Cocaine Toxicity

Cocaine toxicity results from sympathomimetic, CNS stimulant, and local anesthetic (sodium channel blocking) effects, producing a clinical syndrome of tachycardia, hypertension, hyperthermia, agitation, and potentially fatal cardiac dysrhythmias. [1-2] The following is a comprehensive clinical summary organized for emergency medicine and primary care practice.

• Route of use: Intranasal (snorting), IV injection, inhalation/smoking (crack), oral, rectal, vaginal; IV and inhaled routes have onset in seconds with ~30-minute duration, while mucosal routes have slower onset [3-4]
• Timing: When was the last use? How much? Over what time period? Repeated dosing prolongs half-life (baseline 60–120 min) [3]
• Co-ingestions: Alcohol (produces cocaethylene, which aggravates cardiac ion channel inhibition), opioids (speedball), other stimulants [3]
• Symptom characterization: Chest pain (most common ED complaint), palpitations, dyspnea, headache, seizures, agitation, paranoia, hallucinations [5-6]
• Body packing/stuffing: Ask about drug concealment — body stuffing (hastily wrapped, small amounts) vs. body packing (well-wrapped, large amounts for smuggling); packet rupture can cause massive, prolonged toxicity [7-8]
• Important negatives: Deny trauma, suicidal intent, fever/infectious symptoms, prior seizure history

• Hyperthermia >40°C (104°F) — rapidly life-threatening [2]
• Chest pain with ECG changes (ST elevation, QRS widening >120 ms)
• Seizures — may herald severe toxicity or herald cardiac arrest [8]
• Severe agitation unresponsive to verbal de-escalation
• QRS prolongation — indicates sodium channel blockade, risk of VT/VF/asystole [2][7]
• QT prolongation — risk of torsade de pointes [2-3]
• Signs of aortic dissection: Tearing chest/back pain, pulse differential, widened mediastinum [3][5]
• Brugada-type ST elevation — dose-dependent sodium channel effect, VF predisposition [3][9]
• Hemodynamic collapse: Late-stage toxicity with severe bradycardia and circulatory failure [3]

First-line treatments

• Benzodiazepines — mainstay for agitation, hypertension, tachycardia, and seizures (e.g., midazolam 5 mg IM/IV, diazepam 5–10 mg IV, lorazepam 2–4 mg IV; repeat as needed) [1][8]
• Sodium bicarbonate — for QRS widening: 2 ampoules (100 mEq) IV bolus; if unavailable, 3% hypertonic saline 200 mL [7-8]
• Nitroglycerin — for cocaine-associated chest pain/ischemia [5][7]

Second-line/adjunctive

• Calcium channel blockers (e.g., verapamil, nicardipine) — for refractory hypertension and coronary vasospasm [7-8]
• Phentolamine — alpha-1 antagonist for refractory ischemia and hypertensive emergency [1][7]
• Lidocaine — safe for cocaine-induced ventricular arrhythmias; competitively binds sodium channels [1-2]
• Dexmedetomidine — for severe agitation; also treats hypertension and tachycardia [7-8]
• Droperidol — faster onset than lorazepam for agitation, fewer repeat doses needed [2]
• Lipid emulsion 20% (Intralipid 1 mL/kg bolus, ~100 mL in adults) — for refractory QRS widening or cardiac arrest unresponsive to sodium bicarbonate and ACLS [7-8]

Contraindicated/use with extreme caution

• Beta-blockers — generally contraindicated due to risk of unopposed alpha stimulation, worsened coronary vasoconstriction, and potential for hemodynamic collapse. Propranolol exacerbated coronary vasoconstriction in human studies; metoprolol has been associated with PEA arrest and death. If a beta-blocker is absolutely necessary, one with alpha-1 antagonism (labetalol, carvedilol) is preferred, though this remains controversial [2][8]
• Long-acting antihypertensives — risk of abrupt hemodynamic collapse [7]

