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
- T > 38.5°C
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
LITFL
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
- 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
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.
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