The Growing Danger from Caffeine Supplements: Life-threatening Caffeine Overdose

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Dear Editor, Caffeine (1,3,7-trimethylxanthine), naturally occurring in plants, is widely popular as a central nervous system (CNS) stimulant used frequently in foods, beverages, medical products, and preworkout supplements worldwide. In recent times, the consumption of caffeine supplements, especially pure caffeine tablets, has been steadily on the rise, driven by the goal of improving concentration and weight loss. Caffeine is considered safe at normal doses (400 mg/day for adults). Higher doses can lead to the stimulation of the cardiovascular, central nervous, and gastrointestinal systems. A lethal serum caffeine concentration is >80 mg/L; however, evidence suggests that even below this concentration, there may be sensitive individuals experiencing fatal outcomes or serious toxicity. The relationship between serum concentrations of caffeine and the clinical effects it induces is reported to be weak, likely due to pharmacokinetic and pharmacodynamic variations among people.[1,2] Even lower doses can be lethal in susceptible individuals.[3,4] Our patient developed a life-threatening arrhythmia and seizure by consuming life-threatening doses of caffeine supplement with unclear consumer instructions to increase preexamination concentration. An 18-year-old male patient with a body mass index of 31 kg/m², reportedly ingested 50 tablets of caffeine (each tablet containing 200 mg of caffeine) purchased online (branded as “Caffeine 200 mg, 100 tb Nature’s Supreme”), as per information provided by his family. Approximately 1 h after ingestion, the patient felt faint at home and was brought to the emergency department (ED). On arrival at the ED, the patient exhibited excessive sweating, agitation, and clouded consciousness (Glasgow Coma Scale score: 7), with a blood pressure of 80/44 mmHg, heart rate of 164 beats/min, body temperature of 39°C, pulse oxygen saturation of 82% in room air, and a respiratory rate of 28 breaths/min. Shortly after admission to the ED, the patient experienced cardiac arrest due to ventricular fibrillation (VF) and was defibrillated three times. During resuscitation, 150 mL of intravenous 20% lipid was administered. Following a total of 5 min of cardiopulmonary resuscitation, the patient’s spontaneous circulation was restored. After the return of spontaneous circulation, due to the presence of wide complex tachycardia, intralipid therapy was repeated. In addition, activated charcoal was administered. Following resuscitation, the patient, with metabolic acidosis and elevated lactate levels, underwent hemodialysis. The patient experienced two generalized tonic–clonic seizures, for which 5 mg of midazolam was administered. Considering the observed hypokalemia and hyperglycemia in the patient’s investigations, potassium replacement and insulin infusion were administered alongside hydration. The patient had also mild impairment in kidney and liver function tests and leukocytosis. Sodium levels were normal. However, due to unavailability in our hospital, serum caffeine levels could not be assessed. The patient was admitted to the intensive care unit (ICU) with hypotension, and an electrocardiogram revealed wide QRS polymorphic tachycardia. An additional intralipid therapy was administered because the patient was still hemodynamically unstable. During the patient’s ICU stay, no convulsive seizures were observed, and the body temperature remained within normal limits. After 48 h of admission, the patient was successfully extubated without neurologic sequelae. On the 5th day of admission, the patient, who exhibited a favorable clinical and hemodynamic status, was discharged from the ICU in an alert, oriented, and cooperative state. Ingestion exceeding 1–2 g of caffeine per day can lead to toxic symptoms requiring hospitalization, and a dosage of 5 g or more may result in cardiovascular failure, organ dysfunction, and fatal outcomes. Our patient ingested 10 g of caffeine all at once to enhance attention. Despite experiencing cardiac arrest with malignant arrhythmia, prompt and effective intervention, guided by information from close associates, prevented the development of organ failure and neurologic sequelae, allowing the patient to survive. The relatively young age and overall good health of our patient contributed to the favorable outcome. Caffeine intoxication can manifest as hypertension, hypotension, tachycardia, hypokalemia, hyponatremia, hypocalcemia, hyperglycemia, rhabdomyolysis, agitation, cerebral edema, seizures, lactic acidosis, malignant arrhythmias, and cardiac arrest. Deaths often result from VF.[2] Caffeine serves as an antagonist to adenosine receptors, which induces the release of endogenous catecholamines. This leads to positive inotropic and chronotropic effects and stimulation of the CNS. Excessive catecholamine release also leads to electrolyte imbalances, leukocytosis, hyperglycemia, and excessive pyruvate production.[2,3,5] Plasma lactate concentrations may be strongly correlated with caffeine concentrations and may help determine the severity of caffeine poisoning.[6] Caffeine is rapidly absorbed after oral ingestion, and its elimination half-life varies from person to person. Obesity significantly slows down the elimination of caffeine.[7] Decontamination with activated charcoal may be administered within 4 h after caffeine intake to reduce the serum levels of active metabolites through enterohepatic circulation.[2,8,9] There are case reports in the literature suggesting the efficacy of intralipid therapy in caffeine intoxication, whether used in conjunction with hemodialysis or as a standalone treatment.[3,10] Although the exact mechanism of action is not fully understood, intravenous lipid therapy is purported to remove amphiphilic caffeine molecules from the heart and brain through a mechanism referred to as the “lipid sink.”[2,3,5] Our patient, who was obese, received activated charcoal after presenting within the initial hours following oral intake. Subsequent therapeutic interventions included intralipid administration, contributing positively to the return of spontaneous circulation as well as hemodialysis. In conclusion, the popularity of caffeine tablet use is steadily increasing among the youth. Early diagnosis and rapid and effective intervention are crucial in saving lives in cases of caffeine toxicity. Guidelines for the management of caffeine overdose are not yet available, and decisions should be made on a case-by-case basis. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Contribution details The manuscript has been read and approved by all the authors, that the requirements for authorship as stated earlier in this document have been met, and that each author believes that the manuscript represents honest work. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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