Cocaine and sudden cardiac death

J Oral Maxillofac

Surg

47:1188-1191,1989

Cocaine and Sudden CarTHOMAS d. PALLASCH, DDS, MS,* FRANK M. McCARTHY, d. THEODORE JASTAK, DDS, PHD$

Cocaine-related sudden cardiac deaths are being reported with increasing frequency. The oral and maxillofacial surgeon must therefore consider possible substance abuse in the preoperative medical history. This review will briefly summarize the literature, identify the signs and symptoms of both chronic and acute cocaine toxicity, and suggest clinical management guidelines.

mias and/or asystole can occur, but are more likely secondary to the severe metabolic acidosis resulting from hyperthermia and prolonged seizure activity.7 The first clinical report of cocaine abuseassociated cardiac toxicity appeared in 197&8 and since 1982, 41 additional casesp-24 have been reported (42 total cases) which describe pathologic cardiac events temporally associated with’ recreational cocaine use. Of these 42 cases, seven ended in death. 1oZ’1,18,20,22*23 Similar anecdotal reports’appear more frequently in the print and electronic media. Additionally, one instance of acute myocardial infarction associated with topical cocaine for nasal surgery has been reported.25 Several reviews, varying in depth and emphasis, have explored the cocaine-cardiac connection.6,26”2

Historical Summary Cocaine is the major drug of abuse in the United States, excluding alcohol, and the problem continues to grow.“2 It is the most addicting substance known, and dependence can occur in days. Its use by young people has doubled since the 197Os, while abuse of other drugs such as marijuana has markedly decreased. At least 10 million persons in the United States use cocaine on a regular basis.3 Before 1982, the autopsy findings in cocaine-associated deaths were nonspecific and similar to those seen with other drug abuse overdoses: pulmonary edema and generalized visceral congestion,4z5 with little or no mention of cardiac pathology either clinically before death or histologically at autopsy. It is likely that cardiac effects play only a minimal role in most acute cocaine fatalities (cocaine poisoning),6 which are characterized by generalized central nervous system toxicity (agitation, hallucinations, diaphoresis, hyperthermia, seizures) accompanied by hypertension and sinus tachycardia.7 Ventricular arrhyth-

Pharmacology The effect of cocaine is an intense euphoria that may last only minutes.’ The aftereffect is one of depression and craving for more cocaine. Alcohol, sedatives, opioids, and marijuana are often taken concurrently to combat anxiety and irritability. Systemic effects of cocaine include increased strength of cardiac contractions, increased blood pressure and heart rate, dilated pupils, and increase in body temperature. Tolerance to the respiratory and cardiac stimulatory effects of cocaine does occur. Adverse Effects Chronic use of intranasal cocaine commonly causes ulceration or perforation of the nasal septum. Users are often debilitated due to lack of sleep and poor nutrition, and may present a disordered pain/anxiety/stress response. Acute cocaine toxicity includes tachycardia, hypertension, hyperthermia, and arrhythmias, and is followed by seizures and cardiopulmonary collapse. Stroke, coma, myocardial infarction, and sudden death have been observed. Table 1, adapted in part from O’Brien’ and Plum and Posner,’ outlines the mild and severe signs and symptoms of cocaine toxicity.

* Professor and Chairman, Pharmacology Section, University of Southern California School of Dentistry, Los Angeles. t Professor and Chairman, Anesthesia and Medicine Section, University of Southern California School of Dentistry, Los Angeles. $ Professor of Oral and Maxillofacial Surgery and Chairman of Hospital Dentistry, Oregon Health Sciences University, Portland. Address correspondence and reprint requests to Dr Pallasch: University of Southern California, School of Dentistry, University Park MC-0641, Los Angeles, CA 90089-0641.

0 1989 American geons 0278-2391/89/471

Association

of Oral and Maxillofacial

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PALLASCH,

Analysis

of Case Reports

Forty-two case reports describe a temporal association between cardiac pathology and recreational cocaine use.8-24 The average reported age was 31 years (range 19 to 44 years), with 37 men and five women. When reported, the route of cocaine administration was intranasal (21), intravenous (9), and inhalation (3). Time of onset from cocaine administration to the cardiac event varied as follows: instant onset (7), 30 to 60 minutes (6), 1 to 3 hours (7), 3 to 6 hours (.5), and 24 hours (1). The vast majority of victims had no prior history of cardiac disease, and many had no predisposing factors such as family history of heart disease, smoking, or hyperlipidemia. The primary cardiac events were acute myocardial infarction and attendant arrhythmias (33, with five deaths), arrhythmias alone (five, with two deaths), myocarditis (I), cardiomyopathy (2), and cardiac ischemia (1). Thirty-two individuals received coronary arteriography, with one half displaying some degree of atherosclerotic coronary artery occlusion and the other half being free of such pathology. Table 2 summarizes the 42 reports in the literature to date. Autopsy

