Evaluating suspected co-proxamol overdose.

In three instances of suicidal poisoning by co-proxamol (paracetamol and dextropropoxyphene) blood samples were obtained from 11 sites together with eight tissue samples, bile, urine, gastric contents and duodenal contents. Site-dependent differences in blood propoxyphene concentration varied between the three cases but concentrations were consistently lowest in peripheral blood and highest in central sites: 3.9-5.5 (pulmonary vein) mg/l; 4.6-25 (pulmonary vein) mg/l; 3.2-40 (aorta) mg/l. There was a less than twofold variation in corresponding blood paracetamol concentrations. Reference data on fatal propoxyphene blood concentrations do not specify the blood sampling site and can be misleading. The intra-individual variability of propoxyphene concentrations in blood in these three cases underscores this problem. Tissue concentrations of propoxyphene showed considerable inter-individual variability in degree and pattern. Tissue concentrations of paracetamol showed a less than twofold intra-individual variation. Body drug loads were calculated by two methods: from organ weights and tissue concentrations; from published volume of distribution data (Vd). For paracetamol the body drug load is underestimated by the organ weight calculation but the Vd calculation approximates the suspected dose based on anamnestic information. For propoxyphene the body drug load is seriously underestimated by the organ weight calculation and overestimated up to 2.5 times by the Vd calculation. Since the two drugs have a fixed ratio in co-proxamol then the dose of propoxyphene (the effective lethal agent) can be inferred from the paracetamol dose calculated by Vd. This approach may be applicable to cases of overdose with other compounded drug preparations.     

Post-mortem drug redistribution--a toxicological nightmare

Detailed human case data is presented to illustrate the dramatic extent of the phenomenon of post-mortem drug redistribution. The data suggests that there is a post-mortem diffusion of drugs along a concentration gradient, from sites of high concentration in solid organs, into the blood with resultant artefactual elevation of drug levels in blood. Highest drug levels were found in central vessels such as pulmonary artery and vein, and lowest levels were found in peripheral vessels such as subclavian and femoral veins. In individual cases, in multiple blood samples obtained from ligated vessels, concentrations of doxepin and desmethyldoxepin ranged from 3.6 to 12.5 mg/l and 1.2 to 7.5 mg/l, respectively; amobartital, secobarbital and pentobarbital from 4.3 to 25.8 mg/l, 3.9 to 25.3 mg/l and 5.1 to 31.5 mg/l respectively; clomipramine and desmethylclomipramine from 4.0 to 21.5 mg/l and 1.7 to 8.1 mg/l, respectively and flurazepam 0.15 to 0.99 mg/l; imipramine and desipramine from 4.1 to 18.1 mg/l and 1.0 to 3.6 mg/l, respectively. We conclude that this poorly studied phenomenon creates major difficulties in interpretation and undermines the reference value of data bases where the site of origin of post-mortem blood samples is unknown.     

Polydrug fatality involving metaxalone

A 29-year old female with a history of depression was found dead in a hotel room. The death scene investigation found empty pill bottles and an empty liter bottle of wine. Metaxalone, a centrally acting muscle relaxant, along with citalopram, ethanol, and chlorpheniramine were identified in the postmortem samples and quantitated by gas chromatography-mass spectrometry. The concentration of metaxalone in femoral vein blood was 39 mg/L. The heart blood concentration was 54 mg/L. Femoral vein blood concentrations of citalopram and chlorpheniramine were 0.77 mg/L and 0.04 mg/L, respectively. Ethanol levels were 0.13 g/dL in vitreous and 0.08 g/dL in heart blood. Other tissue samples were also analyzed. The authors consider the metaxalone concentrations toxic and potentially fatal. The citalopram concentrations were lower than those reported in fatal cases for this drug alone. Death was ascribed to polydrug abuse/overdose with metaxalone a major contributor. This represents the first reported case to our knowledge in which a metaxalone overdose significantly contributed to death.     

