Distribution of dimethoate in the body after a fatal organphosphateintoxication

Many organophosphate pesticides (OPs) such as dimethoate are used to eradicate household pests, and those occurring in agriculture and forestry sectors. Combinations of two or more different insecticides have been manufactured to increase their effectiveness. A case of death is presented as suspected organophosphates intoxication. Autopsy was unremarkable except for grayish fluid in the stomach, with garlicky odor. A systematic toxicological analysis on post-mortem specimens revealed high concentrations of dimethoate in blood 38 μg/mL, urine 0.47 μg/mL, brain 2.2 μg/g, myocardial muscle 7.6 μg/g, liver 4.6 μg/g, lung 7.6 μg/g, skeletal muscle 21 μg/g, kidney 55 μg/g and gall bladder 31 μg/g. Blood alcohol was 2.85 g/L, cyclohexanone and cyclohexanol were also detected in the blood but not quantified. The cause of death was determined as organophosphate intoxication.     

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.     

Coexistence and concentrations of ethanol and diazepam in postmortem blood specimens: risk for enhanced toxicity?

Both ethanol and diazepam are classified as depressants of the central nervous system and exert their effects via the GABAA receptor complex. We report the coexistence and concentrations of ethanol, diazepam, and its primary metabolite nordiazepam in a case series of 234 forensic autopsies collected over a ten-year period. Diazepam, nordiazepam, and ethanol were determined in femoral venous blood by highly selective gas chromatographic methods. The mean (median) femoral blood concentrations were ethanol 0.24 g/100 mL (0.25 g/100 mL), diazepam (D) 0.23 microg/g (0.10 microg/g), nordiazepam (ND) 0.24 micro/g (0.20 microg/g), sum (D + ND) 0.43 microg/g (0.30 microg/g), and the ratio D/ND was 1.19 (1.0). When cause of death was attributed to alcohol and/or drug intoxication (N = 50), the mean and median blood-ethanol concentration was higher, being 0.36 g/100 mL and 0.38 g/100 mL, respectively, whereas the mean (median) and range of blood-diazepam concentrations were about the same, 0.23 microg/g (0.10 microg/g) and 0.05 to 1.2 microg/g. The femoral-blood concentrations of diazepam and nordiazepam were highly correlated (r = 0.73), but there was no correlation between the concentrations of ethanol and diazepam (r = -0.15). In another 114 fatalities (all causes of death) with diazepam and/or nordiazepam as the only drugs present, the mean (median) and range of blood-diazepam concentrations were 0.22 microg/g (0.10 microg/g) and 0.03 to 3.5 microg/g. The pathologists report showed that none of these deaths were classed as drug intoxications. The impression gleaned from this study of ethanol-diazepam deaths is that high blood-ethanol concentration is the major causative factor. We found no evidence that concurrent use of diazepam enhanced the acute toxicity of ethanol, although interpretation is complicated by the high blood-ethanol concentration (median 0.38 g/100 mL), making it difficult to discern an added effect of diazepam.     

Determination of dimethoate in blood and hemoperfusion cartridge following ingestion of formothion: a case study

A 57-year-old male who had ingested not more than 22 g of formothion was semicomatose on admission to hospital, approximately 1.5 h after ingestion. Dimethoate, a hydrolyzed formothion, was found in blood samples collected from the patient and in the charcoal column in the direct hemoperfusion cartridge which was used 6 to 7.5 h after ingestion. It was extracted and purified by Extrelut column extraction. A gas chromatograph, equipped with a flame photometric detector and a gas chromatograph-mass spectrometer, were used to detect and confirm the presence of dimethoate. The blood dimethoate concentrations which were taken approximately 1.5 and 6 h after ingestion were 21.4 and 12.7 micrograms/g, respectively. A blood dimethoate concentration of 21.4 micrograms/g would appear to indicate a high level of formothion intoxication. The total amount of dimethoate found in the charcoal column used was 15 mg.     

