Toxicological findings in fatal aircraft accidents in the United Kingdom

Toxicology studies can contribute much to investigations into the causes of accidents. This paper examines toxicological data from 485 fatal aircraft accidents over a 24-year period in terms of relevance to causing accidents and difficulties in procuring samples for analysis.     

Toxicological and pathological findings in a series of buprenorphine related deaths. Possible risk factors for fatal outcome

Buprenorphine is considered to have little respiratory side effects at therapeutic doses and the partial agonistic properties should produce a "ceiling effect" for respiratory depression at higher doses. Still, there are several reports on buprenorphine related deaths. Most deaths involve drug users and the co-administration of other CNS depressant drugs as well as reduced tolerance have been suggested to be risk factors. The primary aims were to investigate if lack of tolerance and/or co-ingestion of other psychotropic drugs are significant risk factors in buprenorphine fatalities. From July 2005 to September 2009, all autopsy cases where buprenorphine or norbuprenorphine had been detected in femoral blood and where analysis of buprenorphine had been performed in urine were selected. Results from the postmortem examination and toxicology were compiled. Postmortem toxicology was performed using the routine methodology at the laboratory. In total, 97 subjects were included in the study. These were divided into four groups; Intoxication with buprenorphine (N=41), Possible intoxication with buprenorphine (N=24), Control cases where buprenorphine was not the cause of death (N=14), and Unclear (N=18). The metabolite to parent compound ratios in both blood and urine in the Intoxication group were significantly different from those in the Control and Unclear groups. An extensive poly-drug use was seen in all groups with several additional opioids in the Possible group (54%) and in the Unclear group (78%) and hypnotics or sedatives in more than 75% of the Intoxication, Possible, and Unclear cases. Illicit drugs were present in all groups but not to a great extent with amphetamine and tetrahydrocannabinol as the main findings. Interestingly, 4 cases in the Intoxication group presented with no other significant drugs in blood other than buprenorphine. We conclude that a lethal concentration of buprenorphine in blood cannot be defined. Instead the analysis of blood as well as urine can be an important tool to show that the drug was taken shortly before death and to rule out a continuous use of buprenorphine supporting the notion that abstinence is an important risk factor. The presence of alprazolam in more than 40% of the Intoxications and the presence of hypnotics and sedatives in 75% of the Intoxications suggests that these drugs interact with buprenorphine producing toxic effects that buprenorphine alone would not have produced. Still, in 10% of the Intoxications no other drugs were found indicating that under certain circumstances buprenorphine alone may produce respiratory depression resulting in death.     

Toxicological analysis of a fatal baclofen (Lioresal) ingestion

A fatality following ingestion of the drug baclofen (Lioresal) is described. Baclofen was identified in urine by gas chromatography/mass spectrometry. After derivatization with trinitrobenzene sulfonic acid, baclofen was quantitated in serum and urine by high-performance liquid chromatography. The concentration of baclofen was 17 mg/L in serum and 760 mg/L in urine collected approximately 12 h after the overdose. To our knowledge, this is only the second reported fatality involving a baclofen overdose. The previous case did not include quantitation of baclofen in any biological fluid.     

Timely antemortem and postmortem concentrations in a fatal carbamazepine overdose.

There are no published reports that include both timely antemortem and postmortem carbamazepine concentrations after massive overdose. We report a fatal overdose of carbamazepine with both timely antemortem and postmortem carbamazepine concentrations. Carbamazepine concentrations were 47.7 mcg/mL 2 h antemortem and 53 mcg/mL at 9 h postmortem. The slight rise in drug concentration may reflect continued absorption of the drug in the last 2 h before death. Postmortem carbamazepine concentrations drawn from a peripheral vessel in this patient appeared to reflect drug concentrations at the time of death.     

