Fatality from Drinking Denatured Alcohol and Hypothermia

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Journal of Analytical Toxicology, Vol. 35, June 2011

Case Report

Fatality from Drinking Denatured Alcohol and Hypothermia Alan Wayne Jones* Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, SE-587 58 Linköping, Sweden

Abstract A 19-year-old non-diabetic female suffering from irritable bowel syndrome was found unconscious outdoors in the month of October. She was severely hypothermic and rushed to hospital for life-saving treatment. Evidence emerged that the victim had attempted suicide by drinking denatured alcohol (T-Red). According to the manufacturer of this product, it contains > 85% (v/v) ethanol, ~5% (v/v) acetone, 1–2% (v/v) ethyl acetate, and ~3% (v/v) methyl ethyl ketone (MEK), but no isopropanol. A venous blood sample taken on admission to hospital contained ethanol (660 mg/100 mL), acetone (25 mg/100 mL), isopropanol (78 mg/100 mL), and MEK, although the latter was not quantified. Despite intensive care, the patient died 21 h after admission and postmortem femoral blood contained ethanol (390 mg/100 mL), acetone (14 mg/100 mL), isopropanol (53 mg/100 mL), and MEK. During oxidative metabolism of ethanol, there is a shift in the redox state of the liver to a more reduced potential as reflected in a raised NADH/NAD+ ratio, which impacts on other NADdependent biochemical reactions, including reduction of acetone to isopropanol. The lower concentrations of ethanol, acetone, and isopropnaol in postmortem blood compared with antemortem blood indicate the metabolism of these substances during the 21-h survival period when the patient received emergency hospital treatment.

Introduction The acute toxicity of ethanol depends on numerous factors, including the person’s age, the speed of drinking, the amount ingested, and the degree of cellular tolerance to this depressant drug (1–3). Toxicity is exaggerated if ethanol is taken together with other depressant drugs, during exposure to cold environments, and in the elderly and malnourished (4,5).

* Address for correspondence: Professor A. Wayne Jones, Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, SE-587 58 Linköping, Sweden. Email: [email protected].

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In 693 acute alcohol poisoning deaths in Sweden, the mean concentration of ethanol in femoral blood was 360 mg/100 mL with a 95% range from 220 to 500 mg/100 mL (2). This compares with a mean concentration of 348 mg/100 mL based on 615 alcohol poisoning deaths in Finland (3). In both studies, ethanol was determined in femoral blood by headspace gas chromatography and medical examiners used the same diagnostic criteria to conclude that acute alcohol poisoning was the cause of death (6). This case report concerns a 19-year-old female who attempted suicide by drinking a technical alcohol product (TRed) and was discovered unconscious and severely hypothermic. Both antemortem venous blood and postmortem femoral blood were available for analysis at the same forensic toxicological laboratory, which is an interesting feature of this case.

Case History A 19-year-old non-diabetic female, an in-patient at a psychiatric hospital, was reported missing from her room. She was discovered outdoors in the month of October and suffering from hypothermia. The victim’s body mass index was 18.5 kg/m2, and she suffered from irritable bowel syndrome. An empty bottle of denatured alcohol (T-Red) was found beside the body. An ambulance was called, and the victim was rushed to hospital for life-saving invasive treatment (core body temperature was only 14°C on arrival). A sample of serum was taken for clinical laboratory analysis. The emergency physicians diagnosed pronounced metabolic acidosis with negligible cardiac activity and hypotension, and there were difficulties in oxygenating the blood. A heart-lung machine was used along with active re-warming including sternotomy, but the patient was pronounced dead 21 h after arrival. A forensic autopsy was performed five days after death, and the body showed no signs of decomposition according to the medical examiner’s report. A specimen of femoral venous blood

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after addition of potassium fluoride (2% v/v) was sent for toxicological analysis of alcohols and other drugs. The manner of death was given as suicide by acute alcohol poisoning, and the secondary cause was hypothermia. Venous blood was taken on admission to hospital, and it was sent for analysis to the same laboratory that was responsible for the postmortem toxicology. Volatiles were analyzed in blood by headspace gas chromatography at limits of quantitation of 10 mg/100 mL for ethanol, methanol, acetone, and isopropanol (7). Analytical results for other drugs in ante- and postmortem blood were negative. The technical alcohol (T-Red) consumed by the victim is sold at gas stations and general stores throughout Sweden and is mainly intended for use as a clean fuel on camping trips, etc. (8). According to the manufacturer (Kemetyl AB, Haninge, Sweden), T-Red contains ethanol (~85% v/v), methyl ethyl ketone (~3% v/v), acetone (~5% v/v), ethyl acetate (1–2% v/v), and bitrex (< 1% v/v), which imparts a bitter taste, but there is no isopropanol. The actual denaturing agents are strictly regulated by the authorities because of the potential for abuse of this cheap source of alcohol. Although T-Red was not analyzed in the present study, earlier work using headspace gas chromatography verified that isopropanol was not present in this technical alcohol (8).

