Maria Elena De Benedetti, MD and James McCord, MD

1. How common is cocaine use in the United States?

    Cocaine is the second most commonly used illicit drug in the United States, with only marijuana being used more often. Between 1994 and 1998, the number of new cocaine users per year increased by 82%. In 2005, there were approximately 450,000 cocaine-related emergency department visits in the United States. In 2007, there were 2.1 million cocaine users age 12 or older, comprising 0.8% of the population. Users are more likely to be young, between 18 and 20 years of age. Males are more likely to be users than females by a 2:1 ratio. Cocaine-associated chest pain accounts for approximately 16% of all cocaine-related admissions, leading to the evaluation of approximately 64,000 patients annually. Of these, approximately 57% are admitted to the hospital for further evaluation.

2. What are the pharmacologic effects of cocaine?

    Cocaine is a powerful sympathomimetic that acts by directly stimulating central sympathetic outflow and blocking presynaptic uptake of norepinephrine and dopamine (Fig. 49-1). This augmentation in postsynaptic catecholamines increases heart rate, mean arterial pressure, and left-ventricular contractility through stimulation of both α- and β-adrenergic receptors. Through enhanced α-adrenergic receptor activation, increased endothelin production, and diminished nitric oxide generation, cocaine initiates coronary artery vasoconstriction. Cocaine may also enhance platelet aggregation and thrombus formation through heightened production of adenosine diphosphate, thromboxane A₂, and tissue plasminogen activator inhibitors, as well as reductions in protein C and antithrombin III. Cocaine causes toxic effects on cardiac muscle that arise primarily from Ca²⁺ overload during excessive β-adrenergic stimulation. Cocaine is well absorbed through all body mucous membranes and can be administered by nasal, sublingual, intramuscular, intravenous, and respiratory routes. The onset of action varies from 3 seconds to 5 minutes, depending on the administration route.

3. What are the typical symptoms after cocaine ingestion?

    Cardiopulmonary complaints are the most commonly reported symptoms in patients after cocaine use, occurring in 56% of cases. Chest pain is the most common symptom and is typically described as a pressure sensation. Other common symptoms include dyspnea, anxiety, palpitations, syncope, dizziness, and nausea. The onset of symptoms usually occurs soon after ingestion, with two-thirds of patients presenting within 3 hours.

4. What are the consequences of cocaine use?

    The cardiac and systemic effects of cocaine are complex. Cocaine-induced increase in sympathomimetic activity results in increased myocardial contractility, heart rate, blood pressure, and increased myocardial oxygen demand, while simultaneously decreasing myocardial oxygen supply due to vasoconstriction leading to hypertensive crises, acute myocardial infarction (AMI), aortic dissection, and stroke. Premature coronary atherosclerosis has been seen in young cocaine abusers, with obstructive coronary artery disease (CAD) seen in 35% to 40% of patients who undergo angiography for cocaine-associated chest pain. Cocaine may depress left ventricular function in the absence of acute coronary ischemia because of its direct negative inotropic effect on cardiac muscle, therefore leading to myocarditis and cardiomyopathy. Cocaine exhibits properties of a class I antiarrhythmic agent by Na-channel blockade. It also prolongs the duration of the QT interval by inhibiting myocyte repolarization that occurs by the efflux of potassium. Cocaine also increases intracellular calcium with resultant afterdepolarizations, reduces vagal activity, and increases myocyte irritability by inducing ischemia. Ischemia due to vasospasm and fatal ventricular arrhythmias due to ischemia are presumed to be important mechanisms of sudden death in these patients.

5. How often does AMI occur after cocaine ingestion?

    Reported rates of AMI vary widely (1% to 31%); the variance in the incidence of AMI in studies likely relates to the difference in patient populations, AMI diagnostic criteria, and the use of newer, more sensitive troponin assays that can detect smaller levels of myocardial necrosis in patients that were previously classified as unstable angina. AMI occurs within minutes to days after cocaine exposure, independent of dose, length of use, or route of administration. However, the time during which individuals are at higher risk for developing AMI is within the first hour of cocaine use.

