A fatal case of oral ingestion of methanol. Distribution in postmortem tissues and fluids including pericardial fluid and vitreous humor.

A 41-year-old man ingested orally a large quantity of methanol and was found dead at home. The presence of methanol in body fluids and tissues was determined by head-space gas chromatography. The blood ethanol and acetone were negative. Tissue distribution of methanol showed that the kidney presented the highest content of methanol (5.13 g/kg) followed by liver (4.18 g/kg), vitreous humor (3.96 g/l), heart (3.45 g/kg), urine (3.43 g/l), pericardial fluid (3.29 g/l), blood (2.84 g/l) and finally stomach content (2.21 g/l).     

An unusual case of post-mortem redistribution of ethanol

We report an unusual case of post-mortem redistribution of ethanol in a woman diver who died by drowning in seawater. The ethanol concentrations were right heart blood 0.60 g/l, left heart blood 2.08 g/l, femoral venous blood 0.63 g/l, gastric contents 5.87 g/l, bile 0.83 g/l. The mechanisms of post-mortem redistribution of ethanol described in the literature, that is, early redistribution from the stomach or the lung parenchyma in the case of inhalation of gastric contents, are inadequate to account for the degree of variation observed between the measurements. We believe that this difference in concentration is explained by the presence of seawater in the pulmonary alveoli at the time of death.     

Post-mortem analysis of formic acid disposition in acute methanol intoxication

Fifteen cases of fatal massive methanol intoxication have been investigated. Victims received either no treatment or ethanol therapeutic treatment. Methanol poisoning cases were classified in three groups according to survival time: more than 3 days (group 1), up to 3 days (group 2) and few hours (group 3). Body distribution of methanol and formic acid, as the main metabolite, was analyzed in blood and in different organs (brain, kidney, lung and liver). Relationships between formic acid concentration in the different tissues, survival time and type of treatment applied to victims were studied. Formic acid in blood and tissues was analyzed by head space gas chromatography (head space-GC) with FID detector, previous transformation in methyl formate, essentially as described by Abolin. Formic acid concentration was between 0.03 and 1.10g/l in the samples under study. A good correlation between blood and brain, but poor between blood and the remaining tissues was found. Obtained data suggested that the use of blood and brain could help to improve the analysis of formic acid intoxication. The best correlation among organs was found between lung and kidney for all groups (r(2)=0.91, 0.84 and 0.87, corresponding to groups 1, 2 and 3, respectively). Lethality index was defined as LI = (concentration of formic acid in blood in (g/l)/0.5) x 100, taking into account that 0.5g/l is the concentration reported by Mahieu in severe methanol poisoning. LI parameter was used to estimate formic acid incidence on the lethality of methanol poisoning cases. LI showed a good correlation with total formic acid concentration of the different tissues analyzed (r(2)=0.80). Furthermore, LI allowed us to discriminate between individuals that received therapeutic treatment and survived different periods. LI>100 indicated a severe intoxication and short survival time if the victim was assisted with ethanol therapy and hemodialysis was not applied. With regard to victims who received no therapeutic treatment and died in few hours, LI was in the range 40-100. LI was below 40 for individuals that survived more than 3 days and hemodialysis was not performed. Results showed the importance of performing formic acid analysis to diagnose severe methanol intoxication in post-mortem cases.     

Urine/blood ratios of ethanol in deaths attributed to acute alcohol poisoning and chronic alcoholism

