Cocaine Toxicity

Cocaine toxicity is a sympathomimetic emergency caused by cocaine hydrochloride (snorted or injected), crack or freebase (smoked) and coca paste. It blocks reuptake of noradrenaline, dopamine and serotonin, blocks fast sodium channels (a local anesthetic and class I antiarrhythmic effect) and potassium channels (QT prolongation), and causes vasoconstriction and platelet activation. Plasma and liver esterases clear it with a half-life of about 1 hour. With alcohol it forms cocaethylene, which is more cardiotoxic and lasts longer (2 hours).

Smoked cocaine acts in 1 to 5 minutes and lasts 10 to 20 minutes. Snorted cocaine acts in 15 to 30 minutes and lasts about 1 hour. Chest pain brings about a large share of users to emergency care, and myocardial infarction is found in about 6% of cocaine-associated chest pain. Infarction risk rises about 24-fold in the first hour after use. A dose of 1 to 2 g can be lethal, but susceptible people die from far less.

Complications: acute coronary syndrome, arrhythmia, aortic dissection, stroke (ischemic and hemorrhagic), seizures, hyperthermia, rhabdomyolysis, pulmonary hemorrhage and edema ("crack lung"), bowel ischemia, placental abruption and nasal septal perforation. Levamisole, a common adulterant, causes agranulocytosis and purpuric ear lesions. Fentanyl contamination is an increasing cause of respiratory arrest.

Body packers carry many wrapped packets of 5 to 10 g, and rupture is fatal. Body stuffers swallow loose cocaine when avoiding arrest.

• Agitation, euphoria, paranoia, hallucinations, dilated pupils, sweating, tremor and hyperthermia
• Tachycardia, hypertension, chest pain, palpitations and syncope
• Seizures, headache, focal deficit or coma
• Wheeze, hemoptysis and breathlessness after smoking
• Body packers: abdominal pain, vomiting, absent stool, or sudden sympathomimetic toxicity from rupture
• Red flags: chest pain with ECG change, QRS over 100 ms, temperature over 40 degrees Celsius, tearing chest or back pain, focal neurology and any packet leak

1. ECG at presentation and repeated: ST change, QRS width, QTc and arrhythmia.
2. Troponin at 0 and 3 to 6 hours, creatine kinase, electrolytes, creatinine, glucose, lactate and blood gases.
3. Urine benzoylecgonine immunoassay (positive for 2 to 4 days) confirms exposure. Test serum paracetamol and salicylate.
4. Chest radiograph, and CT head or CT angiography of the aorta when stroke or dissection is suspected.
5. Body packers: abdominal CT without contrast is the most sensitive test and shows packets. Plain films miss some.
6. Full blood count when levamisole exposure is suspected (neutropenia).

Differentials: other stimulant toxicity, acute coronary syndrome of other cause, thyrotoxicosis, alcohol withdrawal, serotonin syndrome, aortic dissection.

1. Resuscitation: airway, IV access, continuous monitoring and rapid temperature measurement.
2. Benzodiazepines are first-line: diazepam 5 to 10 mg IV (children 0.1 to 0.2 mg/kg) or lorazepam 2 to 4 mg IV (children 0.05 to 0.1 mg/kg), repeated every 5 to 10 minutes until calm and the heart rate is under 100 beats a minute. Monitor respiration.
3. Chest pain and acute coronary syndrome:
   • Aspirin 300 mg chewed once, then 75 mg daily.
   • Glyceryl trinitrate 0.4 mg sublingually every 5 minutes up to 3 doses, then 5 to 200 micrograms/min IV.
   • Phentolamine 1 to 5 mg IV every 5 to 15 minutes for persistent hypertension or vasospasm.
   • Verapamil 2.5 to 5 mg IV over 2 minutes if pain continues and the rate is not low.
   • Unfractionated heparin 60 units/kg IV (maximum 4000 units) then 12 units/kg/h (maximum 1000 units/h) for infarction.
   • Percutaneous coronary intervention is preferred. Use thrombolysis only when it is unavailable.
   • Avoid beta blockers in the acute phase, because of unopposed alpha stimulation.
4. QRS over 100 ms or ventricular arrhythmia: sodium bicarbonate 1 to 2 mmol/kg IV (1 to 2 mL/kg of 8.4%), repeated until QRS narrows, with pH target 7.45 to 7.55. Lidocaine 1 to 1.5 mg/kg IV is a second-line option. Give magnesium sulfate 2 g IV for torsades.
5. Hyperthermia over 40 degrees Celsius: rapid cooling, sedation and IV fluids. Antipyretics are ineffective.
6. Seizures: benzodiazepines.
7. Aortic dissection: sodium nitroprusside 0.3 to 10 micrograms/kg/min IV after phentolamine, with esmolol 500 micrograms/kg IV then 50 to 200 micrograms/kg/min once vasodilated, and urgent surgical referral.
8. Rhabdomyolysis: IV 0.9% saline 200 to 300 mL/h to keep urine output over 1 mL/kg/h.
9. Body packers (asymptomatic): polyethylene glycol 1 to 2 L/h orally or by tube until the effluent is clear and CT confirms all packets passed. Monitor for 24 to 72 hours. Body stuffers: activated charcoal 50 g once and observe 6 to 8 hours.
10. Surgery for intestinal obstruction or perforation, or any leak with toxicity.
11. Levamisole neutropenia: stop exposure, filgrastim 5 micrograms/kg SC daily until the neutrophil count exceeds 1.0 × 10^9/L, and piperacillin-tazobactam 4.5 g IV every 6 hours for fever.
12. Pregnancy: assess for placental abruption and fetal compromise.

Follow-up: cardiology review, screening for HIV and hepatitis, and addiction treatment with contingency management and cognitive behavioral therapy. No drug is licensed for dependence. Counsel on the danger of fentanyl contamination.