• Not directly applicable in the acute setting
• Hydration is critical — aggressive IV fluid resuscitation for rhabdomyolysis (target urine output >2 mL/kg/h) [8]
• Avoid urinary alkalinization as it inhibits amphetamine elimination (relevant for co-ingestion) [8]
• Long-term: Nutritional rehabilitation in chronic users who are often malnourished

• Cardiovascular: Chest pain, palpitations, dyspnea on exertion
• Neurologic: Headache (hemorrhagic stroke), focal weakness (ischemic stroke), seizures, visual changes
• Psychiatric: Paranoia, hallucinations (tactile — "coke bugs"), suicidal ideation, agitation
• GI: Abdominal pain (mesenteric ischemia, body packing), nausea/vomiting
• Musculoskeletal: Muscle pain/rigidity (rhabdomyolysis)
• Respiratory: Dyspnea, hemoptysis (crack lung), wheezing
• Renal: Decreased urine output (acute kidney injury from rhabdomyolysis)

• Collateral: EMS report, bystanders, law enforcement — route of use, amount, timing, co-ingestions, body packing/stuffing context
• Family history: Brugada syndrome (cocaine can unmask latent Brugada in susceptible individuals), family history of sudden cardiac death, long QT syndrome [3][9]
• Social context: Incarceration risk (body stuffing), homelessness, IV drug use (endocarditis, HIV, hepatitis), polysubstance use

• IV or inhaled (crack) route — rapid onset, higher peak levels [3]
• Concurrent alcohol use — produces cocaethylene, which prolongs and intensifies cardiotoxicity [3]
• Body packing/stuffing — risk of massive exposure from packet rupture [7][10]
• Pre-existing cardiac disease: CAD, cardiomyopathy, LVH, channelopathies [3][11]
• Chronic cocaine use — accelerated atherosclerosis, LV hypertrophy, myocardial fibrosis [3][12]
• Acidosis — intensifies cocaine's sodium channel blocking effects [3]
• Adulterants: Levamisole (neutropenia, vasculitis), fentanyl (respiratory depression) [7]
• Cigarette smoking — synergistic vascular injury [3]
• Repeated dosing — prolongs half-life considerably [3]

• Other sympathomimetic toxicity: Methamphetamine, cathinones ("bath salts"), synthetic cannabinoids [1-2]
• Serotonin syndrome: Clonus, hyperreflexia, diarrhea — overlapping features with cocaine toxicity
• Neuroleptic malignant syndrome: Rigidity, hyperthermia, altered mental status
• Thyroid storm: Tachycardia, hyperthermia, agitation
• Pheochromocytoma: Paroxysmal hypertension, tachycardia, diaphoresis
• Primary cardiac events: ACS, aortic dissection, arrhythmia unrelated to cocaine
• Anticholinergic toxicity: Mydriasis, tachycardia, dry skin (vs. diaphoresis in cocaine)
• Meningitis/encephalitis: Fever, altered mental status, seizures
• Excited delirium: Overlapping presentation; may be cocaine-induced or from other causes

• Prior cocaine use and complications (prior MI, stroke, seizures)
• Known cardiac disease, arrhythmias, channelopathies
• Psychiatric history (psychosis, bipolar disorder — cocaine exacerbates)
• Prior body packing/stuffing episodes
• Chronic kidney disease (impaired drug clearance)
• Hepatic disease (cocaine metabolized by liver and plasma esterases) [3]
• HIV/hepatitis status (IV use)
• History of endocarditis, DVT/PE

Vital signs

• Tachycardia, hypertension (early); bradycardia and hypotension (late/ominous) [3]
• Hyperthermia — core temperature mandatory (rectal/esophageal); >40°C is life-threatening [2]
• Tachypnea