Findings

Only three of the seven patients who died who were included in this survey were studied by autopsy. In one case, death was due to platelet thrombosis.20 In the two other cases,22 one death was associated with scattered foci of myocardial fibrosis coupled with eosinophilic infiltration; whereas the other did not involve any areas of myocardial fibrosis or necrosis, and death was attributed to cardiac arrhythmia. Recently, two studies examined cardiac autopsy material from persons with cocaine-associated Table 1. Toxicity

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Signs and Symptoms of Cocaine

General

Ulceration or perforation of the nasal septum occur with intranasal use only. The occasional user usually appears to be healthy; the chronic user often is debilitated due to lack of sleep and poor nutrition, and commonly has poor personal hygiene and an unkempt physical appearance. Mild Hyperactive, aggressive, sometimes paranoid but often euphoric, repetitive behavior; dilated pupiles; tremor; hyperthermia; tachycardia; arrhythmia Severe Twitching, irregular breathing, tachycardia, arrhythmia, occasionally convulsions, cardiorespiratory collapse

Table 2. Cocaine=Related Cardiac Events 19784 980 Acute myocardial infarction with arrhythmias Arrhythmias alone Myocarditis Cardiomyopathy Myocardial ischemia Total cardiac events

33 (5 deaths) 5 (2 deaths) 1 2

I 42 (7 deaths)

Data are from 42 incidents, 37 men, five women, average age 31 years (range, 19 to 44 years). Coronary arteriography on 32 individuals revealed a degree of coronary artery occlusion in 16, and no pathology in 16.

deaths (deaths due to general cocaine toxicity or from other causes while cocaine was present in the body) and controls who died from either trauma or sedative-hypnotic drug overdose. Tazelaar et a13’ found cardiac contraction band necrosis in 93% of cases of cocaine-associated death compared with 45% in deaths from sedative-hypnotic overdose. In two cases large numbers of eosinophils were present. Karch and Billingham found myocardial contraction band necrosis in 93% of 30 cases of cocaine-induced sudden death (described as diffuse and abundant in more than 50%), compared with less than 50% in a control group of sedativehypnotic deaths (with less than 10% described as diffuse or abundant). Cardiotoxicity

Effects

Cocaine has two well-established effects that may relate to its cardiotoxicity: 1) local anesthetic activity with quinidine-like effects on the heart, and 2) inhibition of the reuptake of norepinephrine in adrenergic nerve terminals. Quinidine-like type I antiarrhythmic agents may depress the myocardial conduction system and allow for ectopic foci generation. High sympathetic nerve activity in the heart increases heart rate, myocardial contractility, and blood pressure, which results in greater myocardial oxygen requirements.6,22 Such sympathetic nerve activity also initially causes coronary artery vasoconstriction, which may persist if autoregulatory mechanisms are impaired by cocaine.28 In anesthetized dogs, intravenous cocaine (200 mg) causes prolonged and profound myocardial ischemia due to increased coronary artery resistance and decreased blood flo~.~~ The cardiac sympathetic nervous system may be involved in ventricular arrhythmias during myocardial infarction and in sudden death during psychological stress,6 and cocaine potentiates ventricular tachycardia in dogs treated with norepinephrine infusion after acute myocardial infarction.34 A confounding variable is the inclusion of

