Sudden death caused by 1,1-difluoroethane inhalation

A 20-year-old man was found dead on the floor next to a computer, with a nearly full can of "CRC Duster" dust remover located next to the deceased on the floor, and an empty can of the same product on the computer desk. Toxicologic evaluation using either gas chromatography/mass spectrometry (GC/MS) or gas chromatography/flame ionization detector (GC/FID) method identified the active ingredient 1,1-difluoroethane (Freon 152a) in all tissues analyzed. Tissue distribution studies revealed highest concentration in central blood, lung, and liver. It is believed that the 1,1-difluoroethane inhalation was the cause of death.     

Ethyl sulphate and ethyl glucuronide in vitreous humor as postmortem evidence marker for ethanol consumption prior to death

To clarify the circumstances of death, the degree of inebriation is of importance in many cases, but for several reasons the determination of the ethanol concentration in post-mortem samples can be challenging and the synopsis of ethanol and the direct consumption markers ethyl glucuronide (EtG) and ethyl sulphate (EtS) has proved to be useful. The use of a rather stable matrix like vitreous humor offers further advantages. The aim of this study was to determine the concentrations of ethanol and the biomarkers in the robust matrix of vitreous humor and to compare them with the respective levels in peripheral venous blood and urine. Samples of urine, blood from the femoral vein and vitreous humor were taken from 26 deceased with suspected ethanol consumption prior to death and analyzed for ethanol, EtS and EtG. In the urine samples creatinine was also determined. The personal data, the circumstances of death, the post-mortem interval and the information about ethanol consumption prior to death were recorded. EtG and EtS analysis in urine was performed by LC-ESI-MS/MS, creatinine concentration was determined using the Jaffé reaction and ethanol was detected by HS-GC-FID and by an ADH-based method. In general, the highest concentrations of the analytes were found in urine and showed statistical significance. The mean concentrations of EtG were 62.8mg/L (EtG100 206.5mg/L) in urine, 4.3mg/L in blood and 2.1mg/L in vitreous humor. EtS was found in the following mean concentrations: 54.6mg/L in urine (EtS100 123.1mg/L), 1.8mg/L in blood and 0.9mg/L in vitreous humor. Ethanol was detected in more vitreous humor samples (mean concentration 2.0g/kg) than in blood and urine (mean concentration 1.6g/kg and 2.1g/kg respectively). There was no correlation between the ethanol and the marker concentrations and no statistical conclusions could be drawn between the markers and matrices.     

Tissue distribution of lidocaine after fatal accidental injection

The accidental death of a 64-year-old heart patient as a result of the injection of an incorrect dose of lidocaine is presented. The attending nurse inadvertently administered an intravenous bolus of 10 mL of 20% lidocaine (2g). The patient should have received 5 mL of 2% lidocaine (0.1 g). Such iatrogenic overdoses of lidocaine arise from confusion between prepackaged dosage forms. Lidocaine concentrations (mg/L or mg/kg were: blood, 30; brain, 135; heart, 106; kidney, 204; lung, 89; spleen, 115; skeletal muscle, 20; and adipose, 1.3. The results indicate that even during cardiopulmonary resuscitation as much as 38% of the administered dose of lidocaine may be found in poorly perfused tissue such as skeletal muscle and adipose.     