The concentrations of ethanol were determined in femoral venous blood (BAC) and urine (UAC) and the UAC/BAC ratios were evaluated for a large case series of forensic autopsies in which the primary cause of death was either acute alcohol poisoning (N=628) or chronic alcoholism (N=647). In alcohol poisoning deaths both UAC and BAC were higher by about 2g/l compared with chronic alcoholism deaths. In acute alcohol poisoning deaths the minimum BAC was 0.74 g/l and the distribution of UAC/BAC ratios agreed well with the shape of a Gaussian curve with mean+/-standard deviation (S.D.) and median (2.5th and 97.5th centiles) of 1.18+/-0.182 and 1.18 (0.87 and 1.53), respectively. In alcoholism deaths, when the BAC was above 0.74 g/l (N=457) the mean+/-S.D. and median (2.5th and 97.5th centiles) UAC/BAC ratios were 1.30+/-0.29 and 1.26 (0.87 and 2.1), respectively. When the BAC was below 0.74 g/l (N=190), the mean and median UAC/BAC ratios were considerably higher, being 2.24 and 1.58, respectively. BAC and UAC were highly correlated in acute alcohol poisoning deaths (r=0.84, residual S.D.=0.47 g/l) and in chronic alcoholism deaths (r=0.95, residual S.D.=0.41 g/l). For both causes of death (N=1275), the correlation between BAC and UAC was r=0.95 and the residual S.D. was 0.46 g/l. The lower UAC/BAC ratio observed in acute alcohol poisoning deaths (mean and median 1.18:1) suggests that these individuals died before absorption and distribution of ethanol in all body fluids were complete. The higher UAC/BAC ratio in chronic alcoholism (median 1.30:1) is closer to the value expected for complete absorption and distribution of ethanol in all body fluids.     

Fatal outcome of poisoning with ethylene glycol

After an act of violence, a delinquent swallowed about 250 ml ethylene glycol (EG) - probably to commit suicide before being arrested. During an interrogation by the police he appeared to be inebriated. A blood sample taken at this time did not contain ethanol but 5.1 g/l EG, as revealed by the analytical results. Only after a second examination was he taken to an intensive care unit in a hospital in spite of signs of pronounced intoxication after 12 h at the first examination. The patient died 30 h after taking EG without being effectively treated. The correct diagnosis, initiated by information from the poison control center, was made too late. At autopsy, findings were indicative of stage II of EG poisoning with a body burden of still 40-60 g EG. The mean rate of degradation in the blood was approximately 0.15 g/l per hour.     

Comparison of blood-ethanol concentration in deaths attributed to acute alcohol poisoning and chronic alcoholism

Ethanol concentrations were measured in femoral venous blood in deaths attributed to acute alcohol poisoning (N = 693) or chronic alcoholism (N = 825), according to the forensic pathology report. Among acute alcohol poisonings were 529 men (76%) with mean age 53 years and 164 women (24%) with mean age 53 years. In the chronic alcoholism deaths were 705 men (85%) with mean age 55 years and 120 women (15%) with mean age 57 years. The blood-ethanol concentrations were not related to the person's age (r = -0.17 in acute poisonings and r = -0.09 in chronic alcoholism). The distribution of blood-ethanol concentrations in acute poisoning cases agreed with a normal or Gaussian curve with mean, median, standard deviation, coefficient of variation, and spread of 0.36 g/100 mL, 0.36 g/100 mL, 0.086 g/100 mL, 24% and 0.074 to 0.68 g/100 mL, respectively. The corresponding concentrations of ethanol in chronic alcoholism deaths were not normally distributed and showed a mode between 0.01 and 0.05 g/100 mL and mean, median, and spread of 0.172 g/100 mL, 0.150 g/100 mL, and 0.01 to 0.56 g/100 mL, respectively. The 5th and 95th percentiles for blood-ethanol concentration in acute poisoning deaths were 0.22 and 0.50 g/100 mL, respectively. However, these values are probably conservative estimates of the highest blood-ethanol concentrations before death owing to metabolism of ethanol until the time of death. In 98 chronic alcoholism deaths (12%) there was an elevated concentration of acetone in the blood (>0.01 g/100 mL), and 50 of these (6%) also had elevated isopropanol (>0.01 g/100 mL). This compares with 28 cases (4%) with elevated blood-acetone in the acute poisoning deaths and 22 (3%) with elevated blood-isopropanol. We offer various explanations for the differences in blood-ethanol and blood-acetone in acute poisoning and alcoholism deaths such as chronic tolerance, alcohol-related organ and tissue damage (cirrhosis, pancreatitis), positional asphyxia or suffocation by inhalation of vomit, exposure to cold coupled with alcohol-induced hypothermia, as well as various metabolic disturbances such as hypoglycemia and ketoacidosis.     