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lidocaine , procaine, quinine, amphetamines, phencyclidine, heroin, caffeine, lactose, and antihistamines in street cocaine in order to dilute (“cut”) the drug. “J* Rarely is the true concentration of ingested cocaine known, and some of these adulterants have cardiac effects of their own. Also the number of cocaine-induced deaths in general have increased greatly since 1983 as the purity of street cocaine has steadily improved.26 Discussion Cocaine-associated myocardial ischemia and infarction, cardiac arrhythmias, cardiomyopathy, and myocarditis are established by case report studies. These reports involve relatively young individuals (aged 19 to 44 years) in whom untoward cardiac events are unanticipated. Approximately one half of these individuals had evidence of preexisting coronary artery disease and one half did not. The onset of these cardiac events from cocaine ingestion ranged from immediate to 24 hours later. The cocaine dosages used were not generally reliably reported other than being stated as “recreational.” The etiology of cocaine-induced cardiotoxicity is unknown. It may involve excess catecholamines, myocardial oxygen supply imbalance, quinidinelike depression of myocardial contractility and subsequent ectopic foci generation, allergic sensitization, coronary artery spasm, coronary thrombosis, or myocardial contraction band necrosis.35-U Probably, other yet-unknown factors are also involved. Chemical adulterants of street cocaine preparations may also play a role. Cardiotoxic events associated with recreational cocaine use appear to be relatively rare at present but are totally unpredictable. The presence or absence of a history of cardiovascular disease or associated risk factors appears to be unreliable. The patient using cocaine may be difficult to detect. As a minimal precaution, any individual suspected of cocaine use must be considered at risk for a potentially fatal adverse cardiac event. Clinical Considerations Because of the numerous unknowns and the relative rarity of sudden death associated with cocaine use, clinical considerations, of necessity, must be speculative and pragmatic. We make the following suggestions. For the occasional asymptomatic user with a negative physical examination: 1) avoid outpatient general anesthesia, if possible; 2) use medical consultation, if indicated; 3) consider a benzodiazepine for conscious sedation plus local anesthesia (benzo-

diazepines are used in the treatment of both mild and severe cocaine poisoning2); 4) consider intraoperative electrocardiographic, pulse, and blood pressure monitoring; and 5) warn the patient preoperatively of possible serious morbidity or mortality (informed consent). For the chronic user with evidence of debilitation and mild systemic effects (Table l), follow the occasional-user protocol, with emphasis on medical consultation and consideration of hospitalization. For the chronic user with severe cocaine toxicity, restrict treatment to emergency care in the hospital under close medical supervision. Summary Cocaine may induce totally unexpected cardiotoxicity in young individuals at some time distant from the cocaine ingestion. Commonly, such individuals are asymptomatic for coronary artery disease; some have no demonstrable coronary artery disease even after the cardiac event. Those who use cocaine must be considered at risk of cardiotoxicity at any time after recent cocaine ingestion. Guidelines are suggested for clinical management in oral and maxillofacial surgery. References 1. O’Brien CP: Drug abuse and dependence, in Wyngaarden JB, Smith LH Jr (eds): Cecil Textbook of Medicine (ed 18). Philadelphia, PA, Saunders, 1988, pp 54-55 2. Plum F, Posner JB: Disturbances of consciousness and arousal, in Wyngaarden JB, Smith LH Jr (eds): Cecil Textbook of Medicine (ed 18). Philadelphia, PA, Saunders, 1988, p 2069 3. Haddad LM: Cocaine abuse: Background, clinical presentation, and emergency treatment. Intern Med 7:67, 1986 4. Nakamura GR, Noguchi TT: Fatalities from cocaine overdoses in Los Angeles County. Clin Toxic01 18:895, 1981 5. Wetli CV, Wright RK: Death caused by recreational cocaine use. JAMA 241:2519, 1979 6. Gradman AH: Cardiac effects of cocaine: A review. Yale J Biol Med 61:137, 1988 7. Jonsson S, O’Meara M, Young J: Acute cocaine poisoning: Importance of treating seizures and acidosis. Am J Med 75: 1061, 1983 8. Benchimol A, Bartall H, Desser KB: Accelerated ventricular rhythm and cocaine abuse. Ann Intern Med 88:519, 1978 9. Coleman DL, Ross TF, Naughton JL: Myocardial ischemia and infarction related to recreational cocaine use. West J Med 136444, 1982 10. Nanji AA, Filipenko JD: Asystole and ventricular fibrillation associated with cocaine intoxication. Chest 85:132, 1984 11. Kossowsky WA, Lyon AF: Cocaine and acute myocardial infarction: A probable connection. Chest 86:729, 1984 12. Schachne JS, Roberts BH, Thompson PD: Coronary artery spasm and myocardial infarction associated with cocaine use. New Enzl J Med 310:1665. 1984 13. Howard RE, H&ter DC, Davis GJ: Acute myocardial infarction following cocaine abuse in a young woman with normal coronary arteries. JAMA 254:95, 1985

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