Focused exam

• Pupils: Mydriasis (bilateral)
• Skin: Diaphoresis, track marks (IV use), nasal septal perforation (intranasal use), levamisole-induced purpura/vasculitis
• Cardiovascular: Murmurs (endocarditis), irregular rhythm, pulse deficits (aortic dissection)
• Neurologic: Agitation, hyperreflexia, clonus, focal deficits (stroke), seizure activity
• Abdomen: Tenderness (mesenteric ischemia, body packing), distension
• Musculoskeletal: Muscle rigidity, tenderness (rhabdomyolysis)

• Troponin (serial) — cocaine-associated MI incidence ~6% in those with chest pain [6]
• BMP/CMP — electrolytes (hyperkalemia, hyponatremia), renal function, glucose
• CBC — leukocytosis; check for neutropenia (levamisole adulterant) [7]
• CK/CPK — rhabdomyolysis screening; obtain if agitation, hyperthermia, or seizures [7]
• Lactate — acidosis assessment (worsens sodium channel blockade) [7]
• Coagulation studies — DIC screening in severe cases
• Urine drug screen — confirms cocaine use (benzoylecgonine detectable 2–4 days); note: does not quantify acute level
• LFTs — hepatotoxicity (norcocaine metabolite)
• VBG/ABG — acid-base status
• Serum ethanol — cocaethylene formation

• Chest X-ray: Pneumomediastinum (crack inhalation), pulmonary edema, widened mediastinum (aortic dissection), pneumothorax
• CT head (non-contrast): If headache, focal neurologic deficits, or seizures — rule out hemorrhagic/ischemic stroke [13-14]
• CT angiography chest: If concern for aortic dissection
• Abdominal X-ray or CT abdomen: If body packing/stuffing suspected — CT is more sensitive than plain films; note that ~25% of packets may not be visible on plain radiographs [15-16]
• Echocardiography: If concern for wall motion abnormalities, takotsubo cardiomyopathy, or endocarditis [1-2]
• Coronary angiography: For STEMI or refractory ischemia despite medical management

• Point-of-care ultrasound (POCUS): Cardiac function, pericardial effusion, IVC assessment
• Urine myoglobin: If rhabdomyolysis suspected
• Cocaethylene level: Not routinely available but confirms co-ingestion with alcohol
• Levamisole testing: If vasculitis or agranulocytosis suspected (specialized lab)
• HEART score: May be applied for chest pain risk stratification, though its validation in cocaine-associated chest pain is limited

ECG is mandatory in all presentations of cocaine toxicity. [1-2]

Key findings to recognize:

• Sinus tachycardia — most common
• QRS prolongation (>120 ms) — sodium channel blockade; treat with sodium bicarbonate [7]
• QT prolongation — potassium channel blockade; risk of torsade de pointes [2-3]
• Brugada-type coved ST elevation (V1–V3) — cocaine unmasks latent Brugada; dose-dependent [3][9]
• ST elevation/depression — ischemia from coronary vasospasm or thrombosis
• Wide-complex tachycardia — similar to class Ic antiarrhythmic toxicity [1-2]
• Terminal R wave in aVR — sodium channel blockade pattern [2]
• Ventricular ectopy, VT, VF — may occur with or without structural heart disease [3][11]

The following figure demonstrates the dramatic QRS widening seen with cocaine-induced sodium channel blockade:

Severity spectrum: [3]

• Mild: Euphoria, tachycardia, mild hypertension (HR/BP 10–25% above baseline), mydriasis, diaphoresis
• Moderate: Significant agitation, chest pain, marked hypertension/tachycardia, hyperthermia <40°C
• Severe/life-threatening: Seizures, hyperthermia >40°C, QRS widening, ventricular arrhythmias, MI, aortic dissection, stroke, cardiac arrest

Atypical presentations: Body packers may present asymptomatic initially then rapidly deteriorate; late-stage toxicity may present with bradycardia and hypotension rather than the expected hyperadrenergic state [3]

Complications: [7][13]