Delayed elimination in humans after ingestion of colchicine: Two fatal cases of colchicine poisoning

Colchicine has been widely used in the treatment of acute gout over the years, but it has a narrow therapeutic index, and overdose can be life threatening. A method using ultra-high-performance liquid chromatography–tandem mass spectrometry system was applied in two fatal cases of colchicine poisoning in this study to the determination of colchicine in blood. In case 1, a 19-year-old man suffered from depression and ingested 160 colchicine tablets (each 0.5 mg). The concentration of colchicine in his blood samples showed a fluctuating trend and kept above the therapeutic steady-state concentration for 5 days. In case 2, a 70-year-old female patient with a history of gout and chronic colchicine intake ingested five times the usual dose of colchicine (5 mg) and died after 12 days of medical care, with 5 ng/mL of colchicine in her blood sample. Our findings suggest that the delayed elimination and accumulation in humans after colchicine overdose could keep the concentration of colchicine maintaining above the therapeutic steady-state concentration for many days before dying, probably along with a fluctuating trend.     

Exhumation examination to confirm suspicion of fatal lead poisoning

Acute poisonings with inorganic lead compounds are exceptionally rare. In all cases of diagnosis, there are two possible sources of error: failing to recognise lead poisoning when it is present, and mistaking other diseases for lead poisoning. If exposure history is carefully taken and proper laboratory techniques are employed, the diagnosis of lead poisoning should not be difficult. In the described case of the death of a 41-year-old-man, no enzymatic disturbances characteristic of congenital erythropoietic porphyria were ascertained, and furthermore, a considerable concentration of lead was found in antemortem material, 5 months before death (blood: 1584 microg/l, urine: 531 microg/24 h). Postmortem tissue lead content in the biological material, exhumed 6 months after death, were as follows: liver, 47.6 microg/g; kidney, 4.75 microg/g; bone, 103 microg/g of sacral vertebra, 20.4 microg/g of femoral bone, 112 microg/g of pelvis; hair, 30.2 microg/g of scalp hair, 33.7 microg/g of pubic hair; nails, 13.6 microg/g. The results indicated a case of acute lead poisoning (with lead(II) oxide, as it later turned out), which manifested as acute intermittent porphyria.     

Effect of eight solvents on ethanol analysis by Dräger 7110 Evidential breath analyzer

The Dr?ger 7110 MK III FIN Evidential breath analyzer is classified as a quantitative analyzer capable to provide sufficient evidence for establishing legal intoxication. The purpose of this study was to evaluate ethanol specificity of this instrument in the presence of other solvents. Effects of eight possible interfering compounds on ethanol analysis were determined in a procedure simulating a human breathing. Most of the compounds studied had either a negligible effect on ethanol analysis (acetone, methyl ethyl ketone, and methyl isobutyl ketone) or were detected in very low concentrations before influencing ethanol readings (methanol, ethyl acetate, and diethyl ether). However, 1-propanol and 2-propanol increased the ethanol readings significantly. Thus, Dr?ger ethanol readings should be interpreted carefully in the presence of propanol.     

Fatal intoxication with tianeptine (Stablon)

Tianeptine (Stablon), although structurally similar to tricyclic antidepressants, acts by enhancing the reuptake of serotonin. A fatal case is presented involving a 26-year-old man, found lying in bed with a "mushroom of foam" around his mouth. Empty blister packs of Stablon and a suicide note were found next to the body. A liquid-liquid extraction procedure with n-hexane: ethyl acetate and n-hexane: 2-propanol, followed by LC-DAD-MS analysis, using positive mode electrospray ionization was performed. The detection limit was 0.001 microg/mL. The toxicological results revealed the following tianeptine concentrations in the post-mortem samples: blood 5.1 microg/mL; urine 2.0 microg/mL; liver 23 microg/g; stomach contents 22 mg. Femoral blood analyses also revealed an ethanol concentration of 0.53 g/L. The present method was also developed and validated for the other post-mortem specimens, since no previous published data had confirmed the post-mortem distribution of tianeptine. The absence of other suitable direct causes of death (macroscopic or histological) and the positive results achieved with the toxicological analysis led the pathologist to rule that death was due to an intoxication caused by the suicidal ingestion of tianeptine in combination with alcohol.     

