Clinical Toxicology Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
CLINICAL TOXICOLOGY 10(3), pp. 341-344 (1977)
A Fatal Ingestion of Caffeine
J. E. TURNER and R. H. CRAVEY
Office of the Sheriff-Coroner Toxicology Lab0 ratory Santa Ana, California
Caffeine, a n alkaloid occurring in plants throughout the world is consumed in huge quantities both i n over-the-counter preparations and a s a constituent of many common beverages. Of therapeutic i n t e r e s t is its stimulation of the central nervous s y s t e m , its action on the kidneys to produce d i u r e s i s , stimulation of c a r d i a c muscle, and relaxation of smooth muscle. Caffeine is generally accepted a s a s a f e drug, with little o r no toxic effects, even when taken o v e r long periods of time. This case involves the fatal ingestion of an unknown quantity of caffeine. CASE HISTORY During the hours preceding h e r death, a 34-year-old female complained of weakness and experienced episodes of vomiting. Upon retiring, h e r breathing became progressively labored, and s h e began to suffer convulsions. A r e s c u e unit found h e r in coma. Upon a r rival a t the hospital, t h e r e was no audible heart beat, pulse, o r breath sounds. She was in a s t a t e of acidosis (pH 6.8, a r t e r i a l blood) with cyanosis about the neck and mouth. She had assumed a n opisthotonic posture. Resuscitative efforts lasted one hour.
341 Copyright @ 1977 hy Marcel Dekker. I n c All Rights Reserved. Neither thls work nor any p a r t may be reproduced or transmitted in any form or by any meahs. elecrronlc or mechanical. includmg photocopying. microfilming. and recording, or by any informatlon storage and retrieval system. without permission in wrlting from the publuher.
342
TURNER AND CRAVEY
Clinical Toxicology Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
TABLE 1. Tissue Concentrations (given a s mg/100 ml o r mg/100 gm) Specimen
Caffeine
Blood
10.6
Liver
11.6
Kidney
12.4
Brain
10.8
Gastric
43 mg total, plus three partially dissolved tablets
PATHOLOGIC FINDINGS Autopsy revealed general congestion, particularly of the lungs, liver, and brain stem. Direct cause of death was attributed to pulmonary edema. TOXICOLOGIC FINDINGS Tissue samples, along with parallel standards, were extracted a t physiologic pH with chloroform. The organic layer was given a basic wash, then taken gently to dryness. The residue was reconstituted in 0.2 N Hz SO4 and quantitated directly by ultraviolet spectrophotometry a t 272 nm, made possible by the lack of interfering substances in this region. The resulting tissue concentrations are given in Table 1. Confirmation of the caffeine was by thin-layer chromatography. Silica gel plates with fluorescent indicator were utilized and developed in a thin-layer system of acetone:benzene:chloroform (25:40:40). Caffeine demonstrates an absolute Rf of 0.13 in this system, and upon spraying with acidic (10% HC1) iodoplatinate,* yields a gray color. General screening for the presence of acidic, basic, and neutral drugs yielded only one other drug present. Phenobarbital was found, with a blood concentration of 0.4 mg/100 m 1. DISCUSSION Caffeine may well be the most commonly used of all the drugs, considering i t s presence in coffee, tea, and soft drinks, in addition to *Iodoplatinate reagent: 9 gm K1 + 300 ml HZ0 + 10 m l 10% chloroplatinic acid.
