Refractory ventricular fibrillation caused by caffeine intoxication

Abstract

A 30-year-old female with no history of cardiac or systemic disease presented with incessant ventricular fibrillation (VF) after an intake of 12 g of over-the-counter caffeine tablets for a suicidal purpose. Her VF was refractory, and repeated defibrillations were needed to attain a recovery of sinus rhythms. We then performed percutaneous cardiopulmonary support and therapeutic hypothermia to stabilize her circulation and prevent anoxic brain damage, respectively. A blood examination revealed an extremely high concentration of caffeine (172 mg/L). She fully recovered 16 days after her admission. Our findings reveal the potentially lethal arrhythmogenic nature of caffeine.

<Learning objective: Several reports have described lethal cardiac events with caffeine intoxication. However, clinical observations on patients with pure caffeine intoxication are extremely rare. Since the pharmacological actions and proarrhythmic mechanism of caffeine are not fully understood, intensive treatment against refractory arrhythmia may have an impact upon the prognosis of patients with caffeine intoxication.>

Introduction

It is broadly believed that caffeine can exert cardiotoxicity at overdose intakes. Several reports have described cardiac arrest or acute arrhythmia in individuals with caffeine intoxication [1], [2]. However, clinical observations on patients with pure caffeine intoxication have been strongly limited, hence its cardiotoxicity remains to be elucidated. Here, we provide the first report of a female who took caffeine tablets and presented with refractory ventricular fibrillation (VF).

Case report

The patient was a 30-year-old Japanese woman with no significant personal or family medical history. She had taken 120 tablets of over-the-counter caffeine products, containing 100 mg of caffeine each, in her room. One or two hours after the intake, she vomited and then had a generalized seizure. Her family found her and called an ambulance. On the way to the hospital, she went into cardiopulmonary arrest associated with recurrent VFs. After two instances of shocks with an automated external defibrillator, her rhythm changed to pulseless electrical activity (Fig. 1). However, VFs recurred in the emergency department, and three more rounds of 150-J biphasic counter-shocks achieved a recovery to spontaneous circulation. A 12 lead-electrocardiogram (ECG) after the defibrillation showed a sinus tachycardia with multiple supraventricular premature contractions and diffuse T wave inversions. Laboratory examinations on arrival revealed hyperglycemia (19.3 mmol/L; normal range: 3.9–6.1), hypokalemia (3.0 mmol/L; normal range: 3.6–4.9), and an elevated white blood cell count (19400/mm³; normal range: 4000–8500). Arterial blood gas values under intubation revealed lactic acidosis: lactic acid of 18.5 mmol/L, pH of 6.763, pCO₂ of 41.1 mmHg, base excess of −29.4 mmol/L. Other values of blood tests, including electrolyte concentrations, hepatic enzymes, renal function, and creatine kinase were within normal ranges.

Fig. 1.

An electrocardiogram on the way to our hospital revealed ventricular fibrillations refractory to defibrillation. An arrowhead indicates a counter shock with an automated external defibrillator.

Considering the refractory nature of VFs in this patient, we introduced percutaneous cardiopulmonary support (PCPS). Therapeutic hypothermia was also initiated to prevent hypoxic brain damage. No further VFs recurred after the introduction of these therapies. ECG revealed a sinus tachycardia with heart rate between 100 and 140 beats/min and frequent ventricular premature contractions for the initial 10 h. This then changed to QTc interval prolongation, greater than 630 ms, and diffuse notched T waves (Fig. 2), which resolved to normal on the 10th day (Fig. 3). A transthoracic echocardiography and coronary angiography revealed no abnormalities on the valves or wall motions and no stenosis of the coronary arteries, respectively. The PCPS was successfully removed four days after admission. After a recovery of consciousness, she documented an overdose intake of caffeine tablet obtained via internet for a suicidal purpose. A blood examination, which was sampled at the emergency room, revealed an elevated caffeine concentration of 172 mg/L. She was discharged to her home 16 days after admission without any physical deficits. Exercise tolerance test performed after discharge did not induce any arrhythmias. Ultimately, we confirmed caffeine intoxication caused VFs and subsequent complications.

Fig. 2.

On the day after resuscitation, an electrocardiogram showed QTc interval prolongation, greater than 630 ms, and diffuse notched T waves.

Fig. 3.

On the 10th day, an electrocardiogram showed QTc interval within normal range and biphasic T waves in V2–V4.

Discussion

Our clinical findings strongly indicate that caffeine itself harbors life-threatening, arrhythmogenic potential. Caffeine has a half-life of five hours or more [3], hence the introduction of PCPS after defibrillation was an appropriate therapeutic option in our case. Although VF can arise from various causes of cardiac or extracardiac origins, caffeine intoxication should be screened for in refractory VF cases without underlying cardiac disorders.

Caffeine intoxication has been seen in settings of suicidal attempts with taking tablets of caffeine or accidental overdose intakes of caffeine-containing health supplements or anti-drowsiness drugs [1], [2], [3], [4], [5]. In symptomatic cases, however, caffeine was usually taken in combination with other drugs or alcohol or in association with significant systemic disorders involving the heart, liver, or kidney [4], [6]; these settings could increase the risk of adverse effects or modify caffeine metabolism. Furthermore, cardiovascular manifestations have been unclear among the reported patients because they were often found deceased. Recently, Magdalan et al. reported three cases with pure caffeine intoxication [1]. Two of the cases showed sinus tachycardia (110–150 beats/min), and then one of them developed sudden cardiac arrest with electromechanical dissociation resulting in death. When considering their findings together with ours, cardioexcitatory effects might contribute to arrhythmogenesis in caffeine intoxication. It was unclear whether QT-prolongation we observed arose solely from caffeine toxicity. Post-resuscitation, hypokalemic states and hypothermic therapy may also be considerable reasons in our case. Further accumulation and analyses of symptomatic cases with caffeine intoxication are needed to clarify this issue [7]. Although the pharmacological actions of caffeine are not fully understood, catecholamine-induced activity has been proposed as its proarrhythmic mechanism [8]. Caffeine accentuates catecholamine release and sensitizes dopamine receptors in the myocardium. It also inhibits phosphodiesterase with increased accumulation of intracellular cyclic adenosine monophosphate, which enhances the catecholamine-mediated effect [9]. Furthermore, it facilitates calcium release and prevents calcium uptake by the sarcoplasmic reticulum, increasing intracellular calcium concentrations [10]. Elevated calcium concentrations can generate a delayed afterdepolarization, which can lead to triggered arrhythmias. The lethal blood concentration of caffeine in adult humans is estimated to be around 80 mg/dL. To achieve this concentration, 5–10 g of oral intake at once is needed. However, the purchase of caffeine products is unrestricted in many countries, and lethal doses are available as health supplements or anti-drowsiness agents without prescription. Serious intoxication caused by excessive intakes of caffeine-taurine-containing beverages have also been increasingly reported [2]. How to control the health risks that arise from the unrestricted availability of such chemical agents requires consideration and discussion.

In conclusion, we have detailed the potentially lethal arrhythmogenesis of caffeine in a human case. Intensive treatments against refractory arrhythmia may have an impact upon the prognosis of patients with caffeine intoxication. Further discussions are needed to prevent intoxication with caffeine, which is available unrestricted.