Effect of post-mortem changes on peripheral and central whole blood and tissue clozapine and norclozapine concentrations in the domestic pig (Sus scrofa)

Interpretation of the results of psychoactive or other drug measurements in post-mortem blood specimens may not be straightforward, in part because analyte concentrations in blood may change after death. There is also the issue of comparability of plasma (or serum) results to those obtained in whole blood. To investigate these problems with respect to clozapine, this drug (10mg/kg daily) was given orally to two pigs. Blood was collected 3h post-dose on day 7, the animals were sacrificed, and blood taken from central and peripheral veins for up to 48 h after death. Tissue samples were also collected immediately after death and at 48 h. Ante-mortem whole blood clozapine/N-desmethylclozapine (norclozapine) concentrations were 0.86/1.07 and 1.11/1.15 mg/l in pigs 1 and 2, respectively. Blood clozapine and norclozapine concentrations generally increased after death (central vein: clozapine up to 300%, norclozapine up to 460%; peripheral vein: clozapine up to 155%, norclozapine up to 185%). Initial blood and kidney clozapine and norclozapine concentrations were comparable in both animals, but were some two-fold higher in heart, liver and striated muscle in pig 2. In both animals, the heart and striated muscle clozapine and norclozapine concentrations had increased some two- to three-fold at 48 h, whilst the liver and kidney concentrations were essentially unchanged. The reason for the increase in heart and striated muscle concentrations at 48 h is unclear, but could be simple variation in sample site. The plasma:whole blood distribution of clozapine and norclozapine was studied in vitro. In human blood (one volunteer donor, haematocrit 0.50) the plots of plasma versus whole blood concentration were linear for both analytes across the range 0.1-1.5mg/l, although clozapine favoured plasma (plasma:whole blood ratio=1.12), whereas norclozapine favoured whole blood (ratio 0.68). In pig blood, the plots of plasma versus whole blood were non-linear in both cases, although clozapine favoured plasma to a greater extent than norclozapine. This may be due to lower plasma clozapine and norclozapine protein binding capacity in the pig as compared to man.     

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.     

Bupropion and alcohol fatal intoxication: case report.

A fatality due to the ingestion of bupropion and ethanol is presented. Bupropion and its metabolites were extracted from several tissues and identified using gas chromatography with nitrogenphosphorus and mass spectrometry detection. The concentrations of bupropion, hydroxybupropion and the erythroamino and threoamino alcohol metabolites in heart blood were 4.2, 5.0, 0.6 and 4.6 mg/l, respectively. The heart blood ethanol concentration was 0.27 g/dl. In addition, bupropion was distributed as follows: subclavian blood, 6.2 mg/l; bile, 1.4 mg/l; kidney, 2.4 mg/l; liver, 1.0 mg/kg; stomach contents, 16 mg and urine, 37 mg/l.     

Toxicological findings in a multi-drug death involving propoxyphene, caffeine, phenacetin, acetaminophen and salicylate

The toxicological findings of a multi-drug related fatal poisoning are described here. A 35-year-old Caucasian male found dead on the kitchen floor was a known user of abused drugs and had been taking aspirin alone or in combination with phenacetin and caffeine for the relief of joint pains. The gross examination of the organs at autopsy revealed slight grooving of the uncus and various stages of necrosis in the renal papillae. Histological examination confirmed the gross appearance of pulmonary congestion and edema, cerebral edema and interstitial nephritis of the tubules. Toxicological evaluation of the blood and urine samples disclosed the presence of propoxyphene (51 and 250 mg/l), salicylate (185 and 2750 mg/l), caffeine (16 and 37 mg/l), and phenacetin (9.6 and 20 mg/l). Furthermore, acetaminophen also was present in the plasma (54 mg/l) and urine. A gas liquid chromatographic method for simultaneous analysis of phenacetin and caffeine utilizing a nitrogen phosphorus detector was proposed.     

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.     

