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Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products

Marianne E Cannon, Clive T Cooke and James S McCarthy
Med J Aust 2001; 174 (10): 520-521.

Notable Cases

Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products

We describe a 25-year-old woman with pre-existing mitral valve prolapse who developed intractable ventricular fibrillation after consuming a "natural energy" guarana health drink containing a high concentration of caffeine. This case highlights the need for adequate labelling and regulation of such products.

Marianne E Cannon, Clive T Cooke and James S McCarthy

MJA 2001; 174: 520-521

Clinical record - Discussion - References - Authors' details
- - More articles on Toxicology


  While caffeine is widely used in most Western societies, caffeine toxicity is rare, and certainly rarely diagnosed. Case reports of death from caffeine toxicity number approximately 20 in the medical literature.1-3 We report a case of sudden death in a young woman which was associated with ingestion of caffeine present in guarana, a widely available health supplement marketed as a "natural" source of energy, and targeted to young people in advertising.



Clinical record

A 25-year-old woman had been working at a bar where she was seen to collapse. Police at the scene started cardiopulmonary resuscitation shortly afterwards. An ambulance arrived several minutes later and she was defibrillated according to ambulance protocol, with a total of 12 defibrillation attempts. She arrived at the emergency department in ventricular fibrillation and was resuscitated according to advanced cardiac life support guidelines for a further 20 minutes. At no stage did she regain a spontaneous cardiac output.

Further history (which became available later) indicated that the patient had been diagnosed with mitral valve prolapse. She had been referred to a cardiologist because of palpitations. He had raised the issue of caffeine intake, and she had agreed to limit this to a cup of tea daily. Her previously recorded resting electrocardiogram was normal, with no evidence of QT prolongation.

On the day of her death she had been given a 55 mL squirt bottle of "Race 2005 Energy Blast with Guarana and Ginseng", which she had nearly emptied. Other staff working at the bar had also been given bottles of Race 2005. She had not consumed other caffeine-containing substances.

At autopsy, the patient was found to have sclerosis and myxoid change of the mitral valve leaflets. A toxicological screen for all common prescribed and non-prescribed drugs (including opiates, cannabis, amphetamines, and cocaine metabolites) was performed. Assay methods included gas chromatography and mass specrometry (GC-MS) and immunoassay. Caffeine was detected by GC-MS; the toxicology screen was negative for other substances. High pressure liquid chromatography revealed a caffeine concentration of 19 mg/L (non-preserved) in aortic blood. The caffeine concentration in the bottle of Race 2005 Energy Blast was assayed at the Chemistry Centre of Western Australia and yielded a level of 10 g/L, which is more than 60 times the concentration of caffeine in cola beverages (see Box).4 A similar bottle was later shown to have a caffeine concentration of 19 g/L.



Discussion

The wide availability and toxicology of "natural" tonics and remedies and the regulation of such substances has been the subject of vigorous debate in both the lay press and the medical literature.6-10

Guarana is produced from the seeds of the guarana plant (Paullina cupana), a creeping Amazonian shrub. The seeds are black "like an eye" and contain 3.6%-5.8% caffeine.11 The substance is named after the Guarani Amazonian tribe, who originally used the seeds to brew a drink.11 In Brazil, guarana is commonly used as an astringent, a flavouring, and as a stimulant, and it is increasingly being used in similar products internationally. Such products are widely available at pharmacies and natural food outlets, and are marketed as natural sources of energy.

Caffeine is a natural alkaloid methylxanthine. Ninety-nine per cent is absorbed after oral ingestion, the blood concentration peaks 1-1.5 hours after ingestion, and its half-life in adults is 3-6 hours. Caffeine is metabolised by the P450 hepatic enzyme system.12 The pharmacodynamic profile of caffeine is similar to that of theophylline, another methylxanthine, in that it inhibits the adenosine receptor and acts as a phosphodiesterase inhibitor.12 At high serum levels, enzyme saturation occurs, and elimination follows zero-order kinetics, with constant elimination regardless of serum level.12 Caffeine increases intracellular calcium concentrations, causes noradrenaline release and sensitises dopamine receptors. The pharmacological effects of caffeine include central nervous system (CNS) and cardiac stimulation, as well as coronary vasodilatation. It relaxes smooth muscle, stimulates skeletal muscle, has a weak diuretic action, and its metabolic effects include hypoglycaemia.

While toxicity generally occurs at serum levels over 25 mg/L, the correlation between concentration and clinical effects is poor.4 The measured concentration of 19 mg/L in our patient may reflect postmortem changes in drug level, or an enhanced sensitivity to caffeine toxicity in this patient. The measured concentration is the equivalent of what would result from drinking approximately 15-20 cups of coffee.4 The toxic effects of caffeine include vomiting and abdominal pain followed by CNS symptoms, including agitation, altered conscious state, rigidity and seizures.4 Cardiovascular effects include supraventricular and ventricular tachyarrhythmias, and significant metabolic disturbances may occur, including hypokalaemia and hyperglycaemia.