Acute flurazepam intoxication: a case report

A fatality due to ingestion of flurazepam is reported. Flurazepam is a benzodiazepine, a widely prescribed hypnotic drug for use in sleep disorders. There are only few documented reports of the disposition of flurazepam in deaths due to overdose. A 68-year-old woman was found deceased at home with no evidence of trauma or asphyxia. Toxicologic analyses were performed and drug levels measured by means of gas chromatography coupled to mass spectrometry. The flurazepam concentration in each specimen was as follows: heart blood 2.8 microg/mL, bile 323 microg/mL, and urine 172 microg/mL. Presence of flurazepam into gastric content was observed too. Based on the autopsy findings, patient history, and toxicologic results, the cause of death was determined to be acute intoxication of flurazepam and the manner, suicide.     

A fatal case of cocaine poisoning in a body packer

A 27-year-old man was carrying in his digestive tract 99 packages each containing about 10 g of a 86% cocaine powder. The courier died by acute cocaine intoxication due to inflation and rupture of four packages during a flight from Bogotá to Rome. At the autopsy, the external examination was unremarkable. The internal examination showed edema and generalized congestion of the organs. Toxicological analyses were performed by gas chromatography-mass spectrometry after solid phase extraction using Bond Elut Certify columns and derivatization with BSTFA/TMCS. High levels of cocaine and benzoylecgonine were found in blood (4.0 microg/mL and 17.0 microg/mL), urine (152.0 microg/mL and 512.0 microg/mL), bile (99.8 microg/mL and 54.0 microg/mL), vitreous humor (7.1 microg/mL and 5.8 microg/mL), brain (7.5 microg/mL and 3.5 microg/mL), and hair (55.5 ng/mg and 27.7 ng/mg). The presence of the cocaine and its metabolite in the hair suggested that the man was a cocaine user.     

Methamphetamine body packer: acute poisoning death due to massive leaking of methamphetamine

We encountered three methamphetamine (MA) body packers presenting simultaneously, one of whom died. Three Nigerian men (39, 35, and 37 years old) who attempted to smuggle were found to contain 35 (498 g), 21 (292 g), and 5 packages (73 g) of methamphetamine hydrochloride (MA-HCl) in their stomachs, respectively. Packages were wrapped with plastic film and Scotch tape. The 39-year-old man died with acute poisoning from c. 20 g of MA-HCl that had leaked from the packages into the stomach. His plasma MA concentration was 8.6 microg/mL when he was hospitalized (17 h before his death). Autopsy findings showed extreme pulmonary congestion and edema as well as moderate hepatic edema and several petechiae. Quantitative analysis was performed by gas chromatography/mass spectrometry. Extremely high concentrations of MA and its metabolite amphetamine (AP) were found in cardiac blood (63.5 microg/mL and 1.2 microg/mL), urine (4,518 microg/mL and 72.4 microg/mL), gastric contents (8,490 microg/mL and 16.9 microg/mL), and in all other autopsy samples. These high concentrations confirmed that the cause of death was acute MA poisoning. Furthermore, impurity-profiling analysis of the seized MA revealed that the MA smuggled by the three suspects originated from the same batch.     

Suicide due to oral ingestion of lidocaine: a case report and review of the literature

The Authors describe a rare case of suicide in a 31-year-old woman, due to oral ingestion of lidocaine; the histological and toxicological findings are discussed to provide useful information to the present experience with this particular modality of death. Histological examination revealed generalized stasis. In the myocardium we observed segmentation of the myocardial cells and/or widening of intercalated discs and associated group of hypercontracted myocardial cells with "square" nuclei in line with hyperdistended ones. Non-eosinophilic bands of hypercontracted sarcomeres alternating with stretched, often apparently separated sarcomeres, small foci of paradiscal contraction band necrosis, and perivascular fibrosis were observed too. Lidocaine was detected in the subject's urine through immunoenzymatic screening. Toxicological analysis by solid-liquid extraction and gas chromatography-mass spectrometry (GC-MS) analysis, was carried out to identify and quantify the individual substances present in the biological fluids and organs. Lidocaine concentrations were as follows: blood 31 microg/mL, gastric content 2.5 g, liver 10 microg/g, kidney 12 microg/g, brain 9 microg/g, spleen 24 microg/g, lung 84 microg/g, heart 9 microg/g, urine 9 microg/mL, and bile 6 microg/mL. No other drugs or alcohol were detected. When blood lidocaine reaches toxic levels, serious toxic symptoms associated with the central nervous system and cardiac system are noted. The overdose of lidocaine produces death from ventricular fibrillation or cardiac arrest. In this case, according to macroscopic and microscopic findings, the cause of death was most likely cardiac and possibly related to ventricular fibrillation.     