• Acute coronary syndrome, aortic dissection
• Hemorrhagic and ischemic stroke
• Rhabdomyolysis → acute kidney injury
• Mesenteric ischemia, GI perforation
• Takotsubo cardiomyopathy
• Pulmonary hypertension (possibly levamisole-related) [3]
• Infective endocarditis (IV users)

Initial stabilization

• ABCs; continuous cardiac monitoring, pulse oximetry, core temperature
• IV access, supplemental O₂

Agitation/hyperadrenergic state

• Benzodiazepines first-line (midazolam 5–10 mg IM/IV, or diazepam 5–10 mg IV; repeat q5 min as needed) [2][8]
• Droperidol 5 mg IM/IV if benzodiazepines insufficient (faster onset) [2]
• Avoid prolonged physical restraints — exacerbate hyperthermia and rhabdomyolysis [2]

Hyperthermia >40°C

• Immediate ice water immersion or evaporative cooling (mist + fan); cooling blankets and cold packs are inferior [1-2]
• Target cooling rate >0.15°C/min associated with improved survival [2]
• Benzodiazepines to reduce heat-generating muscle activity

Chest pain/ischemia

• Benzodiazepines + nitroglycerin SL/IV [1][7]
• Aspirin 325 mg
• If refractory: phentolamine 5 mg IV or verapamil [1-2]
• PCI for STEMI; fibrinolytics if PCI unavailable [6]

QRS widening

• Sodium bicarbonate 1–2 mEq/kg (2 ampoules) IV bolus; may repeat [7-8]
• If refractory: 3% hypertonic saline 200 mL, or lidocaine 1–1.5 mg/kg IV [1]
• If still refractory or cardiac arrest: consider 20% lipid emulsion 1 mL/kg bolus [7]

Seizures

• Benzodiazepines first-line; phenobarbital or propofol second-line [8]
• Avoid phenytoin (sodium channel blocker — may worsen toxicity)

Hypertensive emergency

• Short-acting agents: phentolamine, nicardipine, sodium nitroprusside [7]
• Avoid long-acting antihypertensives [7]

Cardiac arrest

• Standard ACLS + sodium bicarbonate for wide-complex rhythms [1-2]
• Lidocaine for VT/VF [1]
• Consider VA-ECMO for refractory cardiogenic shock [2]

Body packing

• Asymptomatic: whole bowel irrigation with polyethylene glycol; serial abdominal imaging until all packets passed [18-19]
• Symptomatic (packet rupture): immediate surgical removal — no drug sufficiently antagonizes lethal cocaine effects [19]

Admit/ICU criteria

• Hyperthermia >40°C
• QRS or QT prolongation
• Ventricular arrhythmias
• Acute coronary syndrome / troponin elevation
• Seizures
• Hemodynamic instability
• Rhabdomyolysis with AKI
• Body packing with any symptoms
• Aortic dissection or stroke

Observation (6–12 hours)

• Cocaine-associated chest pain with negative serial troponins and normal/unchanged ECGs
• Mild-moderate agitation that resolves with benzodiazepines
• Asymptomatic body packers (until all packets passed and confirmed by imaging)

Discharge criteria

• Symptom resolution, normal vital signs for ≥1 hour off treatment
• Normal or baseline ECG
• Negative serial troponins (if chest pain was the presenting complaint)
• No ongoing agitation, seizures, or hyperthermia
• Able to ambulate and tolerate PO

Specialist consultation triggers

• Cardiology: STEMI, refractory arrhythmias, cardiogenic shock
• Medical toxicology: Refractory toxicity, body packing, uncertain diagnosis [7-8]
• Surgery: Body packing with obstruction or packet rupture [19]
• Neurology/neurosurgery: Stroke, status epilepticus

Follow-up timing

• PCP or cardiology within 1–2 weeks if discharged after chest pain evaluation
• Addiction medicine/psychiatry referral at discharge — critical for long-term outcomes
• Repeat CBC in 1–2 weeks if levamisole-related neutropenia suspected [7]

