Cocaine intoxication

I. Problem/Condition.

Cocaine abuse and dependence are epidemic in the US. In 2007, over 2 million Americans had recent cocaine use; 1.6 million met criteria for cocaine dependence or abuse. Cocaine use is concentrated among select demographics: individuals 18 to 25 years of age have the highest rate of cocaine use (1.2%); males had more than twice the use rate of females (0.9% vs. 0.4%); and rates according to race are 1.1% for blacks, 0.9% for Hispanics, 0.5% for whites and 0.1% for Asians. In the United States, cocaine continues to be the most frequently mentioned illegal drug reported to the Drug Abuse Warning Network by hospital emergency departments. Chest discomfort has been reported in 40% of patients who present to the ED after cocaine use.

Cocaine is a powerfully addictive stimulant drug made from the leaves of the coca plant (Erythroxylon coca) native to South America. It stimulates key pleasure centers within the brain and causes extremely heightened euphoria. It can be injected intravenously, absorbed through the nasal mucosa (snorting) and (when transformed into its alkaloid form) smoked. In the late 1970s, dealers converted cocaine powder into “crack,” a solid form of cocaine that is cheap, simple to produce and sell in smaller quantities to more people at a bigger profit. Crack is heated and smoked and so named because it makes a cracking or popping sound when heated. Crack is between 75% and 100% pure, and far more potent than regular cocaine; a user can become addicted at first use.

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Cocaine is an indirect sympathomimetic agent. It acts by both promoting the release and inhibiting the reuptake of biogenic amines (dopamine, norepinephrine and serotonin) in the central and peripheral nervous system. It causes a dose-dependent increase in heart rate and blood pressure. Even small doses of cocaine can cause vasoconstriction through stimulation of the α-adrenergic receptors in the smooth muscle cells of the coronary arteries. In addition to α-adrenergic stimulation, cocaine has been shown to increase levels of endothelin (a powerful vasoconstrictor), and to decrease production of nitric oxide (a vasodilator). Acute thrombosis of coronary arteries shortly after cocaine use has been described. Thrombus formation in this setting may be mediated by several mechanisms: an increase in plasminogen-activator inhibitor, an increase in platelet count, increased platelet activation and platelet hyper-aggregability, increased von Willebrand factor and fibrinogen. As a result, cocaine use is associated with premature coronary atherosclerosis and thrombosis.

Cocaine’s euphoric effects are thought to be mediated through increased dopaminergic activity in the mesolimbic reward pathway (ventral tegmental area, nucleus accumbens, amygdala, and hippocampus).

The onset and the duration of action of cocaine depends on the route of administration. However, the symptoms of cocaine intoxication are generally short-lived and immediately followed by the opposite—intense depression, edginess and a craving for more of the drug. Tolerance develops quickly as does a strong psychological dependence. In particular, the symptoms of intravenous (IV) cocaine and smoking usually last 30-60 minutes, while the effects of nasal insufflation can last 60-120 minutes. Symptoms lasting for more than 3 hours should raise the concern for a missed diagnosis or “body packing.” Urine drug screens can detect cocaine metabolites for up to 3 days after exposure and thus cannot be used to diagnose cocaine intoxication, only recent cocaine use.

Cocaine use is highly associated with use of other legal and illegal substances. Polysubstance abuse may complicate both the diagnosis and treatment of cocaine intoxication as well as the treatment of cocaine addiction. Cigarette smoking and alcohol abuse are prevalent among cocaine users. When combined with nicotine, the coronary and peripheral vasoconstriction effects of cocaine are potentiated. When combined with ethanol, the concentration of cocaine increases, the active metabolite cocaethylene is formed and hemodynamic effects are prolonged. Animal models have shown their combination to be significantly more cardiotoxic than cocaine or alcohol alone. Heroin (“speedballing”), marijuana, methamphetamines, and phencyclidine (PCP) are also frequently combined with cocaine to modulate the euphoric effects of the drug.

Crack is also often mixed with other substances to expand its weight or volume (e.g., milk powder, sugars such as glucose, starch, caffeine, lidocaine, benzocaine, amphetamine, scopolamine and strychnine) which can create toxic fumes when burned. As crack smoke does not remain potent for long, crack pipes are generally very short. This often causes cracked and blistered lips, known as “crack lip,” from users having a very hot pipe pressed against their lips.

Street names for cocaine include: Blow, C, Charlie, Coke, Dust, Flake, Snow, Toot and White. Street names for crack include: base, beat, glow, gravel, grit, hard ball, rocks, rox/Roxanne, snow coke and sugar block.

