Cocaine Toxicity

Reviewed and revised 20 May 2016

OVERVIEW

Cocaine Toxicity potentially life-threatening sympathomimetic syndrome with sodium channel blockade.

Preparations

• Cocaine hydrochloride powder or paste: processed from the alkaloid extracted from cocoa leaves, it cannot be smoked as it decomposes at high temperatures
• Cocaine base (crack cocaine) or free-base: created by combining cocaine hydrochloride with an alkaline substance, it is heat stable.

RISK ASSESSMENT

• toxic dose is highly variable
• small doses, particularly in non-tolerant patients, may result in significant intoxication
• hyperthermia, headache, cardiac conduction abnormalities, focal neurological signs or chest pain heralds potentially life-threatening complications

Dose related effects:

• 1-3 mg/kg = safe local anaesthetic dose
• 20-30 mg  = usual recreational dose when a line of cocaine is snorted
• >1 g = potentially lethal

Pregnancy and lactation:

• teratogenic (increased incidence of miscarriage and foetal demise)
• excreted in breast milk (infant intoxication and withdrawal syndromes are possible)

TOXICODYNAMICS

• Sympathomimetic, vasospastic and sodium channel blocking (local anaesthetic) effects
•  blockade of presynaptic catecholamine re-uptake
• Blockade of myocardial fast sodium channels
• CNS excitation

TOXICOKINETICS

• Absorption
  • rapid  through the mucous membranes of nasopharynx, lungs, and GI tract
  • Bioavailability
    • intranasal 25-80%
    • smoked 60%-70%
• Distribution
  • Highly lipid soluble with VD = 2 L/kg
• Metabolism
  • rapid
  • metabolsied by liver and plasma cholinesterases to water-soluble metabolites
• Elimination
  • Only 1% of the drug appears unchanged in the urine
  • Metabolites may persist in the blood and urine for up to 36 hours

CLINICAL FEATURES

Time course

• rapid onset
• duration of effect ~1 hour, but may persist for hours

Neurological

• Euphoria
• Anxiety, dysphoria, agitation and aggression
• Paranoid psychosis with visual and tactile hallucination
• Hyperthermia, rigidity and myoclonic movements
• Seizures

Cardiovascular

• Tachycardia and hypertension may be severe
• Arrhythmia and cardiac conduction abnormalities
• Acute coronary syndromes: vasospastic and /or coronary thrombotic
• QT prolongation
• Acute pulmonary oedema

Peripheral sympathomimetic

• Hyperthermia
• Muscle fasciculations
• Mydriasis, sweating and tremor

Complications

• Hyperthermia induced rhabdomyolysis, renal failure, and cerebral oedema
• Aortic and carotid dissection
• Subarachnoid and intracerebral haemorrhage
• Ischaemic colitis
• Pneumothorax
• Pneumomediastinum

INVESTIGATIONS

Specific investigations as needed

• UEC – renal failure and hyponatraemia
• ECG, CK and troponin — ACS, QT prolongation and rhabdomyolysis; Brugada type pattern
• CXR — aortic dissection; aspiration
• CT head — intracranial haemorrhage
• Serum or urine cocaine levels — not useful acutely

MANAGEMENT

Life threats:

• Cardiac dysrhythmias including ventricular tachycardia
• Hypertension
• Hyperthermia
• Seizures
• Severe agitation
• Vascular emergencies (e.g. ICH, ACS, dissection, arterial thromboembolism)

