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Cardiac Arrhythmia in a Professional Football Player

Was Ephedrine to Blame?

Charles N. Krome, DO; Andrew M. Tucker, MD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 31 - NO. 12 - DECEMBER 2021


In Brief: The use of over-the-counter dietary supplements has risen dramatically, and adverse events can be severe. Physicians should recognize the dangers that ephedrine-containing supplements present and remain vigilant for sympathomimetic symptoms in young, otherwise healthy, patients. This case illustrates how the use of a popular weight-loss supplement by a 27-year-old professional football player apparently resulted in cardiac arrhythmia requiring direct cardioversion.

In the last decade, over-the-counter dietary supplement use has burgeoned in the general population as well as among athletes from high school to the professional level. The adverse reactions of some supplements are not well known, but the side effects of ephedrine (sometimes called an ephedra alkaloid) have been recently publicized in the popular press and in medical journals.

Ephedrine, through its sympathomimetic properties, is causally related to many adverse events, including cardiac arrhythmias, myocardial infarction, hypertension, cerebrovascular accidents, and death.1-14 Physicians should recognize some of the possible effects of supplement use, as in this case report of a National Football League (NFL) lineman who incurred atrial fibrillation by using an ephedra-containing supplement.

Case Report

A 27-year-old NFL player reported having a racing heart, shortness of breath, and substernal chest tightness while on the sideline of the practice field. The player had no history of heart problems and was taken to the training room for further evaluation by the team physician. As the player left the field, he also described dizziness and light-headedness.

History and exams. His pulse was 132/min and regular, with some respiratory variation and occasional dropped beats. The patient's blood pressure (supine) was 112/90 mm Hg. An electrocardiogram (ECG) rhythm strip taken in the training room (figure 1) demonstrated supraventricular tachycardia with an occasional premature ventricular complex. The patient was instructed to perform a Valsalva's maneuver that provided temporary relief from the tachycardia, which ultimately returned. The player was then taken to the head team physician's office for further evaluation.

A more complete history revealed that the patient had taken two ephedra-containing supplements and two ginseng tablets before this practice, and had done so daily since the beginning of the season. He had no history of significant light-headedness or dizzy spells. His family had no history of cardiovascular disease. At this point, he felt somewhat improved but was still light-headed, especially when standing.

The patient's medical history was unremarkable for hypertension or other cardiovascular disease. His medications included piroxicam for elbow pain, which he had discontinued several days before this incident, and an ephedra-containing supplement and ginseng that he took before every practice. Physical examination revealed that the player was not in acute distress. His pulse was 130/min and regular, blood pressure was 105/80 mm Hg, and his lungs were clear to auscultation bilaterally.

Cardiac exam, lab tests, and diagnosis. Cardiac exam revealed tachycardia with normal S1 and S2, no S3 or S4, and no murmurs, rubs, or gallops. An ECG (figure 2) showed narrow complex tachycardia with a rate of 130/min. Some sawtooth P waves in lead II were suggestive of atrial flutter. The team cardiologist reviewed this finding and believed that this event was induced by the stimulant that the player had taken. The player was discharged with instructions to call the head team physician if he felt any symptoms, including severe shortness of breath, chest pain, light-headedness, or dizziness. A cardiology consultation and echocardiogram were arranged for the next morning.

The following morning, the player awoke with an irregular heartbeat. He stated that his heart was "skipping beats." He denied light-headedness or dizziness, overnight episodes of chest pain, dyspnea on exertion, paroxysmal nocturnal dyspnea, or orthopnea.

Physical exam in the cardiologist's office revealed the following findings: blood pressure, 148/68 mm Hg; pulse irregularly irregular at 68/min; and oxygen saturation of 2021%. Examination of his head, eyes, ears, nose, and throat was unremarkable, and his lungs were clear to auscultation bilaterally. Cardiovascular exam revealed no jugular venous distention at 30°, variable S1 and normal split S2, and no extra heart sounds or murmurs. His abdomen was soft and nontender, without guarding. The patient's extremities were free of clubbing, cyanosis, and edema.

Laboratory studies, including serum chemistry, complete blood counts, and thyroid function tests, were all within normal limits. Transesophageal echocardiogram revealed completely normal heart function. No evidence of valvular disease or an atrial thrombus was seen, and left and right ventricular functions were normal. Based on the player's lack of symptoms for acute myocardial infarction (MI), pulmonary embolus, or thyrotoxicosis and the brief (< 24 hour) nature of the arrhythmia, the cardiologist made the diagnosis of atrial arrhythmia secondary to ephedrine use. The player was urged to undergo immediate cardioversion. A single 360-J biphasic shock restored normal sinus rhythm.