II. Diagnostic Approach.

A. Clinical presentation of acute intoxication includes:

  • Increased heart rate, blood pressure, body temperature

  • Vasoconstriction

  • Increased rate of breathing

  • Dilated pupils

  • Disturbed sleep patterns

  • Nausea, loss of appetite

  • Hyperstimulation

  • Bizarre, erratic, sometimes violent behavior

  • Hallucinations, hyperexcitability, irritability

  • Tactile hallucinations (e.g., illusion of bugs burrowing under the skin)

  • Intense euphoria

  • Anxiety and paranoia

  • Depression

  • Intense drug craving

  • Panic and psychosis

  • Convulsions, seizures and sudden death from high doses (even with first use)

What is the differential diagnosis for this problem?

  • Withdrawal syndromes

    Alcohol withdrawal

    Benzodiazepine withdrawal

  • Drug toxicity (sympathomimetic intoxication: amphetamines, 3,4-methylenedioxy-N-methylamphetamine [MDMA also known as “ecstasy”], ephedrine, phencyclidine [PCP]), synthetic cannabinoid abuse [“K2” or “Spice”]), neuroleptic malignant syndrome, serotonin syndrome)

  • Endocrine dysfunction (hypoglycaemia, hyperthyroidism [thyroid storm], pheochromocytoma)

  • Psychiatric (decompensated schizophrenia, manic episode of bipolar disorder)

  • Neurological (subacrachnoid hemorrhage, stroke, seizure)

  • Infection (sepsis, meningitis)

  • Hypoxia

  • Hyperthermia (heat stroke)

B. Describe a diagnostic approach/method to the patient with this problem.

Cocaine use can lead to a host of medical complications with presentations including chest pain, coronary ischemia, arrhythmias, heart failure, cardiomyopathies, aortic dissection, endocarditis, asthma exacerbation, “crack lung” (an acute pulmonary syndrome manifested by hypoxemia, hemoptysis, respiratory failure and diffuse pulmonary infiltrates occurring after inhalation of cocaine), headaches, stroke (hemorrhagic and ischemic), seizure, nose bleeding, abdominal pain, abdominal ischemia and vasculitis/vasculopathy.

Consequently the diagnosis of a cocaine-associated complication rests on careful history taking, including a thorough review of potential illicit drug use with the patient, and where appropriate, family members, friends and first responders. When there remains a high suspicion for cocaine use, urine toxicology may be useful. In most centers, the processing time can be significant and clinical decisions may need to be made without full information.

1. Historical information important in the diagnosis of this problem.

Diagnosis is usually based on a history of cocaine use or typical features of sympathomimetic intoxication.

2. Physical Examination findings maneuvers that are likely to be useful in diagnosing the cause of this problem.

The principal physical exam findings of acute cocaine intoxication are related to catecholamine excess. These findings include tachycardia, hypertension, hyperthermia, pupillary constriction, and psychomotor agitation.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Labs and imaging

  • Finger stick glucose, chemistry panel and complete blood count (CBC), creatine kinase (CK) and cardiac enzymes, urine drug screen, alcohol level, acetaminophen level, salicylate level, pregnancy screen.

  • Electrocardiogram (EKG)

  • Urinalysis for ketones, myoglobin

Other tests to consider

  • Head computed tomography (CT) and lumbar puncture may be useful in the patient who presents with alerted mental status to exclude intracranial bleed.

  • Chest x-ray (CXR): This may be beneficial when the patient complaints of chest discomfort or respiratory difficulties.

  • AXR if body packing is suspected.

  • Consultation with a toxicologist if co-ingestions are suspected.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.


D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.


III. Management while the Diagnostic Process is Proceeding.

A. Initial Management of cocaine intoxication.

Management of cocaine intoxication centers on sedation with benzodiazepines and supportive care.

  • ABCs: As with all patients, initial assessment should focus on airway, breathing and circulation.

  • Hyperthermia: The determination of core temperature is an essential part of the evaluation of a patient with suspected cocaine intoxication. Hyperthermia should be treated aggressively with IV hydration and rapid cooling (with cooling blankets, combined use of mist and fans and/or cool-water washes).

  • Dehydration: Dehydration is common and should be addressed early in the management of cocaine intoxication.

  • Sedation: Benzodiazepines should be used to address the symptoms of catecholamine excess (lorazepam 1mg IV, diazepam 5mg IV repeated every 5 minutes) as needed. In some cases large doses of benzodiazepines are required to achieve sedation. This is thought partly to be due to cocaine-induced benzodiazepine receptor dysfunction.

  • Tachycardia and hypertension: Both the tachycardia and hypertension associated with cocaine intoxication usually respond well to sedation with benzodiazepines and are usually self-limiting.

  • If additional agents are needed to achieve set blood pressure goals direct-acting vasodilators including nicardipine, nitroglycerin, nitroprusside, and phentolamine are preferred. The combination of a benzodiazepine and a non-dihydropyridine calcium channel blocker (verapamil) can also often be sufficient to achieve blood pressure control.