6. What else should be considered in the differential diagnosis after cocaine use?

    Because patients who present to the emergency department after cocaine use are commonly hypertensive and tachycardic, aortic dissection needs to be considered in the differential diagnosis. Information concerning cocaine-induced aortic dissection is limited, but one study of 38 consecutive cases of aortic dissection demonstrated that a surprisingly high number (14, or 37%) were associated with cocaine use. However, among 921 patients in the International Registry of Aortic Dissection (IRAD), only 0.5% of aortic dissection cases were associated with cocaine use. In addition, an acute pulmonary syndrome, “crack lung,” has been described after inhalation of freebase cocaine. The syndrome presents with hypoxemia, hemoptysis, respiratory failure, and diffuse pulmonary infiltrates. Chronic cocaine use can lead to decreased left ventricular systolic function and congestive heart failure. This may relate to accelerated atherosclerosis or myocarditis, both of which are associated with cocaine use.

7. How does cocaine ingestion lead to AMI?

    Cocaine can lead to AMI in a multifactorial fashion, including the following:

Coronary vasospasm, rather than plaque rupture, likely constitutes the primary pathogenesis. In patients with preexisting high-grade coronary arterial narrowing, acute ischemia may be the result of increased myocardial oxygen demand associated with hypertension and tachycardia. In those presenting with no underlying atherosclerotic obstruction, coronary occlusion may be due to vasospasm, thrombus formation, or both. For many years, the conventional assumption was that AMI after cocaine exposure was due solely to coronary vasospasm. Current knowledge suggests that vasospasm may only be the initiating pathophysiological event leading to thrombus formation rather than plaque rupture.

8. Should younger patients with chest pain have a cocaine screening test?

    The American Heart Association (AHA) recommends that establishing cocaine use should depend primarily on self-reporting. Because the use of cocaine influences treatment strategies, patients being evaluated for possible AMI should be queried about cocaine use; this applies especially to younger patients. Even if a young patient with chest pain denies cocaine use, the use of cocaine should be considered. Young patients with nontraumatic chest pain should be questioned regarding cocaine use.

9. Are there any specific electrocardiogram findings in patients that use cocaine?

    Abnormal electrocardiograms (ECGs) have been reported in 56% to 84% of patients with cocaine-associated chest pain. Many of these patients are younger and have the normal variant findings of early repolarization, namely, elevation of the J point as well as concave-up ST elevation and prominent T waves. In a study of 101 patients who had used cocaine, 42% manifested ST segment elevation on the ECG, but all of them ultimately had AMI excluded by serial cardiac marker testing. Left ventricular hypertrophy can also be noted on the ECG. In a series of 238 individuals who used cocaine, 33% had a normal ECG, 23% had nonspecific findings, 13% had left ventricular hypertrophy, 6% had left ventricular hypertrophy and early repolarization, and 13% had early repolarization alone.

10. Should all patients with cocaine-associated chest pain be admitted to the hospital?

    No. Most patients with cocaine-associated chest pain do not have ACS and can safely and efficiently be evaluated in a chest pain observation unit. In a prospective study of 344 patients with cocaine-associated chest pain, 42 (12%) high-risk patients with ST segment elevation or depression, elevated cardiac markers, or hemodynamic instability were directly admitted. The other 302 were evaluated in an observation unit over 9 to 12 hours with telemetry monitoring, serial troponin I measurement, and selective stress testing. Among the patients in the observation unit there were no cardiac deaths, 4 (2%) nonfatal AMIs, and 158 (52%) patients who underwent stress testing.

11. Should all patients with cocaine-associated chest pain have a stress test?

    No. The AHA states that stress testing is optional in patients who have an uneventful 9 to 12 hours of observation. Patients should be counseled about cessation of cocaine use. Patients can be followed in the outpatient setting and stress testing considered later, depending on cardiac risk factors and ongoing symptoms.

12. How should patients with ST elevation myocardial infarction (STEMI) or non–ST elevation myocardial infarction (NSTEMI) be treated in the setting of cocaine use?