Cocaine fatality: an unexplained blood concentration in a fatal overdose

A case is presented of a 26-year-old female who died as a result of cocaine intoxication. A blood cocaine concentration of 330 mg/l, about 1.5 times greater than the highest concentration previously reported, was found. Blood benzoylecgonine and ecgonine methyl ester concentrations were 50 and 18 mg/l, respectively. The unusually high blood concentrations of cocaine and the metabolites are suggestive of a massive administration, however, the history suggests a series of recreational uses. The manner of death was undetermined.     

Acute fatal acetaminophen overdose without liver necrosis

Two unusual cases of suicidal overdose of acetaminophen (paracetamol) without the usual extensive centrilobular necrosis of the liver are reported. Both cases were subjected to comprehensive drug screening by immunoassay, and a combination of gas chromatography with mass spectrometry, nitrogen detection, and electron capture detection. Acetaminophen was detected in both cases. No other drugs were detected in case #1, and only a small amount of olanzapine (<0.1 mg/L) was detected in case #2. No anatomical cause of death was identified in either case. If untreated, the normal outcome of a large acetaminophen overdose would be massive hepatic necrosis with delayed death and low blood and tissue acetaminophen concentrations. In contrast, particularly high postmortem acetaminophen concentrations were measured in both our cases with little hepatic tissue damage. For case #1, femoral blood acetaminophen 1280 mg/L, vitreous 878 mg/L, and liver 729 mg/kg; in case #2, cardiac blood 1220 mg/L, vitreous 779 mg/L, liver 3260 mg/kg, and gastric 11,500 mg/500 g. Acetaminophen was measured using high performance liquid chromatography with UV detection (254 nm) using 3-hydroxyacetanilide as the internal standard. The very high concentrations of acetaminophen is these cases but relatively little hepatic damage suggests an alternative, possibly cardiac, mechanism of death.     

Toxicological findings in a death involving dextromethorphan and terfenadine.

A case of fatal self-poisoning with dextromethorphan, an antitussive, and terfanadine, an antihistamine H1, is reported. Both drugs were quantified in several postmortem tissues and fluids using capillary gas chromatography coupled to mass spectrometry. Results are discussed in the light of the existing literature.     

Toxicological aspects of fatal chloroquine poisoning over a period of several days

The anti-inflammatory and antimalarial drug chloroquine is said to be one of the most frequently used drugs to commit suicide in the Orient and Far East. After the ingestion of large amounts of this 4-amino-chinoline derivate, signs of cardiac conduction disturbances are evidence of cardiotoxic action. For clinical treatment, hemoperfusion by activated charcoal has rather than hemodialysis proved to be partly effective for the removal of the toxic substance. Following a suicidal overdose of chloroquine tablets in a 13-year-old boy, we could confirm the efficiency of hemoperfusion by continued toxicologic examinations. The total elimination was nevertheless slow. Due to high postmortem concentrations in the blood and tissues, we believe that chloroquine is deposited and especially concentrated in the reticulohistiocytary system of the liver. Death after 5 days of clinical treatment in this case may be referred to as the first cardiac arrest with irreversible hypoxic damage of the brain.     

Toxicological findings in a death resulting from the ingestion of trimipramine

A fatality following ingestion of the tricyclic antidepressant trimipramine is presented. Whole blood concentrations of trimipramine and its metabolite N-desmethyltrimipramine were measured by gas-liquid chromatography and found to be 400 and 1130 ng/mL, respectively. These findings are compared to those of previous unpublished trimipramine fatalities and fatalities caused by other tricyclic antidepressants.     

Toxicological findings in victims of traumatic deaths.