  • If further heart rate management is required, non-dihydropyridine calcium channel blockers are again preferred (verapamil and diltiazem).

  • Cocaine induced cardiac dysrhythmias (ventricular ectopy, paroxysmal SVT, atrial flutter/fibrillation) are generally short lived and do not require immediate treatment. If persistent, they can often be managed with benzodiazepines. Ventricular arrhythmias that occur within hours of cocaine use result from the effects of cocaine on sodium channels and are treated preferably with sodium bicarbonate. Beyond several hours from cocaine use, ventricular arrhythmias usually result from ischemia and treatment should focus on managing ischemia. For persistent or recurrent ventricular arrhythmias, standard therapies should be used in consultation with Cardiology.

  • **Caution should be given towards routine administration of Naloxone or Flumazenil in cases of co-ingestion as this may leave the stimulant effects of cocaine unopposed and precipitate a worsening cocaine toxicity. However, in cases of significant respiratory depression, Naloxone is still indicated but should be administered at a slower rate and at lowered doses.


The effects of cocaine are generally short lived. Patients should be monitored until they are no longer tachycardic, hypertensive or symptomatic and until they are calm and cooperative. Testing for HIV and other sexually transmitted disease (STD) should be considered, as appropriate. Consultation with Psychiatry or Mental Health counselors as appropriate for patients with potential ‘dual diagnoses,’ e.g., concurrent mood or psychiatric disorders.

Social work and Addiction Medicine consultation is indicated to assist in counselling regarding cessation of cocaine abuse and for referrals to community-based resources to assist in the management of cocaine addiction. Unfortunately, there are currently no FDA approved medications to treat cocaine addiction. Several medications marketed for other diseases (e.g., Gabapentin, Baclofen, Modafinil, and Disulfiram) showed promise with reducing cocaine use in controlled clinical trials. There are several effective behavioral treatments for cocaine addiction, which include Cognitive-behavioral therapy (CBT), Community reinforcement approach plus vouchers and Contingency management or motivational incentives with group and individual drug counselling.

Specific issues: cocaine-associated chest pain

Among cocaine users, cardiopulmonary complaints are the most frequently reported symptoms, with chest pain being the most common. While cocaine-associated chest pain is usually perceived as pressure-like, there are no historical or presenting features that can reliably distinguish between ischemic vs. nonischemic chest pain. In fact, a little less than half of patients with cocaine-associated MI reported antecedent chest pain in one study.

In the cocaine-associated chest pain (COCHPA) study, cocaine-associated myocardial infarction occurred in 6% of patients who presented to the emergency department with cocaine-associated chest pain. The demographic of these patients differs from the typical patient with ischemic heart disease in that they are typically younger, male and smokers with few other cardiac risk factors -in one study of patients with cocaine-associated MI, the average age was only 38 years.

As reviewed earlier, the mechanisms of cocaine-induced myocardial ischemia includes: (1) increasing myocardial oxygen demand by increasing heart rate, blood pressure, and contractility; (2) decreasing oxygen supply via vasoconstriction; (3) stimulating platelet activation and altering the balance between pro- and anticoagulant factors; and (4) potentiating an accelerated atherosclerosis.

Cocaine-associated risk of MI increases by 24-fold in the first hour after use with a sharp decrease thereafter to a 4-fold increase in the second and third hours. But it is important to note that delayed or recurrent ischemic symptoms can still occur hours after ingestion, even when blood concentrations of cocaine are low or undetectable. This finding can be attributed to cocaine’s metabolites which persist in the circulation for up to 24 hours.

A critical differential diagnosis not to miss in cocaine-associated chest pain is aortic dissection.

Patients with cocaine-associated chest pain or acute coronary syndrome (ACS) should be treated for the most part much like other patients with traditional or suspected ACS. The notable exceptions to this are that beta-blockers have traditionally been avoided and benzodiazepines should be used early to ameliorate the effects of catecholamine excess and relieve chest pain in this population. Beta blockers are avoided because they can worsen coronary artery vasoconstriction when administered in the setting of cocaine use by causing an unopposed α-adrenergic effect. While Labetalol and Carvedilol offer the theoretical advantage of being both and α- and β-blockers, Labetalol did not reverse cocaine-induced coronary artery vasoconstriction in human studies and in animal models of cocaine toxicity, Labetalol use increased the risk of seizure and death. When combined with cocaine, Carvedilol 25 mg tended to increase blood pressure consistent with unopposed α-stimulation, whereas Carvedilol 50 mg decreased blood pressure and heart rate, suggesting that both α- and β-receptors were blocked. Recent, uncontrolled studies of beta blockers in patients with cocaine associated chest pain yielded conflicting results. At this time, use of either Labetalol or Carvedilol cannot be supported in acute chest pain syndromes associated with cocaine use.

