Manners of Death in Drug‐Related Fatalities in Florida

To understand the mortality patterns among drug users and potential risk factors, we evaluated drug‐related deaths reported to the Florida Medical Examiners Commission from 2001 to 2013, by substances, demographics, and manner of death. The annual drug‐related fatalities increased by 57% from 2001 to 2013 (total n = 100,882); 51.8% were accidental, 7.9% homicide, 18.6% natural, and 19.6% suicide. The different manners of death exhibited distinct demographic profiles and drug composition. The gender gap was more prominent in homicide. Age ≥55 years was more closely associated with natural death and suicide. Age <35 years and central nervous system (CNS) stimulants including amphetamines and cocaine showed higher relative risks for accidental death and homicide, whereas CNS depressants including benzodiazepines, carisoprodol, opioids, and zolpidem were more strongly associated with accidental death and/or suicide. The findings aid in identifying populations more vulnerable to drug‐related deaths, developing targeted interventions and thereby improving efficiency of preventive efforts.     

Methadone‐Related Deaths – Epidemiological,Pathohistological, and Toxicological Traits in 10‐year Retrospective Study in Vojvodina,Serbia

The number of methadone‐related deaths (MRDs) during a 10‐year period (2002–2011) in the region of Vojvodina, Serbia, was increased. The cases were evaluated according to epidemiological parameters, pathohistological findings, and toxicological screening. The majority of victims were men, aged from 20 to 38. Pathohistologically, the signs of acute focal myocardial damage were present in the heart of victims with drug abuse history shorter than 2 years, while both signs of recent and chronic focal myocardial damage were developed among victims with longer drug abuse history (2–5 years). In postmortem blood samples of 54.84% of victims, methadone was detected in combination with diazepam, both in therapeutic range. Alcohol was absent in most cases. Other detected drugs were antipsychotics and antidepressants in therapeutic concentrations. These findings raise the attention to the concomitant use of methadone and benzodiazepines with the need for further studies to clarify the mechanism of death in such cases.     

Assessment of the Role Played by N‐propanol Found in Postmortem Blood in the Discrimination Between Antemortem Consumption and Postmortem Formation of Ethanol Using Rats

This study disproves the reliability of n‐propanol as a biomarker to establish whether the ethanol found in postmortem blood is derived from antemortem ingestion or postmortem putrefactive processes. Two groups of rats were given ethanol or normal saline solution, respectively, and sacrificed 1.5 h later. After putrefaction, blood and, in a few cases, urine samples from the rats were analyzed for ethanol and n‐propanol by head‐space gas chromatography equipped with flame ionization detection. Although the concentration ratios of ethanol/n‐propanol in the postmortem blood collected from the bodies without prior alcohol consumption were expected to be <20 (as per limited case reports and previous in vitro studies), in samples from several rats that were on saline solution, this ratio was found to exceed 20. In conclusion, the concentration ratio of ethanol/n‐propanol in postmortem blood does not allow for the discernment between antemortem ingestion and the postmortem synthesis of ethanol.     

Site‐, Technique‐, and Time‐Related Aspects of the Postmortem Redistribution of Diazepam,Methadone, Morphine,and their Metabolites: Interest of Popliteal Vein Blood Sampling

Sampling site, technique, and time influence postmortem drug concentrations. In 57 cases, we studied drug concentration differences as follows: subclavian vein‐dissection/clamping versus blind stick, femoral vein‐dissection/clamping versus blind stick, right cardiac chamber, and popliteal vein‐dissection and clamping only. Cases were distributed in group #1 (all cases with both techniques), group #2 (dissection/clamping), and group #3 (blind stick). Sampled drugs were diazepam, methadone, morphine, and their metabolites. To assess PMR, mean concentrations and ratios were calculated for each group. Time‐dependent variations of blood concentrations and ratios were also assessed. Results indicate that site, method, and time may influence postmortem distribution interpretation in different ways. Popliteal blood seems less subject to PMR. In conclusion, our study is the first to evaluate concurrently three main aspects of PMR and confirms that the popliteal vein may represent a site that is more resistant to the changes seen as a result of PMR.     

Determination of Acetamiprid and IM‐1‐2 in PostMortem Human Blood,Liver, Stomach Contents by HPLC‐DAD

An HPLC‐DAD method was developed to detect and quantify a neonicotinoid insecticide acetamiprid (ATP) and its metabolite IM‐1‐2 in autopsy samples of a fatal intoxication case. The postmortem blood and tissue distribution of ATP and IM‐1‐2 was determined for the first time. The method showed acceptable precisions and recoveries with relative standard deviations of <10% for ATP level and 1.38 % for IM‐1‐2. The detection and quantification limits for ATP were 0.015 μg/mL and 0.030 μg/mL for blood and were 0.035 μg/g and 0.050 μg/g for liver samples, respectively. The mean contents of ATP were 0.79 μg/g in the liver, 47.35 μg/g in the stomach contents and 2.7 μg/mL in the blood. IM‐1‐2 content was 17.0 μg/g in the stomach contents. ATP and IM‐1‐2 were not detected in the urine. The presence of ATP and IM‐1‐2 in the samples was confirmed by GC‐MS. The method can be exploited in future forensic casework.     

