Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam,Methadone, and Morphine

Postmortem redistribution (PMR) refers to the site‐ and time‐related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution.     

Morphine Concentrations in Stomach Contents of Intravenous Opioid Overdose Deaths

Abstract:  Death caused by heroin overdose is almost always the result of intravenous injection of the drug in Australia. We briefly describe a case where a heroin overdose was initially thought to be the result of oral ingestion of the drug, primarily as a result of higher concentrations of morphine in stomach contents than in blood. During the subsequent criminal trial and investigation, however, the issue of the entero-hepatic circulation of morphine was raised as a possible reason for the presence of morphine in the stomach contents. In this study, we report on the distribution of opioids in blood, stomach contents, urine, liver, and bile in 29 deaths caused by intravenous heroin overdose. The mean total and free blood morphine concentrations were 0.60 and 0.32 mg/L , respectively, and the mean stomach contents total morphine concentration was 1.16 mg/kg. All cases had detectable morphine in the stomach contents, and 24 of 29 cases (83%) had higher concentrations of total morphine in stomach contents than in blood. The mean total morphine concentration in bile was c. 100 times that in blood, and the liver total morphine concentration averaged twice that of blood levels. We conclude that the entero-hepatic circulation of morphine and subsequent reflux of duodenal contents back into the stomach can result in the deposition of morphine in gastric contents. Consequently, the relative levels of opioids in blood and stomach contents cannot be used to determine the site of administration of the drug.     

Oral abuse of fentanyl patches (Duragesic): seven case reports

In order to increase the understanding regarding the oral abuse and potential toxicity of fentanyl patches seven cases were identified over a 3-year period where fentanyl, either alone or in combination with other factors, contributed to death following the oral abuse of Duragesic patches. The decedents comprised three females and four males with ages ranging from 20 to 51 years. Postmortem blood fentanyl concentrations were determined in all cases and ranged from 7 to 97 ng/mL. Two deaths were classified as a fentanyl overdose, three deaths were classified as a fentanyl and ethanol overdose, one death was considered a mixed drug intoxication and the remaining death was determined to be a combination of fentanyl and medical causes. These cases represent the largest reported series of deaths following the oral administration of transdermal fentanyl patches and provide detailed information on the potential for the abuse of transdermal Duragesic patches via this route. The postmortem blood fentanyl concentrations detected for each of the decedents demonstrate the potentially fatal blood concentrations that can arise after this relatively rare route of administration.     

Increasing Methamphetamine Detection in Cases of Early Childhood Fatalities

Age and organ maturity can influence drug toxicity in children; however, most clinical data and literature are based on drug concentrations in adults. Therefore, the interpretation of drugs detected in children is often difficult or not possible. Retrospective reviewing of pathology and toxicology information from postmortem cases may assist in future interpretations or identify drug trends. A search of the Forensic Science SA case files was undertaken over 15 years from January 2002 to December 2016 for all children (<13 years). Of the 412 pediatric coronial cases, toxicological information was available on 373. At least one drug was detected in 94 cases with paracetamol, ibuprofen, codeine and hospital-administrated lignocaine and morphine among the most commonly detected agents. Methamphetamine, one of the most commonly abused illicit drugs in Australia, was found in seven cases. In the methamphetamine cases, deaths were associated with shared sleeping in three, pneumonia in one, and stillbirth in one. Methamphetamine was considered potentially contributory to death in two cases. The causes of death in the remaining two cases were undetermined. As six of the seven positive cases occurred in the 2012–2016 (n = 106) timeframe, an increase has occurred over recent years in the number of infants and young children presenting to forensic autopsy in South Australia who have detectable concentrations of methamphetamine. If this is an indication of a more generalized increased childhood exposure in the community there may be significant long-term physical and psychological effects.     

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.     

A Characterization of Sources of Isopropanol Detected on Postmortem Toxicologic Analysis

Abstract: Isopropanol is an important chemical to forensic pathologists in that intoxication can result in death yet presence does not necessarily indicate intoxication. Several reports have been published, which indicate that isopropanol can be created endogenously in certain situations including diabetes mellitus, starvation, dehydration, and chronic ethanol use; however, a large‐scale analysis addressing all of the possible causes of postmortem isopropanol detection has not been performed. A retrospective review of all cases examined at the Bexar County Medical Examiner’s Office between 1993 and 2008 in which isopropanol was detected in routine alcohol screening was undertaken. The cases were categorized by the source of the isopropanol, and the concentrations of isopropanol and acetone were analyzed. Analysis revealed isopropanol concentrations to be low (<100 mg/dL) in cases of antemortem and postmortem creation and in postmortem contamination and high (>100 mg/dL) in cases of antemortem exposure. These results are consistent with other published reports.     

