Ephedrine abuse causing acute myocardial infarction

Ephedrine has both cardiovascular and central nervous system effects, but, although the cardiovascular risks of major psychostimulants such as cocaine are well known,³ little has been reported for ephedrine. We report a patient who injected himself intravenously with ephedrine, sustaining diffuse myocardial injury which resolved with inotropic support and ventilation.

On examination he was conscious but tachypnoeic and cyanosed. He was afebrile, tachycardic (pulse, 140 beats/min), normotensive (110/70 mmHg) and hypoxic (Pao₂, 49 mmHg), with hypocapnia (Paco₂, 33 mmHg), a mild alkalosis (pH, 7.45) and a pronounced leukocytosis (44 x 10⁶ cells/L). He had a reduced cardiac output (2.2 L/min; normal range, 4.5-6.5 L/min), with a pulmonary artery occlusion pressure (an estimate of left atrial pressure) of 30 mmHg. There was bilateral "bat's wing" opacification on chest x-ray, consistent with a clinical diagnosis of pulmonary oedema.

Within an hour of admission and treatment with diuretic and oxygen, further deterioration with cardiogenic shock necessitated intubation, ventilation and admission to an intensive care unit. Initially, the lungs were poorly compliant (49 mL/cmH₂O; normal range, 70-100 mL/cmH₂O) and the alveolar-arterial (A-a) O₂ gradient was elevated (260 mmHg; normal range, < 50 mmHg when on 80% O₂). He received continuous inotropic support with adrenaline, initially at 38 µg/min, which was steadily reduced over three days. By Day 3, his cardiac output was 5.5 L/min without inotropes. His respiratory function and gas exchange improved steadily and he was extubated on Day 5.

Results of microbiological investigations (tracheal aspirate, blood culture and urine culture) were negative and antibiotics were not given.

On admission, electrocardiograms revealed widespread ST-segment depression with T-wave inversion, consistent with subendocardial infarction and ischaemia. A posterior infarction could not be excluded. The peak serum creatine kinase (CK) level was 2360 U/L (normal range, 20-130 U/L) (CK-MB isozyme fraction, 6.1%; normally < 2%), with rises in serum levels of aspartate aminotransferase (to 222 U/L [normal range, < 45 U/L]) and lactate dehydrogenase (to 612 U/L [normal range, 110-230 U/L]). A technetium Tc 99m perfusion scan of the myocardium showed mild tracer uptake in the left myocardium and more intense uptake in the posterolateral wall, consistent with diffuse myocardial damage and an acute posterolateral infarction.

Echocardiography soon after admission showed severe left ventricular dysfunction in all areas except the apex (which showed near-normal contractility), with a poor overall ejection fraction. There was mild mitral regurgitation with no vegetations. Right ventricular function was normal. On Day 6, mild to moderate impairment of left ventricular function was still present, maximum at the base, with mild ventricular dilatation.

The patient continued to improve and was discharged from hospital nine days after admission.

Laboratory analysis of the unused white powder identified only ephedrine.

On review one month later the patient was symptom-free. The resting electrocardiogram showed non-specific ST-segment and T-wave changes. Exercise testing, carried out according to the Bruce protocol,⁴ was 13.5 min in duration and limited by fatigue. His peak heart rate was 192 beats/min, with no chest pain or ST-segment or T-wave changes. He attained an estimated oxygen consumption of 49 mL/kg per min (normal range, 50-70 mL/kg per min) and an aerobic capacity of 106% of the predicted value.

At two months, echocardiography showed normal left ventricular function but persistent trivial mitral regurgitation with a minor prolapse of the anterior leaflet. The patient was counselled about the health risks (such as the risk of bacterial endocarditis) of continuing to inject illegally obtained drugs.

The stimulatory central nervous system effects of ephedrine -- increased arousal, restlessness and insomnia -- have been recognised for many years. Preparations of the herb ephedra were used in ancient Chinese medicines, and ephedrine, the active alkaloid, was identified in the late 19th century.⁵ Ephedrine is a direct agonist of both alpha and beta sympathetic receptors and an indirect adrenoreceptor agonist, causing release of noradrenaline from presynaptic sympathetic nerve terminals. Its cardiovascular effects include tachycardia, increased inotropy, arterial vasoconstriction and hypertension,⁶ and these are the effects for which it is used therapeutically. Amphetamine and pseudoephedrine have similar actions, although amphetamine has more pronounced central nervous system effects.⁷

Ephedrine is widely available, but despite the potential for abuse that this creates there are few reports of its cardiovascular risks.