Treatment. Because the player had no evidence of heart disease and had normal laboratory test results, he was instructed to take an aspirin daily, avoid all cardiac stimulants (including caffeine and ephedrine), and continue his normal daily activities. Recurrence of atrial fibrillation would require an antiarrhythmic agent to maintain normal sinus rhythm. Aspirin serves as prophylaxis against blood clot formation, although the player's young age and good cardiac function put him at low risk of thromboembolic events.

Ephedrine and Adverse Events

Many articles1-14 describe the various adverse events that have been associated with ephedrine use. Haller and Benowitz1 reviewed 140 reports of adverse events related to supplements containing ephedra alkaloids. These reports were submitted to the US Food and Drug Association (FDA) between June 1, 1997, and March 31, 1999, and provide examples of severe cerebrovascular and cardiovascular side effects. Most of the cases described patients between the ages of 20 and 50 who were using ephedrine-containing supplements as an adjunct to an exercise or fitness program.

Among these cases was one of a 22-year-old man who collapsed while lifting weights. He had consumed three bottles per day of an ephedra-containing beverage. The patient had consumed one bottle of the supplement before working out that day. Witnesses reported that he had a seizure, and paramedics found him apneic and in ventricular fibrillation. According to the cardiologist who treated him, the combination of ephedrine and beta-agonists (which he took for asthma) likely caused ventricular arrhythmia that resulted in cardiac arrest. The patient experienced anoxic encephalopathy and remained in a vegetative state for several weeks. He eventually was discharged from a rehabilitation facility with significant residual impairment.

Cardiomyopathy. To et al9 described a young woman who presented with congestive cardiomyopathy of unknown origin. She eventually revealed a history of longstanding abuse of products containing ephedrine. Traub et al7 described a case report of a previously healthy 19-year-old male bodybuilder who had an MI after using an ephedrine-containing supplement. This patient had no history of heart disease or drug use, and a cardiac catheterization demonstrated only minimal intimal disease of the distal left anterior descending artery.

Seizures. A report6 of a 22-year-old man who had unexplained seizure activity and unresponsiveness was attributed to an ephedra- and caffeine-containing supplement. This patient's toxicology screenings were all negative, and he had been healthy until the seizures. His only significant medical history included the recent ingestion of this supplement, which is marketed for its alleged energy-producing, fat-burning, and muscle-building effects. Both ephedrine and caffeine are central nervous system stimulants, so his seizures were attributed to these compounds.

Kidney stones. Ephedrine-containing products have even been shown to cause nephrolithiasis in cases of extreme usage. Blau4 reported a case of a 24-year-old male patient who had groin pain, hematuria, and nausea. The patient's history did not reveal evidence of kidney stones, but after further review, he admitted to taking an average of 40 to 120 ephedrine-containing tablets a day for several years. Each tablet contained 25 mg of ephedrine. He stated he took these for the stimulatory effects. Analysis of the passed stone revealed the presence of ephedrine. The 1,000- to 3,000-mg daily ephedrine intake resulted in a significant renal load; ephedrine is 70% to 80% unchanged during urinary excretion.5

Sudden death. Case reports1,3 also note sudden deaths in young patients. One report3 describes a healthy college student who regularly consumed an ephedrine-containing beverage and another2 a 21-year-old man who presented to the emergency department with an initial blood pressure of 220/110 mm Hg and ventricular dysrhythmias. Three of the cases noted in Haller and Benowitz1 resulted in death from cardiac arrest or stroke. These patients had no preexisting medical conditions, but they all used ephedrine-containing products.

The Burgeoning Supplement Problem

Ephedrine is one of a growing number of supplements that has the potential for abuse and serious adverse side effects.