    Rapid reperfusion by percutaneous coronary intervention (PCI) in a high-volume center by experienced operators is preferred over fibrinolytic therapy in the setting of STEMI, and this is even more desirable after cocaine use. Many young patients will have early repolarization, and only a small percentage of these patients will actually be experiencing an AMI. Furthermore, hypertensive patients after cocaine use are at higher risk for significant bleeding complications. There have been case reports of intracranial hemorrhage after fibrinolytic therapy in the setting of STEMI associated with cocaine use. Fibrinolytic therapy should only be considered for patients who are clearly having a STEMI but cannot receive timely PCI. Patients with NSTEMI should be treated in similar fashion as patients without cocaine, with a notable exception regarding beta-adrenergic blocking agents (β-blockers; see Question 14).

13. How should patients with cocaine-associated chest pain be treated?

    Patients who ingest cocaine are commonly hypertensive, tachycardic, and anxious. In patients who use cocaine, the AHA recommends the early use of intravenous benzodiazepines. Benzodiazepines decrease the central stimulating characteristics of cocaine and lessen anxiety. Their use has been shown to relieve chest pain and to have beneficial hemodynamic effects. Many times the hypertension and tachycardia will not need to be directly treated after the use of benzodiazepines. Aspirin should also be given. In patients who remain hypertensive, nitroglycerin or nitroprusside can be administered. Phentolamine is also an alternative. Calcium channel blockers have not been well studied in this population, but can be considered in patients who do not respond to benzodiazepines and nitroglycerin. However, short-acting nifedipine should not be used, and verapamil and diltiazem should be avoided in the setting of heart failure or decreased left ventricular systolic function (Fig. 49-2).

14. Should β-blockers be given to patients with cocaine-associated chest pain?

    No. The AHA recommends that β-blockers not be administered acutely in patients with ACS or undifferentiated chest pain in the setting of cocaine use. After cocaine use, the administration of propranolol leads to worsening coronary vasoconstriction and increased systemic blood pressure because of the unopposed α-adrenergic effect. Multiple experimental animal models have shown in this setting that β-blockers elevate the coronary vascular resistance and decrease coronary blood flow, increase seizure activity, and increase mortality. There have been case reports of sudden cardiac death in humans shortly after the administration of β-blockers in the setting of cocaine use.

    Although theoretically more attractive, the administration of labetalol in the setting of cocaine use is not recommended. Labetalol has substantially more β-blocking than α-blocking effects. In animal models, labetalol leads to increased seizure activity and death after cocaine administration and does not reverse coronary vasoconstriction in humans. The β₁-adrenoceptor–selective agent metoprolol has not been evaluated in the setting of cocaine, but the β₁-adrenoceptor–selective agent esmolol has been associated with an increase in systemic blood pressure after cocaine use. Compared to labetalol, carvedilol may be four times more effective at the α receptor and, unlike labetalol, carvedilol at recommended doses may attenuate the physiological and behavioral response to smoked cocaine. However, strong clinical evidence to change current guidelines recommendations is still lacking.

15. How should tachyarrhythmias be treated after cocaine use?

    Sinus tachycardia and atrial tachyarrhythmias may respond to benzodiazepines. In cases of atrial tachyarrhythmias that do not respond to benzodiazepines, verapamil or diltiazem can be considered. Ventricular arrhythmias that occur immediately after cocaine use are thought to result from the Na-channel blocking effect of cocaine and may respond to the administration of sodium bicarbonate, similar to arrhythmias associated with type IA agents. Ventricular arrhythmias that occur several hours after cocaine use usually are due to ischemia, which should be treated as directed earlier. In case of persistent ventricular arrhythmias, lidocaine can be used.

16. How should patients be managed after discharge?

    It is estimated that 60% of patients who present with cocaine-associated chest pain will continue to abuse cocaine after hospital discharge. Therefore, the cessation of cocaine use should be the primary goal. The combination of intensive group and individual drug counseling has been shown to be effective. The recurrence of chest pain is unlikely, and the prognosis is good in patients who discontinue cocaine use. Aggressive modification of risk factors is indicated for patients with AMI or CAD, similar to patients who do not use cocaine.

    Although β-blockers should be avoided acutely, special consideration needs to be given in selected patients for chronic use. In patients with left ventricular systolic dysfunction, AMI, or ventricular arrhythmias, the long-term use of β-blockers should be strongly considered. The AHA recommends that this decision be individualized on the basis of risk-benefit assessment and recommends counseling the patient about the potential negative effects of the use of β-blockers and cocaine ingestion.

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