The toxicological findings from 6037 analyses of viscera obtained from victims of traumatic death are used to correlate the relative incidence of carbon monoxide, ethyl alcohol, narcotics, hypnotics, analgesics, and tranquilizers-antidepressants in deaths occurring under the following circumstances: fire related, asphyxia by hanging, by use of plastic bags, from physical obstruction of trachae, and by drowning; traumatic injury from impact of moving train, fall from height, and occupational accident; traumatic injury to pedestrian, driver, and passenger from vehicular accidents; and from violent death by shooting, stabbing, strangulation, and beating. The influence of alcohol, narcotic drugs, and tranquilizers on carbon monoxide can be seen in some of these traumatic deaths. Ethanol alone and in combination with other drugs was present in 42.3% and 19.5% of driver and pedestrian victims, respectively, of vehicular accidents in the year 1974. Comparative analysis is presented for the toxicological data obtained on victims of homicide (shooting, stabbing, strangulation, and beating) in New York City and similar data reported for victims of homicide in Detroit. In New York City 45.9% of such victims died while under the influence of alcohol or narcotic drugs, or both, with methadone predominating in the latter category. Tissue concentrations of drugs found in victims of traumatic death are presented. Diphenylhydantoin, diazepam, meperidine, and slow-acting barbiturates were found in normal therapeutic levels. Higher concentrations of amitriptyline, chlorpromazine, propoxyphene, short-acting barbiturates, and methadone were observed. The concentration of methadone in blood and brain (0.13 +/- 0.14 mg/100 ml) and in liver (0.53 +/- 0.42 mg/100 ml) in cases of traumatic death are not different from those observed in deaths classified as due to methadone overdose.     

Distribution of morphine in body fluids and tissues in fatal overdose

Two cases of fatal overdose with morphine are presented. Large amounts of the drug were involved in both cases, one by oral ingestion, the other by intravenous injection. Morphine concentrations in various body fluids and tissues are compared to those in the literature.     

Postmortem urine immunoassay showing false-positive phencyclidine reactivity in a case of fatal tramadol overdose

This is a report of postmortem false-positive reactivity using an enzyme-multiplied urine phencyclidine (PCP) immunoassay (EMIT II+) due to a single-agent fatal tramadol overdose. An autopsy of a 42-year-old male who died alone at home revealed no identifiable lethal anatomic abnormalities, thus leading to toxicologic analysis. Femoral blood was obtained for drug testing by high-performance liquid chromatography (HPLC) and showed a tramadol level of 14.0 mg/L, 2 orders of magnitude greater than the therapeutic range (0.1 to 0.3 mg/L). Urine was also obtained and EMIT II+ immunoassay revealed positivity for PCP at 88 mAU/min. However, confirmatory testing by HPLC failed to identify PCP in either the urine or serum. To verify the suspicion that this was a false-positive PCP result, stock solutions of tramadol and its major metabolite (O-desmethyltramadol) at concentrations of 100 mg/L in 10% methanol/H2O were compared with a blank solution (10% methanol/H2O) for EMIT II+ PCP reactivity and demonstrated reactivities of 44 mAU/min and 27 mAU/min, respectively. While these individual results were below the cutoff reactivity for a positive EMIT II+ PCP result (ca. 85 mAU/min), they were much more reactive than the blank calibrator (set at 0 mAU/min). Therefore, we conclude that the immunoreactivity of tramadol and its metabolites in aggregate is responsible for the PCP immunoassay interference and false-positive result.     

Toxicologic studies in a fatal overdose of 2,4-D, mecoprop, and dicamba

A suicidal poisoning committed by a 61-year-old woman, who ingested an unknown quantity of Killex, containing in aqueous solution 100 g/L of (2,4-dichlorophenox)acetic acid (2,4-D), 50 g/L of mecoprop, and 9 g/L of dicamba as amine salts is described. Quantitation of chlorophenoxy acids was performed by extraction from an acidified mixture and concentration before high performance liquid chromatography analysis. All three herbicides were separated in a phosphate buffer/acetonitrile mixture at 280 nm on a RP-8 column. Concentrations of herbicides found were: in blood--520-mg/L 2,4-D, 530-mg/L mecoprop, and 170-mg/L dicamba; in urine--670-mg/L 2,4-D and 520-mg/L mecoprop; in bile--340-mg/L 2,4-D, 530-mg/L mecoprop, and 140-mg/L dicamba; and in liver--540-mg/Kg 2,4-D, 500-mg/Kg mecoprop, and less than 100-mg/Kg dicamba. Liquid chromatography was found to be a reliable method for herbicide quantitation in biological tissues and fluids. The technique offered definite advantages over ultraviolet spectrophotometry and avoids the derivatization requirement for gas chromatography.     