Postmortem oxycodone and hydrocodone blood concentrations

There is limited data on postmortem oxycodone concentrations, consisting of three published reports with a total of 11 cases, many of which were polypharmacy cases. This report presents the results of a review of autopsy and coroner's reports from 10 counties for the years 2000 and 2001 to locate cases with oxycodone or hydrocodone exposure as a leading cause of death. Eighty-eight cases were located. Twenty-four deaths were attributed to oxycodone alone. Mean and median postmortem oxycodone blood concentrations were 1.23 mg/L and 0.43 mg/L, respectively. The range was 0.12 to 8.0 mg/L, with 13 cases (54%) < or = 0.5 mg/L. Seventeen deaths were attributed to hydrocodone alone. Mean and median postmortem hydrocodone blood concentrations were 0.53 mg/L and 0.40 mg/L, respectively. The range was 0.12 to 1.6 mg/L, with 11 cases (65%) < or = 0.5 mg/L. There were seven cases where the cause of death was attributed to the effects of a combination of hydrocodone and oxycodone. Mean oxycodone and hydrocodone blood concentrations were 0.34 mg/L and 0.14 mg/L, respectively. Forty cases involved polysubstance overdoses with significant involvement of other drugs and ethanol. Mean oxycodone and hydrocodone blood concentrations were 0.18 mg/L and 0.29 mg/L, respectively. The list of other substances involved was extensive but included ethanol, amitriptyline, methadone, codeine, propoxyphene, and acetaminophen. The findings of this study report oxycodone values associated with a fatality at blood concentrations lower than previously reported. This may represent enhanced information because of the larger sample group. Hydrocodone values associated with a fatality were similar to previously published values.     

Death due to inhalation of ethyl chloride

A 30-year-old white male was found dead in a locked apartment with a rag held loosely in his mouth. Four cans (3 empty, 1 partially empty) containing ethyl chloride and labeled as VCR head cleaner were found next to the body. Phenylpropanolamine and low therapeutic levels of diazepam (64 microg/L) and nordiazepam (126 microg/L) were detected during toxicological analysis. An unidentified peak was observed when performing ethanol analysis by headspace gas chromatography. The peak was identified as ethyl chloride and the concentrations in the blood, urine, vitreous, brain, and lungs of the deceased were 423 mg/L, 35 mg/L, 12 mg/L, 858 mg/kg, and 86 mg/kg, respectively. The results were compared with previously reported levels of ethyl chloride in blood and vitreous and, based on a literature search, we believe that this is the first report of ethyl chloride levels in tissue.     

Thiodicarb and methomyl tissue distribution in a fatal multiple compounds poisoning

Abstract:  Thiodicarb is a nonsystemic carbamate insecticide whose acetylcholinesterase activity is related to its main methomyl degradation product. A 40-year-old woman was found dead in her car. Empty packages of medicines and an open bottle of Larvin^® containing thiodicarb were found near her body. No signs of violence nor traumatic injuries were noticed upon autopsy, and police investigations strongly suggested a suicide. Systematic toxicological analysis performed on postmortem specimens revealed the presence of various sedatives, hypnotics, and antipsychotic drugs in blood, urine, and gastric content. Some of the compounds identified were determined at blood concentrations well above the known therapeutic concentrations: zolpidem (2.87 mg/L), bromazepam (2.39 mg/L), nordazepam (4.21 mg/L), and levopremazine (0.64 mg/L). Specific analysis of thiodicarb and of its methomyl metabolite was then performed on all fluids and tissues collected during autopsy by liquid chromatography ion trap tandem mass spectrometry (LC-MS-MS). The anticholinesterase capacity of blood, urine, and gastric content collected at autopsy was 83%, 82%, and 32%, respectively (normal value: 0%). The presence of thiodicarb in the bottle found near the body corroborates the hypothesis of an intake of that compound. Although thiodicarb was only detected in gastric content (24.3 mg/L), its methomyl metabolite was quantified in most postmortem tissues and fluids: gastric content (19.9 mg/L), peripheral blood (0.7 mg/L), urine (8.5 mg/L), bile (2.7 mg/L), liver (0.7 mg/kg), kidney (1.7 mg/kg), lung (1.5 mg/kg), brain (9.3 mg/kg), and heart (3.6 mg/kg).     

