Jabbar, Seema B. MSIII, BS*; Hanly, Mark G. MBChB, FRCPath(Lond), FCAP, FASCP†
From the *Georgia Regents University, Augusta, GA; and †Office of Glynn County Medical Examiner, Brunswick, GA.
Manuscript received February 24, 2013; accepted May 28, 2013.
The authors report no conflicts of interest.
Reprints: Mark G. Hanly, MBChB, FRCPath (Lond), FCAP, FASCP, Southeastern Pathology Associates, Department of Pathology, Office of Glynn County Medical Examiner, 2415 Parkwood Dr, Brunswick, GA 31520. E-mail: email@example.com.
Caffeine is a central nervous system stimulant that is consumed by large numbers of people on a routine basis, usually in the form of coffee or tea. However, if consumed in high doses, this xanthine alkaloid is profoundly toxic and can result in death.Increasingly being sold as a dietary supplement, many people, particularly those in the health and fitness community, where it is touted as a fitness and muscle building aid, are consuming caffeine anhydrous on a daily basis.We report a case of fatal caffeine overdose in a 39-year-old man resulting from the self-administered ingestion of approximately 12 g of pure caffeine anhydrous. Autopsy blood caffeine levels were 350 mg/L.We recommend mandated labeling of pure caffeine anhydrous, highlighting the toxicity risk of ingesting this chemical; and we recommend ensuring that caffeine levels are included in the comprehensive forensic toxicology panel performed on all cases.
Caffeine (1, 3, 7-Trimethylxanthine) is a bitter, white, crystalline xanthine alkaloid with a molecular weight of 194.9, the structure of which closely resembles purines (Figs. 1 and 2).
Caffeine anhydrous is water soluble and undergoes rapid absorption after oral administration. Ninety percent of an ingested dose is absorbed from the stomach within 20 minutes, with a peak plasma concentration occurring approximately 50 to 60 minutes later.
Caffeine is a mild central nervous system stimulant when consumed in a relatively low dose, as an infusion from coffee beans and from the leaves of certain shrubs, or as an additive to certain commercial soda drinks. Caffeine is now increasingly being consumed in more concentrated forms as an “energy shot” (5-hour energy extrastrength 207-mg per 2-oz container), energy drinks (Monster Assault, 160 mg per can), or, of most concern, as 100% caffeine anhydrous, a high-dose self-administered drink additive. The fatal acute oral caffeine dose in an adult human is estimated to be in the range of 150 to 200-mg/kg body weight.1
MATERIALS AND METHODS
The decedent was a 39-year-old white man who had been employed as a telecommunications worker. The decedent was very physically active and participated in a demanding daily fitness regimen, which included the preparation and consumption of self-formulated “energy drinks”. His employer had recently received several complaints about the decedent, predominantly related to his aggressive behavior. As a result, the decedent was terminated from his position. Approximately 2 hours after his termination, the decedent was found lifeless at the front door of his residence by a friend. Emergency medical services were called, but no vital signs were identified. At the scene, dried white fluid was identified sprayed in the cab of the decedent’s vehicle (Fig. 3) and dried white fluid was also present over the decedent’s shirt (Fig. 4). A recently opened container of caffeine anhydrous powder was present in the cab along with an empty plastic drink container to which it had been added. No suicide note or evidence of suicidal ideation was found. A complete autopsy was performed at the request of the county coroner.
Blood caffeine was identified using solid-phase extraction with gas chromatography and mass spectrometry. Final evaluation was performed using an Agilent 6890 GC with a 5973 mass selective detector.
On external examination, a scalp laceration was identified consistent with a fall against the roughened exterior wall of the decedent’s residence. Other than marked pulmonary edema and congestion (right lung weight, 980 g; left lung weight: 880 g), no other findings of significance were noted at autopsy.