Fatal intoxications in a Swedish forensic autopsy material during 1992-2002

Compilations of substances detected in fatal intoxications are important in order to observe changes in intoxication patterns, to monitor effects of preventive work and to discover new trends in drug usage. The aim of the present study was to describe the current pattern of substances detected in fatal intoxications in Sweden. Fatal intoxications investigated at the Department of Forensic Chemistry, Link?ping, Sweden, during 1992-2002, were analysed. All suicides, uncertain cases and accidents where the cause of death were fatal intoxications (ICD-9: E950, E980 and E859) were included and substances detected in more than 50 fatal intoxications (in femoral blood) were listed. For each substance, a cut off value was set, above which concentrations were considered toxic. Fatal intoxications were detected by forensic-chemical analyses in 12% (6998/60,314) of the forensic autopsies during the study period. Among the suicides, an average of 3.8 substances were detected per case, the corresponding figure for uncertain cases and accidents were 3.5 and 4.1 substances, respectively. Ethanol was by far the most frequently detected substance, detected in 43% (3039) of the fatal intoxications, of which 32% (960) had toxic concentrations, followed by propoxyphene, detected in 27% (1863) of the fatal intoxications of which 74% (1370) had toxic concentrations. The number of cases where ethanol and propoxyphene were detected decreased during the study period. Moreover, other CNS-active drugs such as antidepressants, analgesics and anxiolytics were also frequently detected. The drugs with high proportions of cases with toxic concentrations detected were propoxyphene, amitriptyline, zolpidem, carisoprodol, alprazolam, thioridazine, methadone and ketobemidone. Selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) were detected in 12% (833) and 10% (665), respectively. A significantly (P <0.001) higher proportion of cases where TCA were detected had toxic concentrations when compared with cases where SSRI were detected (64% versus 31%).     

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.     

Incidence and toxicological aspects of cannabis and ethanol detected in 1394 fatally injured drivers and pedestrians in Ontario (1982-1984)

A comprehensive epidemiological study of the involvement of cannabis and ethanol in motor vehicle fatalities in the Province of Ontario, Canada, is described. The study is based on toxicological analyses of blood and, when available, urine specimens. Ethanol was determined by headspace gas chromatography (GC). For cannabis, the methods employed were radioimmunoassays (RIAs) for screening and gas chromatography/mass spectrometry (GC/MS) for the determination of delta-9-tetrahydrocannabinol (THC) in blood. The study sample consisted of 1169 drivers and 225 pedestrians. THC was detected in the blood of 127 driver victims (10.9%) in concentrations ranging from 0.2 to 37 ng/mL, with a mean of 3.1 +/- 5.0 ng/mL. Ethanol was found in 667 driver victims (57.1%), in concentrations ranging from 9 to 441 mg/100 mL, with a mean of 165.8 +/- 79.5 mg/100 mL. For pedestrians, the incidence of THC and ethanol in the blood was 7.6 and 53.3%, respectively. The incidence of THC in the driver victims in this study constitutes an approximately threefold increase over the results of an Ontario study completed in 1979. At least a part of the increase may be attributed to interstudy differences in analytical methodology for cannabinoids.     

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.     

Kinetics of ethanol in biological sections

Ethanol concentration in alveolocapillary blood (ACB), venous blood (VB), capillary blood (CB), saliva and urine was measured in healthy men and women aged 19-45 years 20, 40, 60, 90, 120, 180, 240 and 300 min after a single intake of 20% ethanol solution in soda water in a dose 0.8 g/kg body mass. Two types of kinetic curves were established. Calculations with Vidmark equation for different biomedia were made. Ethanol levels in all BM studied coincided in the resorption phase. In the elimination phase, ethanol concentration forms a sequence: ACB < saliva < VB < urine. Correlations and correlation coefficients of ethanol concentrations in different BM were estimated. The ethanol concentration correlation urine/ACB 1.71 +/- 0.15 and VB/ACB 1.45 +/- 0.07 is proposed for use in tests for alcohol intoxication.     

Fatal tolperisone poisoning: autopsy and toxicology findings in three suicide cases