Tissue distribution of tramadol and metabolites in an overdose fatality

Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. Although it has some affinity for the opiate receptors, tramadol is believed to exert its analgesic effect by inhibiting the re-uptake of norepinephrine and serotonin. There are several published cases of tramadol's involvement in drug-related deaths and impairment. Reports of deaths involving tramadol alone with associated tissue concentrations are rare. This report documents a case in which tramadol overdose was identified as the cause of death. The following tramadol concentrations were found in various tissues: blood, 20 mg/L; urine, 110.2 mg/L; liver, 68.9 mg/kg; and kidney, 37.5 mg/kg. Tissue distributions of the two primary metabolites, N-desmethyl and O-desmethyl tramadol, are also reported. In each tissue or fluid except urine, the tramadol concentration was greater than either metabolite, consistent with other reports of drug-impaired drivers and postmortem cases. The O-desmethyl metabolite concentration was greater than the N-desmethyl metabolite concentration in all tissues; this is in contrast to other postmortem reports, in which the majority of cases report concentrations of O-desmethyl as less than those of N-desmethyl. This may be useful as an indicator of time lapse between ingestion and death.     

Fatal cyclobenzaprine overdose with postmortem values

There are only two published cases of overdose with postmortem blood cyclobenzaprine concentrations, both with confounding factors. We report two additional cases of fatal cyclobenzaprine overdose with postmortem values. Case 1: a 56-year-old female was found in full cardiopulmonary arrest after a verbal suicide threat to a friend. Postmortem blood concentrations were cyclobenzaprine 0.96 mg/L and diazepam 0.3 mg/L. Case 2: a 37-year-old male was found in full arrest by a family member after an intentional ingestion of cyclobenzaprine. Postmortem blood concentrations were cyclobenzaprine 0.8 mg/L and ethanol 0.174 gm/dL. The concentrations of diazepam and ethanol reported in these two patients were not found in quantities usually associated with a fatal outcome, suggesting that the cyclobenzaprine was the primary cause of the fatality. Additionally, the blood was drawn from a femoral site, so that postmortem redistribution is not a likely factor. Blood concentration of > or = 0.8 mg/L cyclobenzaprine may be associated with a fatal outcome.     

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.     

Tissue distribution of olanzapine in a postmortem case

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.     

Postmortem investigation of lamotrigine concentrations

Lamotrigine is a relatively new anticonvulsant. Therapeutic plasma concentrations generally range from 1 to 4 mg/L, although several studies have shown that good control of epilepsy has been achieved with concentrations reaching 10 mg/L generally, with little toxicity. In overdose, however, the drug has been linked to ECG changes that may suggest a possible arrythmogenic effect and hence cardiac toxicity. Lamotrigine has also been shown to cause encephalopathy and thus neurotoxicity. There is no information concerning postmortem lamotrigine concentrations and their interpretation. We describe lamotrigine concentrations in postmortem specimens including blood, liver, bile, vitreous humour, and urine from eight cases. A high performance liquid chromatography (HPLC) method is described with extraction procedures for the various tissues. Two possible groups were identified. The first being the "broader therapeutic" group with blood concentrations ranging from 0.9 to 7.2 mg/L and corresponding liver concentrations ranging from 16 to 36 mg/kg. The second being a "supratherapeutic" group with blood concentrations ranging from 20 to 39 mg/L and corresponding liver concentrations ranging from 53 to 350 mg/kg. Although none of the eight cases described were attributed to overdose by lamotrigine alone, the cause of death for one of the three cases in the "supratherapeutic" group was given as mixed drug toxicity. Cause of death for the remaining two cases in this group was reported as epilepsy. However, both these cases showed elevated concentrations of lamotrigine and both were co-medicated with valproic acid. Such co-administration has been shown in the literature to lead to elevated lamotrigine concentrations and a reduction in lamotrigine dose has been recommended. With such data, we highlight the importance of monitoring lamotrigine concentrations in cases co-medicated, particularly with valproic acid.     

Phenol: tissue distribution in a fatality

A case is reported where phenol, a disinfectant, was ingested and resulted in the death of a 40-year-old white female. Concentrations of phenol were determined in blood (130 mg/L), urine (47 mg/L), bile (187 mg/L), brain (486 mg/kg), kidney (331 mg/kg), muscle (204 mg/kg), liver (228 mg/kg), and stomach content (668 mg) and compared to other cases reported in the literature.     

