Patient Care

How Should a Patient with Cocaine-Associated Chest Pain be Treated?


 

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Cocaine is the second-most-commonly used illicit drug in the U.S. and represents 31% of all ED visits related to substance abuse.

Key

  • Cocaine toxicity can lead to a mismatch in myocardial oxygen supply and demand through various mechanisms, including vigorous central sympathomimetic stimulation, coronary artery vasoconstriction, platelet stimulation, enhanced thrombosis, and accelerated atherosclerosis.
  • Benzodiazepines help reverse the systemic effects of cocaine, while nitroglycerin aids in reversing its vasoconstrictive properties; both medications are mainstay treatments of CACP.
  • Beta-blocker use remains controversial but can be considered at discharge for patients with documented MI, left ventricular systolic dysfunction, or ventricular arrhythmias.

Case

A 38-year-old man with a history of tobacco use presents to the emergency department complaining of constant substernal chest pain for three hours. His temperature is 37.7°C, his heart rate is 110 beats per minute, and his blood pressure is 155/95 mmHg. He appears anxious and diaphoretic but examination is otherwise unremarkable. He admits to cocaine use one hour before the onset of symptoms. What are the appropriate treatments for his condition?

Overview

Cocaine is the second-most-commonly used illicit drug in the U.S. and represents 31% of all ED visits related to substance abuse.1,2 According to recent survey results, 2.1 million people report recent cocaine use, and 1.6 million engage in cocaine abuse or dependence.2 Acute cardiopulmonary complaints are common in individuals who present to the ED after cocaine use, with chest pain being the most frequently reported symptom in 40%.3

Numerous etiologies for cocaine-associated chest pain (CACP) have been discovered, including musculoskeletal pain, pulmonary hypertension, cardiomyopathy, arrhythmias, and endocarditis.4 Only 0.5% of patients with aortic dissection over a four-year period had a recent history of cocaine use, making cocaine a rare cause of a rare condition.5 Cardiac chest pain remains the most frequent underlying etiology, resulting in the most common complication of myocardial infarction (MI) in up to 6% of patients.6,7

The ways in which cocaine use can cause myocardial ischemia and MI are multifactorial. A vigorous central sympathomimetic effect, coronary artery vasoconstriction, stimulation of platelets, and enhanced atherosclerosis all lead to a myocardial oxygen supply-demand imbalance.8 Other key interactions in the cardiovascular system are displayed in Figure 1. Understanding the role of these mechanisms in CACP is crucial to patient care.

Clinician goals in the management of CACP are to rapidly and accurately exclude life-threatening etiologies; assess the need for urgent acute coronary syndrome (ACS) evaluation; risk-stratify patients and ensure appropriate disposition; normalize the toxic effects of cocaine; treat resultant organ damage; and prevent long-term complications. An algorithm detailing this approach is provided in Figure 2.

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Figure 1. Cocaine’s pathophysiologic effects on the cardiovascular system8

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Figure 2. Diagnostic and therapeutic approach to patients with cocaine-associated chest pain18

Review of the Data

Diagnostic evaluation. Given potential differences in treatment regimens, it is imperative to differentiate patients who present with CACP from those whose chest pain is not associated with cocaine either by direct questioning or by screening of urine for cocaine metabolites. Once the presence of cocaine has been confirmed, guideline-based evaluation for potential ACS with serial electrocardiograms (ECG), cardiac biomarkers, and close monitoring of cardiac rhythms and hemodynamics is largely similar to standard management of all patients presenting with chest pain, with a few caveats.

