Central Nervous System

The most significant CNS toxicity associated with cocaine use is stroke; both hemorrhagic and ischemic strokes can occur. Hemorrhagic strokes associated with cocaine use are hypothesized to result from acute elevations of blood pressure, coupled with platelet dysfunction and/or the presence of vascular malformations. The presence of vascular malformations, in particular, was suggested by several reports to be a significant predisposing factor. However, a large retrospective study failed to find a significant association between the presence of vascular malformations and cocaine-induced intracranial hemorrhage. Additionally, there was no predilection for cocaine to affect a particular area of the brain. The study noted that brainstem hemorrhage and intraventricular extension were associated with cocaine use.⁹ Ischemic stroke is also thought to be caused by cocaine use and is likely caused by cerebral vasoconstriction, which has been demonstrated experimentally and may be particularly associated with chronic abuse of the drug.¹⁰ Increased thrombogenic activity as described earlier also may play a role, especially with chronic use. All standard stroke care should be provided to patients with stroke related to cocaine use.

Seizures can be induced by acute use of cocaine, as the drug lowers the seizure threshold. Additionally, seizures can be induced by withdrawal of cocaine. Most seizures are self-limiting and usually respond to administration of IV benzodiazepines. Refractory seizure activity may indicate a severe CNS injury or severe hyperthermia.

Hyperthermia can occur with cocaine abuse and may result in death, especially in overdose situations and in hot climates.¹¹ Cocaine-induced hyperthermia is thought to be related to dysfunction of CNS thermoregulatory centers as well as derangements in regional distribution of blood flow caused by the vasoconstrictor effects of the drug.³ In addition, most patients present with heat exposure and muscle hyperactivity as contributing causes.^11,12 A syndrome of excited delirium manifested by agitation, paranoia, and psychosis sometimes accompanies hyperthermia. In these cases, body temperature can be markedly elevated (>40.6°C). Patients presenting in this manner often have accompanying complications such as disseminated intravascular coagulation, rhabdomyolysis, and/or renal failure.¹³ Other than supportive care and aggressive cooling measures, there are no other standard therapies. Benzodiazepines such as lorazepam (administered IV or intramuscularly) should be used liberally to control agitation and hyperactivity. Haloperidol should be avoided, as this agent can lower the seizure threshold and also itself induce hyperthermia. Evaluation of the agitated cocaine abuser always should include accurate determination of core temperature.

Pulmonary

Pulmonary diseases associated with cocaine use are varied and can range from acute bronchoconstriction to noncardiogenic pulmonary edema to barotrauma. Most reported pulmonary complications have been associated with smoking freebase cocaine. Bronchoconstriction has been shown experimentally to be associated with inhaled cocaine.¹⁴ An increased need for intubation and mechanical ventilation with asthma exacerbations also has been found in cocaine abusers.¹⁵ The term crack lung has been used to refer to pulmonary infiltrates related to cocaine use. The pulmonary infiltrates may be transient or associated with significant disease, especially acute respiratory distress syndrome (ARDS).¹⁶ Noncardiogenic pulmonary edema caused by cocaine use is frequently associated with alveolar hemorrhage.¹⁷ Alternatively, hemoptysis can be the only presenting complaint and usually remits with avoidance of further cocaine exposure. Talc in contaminated cocaine has been reported to cause granulomatous lung disease. This entity is primarily associated with IV administration of cocaine, but chronic inhalation of the drug also can produce a similar form of lung disease.¹⁸ Data are lacking to show that administration of corticosteroids is of benefit for addressing pulmonary abnormalities associated with cocaine abuse.

Pneumothorax and pneumomediastinum have also been associated with smoking crack cocaine and are likely caused by coughing triggered by the inhalation of the drug, or particular behaviors such as breath holding which are employed to enhance the desirable effects of the drug. The cause of pneumothorax also may be related to adulterants in the inhaled cocaine.¹⁹ Treatment is usually conservative with supplemental oxygen and serial imaging. Tube thoracostomy is reserved for moderate to large pneumothoraces. The presence of pneumomediastinum by itself is not an indication for hospital or intensive care unit (ICU) admission.

Cardiovascular

Myocardial ischemia and infarction (acute coronary syndromes [ACS]) related to cocaine use were first reported in 1982.²⁰ Since then, numerous studies have confirmed that cocaine abuse is an epidemiologically significant cause of myocardial ischemia and infarction and morbidity and mortality on this basis. Chest pain is the most frequent reason for cocaine users to present to emergency departments. Cocaine-induced ACS are not related to the amount of cocaine used, route of administration, or frequency of use. First-time users can develop myocardial infarction (MI).⁵ Cocaine-associated myocardial ischemia is likely related to the combination of increased myocardial oxygen demand caused by acute increases in heart rate, blood pressure, and contractility, on the one hand, combined with decreased myocardial oxygen supply caused by coronary vasoconstriction, on the other hand. In addition, coronary artery atherosclerosis can develop prematurely in young cocaine users. In combination with the ability of cocaine to promote a prothrombotic state, cocaine-induced coronary artery disease likely contributes to the risk for ACS among cocaine abusers.⁴ Cocaine-associated myocardial ischemia appears to occur most commonly in the first few hours after cocaine exposure; however, delayed infarction can occur several hours to weeks after exposure to the drug. The effects of the metabolites of cocaine (benzoylecgonine and ecgonine methyl ester) are thought to contribute to the delayed presentation.⁵

Diagnosis of cocaine-associated MI should rely on the measurement of cardiac troponin I, as rhabdomyolysis and consequent elevation of total creatine phosphokinase concentrations can otherwise confound diagnosis.^21,22 Diagnosis using electrocardiogram (ECG) is difficult because the majority of patients who present with chest pain associated with cocaine use have ECG abnormalities. Even ST-segment elevation is difficult to interpret in these patients, because an early repolarization pattern is frequently present.²³

American Heart Association guidelines recommend percutaneous coronary intervention over fibrinolytic therapy for ST-segment elevation MI in the setting of cocaine use. Nitroglycerin and benzodiazepines are advocated as primary therapy aimed at ameliorating the coronary vasoconstriction and the increase in myocardial oxygen demand. Administration of aspirin and heparin is recommended unless contraindicated. Calcium channel blockers may be used in patients unresponsive to nitroglycerin and benzodiazepines.⁴ Beta-blockers, including labetalol, were thought to be associated with worse outcomes in patients with recent history of cocaine use. However, this topic provokes considerable controversy, since beta-blocker use was not found to be detrimental in two retrospective studies of patients with a recent history of cocaine use.^24,25 Administration of beta-blockers might be beneficial for selected patients with ACS and a history of cocaine abuse.

Cocaine’s ability to block sodium channels yields acute type Ic antiarrhythmic properties including QRS prolongation and a variety of arrhythmias. Sinus tachycardia is the most common abnormal rhythm in cocaine users, and it responds to observation or benzodiazepines. Supraventricular arrhythmias are usually self-limited, but benzodiazepines also may be useful. Ventricular arrhythmias may respond to treatment with sodium bicarbonate, and addition of lidocaine may be necessary.²⁶ Arrhythmias due to cocaine-associated myocardial ischemia should be treated by correcting the ischemia. As always, treatment of life-threatening arrhythmias should follow Advanced Cardiac Life Support (ACLS) protocols. Aortic dissection is an important consideration when addressing cocaine-associated chest pain. Though many previous reports linked aortic dissection to cocaine use, a large international registry did not confirm the presence of a significant association.^27,28