mg/kg may be given in 30 to 45 min if seizures are not controlled.

5. •

   For refractory seizures, consider:

   1. 1.

      Pancuronium 0.1 mg/kg IV

   2. 2.

      Halothane general anesthesia

   3. 3.

      Both require EEG monitoring to determine brain seizure activity.

Hypertension

Cocaine-induced hypertension usually responds to benzodiazepines. If this fails:

1. •

   Consider arterial line for continuous blood pressure monitoring.

2. •

   Avoid the use of calcium channel blockers because they may potentiate the incidence of seizures and death, especially in body packers.

3. •

   The use of beta-blockers may exacerbate cocaine-induced vasoconstriction and may cause paradoxical hypertension, worsening patient outcomes.

4. •

   Phentolamine (unopposed adrenergic effects) or nitroglycerin may be required.

5. •

   If diastolic pressure >120 mm Hg: hydralazine hydrochloride 25 mg IM or IV; may repeat q1h.

6. •

   If hypertension is uncontrolled or hypertensive encephalopathy is present: sodium nitroprusside initially at 0.5 mg/kg/min not to exceed 10 mg/kg/min.

Chest pain

1. •

   Chest radiograph, ECG, cardiac enzymes

2. •

   Benzodiazepines for agitation

3. •

   Acetylsalicylic acid and nitroglycerin for ischemic pain (Aspirin is contraindicated if dissection is suspected.)

4. •

   Percutaneous transluminal coronary angioplasty possibly better than thrombolysis for cocaine-associated myocardial infarction

5. •

   Phentolamine will reverse cocaine-induced vasoconstriction and may be administered 5 to 10 mg every 5 to 10 minutes.

6. •

   The use of beta-adrenergic blockers is not generally recommended for reasons highlighted earlier.

7. •

   If beta-blockers are to be used, this should be preceded by administration of phentolamine to prevent unopposed alpha-adrenergic stimulation. Many authors recommend not using beta-blockers until the cocaine has been systemically eliminated.

Ventricular Arrhythmias (Considerations)

1. •

   The Advanced Cardiac Life Support (ACLS) protocol should be followed.

2. •

   Antiarrhythmic agents should be used with caution during the early period after cocaine exposure as a result of their proarrhythmic and proconvulsant effects.

3. •

   Termination of ventricular arrhythmias may be resistant to lidocaine and even cardioversion.

4. •

   In a cardiac arrest situation secondary to cocaine toxicity, vasopressin offers a theoretical advantage over epinephrine as it increases coronary blood flow and myocardial oxygen availability. In the 2015 ACLS update, however, vasopressin was removed from the treatment algorithm, so it may not be readily available.

Disposition

Although many patients who use cocaine may not require treatment because of the short half-life of the drug, others may require specific treatment for possible cocaine-related complications. Box 1 summarizes complications associated with cocaine use.

BOX 1Complications Associated With Cocaine Use

Cardiovascular

1. Myocardial ischemia, infarction

2. Arrhythmias

3. Aortic dissection, rupture

4. Hypertension

5. Atherosclerosis

6. Cardiomyopathy

7. Vasculitis

Central Nervous System

1. Seizures

2. Cerebral infarction

3. Transient ischemic attack

4. Intracranial hemorrhage (intraparenchymal, intraventricular, subarachnoid)

5. Cerebral vasculitis

6. Cognitive dysfunction

Pulmonary

1. Bronchospasm

2. Barotrauma

3. Noncardiogenic edema

4. Pulmonary hypertension

Renal

1. Renal infarction

2. Renal failure

3. Scleroderma renal crisis

Gastrointestinal

1. Mesenteric ischemia, infarction

2. Gastrointestinal tract perforations

Metabolic

1. Hyperthermia

2. Rhabdomyolysis

3. Weight loss

4. Multiple organ failure

Other

1. Deep venous thrombosis

2. Skin ischemia

3. Dystonic reactions

From Parrillo JE, Dellinger RP: Critical care medicine, principles of diagnosis and management in the adult, ed 4, Philadelphia, 2014, Elsevier.

Referral

Consider psychotherapy or behavioral therapy once stable. There is some evidence that topiramate 300 mg orally daily added to cognitive behavioral therapy may be beneficial in patients with severe withdrawal symptoms.

Pearls & Considerations

1. •

   Cocaine-induced vasoconstriction may be exacerbated by the use of selective and nonselective beta-adrenergic blocking agents.

2. •

   The use of lidocaine in treating ventricular arrhythmias may precipitate seizures and further arrhythmias.

3. •

   Clinical trials with the SSRI sertraline 200 mg/day have shown that it may help prevent relapse in individuals with some depression symptoms.

Suggested Readings

• M. Bashiri, et al.: Moderators of response to sertraline versus placebo among recently abstinent, cocaine dependent patients: a retrospective analysis of two clinical trials. Am J Addict. 26:807 2017 29115703

• N. Dinwahar, J.H. Woods, R.K. Sunahara: Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction. Future Med Chem. 4 (2):137–150 2012 22300094

• R.L. Gross, J. Brucker: A novel cutaneous vasculitis syndrome induced by levasimole contaminated cocaine. Clin Rheumatol. 30 (10):1385 2011 21706168

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