Bruno et al. described two cases of intracranial haemorrhage and one of a thalamic infarct following excessive ephedrine ingestion,⁶ highlighting the potential dangers of non-prescribed self-administration of this drug. Chronic cardiomyopathy was documented after long-term ingestion of ephedrine in a cough mixture.⁸ Myocardial injury occurred after ephedrine given therapeutically for hypotension during labour,⁹ and coronary artery spasm leading to myocardial injury has been described with pseudoephedrine ingestion.¹⁰

The mechanism of the myocardial injury caused by ephedrine overdose is probably similar to that caused by cocaine -- intense diffuse vasoconstriction of both the coronary and the systemic arterial systems, decreasing myocardial perfusion, increasing afterload, and increasing myocardial oxygen utilisation.³ Although severe hypertension would be expected with ephedrine overdose, and may have been present in our patient soon after the injection of ephedrine, on presentation he had severe acute left ventricular failure with a consequent fall in contractility and blood pressure. This necessitated inotropic support rather than the use of vasodilators.

Various other factors may have contributed to the myocardial injury in our patient. There may have been contaminants in the syringe, and the injection of insoluble particulate matter may have caused vascular occlusion. This could have been compounded by catecholamine-enhanced platelet aggregation induced by ephedrine. Further, although no other agents were identified in the remaining unused powder, the original injection may have included another myotoxin. Pre-existing coronary artery disease was unlikely in an otherwise healthy young non-smoker. A coronary angiogram was not performed. Although the leukocytosis was pronounced, this was consistent with the severe physiological stress.

Nevertheless, in the absence of any other antecedent events or prior myocardial disease, this case report strongly suggests that the acute myocardial infarction was precipitated by the self-injection of ephedrine. "On the street", small quantities of a cheaper drug such as ephedrine may be mixed with stimulants such as amphetamine. This case illustrates the risks associated with the total substitution of ephedrine and the subsequent injection of what is likely to have been a high dose of this drug.

1. Australian Social Issues Research 1991. Report on the national campaign against drug abuse. Sydney: Social Issues Household Survey 1985-1991. Canberra: AGPS, 1991.
2. Staysafe Committee of NSW 1992. Staysafe 19: Alcohol and other drugs on NSW roads 1. The problem and countermeasures. Sydney: NSW Parliament, 1992.
3. Goldfrank LR, Hoffman RS. The cardiovascular effects of cocaine. Ann Emerg Med 1991; 20: 165-175.
4. Bruce RA. Exercise testing of patients with coronary artery disease. Principles and normal standards for evaluation. Ann Clin Res 1971; 3: 323-332.
5. Kalix P. The pharmacology of psychoactive alkaloids from Ephedra and Catha. J Enthnopharmacol 1991; 32: 201-208.
6. Bruno A, Nolte KB, Chapin J. Stroke associated with ephedrine use. Neurology 1993; 43: 1313-1316.
7. Gawin FH, Ellinwood EH. Cocaine and other stimulants: actions, abuse and treatment. N Engl J Med 1988; 318: 1173-1182.
8. To LB, Sangster JF, Rampling D, Cammens I. Ephedrine-induced cardiomyopathy. Med J Aust 1980; 2: 35-36.
9. Menegakis NE, Amstey MS. Case report of myocardial infarction in labour. Am J Obstet Gynecol 1991; 165: 1383-1384.
10. Weiner I, Tilkian AG, Palazzolo M. Coronary artery spasm and myocardial infarction in a patient with normal coronary arteries: temporal relationship to pseudo-ephedrine ingestion. Cathet Cardiovasc Diagn 1990; 20: 51-53.

Reprints will not be available from the authors.
Correspondence: Dr J G L Cockings, Consultant Intensivist, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, QLD 4102.
E-mail: J.Cockings@mailbox.uq.edu.au

Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>".
<URL: http://www.mja.com.au/>