Suggested management for caffeine toxicity, in addition to general supportive measures, includes multidose charcoal therapy, and extracorporeal elimination by charcoal haemoperfusion.13 One proposed mechanism for the seizures and cardiac arrhythmias is the blockade of adenosine receptors.12 Thus, there is a theoretical rationale for the use of adenosine in this setting, particularly if seizures are refractory to benzodiazepine agents.14 Likewise, as there is adrenergic stimulation, parenteral -blocker therapy (propranolol or esmolol) should be considered for treating ventricular arrhythmias.15

Most deaths associated with caffeine intoxication have occurred after overdose with diet pills and stimulants, and most have occurred in young patients without known underlying heart disease or variant of normal, such as mitral valve prolapse. At least two case reports document sudden death in patients who "walked" into an emergency department.14

After the death of our patient, the Western Australian Coroner recommended that Race 2005 Energy Blast be removed from the local market, and the product was recalled nationally by letter to distributors in August 1999. However, many other products containing guarana (eg, "energy" tablets containing 35 mg of caffeine each, as well as a variety of energy drinks) remain available Australia-wide. With the growing use of guarana-based products containing high levels of caffeine, there is an obvious potential for lethal overdose.

Our patient had a relatively common cardiac abnormality, present in 2.4% of the population.16 While mitral valve prolapse has been associated with sudden death, the risk of this is low.17 Malignant arrhythmias may occur in the absence of cardiac stimulants, but the association of arrhythmia with drugs that increase cardiac irritability is well known. The role of caffeine in this woman's death is supported by her history of palpitations associated with caffeine ingestion, a history that had prompted her cardiologist to advise her to limit her caffeine intake. In this patient's case the Coroner found that the high level of caffeine was associated with the development of an intractable arrhythmia.

This case highlights the need for more careful regulation of "natural" products, including warnings for patients with underlying health problems, and clear labelling to document the presence of any constituents with potentially toxic effects. It also shows the need for medical practitioners to be familiar with the more widely used "natural"-remedy substances, and their toxicological profile.

Acknowledgements: We thank Dr Julian Stella and Dr Peter Sprivulis for their assistance in the preparation of this manuscript.

Disclosure: We did not receive any financial or other support for this work, and have no financial or professional relationships that may pose a conflict of interest.


References

  1. Garriott JC, Simmons LM, Poklis A, Mackell MA. Five cases of fatal overdose from caffeine-containing "look-alike" drugs. J Anal Toxicol 1985; 9: 141-143.
  2. Mrvos RM, Reilly PE, Dean BS, Krenzelok EP. Massive caffeine ingestion resulting in death. Vet Hum Toxicol 1989; 31: 571-572.
  3. Walsh I, Wasserman GS, Mestad P, Lanman RC. Near-fatal caffeine intoxication treated with peritoneal dialysis. Pediatr Emerg Care 1987; 3: 244-249.
  4. Lewin NA. Caffeine. In: Goldfrank LR, editor. Goldfrank's toxicologic emergencies. 6th ed. Stamford: Appleton & Lange, 1998: 555-562.
  5. Abbott PJ. Caffeine: a toxicological overview. Med J Aust 1986; 145: 518-521.
  6. Angell M, Kassirer JP. Alternative medicine — the risks of untested and unregulated remedies. N Engl J Med 1998; 339: 839-841.
  7. De Smet PA. Should herbal medicine-like products be licensed as medicines? BMJ 1995; 310: 1023-1024.
  8. Ernst E. Harmless herbs? A review of the recent literature. Am J Med 1998; 104: 170-178.
  9. Shaw D. Risks or remedies? Safety aspects of herbal remedies in the UK. J R Soc Med 1998; 91: 294-296.
  10. Kessler DA. Cancer and herbs. N Engl J Med 2000; 342: 1742-1743.
  11. Duke JA. CRC Handbook of medicinal herbs. Boca Raton: CRC Press, 1985.
  12. Serafin WE. Drugs used in the treatment of asthma. In: Hardman JG, Limbird LE, editors. Goodman & Gilman's the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996.
  13. Nagesh RV, Murphy KA. Caffeine poisoning treated by hemoperfusion. Am J Kidney Dis 1988; 4: 316-318.
  14. Shum S, Seale C, Hathaway D, et al. Acute caffeine ingestion fatalities: management issues. Vet Hum Toxicol 1997; 39: 228-230.
  15. Pentel P. Toxicity of over-the-counter stimulants. JAMA 1984; 252: 1898-1903.
  16. Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999; 341: 1-7.
  17. Duren DR, Becker AE, Dunning AJ. Long-term follow-up of idiopathic mitral valve prolapse in 300 patients: a prospective study. J Am Coll Cardiol 1988; 11: 42-47.

(Received 5 Oct 2000, accepted 13 Mar 2001)



Authors' details

Department of Emergency Medicine, Fremantle Hospital, Fremantle, WA.
Marianne E Cannon, MB BS, FACEM, Emergency Medicine Staff Specialist.

PathCentre, QEII Medical Centre, Nedlands, WA.
Clive T Cooke, BMedSci, FRCPA, Forensic Pathologist.

University of Western Australia, Department of Medicine, Fremantle Hospital, Fremantle, WA.
James S McCarthy, MB BS, FRACP, Senior Lecturer.

Reprints will not be available from the authors.
Correspondence: Dr M E Cannon, Department of Emergency Medicine, Fremantle Hospital, Fremantle, WA 6959.
mariannecannonAThotmail.com


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Caffeine content of various food, drinks and medicines
     
Substance Defined dose* Concentration

Tea 40mg per cup (approx.) 0.16g/L
Coffee 100mg per cup (approx.) 0.4-1.6g/L
Chocolate (30g) 4mg
Cola 0.15g/L
Diet pills 75-200mg
Race 2005 (30mL "dose") 300-570mg 10-19g/L

*After Lewin4 and Abbott.5
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Marianne E Cannon
Clive T Cooke
James S McCarthy