Disposition of citalopram in biological specimens from postmortem cases

Citalopram is a bicyclic phthalate compound approved in 1998 by the U.S. Food and Drug Administration for the treatment of depression. It is a highly selective serotonin reuptake inhibitor that appears to have little effect on noradrenaline or dopamine reuptake. Since this drug has only recently been released on the U.S. market, information regarding therapeutic, toxic, and lethal concentrations is sparse. This study reports the detection of citalopram in 22 postmortem cases. Citalopram was identified and quantitated by capillary column gas chromatography with nitrogen phosphorus detection after basic liquid-liquid extraction. Confirmation was achieved by full scan electron impact gas chromatography/mass spectrometry. In the 22 cases studied, heart blood citalopram concentrations ranged from 0.09 to 1.64 mg/L (n = 22, mean +/- SD = 0.51+/-0.43, median = 0.34); femoral blood concentrations ranged from 0.09 to 0.76 mg/L (n = 14, mean +/- SD = 0.34+/-0.23, median = 0.28); and urine concentrations ranged from 0.05 to 276.00 mg/L (n = 13). Liver was analyzed in three cases with citalopram concentrations ranging from 2.22 to 8.08 mg/kg. The average heart blood/femoral blood ratio was 1.26 (range 0.75 to 1.98, n = 14). In each case, the cause of death was not considered to be related to citalopram toxicity. These data may therefore provide a basis for establishing post mortem citalopram concentrations following therapeutic doses.     

Postmortem concentrations of citalopram

The postmortem concentrations of citalopram in blood, bile, liver, and vitreous humour were investigated in 14 cases using a specially developed high performance liquid chromatography assay. Concentrations from drug and non-drug related deaths were categorized to determine a postmortem therapeutic and toxic range. Therapeutic citalopram concentrations for blood, bile, liver, and vitreous humour ranged to 0.4 mg/L, 2.1 mg/l, 6.6 mg/kg, and 0.2 mg/L, respectively. In one potentially fatal response to citalopram, concentrations were 0.8 mg/L, 6.0 mg/L, 0.3 mg/L for blood, bile and vitreous humour, respectively.     

Morbus Fahr--considerations on a case of sudden death

This paper presents 21 cases related to cyanide intoxication by oral ingestion. Cyanide concentrations in biological specimens are especially different from the type of postmortem specimens, and very important in interpreting the cause of death in postmortem forensic toxicology. Besides the detection of cyanide in autopsy specimens, the autopsy findings were unremarkable. Biological samples (0.2mL or equal to less than 10μg of cyanide) were analyzed colorimetrically for cyanide. In a series of 21 cyanide fatalities, the concentration ranges (mean±SD) of cyanide in heart blood, peripheral blood and gastric contents were 0.1-248.6mg/L (38.1±56.6mg/L), 0.3-212.4mg/L (17.1±45.1mg/L) and 2.0-6398.0mg/kg (859.0±1486.2mg/kg), respectively. The ranges of the heart/peripheral blood concentration ratio and gastric contents/peripheral blood concentration ratio were 0.3-10.6 (mean 3.4) and 3.4-402.4 (mean 86.0), respectively. From the difference of cyanide concentration and the concentration ratio of cyanide in different types of postmortem specimens, the possibility of the postmortem redistribution of cyanide and death by oral ingestion of cyanide could be confirmed. We reported cyanide fatal cases along with a review of literature.     

Postmortem hydroxychloroquine concentrations in nontoxic cases

Hydroxychloroquine (HCQ) is a 4-aminoquinoline compound used to treat malaria and chronic autoimmune disorders and is not uncommonly found in the medical examiner setting. Studies have shown HCQ to have a long half-life (32-56 days in blood), high volume of distribution (580-815 L/kg), and therapeutic concentrations ranging from 0.03 to 15 mg/L, depending on the chronicity of treatment. Previous reports have shown that the toxic concentration of HCQ ranges from 3 to 26 mg/L, whereas the lethal concentration ranges from 20 to 104 mg/L. A report addressing nontoxic postmortem concentrations of HCQ in individuals known to be taking the medication, and in whom there is no evidence of toxicity, has not been previously undertaken. This study found that postmortem concentrations in nontoxic cases can range from 0.3 to 39 mg/L, which is well within the reported range of both lethal and toxic concentrations. It is recommended that all investigative and autopsy data be considered and that the cause of death not be certified based purely on blood HCQ concentrations.     