Pharmacokinetics of ethanol in patients with renal failure before and after hemodialysis

We studied the pharmacokinetics of ethanol in seven patients suffering from terminal renal failure before and after they underwent hemodialysis. Ethanol (0.40 g/kg) was administered in the morning after an overnight fast by a constant rate intravenous (IV) infusion over 45 min. After removing a mean fluid volume of 2.46±0.48 liters (±SD), span 1.76–3.43 liters by hemodialysis, the same subjects received a second IV infusion of ethanol after they had eaten lunch. At exactly timed intervals of 0, 45, 90, 105, 120, 135, 150, 165, and 180 min from the start of the infusion, two blood-samples were drawn and the plasma portion of one of them was obtained by centrifugation. The concentration of ethanol in blood and plasma was determined by headspace gas chromatography and the water-content of whole blood was determined from the change in weight after desiccation. Plasma always contained a higher concentration of ethanol than whole blood and the mean plasma/whole blood ratio in patients with renal failure was 1.07:1 (span 1.05–1.10). The rate of ethanol disappearance from blood (β-slope) was faster (0.185±0.013 versus 0.157±0.022 g/l/h), the C₀ value was higher (0.79±0.08 versus 0.73±0.10 g/l) and the apparent volume of distribution (V_d) of ethanol was lower (0.507±0.049 versus 0.558±0.078 l/kg) after hemodialysis. The water content of whole blood was significantly higher (P<0.001) before dialysis (88.6±1.97 g/100 ml) compared with after dialysis (87.4±2.01 g/100 ml). The higher V_d for ethanol and lower C₀ as well as higher blood-water content are to be expected for a over hydrated condition before hemodialysis. The swifter rate of ethanol elimination from blood (β-slope) after hemodialysis should be interpreted with caution because eating a meal before the second infusion of ethanol is a confounding factor. Nevertheless, the rate of elimination of ethanol from blood in patients with renal failure agreed reasonably well with values expected for healthy subjects, namely mean 0.15 g/l/h spanning from 0.10 to 0.20 g/l/h.     

Simple and simultaneous quantification of cyanide,ethanol, and 1-propanol in blood by headspace GC–MS/NPD with Deans switch dual detector system

Cyanide is a powerful and rapidly acting poison. In Japan, cyanide poisoning is rare, and regular cyanide testing can be costly and time consuming. In contrast, alcohol analysis is routinely performed in most forensic laboratories. In this study, we attempted to develop a method for the simultaneous quantification of cyanide and alcohols in blood using headspace gas chromatography (HS–GC). As nitrogen-phosphorus detection (NPD) is more sensitive to hydrogen cyanide than mass spectrometry (MS), a Deans switch was used to switch the detectors during a single run. The separation provided by three analytical columns, PoraBOND Q, CP-Sil 5 CB, and HP-INNOWax, was investigated, and PoraBOND Q was selected. The use of HS–GC–MS/NPD with a Deans switch enabled the simple and simultaneous quantification of cyanide, ethanol, and 1-propanol. Eighteen other volatile compounds were detected in the SIM/scan mode of the MS.     

Postmortem blood and vitreous humor ethanol concentrations in a victim of a fatal motor vehicle crash

A 20-year-old male was found on the passenger side of a small car after a collision with a semi-trailer truck. Postmortem blood, collected from the chest cavity, and vitreous humor samples were collected following harvesting of the heart and bones. Gas chromatographic analysis revealed a blood ethanol concentration of 0.32 g/dL and a vitreous humor ethanol concentration of 0.09 g/dL. The stomach was intact and full of fluid and food, but its contents were not collected. Possible explanations for the large difference between the two results include diffusion of ethanol from the stomach into the chest cavity, contamination of the blood sample prior to collection, and ingestion of a large quantity of ethanol shortly before death. This case demonstrates the importance of proper quality assurance procedures in collecting postmortem specimens and of collecting a vitreous humor sample for ethanol analysis in postmortem toxicology cases.     