Initial therapy for cocaine-induced chest pain or ACS should include full strength aspirin and adequate sedation with benzodiazepines. Chest pain should also be treated initially with nitroglycerin (either sublingual or IV infusion) to reduce coronary artery vasoconstriction. Morphine can also reverse cocaine-induced coronary vasoconstriction. If chest pain persists despite adequate sedation with benzodiazepines, nitroglycerin, and morphine, cardiac oxygen requirements can be reduced by addressing any persistent tachycardia and hypertension with a non-dihydropyridine calcium channel blocker (Verapamil or Diltiazem). However, in patients with heart failure, systolic dysfunction, bradycardia, or heart block, Verapamil and Diltiazem should be avoided. For additional hypertension management, Sodium nitroprusside or intravenous α- antagonist Phentolamine use can be considered. Further management of cocaine-associated ACS is similar to management of patients who have not used cocaine.

Patients with cocaine-associated chest pain who do not have evidence of ischemia or cardiovascular complications over a 9-to-12 hour period of observation have been shown to have a very low risk of death or myocardial infarction during the 30 days after discharge. Such patients should be counselled to stop using cocaine and can usually be safely discharged home without further evaluation.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem.

Consider ddx of acute aortic dissection in cocaine-associated chest pain syndromes.

Contraindicated medications in the setting of cocaine use

  • Beta-Blockers including labetalol and carvedilol, are to be avoided due to concerns for causing an unopposed α-adrenergic effect thereby worsening coronary artery and peripheral vasoconstriction.

  • Antipsychotics

  • Phenothiazines (chlorpromazine) and butyrophenone antipsychotics (Haldol) in particular are generally avoided given concerns that they may lower the seizure threshold and prolong the QT interval.

  • Succinylcholine

  • Generally succinylcholine is avoided when tracheal intubation is required to secure the airway. In the setting of rhabdomyolysis, hyperkalemia may be exacerbated by succinylcholine. Additionally, both cocaine and succinylcholine are metabolized by plasma cholinesterase and coadministration of these drugs could theoretically decrease the clearance of either or both agents.

  • Monoamine oxidase inhibitors (MAOIs)

  • MAOIs block the degradation of catecholamines and in combination with cocaine may precipitate a state of excessive catecholamine release.

  • Class Ia antiarrhythmic agents (quinidine, procainamide)

  • The concern is raised for additive QT prolongation and pro-arrhythmic effect.


For patients with cocaine-induced chest pain and ACS, cessation of cocaine use is paramount. For those who do abstain, recurrent chest pain is less common and MI and death are rare. Aggressive modification of the traditional risk factors is still indicated for those with MI or evidence for atherosclerosis. When appropriate, dual antiplatelet therapy, ACE inhibitors or ARBs and statins should still be used despite lack of extensive study in cocaine use. While beta blockers are to be avoided in the acute setting, secondary prevention using beta blockers may be considered in select cases, such as for those with the strongest indications including documented MI, LV systolic dysfunction or ventricular arrhythmias. However, since many patients will continue to use cocaine after discharge, post-discharge beta blocker therapy should be considered after careful risk-benefit assessment and possibly withheld until cessation of cocaine use has been proven. Patients should also be counselled on the potential hazards of combining cocaine with beta blockers.

IV. What’s the evidence?

Forrester, JM, Steele, AW, Waldron, JA, Parsons, PE. “Crack lung: an acute pulmonary syndrome with a spectrum of clinical and histopathologic findings”. . vol. 142. 1990. pp. 462-467.

Freeman, K, Feldman, JA. “Cocaine, myocardial infarction, and beta-blockers: time to rethink the equation”. . vol. 51. 2008. pp. 130-134.

Lange, RA, Hillis, LD. “Cardiovascular complications of cocaine use”. . vol. 345. 2001. pp. 351-358.

McCord, J, Jneid, H, Hollander, JE, de Lemos, JA, Cercek, B, Hsue, P, Gibler, WB, Ohman, EM, Drew, B, Philippides, G, Newby, LK. “American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology: Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology”. . vol. 117. 2008. pp. 1897-1907.

Weber, JE, Shofer, FS, Larkin, GL, Kalaria, AS, Hollander, JE. “Validation of a brief observation period for patients with cocaine-associated chest pain”. . vol. 348. 2003. pp. 510-517.

Schwartz, Bryan, G, Rezkalla, Shereif, Kloner, Robert, A. “Cardiovascular effects of cocaine”. . vol. 122. 2010. pp. 2558-2569.