Tolperisone (Mydocalm) is a centrally acting muscle relaxant with few sedative side effects that is used for the treatment of chronic pain conditions. We describe three cases of suicidal tolperisone poisoning in three healthy young subjects in the years 2006, 2008 and 2009. In all cases, macroscopic and microscopic autopsy findings did not reveal the cause of death. Systematic toxicological analysis (STA) including immunological tests, screening for volatile substances and blood, urine and gastric content screening by GC-MS and HPLC-DAD demonstrated the presence of tolperisone in all cases. In addition to tolperisone, only the analgesics paracetamol (acetaminophen), ibuprofen and naproxen could be detected. The blood ethanol concentrations were all lower than 0.10 g/kg. Tolperisone was extracted by liquid-liquid extraction using n-chlorobutane as the extraction solvent. The quantification was performed by GC-NPD analysis of blood, urine and gastric content. Tolperisone concentrations of 7.0 mg/l, 14 mg/l and 19 mg/l were found in the blood of the deceased. In the absence of other autopsy findings, the deaths in these three cases were finally explained as a result of lethal tolperisone ingestion. To the best of our knowledge, these three cases are the first reported cases of suicidal tolperisone poisonings.     

A "back door" approach to analysis of ethanol-associated risks and behavior

Ethanol has been detected in the majority of medical examiner cases involving nonnatural death and in a substantial number of natural deaths. The higher the serum alcohol concentration (SAC), the greater were the odds that death was due to external (traumatic) causes. We identified 149 medical examiner cases that were positive for ethanol and negative for 11 major drug of abuse groups, and studied those cases to further clarify ethanol-related risk factors and behaviors. Based on terms of frequency of occurrence, the data identify SACs of 201 mg% to 300 mg% as a particularly high risk factor for sudden, unexpected, traumatic death. Traumatic deaths associated with SACs below 100 mg% were infrequent, and attendant opinions concerning the contributory role of ethanol must be made with circumspection. SACs below 150 mg% could not be used to predict whether or not the decedents had been engaged in active or sedentary behavior prior to death because both situations occurred with equal frequency. At SACs between 151 mg% and 350 mg%, active situations were observed three times as often as sedentary situations. When SACs were 350 mg%, sedentary situations were observed twice as often as active situations. Suicide victims and driver fatalities rarely showed SACs above 350 mg%; therefore finding such SACs in apparent suicidal or driver fatality situations should prompt a thorough investigation to rule out other possibilities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post-mortem toxico-kinetics of trazodone.

Trazodone is a structurally unique bicyclic anti-depressant, said to be significantly less toxic than other anti-depressants following an acute overdose. We studied the tissue distribution and post-mortem redistribution of trazodone in two fatalities, one of which allowed comparison with trimipramine, a typical tricyclic anti-depressant. Case 1, a 53-year-old female weighing 72 kg, had femoral vein concentrations of trimipramine 5.5 micrograms/ml, trazodone 14.4 micrograms/ml and alcohol 107 mg%. Case 2, a 48-year-old female of 70 kg, had a femoral vein trazodone of 15.5 micrograms/ml and alcohol 34 mg%, with no other drugs detected. For case 1 and case 2 respectively, trazodone tissue concentrations were: skeletal muscle 7.3 and 9.0 micrograms/g; left and right lungs 13.3, 12.9 and 35.3, 40.1; myocardium, 30.9 and 28.9; kidneys 34.7 and 39.6; liver 73.7 and 82.4; fat 18.5 and 16.5; brain 48.6 and 20.9. For case 1 and 2, respectively, blood trazodone concentrations in 10 initial autopsy samples ranged from 13.7-17.3 and 14.4-16.9 micrograms/ml. Twenty-four and forty-eight hours later the respective ranges were 12.8-18.0 and 12.4-19.9 for case 1, 12.5-20.1 and 12.7-27.0 for case 2. By contrast, for trimipramine, blood concentrations at 0 time, 24 h and 48 hours ranged from 5.5-11.4, 5.2-14.3, and 4.2-18.2, respectively. We conclude that trazodone shows little preferential concentration in solid organs and consequently has relatively stable post-mortem blood concentrations with little drug redistribution artefact. Both the clinical pharmacokinetics and post-mortem toxicokinetics of trazodone differ significantly from the tricyclic anti-depressants.     