Ephedrine metabolism and interactions. Ephedrine, derived from the ma huang plant, is a sympathomimetic amine with good bioavailability6 and is metabolized by N-demethylation to norephedrine. Ephedrine has a half-life of approximately 7 hours, and the compound increases the bioavailability of naturally released catecholamines at synapses in the brain and heart. In addition, ephedrine stimulates catecholamine receptors directly, acting as a direct sympathomimetic agent.15 This catecholamine stimulation increases heart rate, cardiac output, and peripheral resistance, leading to elevated blood pressure. Sustained ephedrine use may lead to both cardiac hypertrophy and focal myocardial necrosis.9,12,16 Depending on where in the heart such pathology develops, the pacemaker centers may be "short-circuited," and sudden fatal arrhythmias may result.13

Perrotta et al11 reported that ephedrine has been linked to more than 500 known incidences of serious adverse reactions, including 15 fatalities—at least half of which were attributed to MI or cerebrovascular accidents. Constriction of coronary arteries and, in some cases, vasospasm are believed to be the mechanisms of myocarditis and MI.1 As in our case, reentrant arrhythmias are secondary to the adrenergic effects of ephedrine. Ephedrine shortens cardiac refractory periods. In this case, atrial tachycardia progressed to atrial fibrillation overnight, requiring direct cardioversion.

Synergistic interactions. Concurrent use of caffeine exacerbates this pathophysiologic response as the phosphodiesterase inhibitors increase the levels of cyclic adenosine monophosphate and intensify the effect of both ephedrine and catecholamines.17-21 Caffeine acts by competitively antagonizing the receptors for adenosine, a compound released by endothelial cells that dilates blood vessels.1 Thus, adenosine-mediated dilation of blood vessels is blocked, increasing blood pressure.

The use of ephedrine and caffeine supplements as ergogenic aids to enhance performance is supported by evidence from physiologic studies. Bell et al22 found that ingestion of ephedrine and caffeine before supramaximal bouts of exercise led to increased time to exhaustion and increased blood glucose, lactate, and catecholamine levels. Both aerobic and anaerobic performance improves after ingestion of ephedrine and caffeine. As noted, ephedrine acts as a central nervous system stimulant, while caffeine works peripherally by enhancing muscle metabolic processes.

Most recent cases. Steve Bechler, a pitcher for the Baltimore Orioles, died from heatstroke in February 2021 during spring training. His death was at least partially attributed to his consumption of an ephedrine-containing dietary supplement. This event led minor league baseball to ban ephedrine later that month.23 As of this writing, Major League Baseball still has not banned the substance for its own players. Ironically, shortly after the player described in our report was treated for his arrhythmia, ephedrine was banned by the NFL in the fall of 2021.

Spokespersons for Northwestern University in Evanston, Illinois, admitted that several of their football players were using banned supplements containing ephedrine during workouts in August 2021.24 Rashidi Wheeler, a cornerback on Northwestern's football team, collapsed and died during one of those workouts. Canisters of an ephedrine-containing beverage were found in the lockers of several players. One of the team physicians for the school later admitted he knew of Wheeler's use of the supplement and had destroyed the player's medical records.25

Addressing the Supplement Problem

On several occasions, the FDA has attempted to regulate ephedrine-containing supplements,26,27 but its attempts have been opposed by supplement makers and their lobbyists. Physicians must be aware of other ephedrine side effects, including palpitations, anxiety, tremulousness, and agitation, that may alert them to patient use.28-30 Often the patients who are using these products are young, healthy, and active individuals who seek that "natural" edge to help shed several extra pounds, obtain "six-pack abs," or gain some extra energy to get through a workout.

When physicians see young patients who have symptoms suggestive of stimulant use (eg, hypertension), they should inquire about supplements and discourage their use. We strongly recommend that physicians educate themselves and their patients about the associated risks. The recent supplement-related deaths serve as a grim reminder of failure to do so.

