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Fatal caffeine intoxication
Forensic Science International 103 (1999) S49–S52
Fatal caffeine intoxication B. Riesselmann*, F. Rosenbaum, S. Roscher, V. Schneider ¨ gerichtliche und soziale Medizin Berlin, Invalidenstraße 52, D-10557 Berlin, Germany Landesinstitut f ur
Abstract Caffeine is the most frequently consumed substance with centrally stimulating effects. It is contained in many soft drinks, but also active ingredient in several drugs. Caffeine concentrations in plasma above 15 mg / l can cause toxic symptoms while values above 80 mg / l are considered to be comatose-fatal. Publications about fatal caffeine overdose are relatively rare. We were able to detect fatal caffeine intoxications twice during the last year in toxicological analyses. The caffeine concentrations in femoral blood were 220 and 190 mg / l respectively. 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Caffeine; Fatal intoxication
1. Introduction Caffeine is the most consumed stimulating substance. It occurs naturally in coffee and cocoa beans, kola nuts and tea leaves which are traditionally used as stimulants by the natives in their particular growing areas. In central Europe it is mainly consumed in drinks (coffee, tea and soft drinks) because of its stimulating effect. Caffeine is also active substance of many drugs. The German drug index ‘Rote Liste’ lists 61 drugs containing caffeine for 11 different indications [1]. The majority are analgesic drug combinations as well as analeptics and restoratives. Although drugs containing caffeine are easily available one can only find a few publications about caffeine intoxications. We want to report on two cases of death during the last year in which we could detect a caffeine intoxication.
*Corresponding author. Tel.: 149-30-39784-571; fax: 149-30-39784-395. 0379-0738 / 99 / $ – see front matter 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S0379-0738( 99 )00073-0
B. Riesselmann et al. / Forensic Science International 103 (1999) S49 –S52
S50
2. Pharmacological properties Caffeine is a drug which is available without prescription. After the ingestion of therapeutic doses of 50–200 mg it takes effect as an antagonist to the adenosine receptor. This leads to a psychical stimulation and hereby causes e.g. the • reduction of tiredness • increase of psychical efficiency • increase of concentration ability. A normal cup of coffee contains averagely 80 mg caffeine. After drinking the concentration of caffeine in plasma amounts to max. 2 mg / l [2]. The consumption of a tablet with 200 mg caffeine leads to a concentration of up 10 mg / l. Values above 15 mg / l can cause toxic symptoms, above 80 mg / l they are considered to be comatose-fatal [3,4]. After oral ingestion of about 1 g of caffeine toxic symptoms can appear while the application of more than 3 g can lead to death [2]. An overdose can cause the following symptoms: • • • •
stimulation of the respiratory centre tachycardia arrhythmia tremor
3. Method Caffeine and other substance were determined in the postmortem specimen by liquid chromatography (HPLC). Instrumentation: Column: Mobile phase: Sample preparation:
HPLC system with DAD UVD 340 S (Gynkotek, Germering) Superspher 60 RP select B, 12534 mm i.d. combined with a pre-column (Merck, Darmstadt) Acetonitrile / 0.1% orthophosphoric acid 1 ml sample was deproteinized with 1 ml acetonitrile; the clear supernatant was injected onto the column
4. Case 1 A 19-year-old female student was found dead, lying on her bathroom floor. Diseases were not known. In the kitchen a pot with remains of white mash was found and next to it there was an empty pack of guarana capsules. The autopsy didn’t show any signs of
B. Riesselmann et al. / Forensic Science International 103 (1999) S49 –S52
S51
Table 1 Toxicological findings
Caffeine Theophylline
Stomach [mg / 1]
Femoral blood [mg / 1]
Heart blood [mg / 1]
Urine [mg / 1]
Liver [mg / kg]
2000 ,5
220 2
260 3
350 Qualitative
Qualitative Qualitative
Table 2 Toxicological findings
Caffeine Salicylic acid Acetaminophen
Stomach [mg / l]
Femoral blood [mg / l]
Heart blood [mg / l]
Liver [mg / kg]
190 2900 700
190 360 600
180 360 700
Qualitative Qualitative Qualitative
violence or pathological change of organs but only signs of sudden death. In the stomach remains of tablets were found (Table 1).
5. Case 2 An 81-year-old woman was found on the floor in her apartment. A farewell letter was lying on the living-room table. The corpse already showed a slight putrefaction. During the autopsy a humorous fracture at the right side (probably due to an accident) as well as a serious pulmonary emphysema and a medium arteriosclerosis were found. The stomach did not contain any remains of tablets (Table 2).
6. Conclusion Caffeine intoxications are rare. Caffeine is detected in many toxicological analyses because of its diverse applications in medicine and other common uses. However, its toxicological significance is often underestimated since as a medical product it is almost exclusively applied together with other substances. The presented cases point out that because of its effects on the cardiovascular system caffeine is an important substance in forensic reports.
Acknowledgements We would like to thank Mrs. Erika Karger for the careful performance of the analyses.
S52
B. Riesselmann et al. / Forensic Science International 103 (1999) S49 –S52
References [1] Bundesverband der Pharmazeutischen Industrie e.V, Rote Liste 1998, Cantor Verlag, Aulendorf / Wurtt, 1998. [2] Bundesgesundheitsamt Aufbereitungsmonographie ‘Coffein’. Bundesanzeiger-Nr. 209 (1989) vom 08.11.1989. [3] M. Schulz, A. Schmoldt, Therapeutic and toxic blood concentrations of more than 500 drugs, Pharmazie 52 (1997) 895–911. [4] R.C. Baselt, R.H. Cravey, Disposition of Toxic Drugs and Chemicals in Man, Chemical Toxicology Institute, Foster City, CA, 1995.