Fatality due to methyl acetylene-propadiene (MAPP) inhalation

A 33-year-old man died after intentionally inhaling a gaseous mix of methyl acetylene (propyne) and propadiene (allene) commonly known as MAPP, which is used for soldering and welding. He was found with a plastic bag securely placed over his head and a cylinder of MAPP alongside his head. The cylinder had been vented into the bag using a flexible hose. A comprehensive toxicological analysis revealed only a trace of diphenhydramine in the liver and 0.02 mg/L of morphine in the urine. Analysis of blood by headspace gas chromatography (HS-GC) detected two unknown peaks. These were determined to be the components of MAPP gas. MAPP was quantitated in femoral blood (59.6 mg/L) and brain (43.6 mg/kg) using a HS-GC method. The cause of death was attributed to acute MAPP intoxication, and the manner was determined to be suicide. A discussion on the analytical and interpretive considerations commonly encountered when analyzing volatile compounds is also presented.     

Fatal outcome of poisoning with the benzodiazepines flunitrazepam and diazepam

On a wintry day a 29-year-old woman was found dead beside her car showing head injuries and signs of hypothermia. Several empty packets of sedative and hypnotic drugs were lying inside the car. Toxicological analysis revealed the presence of flunitrazepam (heart blood of the left and right chamber 0.033 mg/L each), norflunitrazepam (left heart blood 0.029 mg/L, right heart blood 0.027 mg/L), 7-amino-flunitrazepam (left heart blood 0.090 mg/L, right heart blood 0.104 mg/L), diazepam (left heart blood 0.395 mg/L, right heart blood 0.386 mg/L), nordazepam (left heart blood 0.112 mg/L, right heart blood 0.115 mg/L) and temazepam (left heart blood 0.034 mg/L, right heart blood 0.033 mg/L). Neither alcohol nor other drugs were found. It was concluded that benzodiazepine intake led to a disturbance of consciousness. Whether the woman died in this situation due to the icy temperature as a result of hypothermia or whether she died or would have died solely due to benzodiazepine overdosage could not be clarified.     

Concentrations of cocaine and its major metabolite benzoylecgonine in blood samples from apprehended drivers in Sweden

Cocaine and its major metabolite benzoylecgonine (BZE) were determined in blood samples from people arrested in Sweden for driving under the influence of drugs (DUID) over a 5-year period (2000-2004). Venous blood or urine if available, was subjected to a broad toxicological screening analysis for cannabis, cocaine metabolite, amphetamines, opiates and the major benzodiazepines. Verification and quantitative analysis of cocaine and BZE in blood was done by gas chromatography-mass spectrometry (GC-MS) at limits of quantitation (LOQ) of 0.02mg/L for both substances. Over the study period 26,567 blood samples were analyzed and cocaine and/or BZE were verified in 795 cases (3%). The motorists using cocaine were predominantly men (>96%) with an average age of 28.3+/-7.1 years (+/-standard deviation, S.D.). The concentration of cocaine was below LOQ in 574 cases although BZE was determined at mean, median and highest concentrations of 0.19mg/L, 0.12mg/L and 1.3mg/L, respectively. In 221 cases, cocaine and BZE were together in the blood samples at mean and (median) concentrations of 0.076mg/L (0.05mg/L) and 0.859mg/L (0.70mg/L), respectively. The concentrations of BZE were always higher than the parent drug; mean BZE/cocaine ratio 14.2 (median 10.9) range 1-55. Cocaine and BZE were the only psychoactive substances reported in N=61 cases at mean (median) and highest concentrations of 0.095 (0.07) and 0.5mg/L for cocaine and 1.01 (0.70) and 3.1mg/L for BZE. Typical signs of drug influence noted by the arresting police officers included bloodshot and glossy eyes, agitation, difficulty in sitting still and incoherent speech.