Toxicological findings in Federal Aviation Administration general aviation accidents

Blood, urine, and tissue specimens were received from 377 Federal Aviation Administration (FAA) aviation fatalities during fiscal year 1989. Carbon monoxide at less than 10% saturation was found in 94% of the cases, and cyanide at less than 0.5 mg/L was found in 96% of the cases. Ethanol at greater than 10 mg/dL was found in 14.8% of the cases, but only 4.5% were determined to be due to ethanol ingestion from toxicological findings. Excluding nicotine and ethanol, 12.6% of the cases were positive for one or more drugs. Acetaminophen and salicylate were the most frequently found drugs. Cannabinoids were found in 1.3% of the cases and benzoylecgonine in 1.6%. There was minimal use of therapeutic drugs that cause central nervous system depression or stimulation. These results show no consistent pattern of drug involvement in civilian aviation fatalities.     

Chemico-toxicologic findings in fatal suicidal poisoning by demeton-S-methyl

A case of lethal suicidal intoxication with demeton-S-methyl is reported. Capillary chromatography on wide-bore columns (CP-sil 5, 0.53 mm ID, 1 micron film thickness) was used for the quantitative determinations of this substance in the body fluids and tissues.     

Tissue concentrations of MDMA and its metabolite MDA in three fatal cases of overdose

The recreational use of amphetamine derivatives has become increasingly popular in our country in past recent years. Their use is especially common among young people participating in dance parties known as "raves." As a direct consequence of their increased use, the number of fatal cases in which these compounds have been involved have increased dramatically since the second half of the last decade. In our laboratory, we have registered 25 cases related to amphetamine derivatives use since 1996. Three of them were deeply studied and the results obtained are presented in this paper. This information may be useful for the interpretation of the results obtained in toxicological analysis in the cases in which death may be attributed to MDMA use.     

Vascular lesions in intestinal ischemia induced by cocaine-alcohol abuse: report of a fatal case due to overdose

Intestinal ischemia induced by cocaine abuse is a rare condition. To this date, only three cases have been described. The diagnosis of bowel ischemia should be suspected whenever a cocaine addict has severe abdominal pain. A pathological examination of the resected bowel segment was performed in one case, and the diagnosis was confirmed microscopically. However, the existence of pathologic alterations of the intestinal vessels was not confirmed. Why the intestinal injury is segmental and whether it is related to the dose ingested, the administration route, or the combination of cocaine with alcohol, caffeine, or marijuana remain unclear. The authors report one fatal case associated with cocaine-alcohol overdose. The postmortem examination demonstrated the existence of segmental intestinal ischemia. Microscopic study failed to demonstrate thrombosis in the mesenteric vessels; however, we found an unusual lesion affecting the arterioles located in the intestinal submucosa of the hemorrhagic areas.     

Toxicological findings in military aircraft fatalities from 1986-1990.

Toxicological findings in all military aircraft fatalities investigated by the Division of Forensic Toxicology at the Armed Forces Institute of Pathology from 1986-1990 are presented. Carbon monoxide saturation levels greater than 10% were found in 4% of the 535 cases where appropriate specimens were collected. Positive ethanol findings were more indicative of postmortem formation than antemortem consumption. In only 1 case were abused drugs (cannabinoids in a passenger) detected. Other drugs identified included nicotine, chloroquine and over-the-counter analgesic agents, antihistamines and sympathomimetic drugs.