Resuscitation, supportive care and monitoring

• VT
  • 50-100 mmol NaHCO3 IV boluses q3-5 min and assess for response
  • If refractory to bicarbonate and defibrillation, use  lignocaine 1.5 mg/kg IV + infusion of 2 mg/min
  • If intubated consider inducing alkalaemia through hyperventilation to pH 7.5-7.55
• Chest pain and acute coronary syndrome
  • Aspirin (and other anti platelets depending on your hospital protocols)
  • Nitroglycerine
  • Calcium channel antagonists
  • Coronary angiography +/- stenting – if  ST elevation that persists after medical treatment
  • Avoid beta-blockers (including labetolol) due to risk of unopposed alpha-agonism
  • Thrombolytics are contraindicated if severe hypertension, seizures, intracerebral haemorrhage or aortic dissection
• Hypertension and tachycardia
  • IV benzodiazepines if agitated
  • if refractory to sedation:
    • Phentolamine 1 mg IV q5min
    • titrated SNP or GTN infusion
    • Avoid beta-blockers
• SVT
  • IV benzodiazepines if agitated
  • if refractory to sedation:
    • verapamil 5mg IV, or adenosine 6-12 mg IV
    • Electrical cardioversion  if unstable
• Seizures and agitated delirium
  • 5 mg diazepam IV q2-5min until seizures stop or gentle sedation
  • consider NaHCO3 if evidence of sodium channel blockade
• Hyperthermia
  • T > 38.5°C
    • continuous core-temperature monitoring
    • benzodiazepine sedation
    • fluid resuscitation
  • T> 39.5°C
    • rapid external cooling to prevent MODS  and neurological injury
    • Consider paralysis, intubation and ventilation

Decontamination

• activated charcoal only in body packers or following intubation

Enhanced elimination

• nil

Antidotes

• NaHOC3 for sodium channel blockade (see management of VT above)

Disposition

• Observe children with potential ingestion for 4 hours
• If intoxication is controlled with benzodiazepine sedation with normal BP and  ECG,  manage supportively in a ward until clinically well
• HDU/ICU if altered mental state, hyperthermia, on-going chest pain, intubation or significant complications
• Body packers or stuffers require GI decontamination under medical supervision until all cleared

OTHER INFORMATION

Levamisole

• Levamisole is an antihelminthic agent used in humans to treat certain parasitic infections and cancers, and more commonly used in veterinary medicine
• It has been used as a cutting agent for cocaine and heroin, found in up to 70% of cocaine sample seized by the DEA
• It adds bulk and weight to powdered cocaine and is even theorized to increase the stimulant effects
• Toxicity of levamisole includes agranulocytosis and vasculitis

References and Links

Journal articles

• Afonso L. Mohammad T. Thatai D. Crack whips the heart: a review of the cardiovascular toxicity of cocaine. American Journal of Cardiology 2007; 100(6):1040-1043.
• Hatsukami DK, Fischman MW. Crack cocaine and cocaine hydrochloride. Are the differences myth or reality? Journal of the American Medical Association 1996; 276:1580-1588.
• Lange RA, Hillis LD. Cardiovascular Complications of Cocaine Use. New England Journal of Medicine. 2001; 345(5):351-358.
• Lange RA, Cigarroa RG, et al. Pontetiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade. Ann Internal Med 1990;112:897-903
• Richard JR, et al. Treatment of cocaine cardiovascular toxicity: a systematic review. Clin Toxicol. 2016 Feb 26:1-20. [Epub ahead of print] [pubmed]
• Shih RD, Hollander JE, Burstein JL et al. Clinical safety of lidocaine in patients with cocaine-associated myocardial infarction. Annals of Emergency Medicine 1995;26:702-706.

FOAM and web resources

• The Poison Review on Cocaine
  • Case report: cocaine cardiotoxicity treated with intravenous lipid infusion
  • Cocaine-associated arrhythmias
• The Poison Review on Levamisole
  • Dramatic pictures: vasculitis caused by levamisole-contaminated cocaine
  • Scrotal gangrene after smoking crack
  • Unusual complication of cocaine abuse
  • Case reports: neutropenia associated with levamisole-adulterated cocaine
  • Why is the antihelminthic drug levamisole used to adulterate cocaine?
  • Cocaine adulterated with levamisole implicated in 21 cases of agranulocytosis