Clinical Toxicology Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
FATAL INGESTION O F CAFFEINE
343
diuretics and sleep inhibitors. Existing in the stomach in a water soluble form, caffeine is slowly and completely absorbed into the bloodstream and is freely and equally distributed throughout the total body water [l]. Garriott [2] found that a 300-mg dose of pure caffeine in a 200-lb man resulted in a maximum blood concentration of 0.49 mg/100 ml. A review of the literature yields few fatal cases where caffeine was the causative agent. Most of these cases were the result of doses erroneously administered by hospital personnel. Two cases, one reported by Farango [3] and another by Borkowski [4], involved a 15-month-old male and a 61-year-old male, each administered approximately 18 gm of caffeine in a sodium benzoate solution. A third case reported by Grusz-Hardy [5] concerned a 45-year-old female mistakenly given 50 gm of caffeine instead of 50 gm of glucose. It is generally accepted that the fatal dose of caffeine in humans is 10 gm, although or al doses in reported fatalities range from 5 to 50 gm. A single fatal cas e involving intravenous caffeine injection was reported by Jokela and Varlianinen [6]. A 35-year-old female was accidently given 3.2 gm of caffeine intravenously. High doses of caffeine given to laboratory animals cause convulsions [7], a common occurrence in human fatalities due to caffeine and due to the central stimulating effect. Dimaio and Garriott [8] reported the case of a 5-year-old female who ingested 53 of her m ot her 's diuretic tablets, and Alstott et a1 [9] reported a case in which a 27-year-old female was found dead in bed, with a suicide note nearby. Death in each case was attributed to overdose of caffeine. The infrequency of death as a result of ingestion of l a r g e amounts of caffeine is perhaps due in par t to the emetic effect of the drug and in general to ignorance of the potential of caffeine. SUMMARY Tissue concentrations a r e given in a fatal c a s e involving caffeine. Methods for the detection and quantitation of the drug are described. A brief review of reported caffeine fatalities is given. REFERENCES
[ 11 A. Goldstein, L. Aronow, and S. Kalman, Principles of Drug
Action, Harper and Row, New York, 1969, p. 185. [2] J. Garriott, Foren. Sci. Gazette, 5(3), 2 (1974). 5, 2 (1968). [3] A. Farago, Bull. Intern. Assoc. Foren. Toxicol., -
Clinical Toxicology Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
344
TURNER AND CRAVEY
[4] T. Borkowski, Bull. Intern. Assoc. Foren. Toxicol., -9, June, 13 (1972). [5] E. Grusz-Hardy, Bull. Intern. Assoc. Foren. Toxicol., 10, April, 6 (1973). [6] S. Jokela and A. Varliainen, Acta Pharmacol. Toxicol., 15, 331 (1959). [7] L. Goodman and A. Gilman, The Pharmacological Basis of Therapeutics, 5th ed. MacMillan, New York, 1975, p. 373. [8 V. Dimaio and J. Garriott, Forensic Sci., 3(3), 275 ( 1974). [9 R. Alstott, A. Miller, and R. Forney, J. Foren. Sci., 18, 135 (1973).
1
CLINICAL TOXICOLOGY 10(3), pp. 341-344 (1977)
A Fatal Ingestion of Caffeine
J. E. TURNER and R. H. CRAVEY
Office of the Sheriff-Coroner Toxicology Lab0 ratory Santa Ana, California
Caffeine, a n alkaloid occurring in plants throughout the world is consumed in huge quantities both i n over-the-counter preparations and a s a constituent of many common beverages. Of therapeutic i n t e r e s t is its stimulation of the central nervous s y s t e m , its action on the kidneys to produce d i u r e s i s , stimulation of c a r d i a c muscle, and relaxation of smooth muscle. Caffeine is generally accepted a s a s a f e drug, with little o r no toxic effects, even when taken o v e r long periods of time. This case involves the fatal ingestion of an unknown quantity of caffeine. CASE HISTORY During the hours preceding h e r death, a 34-year-old female complained of weakness and experienced episodes of vomiting. Upon retiring, h e r breathing became progressively labored, and s h e began to suffer convulsions. A r e s c u e unit found h e r in coma. Upon a r rival a t the hospital, t h e r e was no audible heart beat, pulse, o r breath sounds. She was in a s t a t e of acidosis (pH 6.8, a r t e r i a l blood) with cyanosis about the neck and mouth. She had assumed a n opisthotonic posture. Resuscitative efforts lasted one hour.
341 Copyright @ 1977 hy Marcel Dekker. I n c All Rights Reserved. Neither thls work nor any p a r t may be reproduced or transmitted in any form or by any meahs. elecrronlc or mechanical. includmg photocopying. microfilming. and recording, or by any informatlon storage and retrieval system. without permission in wrlting from the publuher.