Fatal mephenesin intoxication

This report describes a death related to the abuse of and intoxication by mephenesin. To the best of our knowledge, this is the first report case of lethal intoxication involving solely mephenesin and reporting mephenesin blood concentrations. The victim was a 48-year-old woman found unconscious at home. Resuscitation was unsuccessful. Toxicological analysis was performed on a blood sample collected during resuscitation. The results being negative, the body was exhumed for an autopsy, which revealed bronchial inhalation syndrome. Analysis in a second laboratory has revealed the presence of mephenesin in samples collected during autopsy. No other drug/toxin was found, and alcohol was negative. Reanalysis of the peripheral blood collected during resuscitation found a mephenesin concentration of 15.81 microg/mL (15-fold greater that the maximum concentration that would result from a single intake of a 500 mg formulation). The pathologist has concluded on a bronchial inhalation syndrome consecutive to a mephenesin overdose as the cause of death. The manner of this death is discussed in the light of the toxicological hair analysis and the medical past of the victim.     

Fatal intoxication with labetalol (Trandate)

The dead body of a 44-year-old woman, previously known for depression and alcoholism, has been discovered at her place of residence by her husband. A forensic autopsy has been carried out. The results indicated unspecific histological lesions (alveolar oedema, liver steatosis and interstitial nephritis) but did not reveal any apparent cause of death. Several boxes of medicines have been found near the body, justifying a toxicological analysis. This has been performed on peripheral blood and urine samples using liquid chromatography with diode array and mass spectrometric detections, in conjunction with gas chromatography coupled with mass spectrometry. Ethanol has been found (1.24 g/L in blood, 2.63 g/L in urine and 1.33 g/kg in gastric content), as well as therapeutic concentrations of meprobamate (14.1mg/L) and low concentrations of nordazepam (0.12 mg/L) in blood. On the other hand, particularly high levels of labetalol, a widely used beta-blocker, have been found both in blood (1.7 mg/L) and urine (20.2mg/L), which led us to measure labetalol levels in available viscera samples (liver, heart, kidney, and lung) and gastric content. Measured concentrations were 14.2 microg/g, 7.8 microg/g, 5.4 microg/g, 5.2 microg/g and 31.1 microg/g, respectively. We describe here the first report of a fatal intoxication attributed to labetalol that is linked to its acute toxicity, with tissue distribution of this beta-blocker.     

An autopsy case of imipramine poisoning

We present a fatal imipramine poisoning. Quantitative analysis of imipramine and its metabolite, desipramine, was performed by high-performance liquid chromatography. The concentrations of imipramine and desipramine were 18.67 microg/mL and 6.21 microg/mL in heart blood and 6.90 microg/mL and 1.77 microg/mL in the femoral venous blood, respectively. We concluded that the cause of death was due to imipramine poisoning.     

Postmortem determination of the biological distribution of sufentanil and midazolam after an acute intoxication

A case is presented of a death caused by self-injection of sufentanil and midazolam. Biological fluids and tissues were analyzed for midazolam by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS) and for sufentanil by GC/MS. Midazolam was extracted from basified fluids or tissues homogenated with n-butyl chloride and analyzed by HPLC by using a phosphate buffer: acetonitrile (60:40) mobile phase on a mu-Bondapak C18 column at 240 nm. Sufentanil was extracted from basified fluids and tissue homogenates with hexane:ethanol (19:1). GC/MS methodology for both compounds consisted of chromatographic separation on a 15-m by 0.25-mm inside diameter (ID) DB-5 (1.0-micron-thick film) bonded phase fused silica capillary column with helium carrier (29 cm/s) splitless injection at 260 degrees C; column 200 degrees C (0.8 min) 10 degrees C/min to 270 degrees C; and electron ionization and multiple ion detection for midazolam (m/z 310), methaqualone (IS, m/z 235), sufentanil (m/z 289), and fentanyl (IS, m/z 245). Sufentanil concentrations were: blood 1.1 ng/mL, urine 1.3 ng/mL, vitreous humor 1.2 ng/mL, liver 1.75 ng/g, and kidney 5.5 ng/g. Midazolam concentrations were: blood 50 ng/mL, urine 300 ng/mL, liver 930 ng/g, and kidney 290 ng/g. Cause of death was attributed to an acute sufentanil/midazolam intoxication and manner of death a suicide.     