References

  1. Haller CA, Benowitz NL: Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2021;343(25):1833-1838
  2. Zahn KA, Li RL, Purssell RA: Cardiovascular toxicity after ingestion of "herbal ecstacy." J Emerg Med 1999;17(2):289-291
  3. Theoharides TC: Sudden death of a healthy college student related to ephedrine toxicity from a ma huang-containing drink. J Clin Psychopharmacol 1997;17(5):437-439
  4. Blau JJ: Ephedrine nephrolithiasis associated with chronic ephedrine abuse. J Urol 192021;160(3 pt 1):825
  5. Doyon S: The many faces of ecstasy. Curr Opin Pediatr 2021;13(2):170-176
  6. Kockler DR, McCarthy MW, Lawson CL: Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2021;21(5):647-651
  7. Traub SJ, Hoyek W, Hoffman RS: Dietary supplements containing ephedra alkaloids, letter. N Engl J Med 2021;344(14):1095-1096; author reply, pp 1096-1097
  8. Bruno A, Nolte KB, Chapin J: Stroke associated with ephedrine use. Neurology 1993;43(7):1313-1316
  9. To LB, Sangster JF, Rampling D, et al: Ephedrine-induced cardiomyopathy. Med J Aust 120210;2(1):35-36
  10. Adverse events with ephedra and other botanical dietary supplements. FDA Med Bull 1994;24:3
  11. Perrotta DM, Coody G, Culmo C: Adverse events associated with ephedrine-containing products—Texas, December 1993-September 1995. JAMA 1996;276(21):1711-1712. Available at https://www.cfsan.fda.gov/~dms/ds-ephe2.html. Accessed November 13, 2021
  12. Wiener I, Tilkian AG, Palazzolo M: Coronary artery spasm and myocardial infarction in a patient with normal coronary arteries: temporal relationship to pseudoephedrine ingestion. Cathet Cardiovasc Diagn 1990;20(1):51-53
  13. Weesner KM, Denison M, Roberts RJ: Cardiac arrhythmias in an adolescent following ingestion of an over-the-counter stimulant. Clin Pediatr (Phila) 120212;21(11):700-701
  14. Maron BJ, Shirani J, Poliac LC, et al: Sudden death in young competitive athletes: clinical, demographic, and pathological profiles. JAMA 1996;276(3):199-204
  15. Theoharides TC (ed): Essentials of Pharmacology. Boston, Little, Brown, 1996
  16. Battig K: Acute and chronic cardiovascular and behavioural effects of caffeine, aspirin and ephedrine. Int J Obes Relat Metab Disord 1993;17(suppl 1):S61-S64
  17. Dulloo AG, Miller DS: Ephedrine, caffeine and aspirin: "over-the-counter" drugs that interact to stimulate thermogenesis in the obese. Nutrition 120219;5(1):7-9
  18. Breum L, Pedersen JK, Ahlstrom F, et al: Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity: a double-blind, multi-centre trial in general practice. Int J Obes Relat Metab Disord 1994;18(2):99-103
  19. Astrup A, Toubro S: Thermogenic, metabolic, and cardiovascular responses to ephedrine and caffeine in man. Int J Obes Relat Metab Disord 1993;17(suppl 1):S41-S43
  20. Astrup A, Breum L, Toubro S, et al: The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet: a double blind trial. Int J Obes Relat Metab Disord 1992;16(4):269-277
  21. Daly PA, Krieger DR, Dulloo AG, et al: Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity. Int J Obes Relat Metab Disord 1993;17(suppl 1):S73-S78
  22. Bell DG, Jacobs I, Ellerington K: Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2021;33(8):1399-1403
  23. Associated Press: Baseball bans ephedra in minors. The Columbus Dispatch, February 28, 2021, p D4
  24. Sports Capsules: Northwestern admits several players used banned supplements. The Columbus Dispatch, January 23, 2021, p D2
  25. Dizon NZ: Doctor destroyed Wheeler's records after death. USA Today, June 4, 2021, p 9C
  26. Future marketing of ephedrine "street drugs" is "irresponsible," FDA tells six companies. Tan Sheet 1997;4(36):9 Available at https://www.fda.gov/medwatch/safety/1997/ephedr.htm. Accessed November 13, 2021
  27. FDA backs away from elements of plan to regulate ephedrine supplements. Am J Health-System Pharm 2021;57(10):922
  28. Bent S, Tiedt TN, Odden MC, et al: The relative safety of ephedra compared with other herbal products. Ann Intern Med 2021;138(6):468-471
  29. Cupp MJ: Herbal remedies: adverse effects and drug interactions. Am Fam Physician 1999;59(5):1239-1245
  30. Ahrendt DM: Ergogenic aids: counseling the athlete. Am Fam Physician 2021;63(5):913-922


Dr Krome is a primary care sports medicine physician with Precision Orthopedic Specialties in Cleveland. Dr Tucker is director of Primary Care Sports Medicine at the University of Maryland in Timonium, Maryland, and assistant professor of family medicine at the University of Maryland in Baltimore. Address correspondence to Charles N. Krome, DO, 228 Manchester Dr, Aurora, OH 44202; e-mail to [email protected].

Disclosure information: Drs Krome and Tucker disclose no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use.


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