Postmortem Blood Concentrations of R‐ and S‐Enantiomers of Methadone and EDDP in Drug Users: Influence of Co‐Medication and P‐glycoprotein Genotype

Abstract: We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R‐ and S‐methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R‐enantiomer concentrations significantly exceeded that of the S‐enantiomers (Wilcoxon’s test, p < 0.001). The samples were divided into four groups according to other drugs detected (methadone only, methadone and strong analgesics, methadone and benzodiazepines, or methadone and other drugs). There was no significant difference in any of the R‐methadone/total methadone ratios among the four groups. The median R/S ratio was 1.38, which tends to be higher than that reported for the plasma of living subjects. In addition, we investigated whether small nucleotide polymorphisms in the MDR1 gene that encode the drug transporter P‐glycoprotein were associated with the concentrations of R‐ and S‐methadone and its metabolite 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine. No significant association was detected.     

Machinery‐Related Deaths: Relevance of Workplace Investigation and Antemortem Radiological Data in Reconstructing the Fatality

Abstract: Machinery‐related fatalities are one of the leading causes of traumatic occupational deaths. In our report, we present the case of a 40‐year‐old male who suffered a severe head trauma while working in a cut‐foam industry and died despite an early craniectomy. The radiological reconstruction of the skull based on preoperative computed tomography scans disclosed a large depressed conical fracture of the left parietal bone. The 3D‐reconstruction of the work area, combined with a fit‐matching analysis between the machinery and the depressed skull fracture allowed us to conclude that the head was crushed between the sliding bar of the cutting device and the metallic protuberance on the opposite side. The case underlines the importance of a detailed workplace investigation and of a thorough evaluation of all circumstantial, clinical, radiological, and autopsy data in the reconstruction of machinery‐related fatalities to identify any possible legal responsibilities of the worker and/or the employer.     

Distribution of Venlafaxine,O‐desmethylvenlafaxine,and O‐desmethylvenlafaxine to Venlafaxine Ratio in Postmortem Human Brain Tissue

Venlafaxine (VEN) and its metabolite O‐desmethylvenlafaxine (ODV) inhibit reuptake of serotonin and norepinephrine. This study examines whether VEN is differentially distributed in postmortem brain and examines relationships between brain and femoral blood concentrations from donors prescribed VEN for treatment of depression. Using high‐pressure liquid chromatography‐ultraviolet detection, VEN and ODV concentrations were measured in temporal, occipital, and cerebellar cortex of six postmortem brains. The ODV/VEN ratio was calculated as a relative measure of drug metabolism within each region where higher ratios indicated a greater conversion of VEN to ODV. Compared to the other regions examined, the cerebellum showed decreased VEN (p = 0.056), ODV (p = 0.006), and ODV/VEN (p = 0.027) ratios. In parts per million, VEN was higher in temporal and occipital cortex, but not cerebellum, as compared to femoral blood concentration. These observations suggest that VEN and ODV are differentially distributed in the brain, and metabolism of VEN to ODV may vary across brain regions.     

Nonchemical Suffocation Deaths in Forensic Setting: A 6‐Year Retrospective Study of Environmental Suffocation,Smothering, Choking,and Traumatic/Positional Asphyxia*

Abstract: There are still several areas of forensic pathology mainly based on tradition, with textbooks explaining and describing common knowledge that is not supported by modern research data. This study is intended to contribute to evidence‐based data on nonchemical suffocation deaths in the forensic population aged more than 1 year. From 2000 to 2005, all autopsy cases were reviewed: age, gender, type of suffocation, and manner of death were compiled for all victims (96 cases). In general, the results from this study are concordant with the textbook literature, therefore supporting common knowledge related to manner of death in nonchemical suffocation. However, discrepancies have been underscored in smothering: smothering, contrary to the general belief, is probably not mostly homicidal, and accidental smothering is probably not that unusual. Furthermore, new data without actual literature correlates were obtained in the conducting of this study and are presented here.     

The Outbreak of Fentanyl‐Related Deaths in Cook County,Illinois, Between October 2015 and December 2017: A Retrospective Study and a Comparison with Previous Data

The National Institute on Drug Abuse has observed an increase in fentanyl deaths in the United States. One epidemic related to the abuse of fentanyl happened in Cook County in 2005–2007 (350 deaths). Another outbreak of fentanyl deaths occurred in 2015–2017 in the same area. The database of the Cook County Medical Examiner's Office was searched for cases of fentanyl deaths between 2015 and 2017: 1244 deaths were found. A comparison was performed with the previous data: an increase in the number of females was observed in 2015–2017. Also, in 2005–2007, the majority of deaths occurred among African American, while in 2015–2017, Caucasians were more involved. Within our population, some drug combinations were more common in specific demographic subgroups (male/females; Caucasian/African American; and certain age groups). The epidemiology and the most significant drug associations found at the toxicology are discussed, highlighting the usefulness of the knowledge about this outbreak for public health.