Interpretation of the ECG can be challenging in the setting of cocaine. Studies have shown “abnormal” ECGs in 56% to 84% of patients, with many representing early repolarization or left ventricular hypertrophy.9,10 Likewise, patients with MI are as likely to present with normal or nonspecific ECG findings as with ischemic findings.7,11 ECG interpretation to diagnose ischemia or infarction in patients with CACP yields a sensitivity of 36% and specificity of 90%.7

Creatine kinase (CK), CK-MB fraction, and myoglobin have low specificity for the diagnosis of ischemia, as cocaine can induce skeletal muscle injury and rhabdomyolysis.9,12 Cardiac troponins demonstrate a superior specificity compared to CK and CK-MB and are thus the preferred cardiac biomarkers in diagnosing cocaine-associated MI.12

Initial management and disposition. Patients at high risk for cardiovascular events are generally admitted to a monitored bed.13 Immediate reperfusion therapy with primary percutaneous coronary intervention is recommended in patients with ST-elevation MI (STEMI). Treatment with thrombolytic agents is associated with an increased risk of intracerebral hemorrhage and lacks documented efficacy in patients with CACP. Thrombolysis should therefore only be utilized if the diagnosis of STEMI is unequivocal and an experienced cardiac catheterization laboratory is unavailable.14,15

Patients with unstable angina (UA) or non-ST-elevation MI (NSTEMI) are at higher risk for further cardiac events in a similar manner to those with ACS unrelated to cocaine. These cases might benefit from early cardiac catheterization and revascularization.16 Because of the increased risk of stent thrombosis in cocaine-users, thought to be due to recidivism, a detailed risk-benefit analysis should be undertaken prior to the implantation of cardiac stents.

Other diagnostic tests, such as stress testing and myocardial imaging, have not shown significant accuracy in diagnosing MI in this setting; moreover, these patients are at low overall risk for cardiac events and mortality. Consequently, an extensive diagnostic evaluation might not be cost-effective.7,10,13,17 Patients who have CACP without MI have a very low frequency of delayed complications.3,17 As such, cost-effective evaluation strategies, such as nine- or 12-hour observation periods in a chest pain unit, are appropriate for many of these low- to moderate-risk patients.13 For all CACP patients, the most critical post-discharge interventions are cardiac risk modification and cocaine cessation.13

Normalizing the toxic effects of cocaine with medications.

Aspirin: While no specific study has been performed in patients with CACP and aspirin, CACP guidelines, based on data supporting ACS guidelines for all patients, recommend administration of full-dose aspirin given its associated reduction in morbidity and mortality.18,19 Furthermore, given the platelet-stimulating effects of cocaine, using aspirin in this setting seems very reasonable.

Benzodiazepines: CACP guidelines support the use of benzodiazepines early in management to indirectly combat the agitation, hypertension, and tachycardia resulting from the stimulatory effects of cocaine.18,20 These recommendations are based on several animal and human studies that demonstrate significant reduction in heart rate and systemic arterial pressure with the use of these agents.21,22

Nitroglycerin: Cardiac catheterization studies have shown reversal of vasoconstriction with administration of nitroglycerin. One study demonstrated a benefit of the drug in 49% of participants.23 Additional investigation into the benefit of benzodiazepine and nitroglycerin combination therapy revealed mixed results. In one study, lorazepam plus nitroglycerin was found to be more efficacious than nitroglycerin alone.24 In another, however, use of diazepam in combination with nitroglycerin did not show benefit when evaluating pain relief, cardiac dynamics, and left ventricular function.25

Phentolamine: Phentolamine administration has been studied much less in the literature. This nonselective alpha-adrenergic antagonist exerts a dose-dependent reversal of cocaine’s vasoconstrictive properties in monkeys and humans.26,27 International guidelines for Emergency Cardiovascular Care recommend its use in treatment of cocaine-associated ACS;27 however, the AHA recommends it less strongly.18

Calcium channel blockers: Calcium channel blockers (CCBs) have not shown promise as first-line agents. While catheterization studies demonstrate the vasodilatory properties of verapamil, larger studies looking at all-cause mortality conclude that CCBs might worsen mortality rates,28 and animal studies indicate an increased risk of seizures.29 At this time, CCBs are recommended only if cardiac symptoms continue after both benzodiazepines and nitroglycerin are administered.18

The beta-blocker controversy: The use of beta-blockers in patients with CACP remains controversial given the theoretical risk of unopposed alpha-adrenergic activation. Coronary vasospasm, decreased myocardial oxygen delivery, and increased systemic vascular resistance can result from their use.30