Headspace gas chromatographic determination of ethanol: the use of factorial design to study effects of blood storage and headspace conditions on ethanol stability and acetaldehyde formation in whole blood and plasma

Our headspace gas chromatographic flame ionization detection (HS-GC-FID) method for ethanol determination showed slightly, but consistently, low ethanol concentrations in whole blood (blood) in proficiency testing programs (QC-samples). Ethanol and acetaldehyde were determined using HS-GC-FID with capillary columns, headspace equilibration temperature (HS-T degrees ) of 70 degrees C and 20 min equilibration time (HS-EqT). Full factorial designs were used to study the variables HS-T degrees (50 degrees -70 degrees C), HS-EqT (15-25 min), ethanol concentration (0.20-1.20 g/kg) and storage at room temperature (0-6 days) with three sample-sets; plasma, hemolyzed blood and non-hemolyzed blood. A decrease in the ethanol concentration in blood was seen as a nearly equivalent increase in the acetaldehyde concentration. This effect was not observed in plasma, indicating chemical oxidation of ethanol to acetaldehyde in the presence of red blood cells. The variables showed different magnitude of effects in hemolyzed and non-hemolyzed blood. A decrease in ethanol concentration was seen even after a few days of storage and also when changing the HS-T degrees from 50 to 70 degrees C. The formation of acetaldehyde was dependent on all the variables and combinations of these (interactions) and HS-T degrees was involved in all the significant interaction effects. Favorable instrumental conditions were found to be HS-T degrees of 50 degrees C and HS-EqT of 15-25 min. The ethanol concentrations obtained for the range 0.04-2.5 g/kg after analyzing authentic forensic blood samples with a HS-T degrees of 50 degrees C were statistically significantly higher than at 70 degrees C (+0.0154 g/kg, p < 0.0001, n = 180). In conclusion, chemical oxidation of ethanol to acetaldehyde in the presence of red blood cells has been shown to contribute to lowered ethanol concentrations in blood samples. Storage conditions before analysis and the headspace equilibration temperature during analysis were important for the determination of blood ethanol concentrations.     

The PMMA epidemic in Norway: comparison of fatal and non-fatal intoxications

During a 6 month period (July 2010-January 2011) we observed 12 fatal intoxications and 22 non-fatal cases related to the drug paramethoxymethamphetamine (PMMA) in Norway (4.8 mill inhabitants). This toxic designer drug, also known as "Death", is occasionally found in street drugs offered as "ecstasy" or "amphetamine". The present study aimed to evaluate the cause of death, and to compare the PMMA blood concentrations in fatal and non-fatal cases. Methods for identification and quantification of PMMA are presented. The median age of fatalities was 30 years (range 15-50) with 67% males; in non-fatal cases 27 years (20-47) with 86% males. In the 12 fatalities, the median PMMA blood concentration was 1.92 mg/L (range 0.17-3.30), which is in the reported lethal range of 0.6-3.1 mg/L in peripheral blood and 1.2-15.8 mg/L in heart blood. In the 22 non-fatal cases, the median PMMA concentration was 0.07 mg/L (range 0.01-0.65). Poly-drug use was frequent both in fatal and non-fatal cases. The PMA concentrations ranging from 0.00 to 0.26 mg/L in both groups likely represented a PMMA metabolite. Three fatalities were attributed to PMMA only, six to PMMA and other psychostimulant drugs, and three to PMMA and CNS depressant drugs, with median PMMA concentrations of 3.05 mg/L (range 1.58-3.30), 2.56 (1.52-3.23) and 0.52 mg/L (0.17-1.24), respectively. Eight victims were found dead, while death was witnessed in four cases, with symptoms of acute respiratory distress, hyperthermia, cardiac arrest, convulsions, sudden collapse and/or multiple organ failure. In summary, all fatalities attributed to PMMA had high PMMA blood concentrations compared to non-fatal cases. Our sample size was too small to evaluate a possible impact of poly-drug use. A public warning is warranted against use and overdose with illegal "ecstasy" or "speed" drugs.     

Heroin fatality due to penile injection

Death due to heroin overdose and/or rapid injection of heroin is a frequent occurrence among opioid addicts. We present an unusual case of heroin fatality due to the injection of the drug in the penis. Blood, urine, bile, and vitreous humor concentrations of morphine were 0.68, 0.49, 0.32 and 0.062 microg/ml, respectively. Ethanol was detected at concentrations of 104, 124, 106, and 94 mg/dl in the blood, urine, bile, and vitreous humor, respectively. The cause of death was determined to be due to heroin and ethanol intoxication.