Fatal caffeine overdose: Two case reports
Introduction
Caffeine (1,3,7-trimethylxanthine, guaranine) is a plant-derived alkaloid and psychostimulant that is present in tea leaves, coffee, cocoa beans and kola nuts. Caffeine, theophylline, theobromine and paraxanthine are routinely detectable in toxicological samples due to dietary exposure to caffeine. The average cup of coffee or tea in the United States is reported to contain between 40 and 150 mg caffeine [1] although specialty coffees may contain much higher doses [2]. Caffeine undergoes rapid absorption following oral administration. A single 130 mg oral dose in 36 subjects produced peak plasma concentrations of 2.5–6.8 mg/L (mean 4.0 mg/L) within 20–40 min [3]. Approximately, 90% of the caffeine in a cup of coffee is absorbed from the stomach within 20 min with peak plasma concentrations occurring approximately 40–60 min later.
Plasma/blood ratios of 0.93 have been reported and the volume of distribution is 0.5 L/kg [4]. The drug is widely distributed and undergoes placental transfer, which is the reason for limiting dietary intake of caffeine during pregnancy. Caffeine undergoes hepatic metabolism via N-demethylation, acetylation and oxidation. The CYP450 1A2 isoenzyme is largely responsible for the N-demethylation of caffeine to paraxanthine, the major metabolite. However, more than 25 metabolites have been identified and many are pharmacologically active. During elimination, approximately 85% of a dose is excreted in the urine within 48 h, with approximately 1% as unchanged drug [4]. Although the plasma half-life is reported to be 2–10 h (mean 4 h) in adults [4], it may be as long as 4 days in neonates due to impaired metabolism [5].
Individuals may be exposed to caffeine via beverages, food, over-the-counter drugs, prescription drugs, herbals or dietary supplements. A dose of 50–200 mg is generally consistent with mild stimulation. An average cup of coffee is reported to contain 100 mg caffeine, although much higher doses have been reported, particularly among specialty coffees. Caffeine is also available in numerous dietary supplements, over-the-counter drugs and in prescription drug mixtures at doses ranging from 32–200 mg [1].
Caffeine is a mild central nervous system stimulant. At sufficient dose, however, it may produce flushing, chills, agitation, irritability, loss of appetite, weakness and tremor. Hypertension, hypotension, tachycardia, vomiting, fever, delusions, hallucinations, seizures, arrhythmia, cardiac arrest, coma and death have been reported in cases of overdose. Once absorbed, caffeine exerts a variety of pharmacological actions both centrally and peripherally at multiple sites. The principle mechanism of action is antagonism of adenosine. Caffeine is structurally similar to adenosine, which has a generalized inhibitory function (Fig. 1). Caffeine has the potential to occupy adenosine receptor sites. This blocks the regulatory effects of adenosine and produces a stimulant-type effect. Antagonism of the A1 and A2 receptors can cause seizures and cerebral vasoconstriction. Cardiovascular effects may result due to multiple mechanisms including increased circulation of catecholamines, while hypotension may result from decreased cardiac output and vasodilation.
Section snippets
Case history
Case #1 involved a 39-year-old female with a history of intravenous drug use. She was discovered in the bushes outside a restaurant. The decedent was fully clothed with the pockets turned out. There were minor abrasions on the chin and back with needle marks on the arms. A syringe was found 6 ft from body, although this appeared to be old. The autopsy was unremarkable and comprehensive toxicology was ordered on femoral blood.
Case #2 involved a 29-year-old male with a history of diabetes and
Results and conclusion
Toxicology results for case #1 indicated a trace of ibuprofen and 192 mg/L caffeine in femoral blood. In this case, the source of the caffeine was unknown although this individual had a history of drug abuse and caffeine is sometimes used as a cutting agent or diluent for illicit drugs. Toxicology tests on case #2, revealed acetone 0.017 g/100 mL, phenytoin 7 mg/L and caffeine 567 mg/L. The acetone and phenytoin concentrations are consistent with diabetes and medical intervention to control the
Acknowledgement
Specimens and case information were provided by the Office of the Medical Investigator, Albuquerque, NM.
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