Nutmeg (myristicin) poisoning--report on a fatal case and a series of cases recorded by a poison information centre

In literature, cases of nutmeg abuse have been described repeatedly, but only one fatal case of poisoning was reported [1]. In the present case, myristicin (4 microg/ml) was detected for the first time in the postmortal serum of a 55-year-old woman. Identification was achieved with the aid of UV-VIS spectroscopy and TLC; for quantification, HPLC was used. Because also flunitrazepam (0.072 microg/ml) was found, death had probably been due to the combined toxic effect of both substances. From 1996 to 1998, in a series of cases, seven poisonings with nutmeg were recorded by the Erfurt Poison Information Centre. Even where higher doses (20-80 g of powder) had been ingested, a life-threatening situation was never observed. In one of these cases, a myristicin blood level of 2 microg/ml was measured 8h after ingestion of two to three tablespoonful of nutmeg powder (approx. 14-21 g, or 280-420 mg/kg).     

Comparison of ethanol concentrations in venous blood and end-expired breath during a controlled drinking study

Concentration-time profiles of ethanol were determined for venous whole blood and end-expired breath during a controlled drinking experiment in which healthy men (n=9) and women (n=9) drank 0.40-0.65 g ethanol per kg body weight in 20-30 min. Specimens of blood and breath were obtained for analysis of ethanol starting at 50-60 min post-dosing and then every 30-60 min for 3-6 h. This protocol furnished 130 blood-breath pairs for statistical evaluation. Blood-ethanol concentration (BAC, mg/g) was determined by headspace gas chromatography and breath-ethanol concentration (BrAC, mg/2l) was determined with a quantitative infrared analyzer (Intoxilyzer 5000S), which is the instrument currently used in Sweden for legal purposes. In 18 instances the Intoxilyzer 5000S gave readings of 0.00 mg/2l whereas the actual BAC was 0.08 mg/g on average (range 0.04-0.15 mg/g). The remaining 112 blood- and breath-alcohol measurements were highly correlated (r=0.97) and the regression relationship was BAC=0.10+0.91BrAC and the residual standard deviation (S.D.) was 0.042 mg/g (8.4%). The slope (0.91+/-0.0217) differed significantly from unity being 9% low and the intercept (0.10+/-0.0101) deviated from zero (t=10.2, P<0.001), indicating the presence of both proportional and constant bias, respectively. The mean bias (BAC - BrAC) was 0.068 mg/g and the 95% limits of agreement were -0.021 and 0.156 mg/g. The average BAC/BrAC ratio was 2448+/-540 (+/-S.D.) with a median of 2351 and 2.5th and 97.5th percentiles of 1836 and 4082. We found no significant gender-related differences in BAC/BrAC ratios, being 2553+/-576 for men and 2417+/-494 for women (t=1.34, P>0.05). The mean rate of ethanol disappearance from blood was 0.157+/-0.021 mg/(g per hour), which was very close to the elimination rate from breath of 0.161+/-0.021 mg/(2l per hour) (P>0.05). Breath-test results obtained with Intoxilyzer 5000S (mg/2l) were generally less than the coexisting concentrations of ethanol in venous blood (mg/g), which gives an advantage to the suspect who provides breath compared with blood in cases close to a threshold alcohol limit.     

An unusual case of accidental poisoning: fatal methadone inhalation

In this report, the authors present a case of unusual, accidental methadone intoxication in a 40-year-old man, who had inhaled methadone powder. The drug dealer was a pharmacy technician; methadone had been stolen from a pharmacy and sold as cocaine. After having inhaled methadone powder, he suffered cardiopulmonary arrest. He was admitted to hospital where he died after 24 h of intensive care. The autopsy revealed congestion of internal organs and cerebral and pulmonary edema. Microscopically, the heart showed no changes. The toxicological analyses performed on blood and urine taken at the hospital revealed methadone, cannabinoids, and ethanol. The blood methadone concentration was 290 μg/L. The urine methadone concentration was 160 μg/L. Midazolam and lidocaine, which were administered to the patient at the hospital, were also detected in the blood. The cause of death was determined to be methadone intoxication. The literature has been reviewed and discussed. To date, and to our knowledge, only very few cases of accidental death resulting from methadone inhalation have been described up to the case presented herein.     