No white fluid was identified in the decedent’s stomach or small intestine. The stomach contained approximately 50 mL of clear watery fluid admixed with mucus. Caffeine anhydrous is colorless when dissolved in water. Initial toxicological studies were negative for common drugs of abuse, but the presence of dried white powdery fluid within the decedent’s vehicle and on his shirt along with the presence of an opened bag of caffeine anhydrous (Fig. 5) prompted quantitative analysis for blood caffeine levels.
Blood caffeine levels were measured as 350 mg/L.
The opened bag of caffeine anhydrous was marked as containing 200 g of 100% pure compound. On weighing the residual bag contents, only 178 g of caffeine powder was present, indicating that approximately 22 g had been mixed for consumption. Given that 50 mL of watery fluid was present in the stomach and dried caffeine anhydrous solution was present in the vehicle and down the front of the decedent’s shirt, it was estimated that approximately 50% to 60% of the initial oral dose had been retained after ingestion, giving a dose of 10 to 12 g of caffeine.
As no other significant findings were made at autopsy, the cause of death in this case was attributed to fatal caffeine intoxication, with the manner of death designated as accidental.
Caffeine is well absorbed after oral administration, and clinical effects can be identified within 15 minutes of ingesting a dose. Peak plasma levels are attained in 50 to 60 minutes after ingestion.
The toxic effects of high-dose caffeine ingestion include vomiting and abdominal pain, resulting from intense gastric irritation, as well as significant central nervous system symptoms such as agitation, altered consciousness, rigidity, and seizures.2 Cardiovascular effects can include supraventricular and ventricular tachyarrhythmia. The mechanism of death is often ascribed to ventricular fibrillation, as in this case.
In recent years, the risk of ingesting toxic levels of caffeine has been heightened by the easy availability of “energy shots”, energy drinks with high caffeine content and caffeine anhydrous at shops, health stores, and online purchase.
Reports associated with energy drink exposures (ie, adverse reactions) have increased. Between 2005 and 2011, there has been a 20-fold increase in the number of emergency department visits due to energy drink consumption (1494–20,783 visits).3 Last year alone, there were a total of 3147 energy drink–related exposures reported to local poison centers across the United States compared to only 647 reports made in 2010.4 Owing to these recent reports, the news media has published articles highlighting a potential link between energy drinks (ie, 5-hour energy Monster) and caffeine overdose as well as concern about the risks associated with these drinks.5–7
Fatalities among adults and children related to the ingestion of caffeine are rare. A review of the medical literature reveals approximately 45 caffeine-related fatalities reported between 1959 and 2010.8–21 Twenty of these cases occurred between 1993 and 2009.21 Fatal outcomes have been reported with the ingestion of 5 to 50 g of caffeine. Death has been reported in cases where the blood caffeine level has been as low as 80 mg/L.22
Although there have been reports of caffeine toxicity in the literature and the media, few people in the general population are aware of the potential risks involved with the ingestion of large quantities of caffeine. The purchase of pure caffeine anhydrous is unrestricted in the United States and even large potentially toxic quantities of the substance from reputable retail outlets are sold in containers without adequate warnings with regard to the risk of fatal overdose (Fig. 6).
It is important to remember that ingestion of caffeine anhydrous can cause fatal intoxication. The cause of death is, in most cases, probably related to a fatal cardiac arrhythmia; but death may also be related to complications of caffeine-associated seizures.
Fatal caffeine intoxication may become more common over the years owing to the easy availability, increased use of caffeine, and the lack of adequate warning labels on caffeine-containing products. Therefore, blood caffeine levels should be included in all toxicology tests even if other more commonly used drugs of abuse are identified as caffeine anhydrous may be used to “cut” certain “street drugs.” Finally, it is recommended that placement of more informative warning labels on caffeine containers be encouraged.
The authors thank Southeastern Pathology Associates, the autopsy staff at the Glynn County Medical Examiner’s Office, particularly Mrs Christina Miller, for their assistance; and to Mr Jimmy Durden, Glynn County coroner, for permission to report this case.
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