Return precautions (counsel patient)

• Return immediately for: chest pain, palpitations, shortness of breath, headache, weakness/numbness, seizures, fever, dark urine, abdominal pain
• Cocaine effects may recur if co-ingested with alcohol (cocaethylene has longer half-life)
• Educate on fentanyl contamination risk in current drug supply

Expected recovery

• Uncomplicated cocaine toxicity typically resolves within 4–6 hours
• Cocaethylene effects may persist longer with alcohol co-ingestion
• Chronic users: LV hypertrophy and accelerated atherosclerosis persist and require long-term cardiovascular follow-up [3][12]

1. 2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. — Lavonas EJ, Akpunonu PD, Arens AM, et al. Circulation. 2023.

2. Part 10: Adult and Pediatric Special Circumstances of Resuscitation: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. — Cao D, Arens AM, Chow SL, et al. Circulation. 2025.

3. The Cardiovascular Effects of Cocaine. — Havakuk O, Rezkalla SH, Kloner RA. Journal of the American College of Cardiology. 2017.

4. Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects Including Abuse Pattern. — Roque Bravo R, Faria AC, Brito-da-Costa AM, et al. Toxins. 2022.

5. 2021 AHA/­ACC/­ASE/­CHEST/­SAEM/­SCCT/­SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/­American Heart Association Joint Committee on Clinical Practice Guidelines. — Gulati M, Levy PD, Mukherjee D, et al. Journal of the American College of Cardiology. 2021.

6. Acute Cardiovascular Toxicity of Cocaine. — Lucyk SN. The Canadian Journal of Cardiology. 2022.

7. Management of Stimulant Use Disorder. — Steven Batki MD, Daniel Ciccarone MD MPH, Scott E. Hadland MD MPH, et al American Academy of Addiction Psychiatry (2023). 2023.

8. The ASAM/­AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder. — Journal of Addiction Medicine. 2024.

9. A Tale of 2 Diseases: The History of Long-Qt Syndrome and Brugada Syndrome. — Havakuk O, Viskin S. Journal of the American College of Cardiology. 2016.

10. Body Packers and Body Stuffers: Cocaine Intoxications Reported to French Poison Centers (January 1, 2020-December 31, 2024). — von Fabeck K, Glaizal M, Simon N. Clinical Toxicology. 2025.

11. Cardiovascular Complications of Cocaine Use. — Lange RA, Hillis LD. The New England Journal of Medicine. 2001.

12. Side Effects of Cocaine Abuse: Multiorgan Toxicity and Pathological Consequences. — Riezzo I, Fiore C, De Carlo D, et al. Current Medicinal Chemistry. 2012.

13. Cocaine Intoxication. — Zimmerman JL. Critical Care Clinics. 2012.

14. Progress in Psychiatry. — Michels R, Marzuk PM. The New England Journal of Medicine. 1993.

15. The Cocaine 'Body Packer' Syndrome. Diagnosis and Treatment. — McCarron MM, Wood JD. The Journal of the American Medical Association. 1983.

16. Emergency Department Management of Body Packers and Body Stuffers. — Heymann-Maier L, Trueb L, Schmidt S, et al. Swiss Medical Weekly. 2017.

17. Cocaine-Induced Na+ Channel Blocking Effect. — Dehout C, Werion A, Grimaldi D. JACC. Clinical Electrophysiology. 2023.

18. Clinical Management of Cocaine Body Packers: The Hillingdon Experience. — Beckley I, Ansari NA, Khwaja HA, Mohsen Y. Canadian Journal of Surgery. Journal Canadien De Chirurgie. 2009.

19. Body Packing — The Internal Concealment of Illicit Drugs. — Traub SJ, Hoffman RS, Nelson LS. The New England Journal of Medicine. 2003.