Fatal caffeine intoxication B. Riesselmann*, F. Rosenbaum, S. Roscher, V. Schneider ¨ gerichtliche und soziale Medizin Berlin, Invalidenstraße 52, D-10557 Berlin, Germany Landesinstitut f ur
Abstract Caffeine is the most frequently consumed substance with centrally stimulating effects. It is contained in many soft drinks, but also active ingredient in several drugs. Caffeine concentrations in plasma above 15 mg / l can cause toxic symptoms while values above 80 mg / l are considered to be comatose-fatal. Publications about fatal caffeine overdose are relatively rare. We were able to detect fatal caffeine intoxications twice during the last year in toxicological analyses. The caffeine concentrations in femoral blood were 220 and 190 mg / l respectively. 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Caffeine; Fatal intoxication
1. Introduction Caffeine is the most consumed stimulating substance. It occurs naturally in coffee and cocoa beans, kola nuts and tea leaves which are traditionally used as stimulants by the natives in their particular growing areas. In central Europe it is mainly consumed in drinks (coffee, tea and soft drinks) because of its stimulating effect. Caffeine is also active substance of many drugs. The German drug index ‘Rote Liste’ lists 61 drugs containing caffeine for 11 different indications [1]. The majority are analgesic drug combinations as well as analeptics and restoratives. Although drugs containing caffeine are easily available one can only find a few publications about caffeine intoxications. We want to report on two cases of death during the last year in which we could detect a caffeine intoxication.
*Corresponding author. Tel.: 149-30-39784-571; fax: 149-30-39784-395. 0379-0738 / 99 / $ – see front matter 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S0379-0738( 99 )00073-0
B. Riesselmann et al. / Forensic Science International 103 (1999) S49 –S52
S50
2. Pharmacological properties Caffeine is a drug which is available without prescription. After the ingestion of therapeutic doses of 50–200 mg it takes effect as an antagonist to the adenosine receptor. This leads to a psychical stimulation and hereby causes e.g. the • reduction of tiredness • increase of psychical efficiency • increase of concentration ability. A normal cup of coffee contains averagely 80 mg caffeine. After drinking the concentration of caffeine in plasma amounts to max. 2 mg / l [2]. The consumption of a tablet with 200 mg caffeine leads to a concentration of up 10 mg / l. Values above 15 mg / l can cause toxic symptoms, above 80 mg / l they are considered to be comatose-fatal [3,4]. After oral ingestion of about 1 g of caffeine toxic symptoms can appear while the application of more than 3 g can lead to death [2]. An overdose can cause the following symptoms: • • • •
stimulation of the respiratory centre tachycardia arrhythmia tremor
3. Method Caffeine and other substance were determined in the postmortem specimen by liquid chromatography (HPLC). Instrumentation: Column: Mobile phase: Sample preparation:
HPLC system with DAD UVD 340 S (Gynkotek, Germering) Superspher 60 RP select B, 12534 mm i.d. combined with a pre-column (Merck, Darmstadt) Acetonitrile / 0.1% orthophosphoric acid 1 ml sample was deproteinized with 1 ml acetonitrile; the clear supernatant was injected onto the column
4. Case 1 A 19-year-old female student was found dead, lying on her bathroom floor. Diseases were not known. In the kitchen a pot with remains of white mash was found and next to it there was an empty pack of guarana capsules. The autopsy didn’t show any signs of
B. Riesselmann et al. / Forensic Science International 103 (1999) S49 –S52
S51
Table 1 Toxicological findings
Caffeine Theophylline
Stomach [mg / 1]
Femoral blood [mg / 1]
Heart blood [mg / 1]
Urine [mg / 1]
Liver [mg / kg]
2000 ,5
220 2
260 3
350 Qualitative
Qualitative Qualitative
Table 2 Toxicological findings
Caffeine Salicylic acid Acetaminophen
Stomach [mg / l]
Femoral blood [mg / l]
Heart blood [mg / l]
Liver [mg / kg]
190 2900 700
190 360 600
180 360 700
Qualitative Qualitative Qualitative
violence or pathological change of organs but only signs of sudden death. In the stomach remains of tablets were found (Table 1).
5. Case 2 An 81-year-old woman was found on the floor in her apartment. A farewell letter was lying on the living-room table. The corpse already showed a slight putrefaction. During the autopsy a humorous fracture at the right side (probably due to an accident) as well as a serious pulmonary emphysema and a medium arteriosclerosis were found. The stomach did not contain any remains of tablets (Table 2).
6. Conclusion Caffeine intoxications are rare. Caffeine is detected in many toxicological analyses because of its diverse applications in medicine and other common uses. However, its toxicological significance is often underestimated since as a medical product it is almost exclusively applied together with other substances. The presented cases point out that because of its effects on the cardiovascular system caffeine is an important substance in forensic reports.
Acknowledgements We would like to thank Mrs. Erika Karger for the careful performance of the analyses.
S52
B. Riesselmann et al. / Forensic Science International 103 (1999) S49 –S52
References [1] Bundesverband der Pharmazeutischen Industrie e.V, Rote Liste 1998, Cantor Verlag, Aulendorf / Wurtt, 1998. [2] Bundesgesundheitsamt Aufbereitungsmonographie ‘Coffein’. Bundesanzeiger-Nr. 209 (1989) vom 08.11.1989. [3] M. Schulz, A. Schmoldt, Therapeutic and toxic blood concentrations of more than 500 drugs, Pharmazie 52 (1997) 895–911. [4] R.C. Baselt, R.H. Cravey, Disposition of Toxic Drugs and Chemicals in Man, Chemical Toxicology Institute, Foster City, CA, 1995.