Propranolol, a nonselective beta-blocker, was shown in catheterization studies to potentiate the coronary vasoconstriction of cocaine.31 Labetalol, a combined alpha/beta-blocker, reduced mean arterial pressure after cocaine administration during cardiac catheterization but did not reverse coronary vasoconstriction.32 This was attributed to the predominating beta greater than alpha blockade at doses administered. The selective beta-1 antagonists esmolol and metoprolol have shown no benefit in CACP.33 Carvedilol, a combined alpha/beta-blocker with both peripheral and central nervous system activity, has potential to attenuate both physiologic and behavioral response to cocaine, but it has not been well studied in this patient subset.34

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Table 1. Initial medical therapies for cocaine-associated chest pain18,38

The 2005 ACC/AHA STEMI guidelines recommended against beta-blockers in the setting of STEMI precipitated by cocaine use due to the potential of exacerbating coronary vasoconstriction.35 The 2007 ACC/AHA UA/NSTEMI guidelines stated that the use of a combined alpha/beta-blocker in patients with cocaine-induced ACS may be reasonable for patients with hypertension or tachycardia if pre-treated with a vasodilator.19 The 2008 ACC/AHA guidelines on the management of cocaine-related chest pain and MI recommended against the use of beta-blockers in the acute setting given the low incidence of cocaine-related MI and death.18

In a more recent study, Dattilo et al showed that beta-blockers administered to patients admitted with positive urine toxicology for cocaine significantly reduced MI and in-hospital mortality. Reduction of MI was of borderline significance in those admitted with a chief complaint of chest pain.36 Limitations of this study include unknown time of cocaine ingestion, lack of follow-up on discharge mortality, and a small sample size of 348 patients lacking statistical power.

Another retrospective cohort study examined patients admitted with chest pain and urine toxicology positive for cocaine and found that beta-blocker administration during hospitalization was not associated with increased incident mortality. Further, after a mean follow-up of 2.5 years, there was a statistically significant decrease in cardiovascular death.37 Drawbacks of this study included an older patient population, greater proportion of coronary artery disease, and higher follow-up of cardiovascular mortality rates than in previous studies, suggesting this subset might have received greater benefit from beta-blockers as a result of these characteristics.

The 2008 ACC/AHA guidelines instruct individualized consideration of the risk/benefit ratio for beta-blocker use in patients with CACP given the high rate of recidivism in cocaine abusers. The strongest indication is given to those with documented MI, left ventricular systolic dysfunction, or ventricular arrhythmias.18

It is important to note that these recommendations are based on cardiac catheterization laboratory studies, case reports, retrospective analyses, and animal experiments. No prospective controlled trials evaluating the role of beta-blockers in CACP and MI exist, and no trials regarding therapies to improve outcomes of patients sustaining a cocaine-associated MI have been reported.18

Back to the Case

This patient was experiencing cocaine-associated chest pain, which was confirmed with positive urine toxicology. Initial diagnostic workup with basic laboratory studies and cardiac biomarkers showed mild elevation in CK with troponin levels within normal limits. His ECG showed changes consistent with left ventricular hypertrophy. Chest radiograph was unremarkable.

He received aspirin, benzodiazepines, and nitroglycerin with normalization of vital signs, as well as subjective improvement in chest pain and anxiety. He was deemed to be at low risk for potential cardiac complications; thus, further cardiac testing was not pursued. Rather, he was admitted to an overnight observation unit with telemetry monitoring, where his chest pain did not recur.

He was seen in consultation with social work staff who arranged for drug abuse counseling after discharge. Given the uncertainty of relapse to cocaine use, as well as lack of known cardiac risk factors, he was not discharged on any new medications.

Bottom Line

The treatment of CACP includes normalizing the toxic systemic effects of the drug and minimizing the direct ischemic damage to the myocardium. Management varies slightly from traditional chest pain algorithms and includes benzodiazepines as well as antiplatelet agents and vasodilators to achieve this goal. Initial therapy with beta-blockers remains undefined and is largely discouraged in the acute setting. The role of beta-blockade upon discharge, however, can be beneficial in specific populations, especially those found to have underlying coronary disease.


Dr. Houchens and Dr. Czarnik are clinical instructors and Dr. Mack is a clinical lecturer at the University of Michigan Health System in Ann Arbor.

References

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