Results The concentrations of ethanol, acetone, and isopropanol determined in antemortem and postmortem blood are shown in Table I. The very high blood-ethanol concentration on admission (660 mg/100 mL) was verified by the hospital laboratory serum sample (182 mmol/L), which corresponds to a blood ethanol concentration of 680 mg/100 mL, assuming a serum/ blood ratio of 1.16:1. Table I shows that the concentrations of ethanol, acetone, isopropanol, and MEK were lower in postmortem femoral blood compared with antemortem venous blood and indicates metabolism of these substances during the 21-h survival time.

concentration of acetone in blood after drinking T-Red and the fact that oxidative metabolism of acetone is a slow process opens the possibility of a reductive pathway towards isopropanol (14,15). As shown in Figure 1, the reduction of acetone to isopropanol is favorable when the hepatic NADH/NAD+ ratio is elevated as it is when the liver is engaged in the oxidative metabolism of ethanol (10). Acetone is an endogenous metabolite, and the concentrations determined in blood from healthy individuals, diabetic outpatients, and impaired drivers are low and in the range 1– 10 mg/L (16). However, these concentrations are likely to increase appreciably after periods of fasting, after eating low carbohydrate diets, with poorly controlled diabetes, and, as in this case, after drinking denatured alcohol spiked with acetone (8,17,18). The most plausible explanation for finding isopropanol in ante- and postmortem blood in this patient is by the reduction of acetone originating from drinking the T-Red (13,14). Hypothermia triggers a number of hormonal, physiological, and biochemical changes as the body attempts to conserve energy (19,20). The activity of metabolizing enzymes might be altered, and glycogen stores are depleted as energy reserves are re-directed to counteract the cold environment (19). Metabolic Table I. Concentrations of Ethanol, Acetone, and Isopropanol and Presence of Methyl Ethyl Ketone (MEK) in Antemortem Venous Blood and Postmortem Femoral Blood in a 19-Year-Old Female Patient Who Died 21 h after Admission to Hospital Blood Specimen

Ethanol Acetone (mg/100 mL) (mg/100 mL)

Isopropanol (mg/100 mL)

MEK*

Antemortem†

660

25

78

+

Postmortem

390

14

53

+

* MEK was present but not quantified. † Serum taken on admission to hospital contained 182 mmol/L ethanol (~680 mg/100 mL blood).

Discussion Human metabolism of ethanol occurs primarily in the liver by two main oxidative enzymes, namely alcohol dehydrogenase (ADH) located in the cytosolic fraction of hepatocytes and aldehyde dehydrogenase (ALDH) in the mitochondria (9,10). Furthermore, there is a microsomal enzyme CYP2E1 located in the smooth endoplasmic reticulum, which contributes to the metabolism of ethanol after moderate to heavy drinking (10). Isopropanol is also a substrate for ADH, although this secondary alcohol is oxidized to acetone, whereas ethanol is converted to acetaldehyde as illustrated in Figure 1 (11,12). Unlike the rapid and effective oxidation of acetaldehyde to acetate by low km ALDH, the further oxidation of acetone is a relatively slow process (half-life 18–20 h) and involves monooxygenase enzymes such as CYP2E1 (13). The elevated

Figure 1. Oxidative metabolism of primary (ethanol) and secondary (isopropanol) alcohols in the liver by alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) where NAD+ and NADH are oxidized and reduced forms of the coenzyme nicotinamide adenine dinucleotide, respectively.

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acidosis is a well-known clinical feature of hypothermia and was evident also in the present case. An elevated concentration of NADH during metabolism of ethanol promotes reduction of pyruvate to lactate and the resulting lactacidosis exacerbates hypothermia-induced acidosis (10). Whether the metabolic response to hypothermia plays any role in the conversion of acetone to isopropanol is an open question (21). Little is known about the effect of hypothermia on the activity of alcohol metabolizing enzymes and the rate of ethanol metabolism (22). However, the concentrations of acetone, ethanol, and isopropanol were lower in postmortem blood compared with antemortem blood taken 21 h before death, which indicates an active metabolism of these substances during the hospital treatment. This case of acute alcohol poisoning with denatured alcohol confirms earlier work that acetone is reduced to isopropanol when there is an ethanol-induced shift in redox state of the liver towards a more reduced potential (elevated NADH).

Acknowledgments There was no external funding for the preparation of this manuscript. Forensic pathologist Dr. Sara Hallander is acknowledged for bringing this case to the author’s attention.

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