Acephate in biological fluids of two autopsy cases after ingestion of the chemical

Two autopsy cases, where the individuals were suspected of having ingested acephate, an organophosphorous insecticide, are reported. Acephate and its active metabolite, methamidophos (MP), were analyzed in the biological fluids by GC/MS, using the salting out method with liquid-liquid extraction columns. The first case was that of a 70-year-old man whose blood acephate was 149 microg/mL, and MP was 3.0 microg/mL. Serum pseudocholinesterase (ChE) activity was inhibited. No remarkable finding of injury or disease was determined as the cause of his death, but acute poisoning by acephate was mostly suspected. The second case was that of a 60-year-old man. A deep gash in the left neck injured the left common carotid artery in addition to the severely ischemic state of the primary organs. His blood acephate was 46 microg/mL, and MP was not detected. ChE activity was in the normal range. Hemorrhage was mainly suspected as the cause of his death. The concentrations of acephate and MP in human blood after oral ingestion are first reported here, and the acute toxic level of acephate is discussed.     

A fatal interaction of methocarbamol and ethanol in an accidental poisoning

A case is presented of a fatal drug interaction caused by ingestion of methocarbamol (Robaxin) and ethanol. Methocarbamol is a carbamate derivative used as a muscle relaxant with sedative effects. Therapeutic concentrations of methocarbamol are reported to be 24 to 41 micrograms/mL. Biological fluids were screened for ethanol using the Abbott TDx system and quantitated by gas-liquid chromatography (GLC). Determination of methocarbamol concentrations in biological tissue homogenates and fluids were obtained by colorimetric analysis of diazotized methocarbamol. Blood ethanol concentration was 135 mg/dL (0.135% w/v) and urine ethanol was 249 mg/dL (0.249% w/v). Methocarbamol concentrations were: blood, 257 micrograms/mL; bile, 927 micrograms/L; urine, 255 micrograms/L; gastric, 3.7 g; liver, 459 micrograms/g; and kidney, 83 micrograms/g. The combination of ethanol and carbamates is contraindicated since acute alcohol intoxication combined with carbamate usage can lead to combined central nervous system depression as a result of the interactive sedative-hypnotic properties of the compounds.     

Fatal unintentional intoxications with tramadol during 1995-2005

Tramadol is an extensively used centrally acting analgesic and is considered a safe drug devoid of many serious adverse effects of traditional opioids. However, recently, toxicity and an abuse potential of tramadol have been reported. This study examined fatal unintentional tramadol intoxications among Swedish forensic autopsy cases between 1995 and 2005. All fatal intoxications were selected, in which toxic concentrations of tramadol (>1 microg/g femoral blood) had been detected, and where the forensic pathologist considered the intoxication unintentional and the fatal outcome at least partly explained by tramadol. Toxicology analyses, police reports, autopsy protocols and medical records were scrutinized. A total of 17 cases (eleven men and six women) of fatal unintentional tramadol intoxications were identified. For these cases the median age was 44 years (range 18-78 years) and the median tramadol concentration was 2.0 microg/g (range 1.1-12.0 microg/g). Other pharmaceutical substances, illicit drugs or ethanol were detected in addition to tramadol in all of these cases. In fact, intoxication with multiple drugs was considered the cause of death in 10 (59%) cases. However, in seven cases tramadol was the only substance present in toxic concentrations. A history of substance abuse was identified in 14 (82%) subjects and a present tramadol abuse in 8 (47%). These results suggest that fatal intoxications with tramadol may occur unintentionally and that subjects with a history of substance abuse may be at certain risk. Precaution is therefore warranted when prescribing tramadol in such patients.     