Fatal intoxication by Remoxipride

The case history and toxicologic findings of a 23-year-old woman who committed suicide with Remoxipride are described. Remoxipride is a recently developed neuroleptic drug of the benzamide type. Remoxipride was detected in the liver, stomach content, blood, and urine. The concentration of Remoxipride in the blood was 230 mg/L. The recommended therapeutic level for Remoxipride should not exceed 7 to 8 mg/L. The victim had no blood alcohol, but an ethanol concentration of 0.048 g/100 L was detected in the urine. The mechanism of death from Remoxipride intoxication is not known. In clinical studies, sinus bradycardia and infrequent supraventricular and ventricular ectopic beats have been noted.     

Relationship between the concentration of ethanol and methanol in blood samples from Swedish drinking drivers

Headspace gas chromatography was used to determine the concentration of ethanol and methanol in blood samples from 519 individuals suspected of drinking and driving in Sweden where the legal alcohol limit is 0.50 mg/g in whole blood (11 mmol/l). The concentration of ethanol in blood ranged from 0.01 to 3.52 mg/g with a mean of 1.83 +/- 0.82 mg/g (+/- S.D.). The frequency distribution was symmetrical about the mean but deviated from normality. A plot of the same data on normal probability paper indicated that it might be composed of two subpopulations (bimodal). The concentration of methanol in the same blood specimens ranged from 1 to 23 mg/l with a mean of 7.3 +/- 3.6 mg/l (+/- S.D.) and this distribution was markedly skew (+). The concentration of ethanol (x) and methanol (y) were positively correlated (r = 0.47, P less than 0.001) and implies that 22% (r2) of the variance in blood-methanol can be attributed to its linear regression on blood-ethanol. The regression equation was y = 3.6 + 2.1 x and the standard error estimate was 0.32 mg/l. This large scatter precludes making reliable estimates of blood-methanol concentration from measurements of blood-ethanol concentration and the regression equation. But higher blood-methanol concentrations are definitely associated with higher blood-ethanol in this sample of Swedish drinking drivers. Frequent exposure to methanol and its toxic products of metabolism, formaldehyde and formic acid, might constitute an additional health risk associated with heavy drinking in predisposed individuals. The determination of methanol in blood of drinking drivers in addition to ethanol could indicate long-standing ethanol intoxication and therefore potential problem drinkers or alcoholics.     

Commotio cordis as a result of a fight: report of a case considered to be imprudent homicide

The report describes a fatal outcome in a 5-year-old male who died after drinking a fatal dose of ethanol at the party held by his parents. Urine and blood alcohol level of the deceased was 0.4 and 0.5 g/dL, what might explain the sudden death of the child. In addition, the analysis of the boy's hair demonstrated the presence of ethyl glucuronide (EtG), a marker of alcohol consumption; hair EtG concentration levels indicated that the boy might have occasionally imbibed alcohol prior to death. Pathological lesions of the liver observed in histopathology did not contradict such a hypothesis.     

Fatal brodifacoum rodenticide poisoning: autopsy and toxicologic findings.

This report details the pathologic and toxicologic findings in the case of a 15-year-old girl who deliberately and fatally ingested brodifacoum, a commonly used rodenticide. The mechanism of death, massive pulmonary hemorrhage, has not been previously reported. Brodifacoum was quantitated in liver, spleen, lung, brain, bile, vitreous humor, heart blood, and femoral blood using HPLC with fluorescence detection. The highest brodifacoum concentrations were detected in bile (4276 ng/mL) and femoral blood (3919 ng/mL). No brodifacoum was detected in brain or vitreous humor. A brodifacoum concentration of 50 ng/g was observed in frozen liver while formalin fixed liver exhibited a concentration of 820 ng/g. A very high blood:liver brodifacoum concentration ratio suggested acute poisoning but the historical and pathologic findings suggested a longer period of anticoagulation. Though most cases of brodifacoum poisoning in humans are non-fatal, this compound can be deadly because of its very long half-life. Forensic pathologists and toxicologists should suspect superwarfarin rodenticides when confronted with cases of unexplained bleeding. Anticoagulant poisoning can mimic fatal leukemia or infectious diseases such as bacterial sepsis, rickettsioses, plague, and leptospirosis. A thorough death scene investigation may provide clues that a person has ingested these substances.