342
TURNER AND CRAVEY
Clinical Toxicology Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
TABLE 1. Tissue Concentrations (given a s mg/100 ml o r mg/100 gm) Specimen
Caffeine
Blood
10.6
Liver
11.6
Kidney
12.4
Brain
10.8
Gastric
43 mg total, plus three partially dissolved tablets
PATHOLOGIC FINDINGS Autopsy revealed general congestion, particularly of the lungs, liver, and brain stem. Direct cause of death was attributed to pulmonary edema. TOXICOLOGIC FINDINGS Tissue samples, along with parallel standards, were extracted a t physiologic pH with chloroform. The organic layer was given a basic wash, then taken gently to dryness. The residue was reconstituted in 0.2 N Hz SO4 and quantitated directly by ultraviolet spectrophotometry a t 272 nm, made possible by the lack of interfering substances in this region. The resulting tissue concentrations are given in Table 1. Confirmation of the caffeine was by thin-layer chromatography. Silica gel plates with fluorescent indicator were utilized and developed in a thin-layer system of acetone:benzene:chloroform (25:40:40). Caffeine demonstrates an absolute Rf of 0.13 in this system, and upon spraying with acidic (10% HC1) iodoplatinate,* yields a gray color. General screening for the presence of acidic, basic, and neutral drugs yielded only one other drug present. Phenobarbital was found, with a blood concentration of 0.4 mg/100 m 1. DISCUSSION Caffeine may well be the most commonly used of all the drugs, considering i t s presence in coffee, tea, and soft drinks, in addition to *Iodoplatinate reagent: 9 gm K1 + 300 ml HZ0 + 10 m l 10% chloroplatinic acid.
Clinical Toxicology Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
FATAL INGESTION O F CAFFEINE
343
diuretics and sleep inhibitors. Existing in the stomach in a water soluble form, caffeine is slowly and completely absorbed into the bloodstream and is freely and equally distributed throughout the total body water [l]. Garriott [2] found that a 300-mg dose of pure caffeine in a 200-lb man resulted in a maximum blood concentration of 0.49 mg/100 ml. A review of the literature yields few fatal cases where caffeine was the causative agent. Most of these cases were the result of doses erroneously administered by hospital personnel. Two cases, one reported by Farango [3] and another by Borkowski [4], involved a 15-month-old male and a 61-year-old male, each administered approximately 18 gm of caffeine in a sodium benzoate solution. A third case reported by Grusz-Hardy [5] concerned a 45-year-old female mistakenly given 50 gm of caffeine instead of 50 gm of glucose. It is generally accepted that the fatal dose of caffeine in humans is 10 gm, although or al doses in reported fatalities range from 5 to 50 gm. A single fatal cas e involving intravenous caffeine injection was reported by Jokela and Varlianinen [6]. A 35-year-old female was accidently given 3.2 gm of caffeine intravenously. High doses of caffeine given to laboratory animals cause convulsions [7], a common occurrence in human fatalities due to caffeine and due to the central stimulating effect. Dimaio and Garriott [8] reported the case of a 5-year-old female who ingested 53 of her m ot her 's diuretic tablets, and Alstott et a1 [9] reported a case in which a 27-year-old female was found dead in bed, with a suicide note nearby. Death in each case was attributed to overdose of caffeine. The infrequency of death as a result of ingestion of l a r g e amounts of caffeine is perhaps due in par t to the emetic effect of the drug and in general to ignorance of the potential of caffeine. SUMMARY Tissue concentrations a r e given in a fatal c a s e involving caffeine. Methods for the detection and quantitation of the drug are described. A brief review of reported caffeine fatalities is given. REFERENCES
[ 11 A. Goldstein, L. Aronow, and S. Kalman, Principles of Drug
Action, Harper and Row, New York, 1969, p. 185. [2] J. Garriott, Foren. Sci. Gazette, 5(3), 2 (1974). 5, 2 (1968). [3] A. Farago, Bull. Intern. Assoc. Foren. Toxicol., -
Clinical Toxicology Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
344
TURNER AND CRAVEY
[4] T. Borkowski, Bull. Intern. Assoc. Foren. Toxicol., -9, June, 13 (1972). [5] E. Grusz-Hardy, Bull. Intern. Assoc. Foren. Toxicol., 10, April, 6 (1973). [6] S. Jokela and A. Varliainen, Acta Pharmacol. Toxicol., 15, 331 (1959). [7] L. Goodman and A. Gilman, The Pharmacological Basis of Therapeutics, 5th ed. MacMillan, New York, 1975, p. 373. [8 V. Dimaio and J. Garriott, Forensic Sci., 3(3), 275 ( 1974). [9 R. Alstott, A. Miller, and R. Forney, J. Foren. Sci., 18, 135 (1973).
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