Poisonings with diphenhydramine--a survey of 68 clinical and 55 death cases

The antihistaminic drug diphenhydramine (DPH) is mainly used as a sedative, hypnotic and antiemetic. In many countries it is over-the-counter available, very common, and generally regarded as a harmless drug. Sixty-eight non-fatal and 55 fatal poisonings with DPH alone or in combination with other drugs were investigated in the Institute of Legal Medicine of the University Hospital Charité between 1992 and 2004. The analytical investigations were performed by HPLC with photodiode array detector (HPLC-DAD). The DPH concentrations ranged from 0.5 to 8.9 microg/mL in the non-fatal cases and from 0.3 to 119 microg/mL in fatal cases. The intoxication symptoms stated during emergency admission were inconsistent, with somnolence, sedation and retardation on one hand and tachycardia, anticholinergic syndrome, agitation, hallucinations, confusion, tremor, convulsions, delirium and coma on the other. In three cases rhabdomyolysis occurred. A concentration above 5 microg/mL can be regarded as potentially lethal. In many of the survivors the time course of the concentrations of DPH and the metabolites desmethyldiphenhydramine (DM-DPH) and diphenylmethoxyacetic acid (DPMA) were investigated. Whereas DM-DPH is present in blood from the very beginning because of the high first pass metabolism, DPMA is slowly formed over several metabolic steps. For this reason, the concentration ratio DPMA/DPH can be used for an approximate estimation of the time between drug intake and sampling in clinical cases or of the survival time after drug ingestion in death cases. In some of the deaths the concentrations in heart blood were much higher than in venous blood. This is explained mainly by agonal aspiration of the vomited gastric content. Besides the majority of suicidal cases also a case of child maltreatment and a case, in which the drug was forcibly administrated in a drug facilitated crime, were investigated. From the results it follows that diphenhydramine is not less poisonous than other prescribed hypnotics. However, despite the hallucinogenic effects, an abuse for recreational purposes was not observed until now.     

Death related to midazolam overdose during endoscopic retrograde cholangiopancreatography

We report a midazolam-related death that occurred during endoscopic retrograde cholangiopancreatography (ERCP). The acute intoxication due to midazolam overdose was confirmed by high-pressure liquid chromatography (HPLC) analysis of the blood samples taken from the patient in the intensive care unit (2.8 microg/ml) and postmortem (2.4 microg/ml). The case strongly emphasizes the necessity of the precautions that should be taken when midazolam is intravenously administered.     

Immunohistochemistry of pulmonary surfactant apoprotein A in forensic autopsy: reassessment in relation to the causes of death

To reassess the immunohistochemical distribution of pulmonary surfactant apoprotein A (SP-A) in relation to the causes of death, 282 forensic autopsy cases were reviewed. The most intense and dense granular immunostaining of intra-alveolar SP-A was observed in the hyaline membrane syndrome from various traumas, protracted death from drowning, and perinatal aspiration of amniotic fluid. Similar granular staining pattern was found in fatal poisoning by a muscle relaxant and organophosphate pesticides. An evident increase of intra-alveolar granular staining was noted in most fatalities from mechanical asphyxia and drowning, and some cases of fire death. SP-A staining was usually very weak or sparse in alcohol intoxication, poisoning by hypnotics and also carbon monoxide poisoning. These findings suggest that the amount of intra-alveolar granular SP-A staining may be a possible indicator of severity and duration of respiratory distress (agony) from peripheral (non-central nervous system) origin and alveolar damage.     

Fatal Intoxication with α‐PVP,a Synthetic Cathinone Derivative

This study presents the fatal case of a young man who was admitted to the ICAU due to sudden cardiac arrest. An interview revealed that the patient had taken some unspecified crystals. From the moment of admission, his condition deteriorated dramatically as a result of increasing circulatory insufficiency. After a few hours, sudden cardiac arrest occurred again and the patient was pronounced dead. In the course of a medicolegal autopsy, samples of biological material were preserved for toxicology tests and histopathological examination. The analysis of samples using the LC‐MS/MS technique revealed the presence of α‐PVP in the following concentrations: blood—174 ng/mL, urine—401 ng/mL, brain—292 ng/g, liver—190 ng/g, kidney—122 ng/g, gastric contents—606 ng/g. The study also presents findings from the parallel histopathological examination. Based on these findings, cardiac arrest secondary to intoxication with alpha‐PVP was determined as the direct cause of the patient's death.