Concentrations of Opiates and Psychotropic Agents in Polydrug Overdoses: A Surprising Correlation Between Morphine and Antidepressants

Abstract: The relationship between postmortem concentrations of morphine and co‐detected psychoactive drugs in fatal overdoses is examined. Morphine and other drugs were detected in 161 medicolegal autopsy cases. Subsets of these morphine‐positive cases based on drug class were established, including opioids, antidepressants, ethanol, benzodiazepines, and “other.” Each subset was split into high or low concentration groups based on median drug concentrations. Morphine concentrations of the [high] and [low] groups were compared, with no significant difference in morphine concentration identified in the opioid, ethanol, or benzodiazepine subsets. The “other” drug class was too heterogeneous for statistical assessment. Morphine concentrations did show a significant direct relationship (p = 0.01) with antidepressants, namely increased concentrations of antidepressant drugs are associated with an increased concentration of morphine. This trend probably remains even after excluding cocaine‐positive cases. The unsuspected finding that postmortem concentrations of antidepressants positively correlate with morphine levels may be important in the treatment of depression in drug addicts.     

Use of Cardiac Injury Markers in the Postmortem Diagnosis of Sudden Cardiac Death

In the daily practice of forensic pathology, sudden cardiac death (SCD) is a diagnostic challenge. Our aim was to determine the usefulness of blood biomarkers [creatine kinase CK‐MB, myoglobin, troponins I and T (cTn‐I and T), and lactate dehydrogenase] measured by immunoassay technique, in the postmortem diagnosis of SCD. Two groups were compared, 20 corpses with SCD and 8 controls. Statistical significance was determined by variance analysis procedures, with a post hoc Tukey multiple range test for comparison of means (p < 0.05). SCD cases showed significantly higher levels (p < 0.05) of cTn‐T and cTn‐I compared to the control group. Although only cases within the first 8 h of postmortem interval were included, and the control group consisted mainly of violent death cases, our results suggest that blood troponin levels may be useful to support a diagnosis of SCD.     

Disopyramide and Mianserin Intoxication: A Unique Fatal Case – Review of the Literature

Lethal occurrence is exceptional after disopyramide or mianserin poisoning. A case of intentional lethal intoxication with these drugs was reported, as well as a review of the literature. Pre‐ and postmortem blood concentrations of disopyramide or mianserin were assessed in a woman who died from acute cardiac failure after ingestion. The premortem blood concentration of disopyramide alone was considered lethal, and a toxic premortem concentration of mianserin was observed that may have increased cardiovascular failure induced by disopyramide because the metabolism of both drugs is mediated via cytochrome P450. Moreover, it was shown that the postmortem redistribution of disopyramide was limited, as pre‐ and postmortem concentrations were 48 and 65 mg/L, respectively. As regards mianserin, redistribution was observed after death with pre‐ and portmortem concentrations at 0.23 and 0.79 mg/L, respectively. This case illustrates that if postmortem blood concentration of disopyramide is known, the premortem concentration can be deduced.     

阿维菌素在急性中毒死家兔体内的再分布研究

目的考察阿维菌素在急性中毒死家兔体内的再分布。方法按最小致死量一次性灌胃250mg/kg阿维菌素,HPLC法检测家兔死后0h、24h、48h和72h中阿维菌素的含量。结果给家兔一次性灌胃250mg/kg阿维菌素的临床死亡时间为120.6±9.2min(±s,n=10);测定了阿维菌素的致死血浓度和致死组织浓度;家兔死后0h~72h心血和各主要脏器组织中阿维菌素含量存在体内再分布现象;确定肝、肾、肺为最佳组织检材。结论阿维菌素在急性中毒死家兔体内的再分布数据,对法医办理此类案件具有重要参考价值。     

Specific Patterns of Canine Scavenging in Indoor Settings

Postmortem animal mutilations due to domestic dogs in isolated domestic deaths are taphonomic modifications regularly observed by forensic pathologists. They are rarely described in the literature; however, even though they present specific patterns. Through 41 cases, 10 at the forensic institute in Lille (France) and 31 at the New York City Office of Chief Medical Examiner (USA), plus 22 cases from the literature, specific locations and patterns of postmortem scavenging lesions are proposed. These lesions are mainly distributed in three locations: the face, especially the nose and the mouth (73.1%), the neck (43.1%), and the arm (shoulder/upper limb [29.2%], hand [26.8%]). We discuss the time span between death and scavenging, the consequences on identification, and comparison with outdoor settings. Outdoor scavenging lesions are mainly located on the trunk and limbs usually sparing the head, which strongly differs from indoor distribution and imply different animal motivations.     

n‐Ethyl Pentylone‐Related Deaths in Alabama

n‐Ethyl pentylone (NEP) is a chemical substance derived from cathinone. Synthetic cathinones are an evolving group of drugs with stimulating, mind‐altering effects sometimes referred to as novel or new psychoactive substances (NPS). There is scarce information in the medical literature regarding forensic cases in which NEP is detected in toxicological testing. We present four fatalities involving NEP from Alabama in 2017. Deaths were attributed to NEP toxicity in two cases (peripheral blood concentrations of 0.121 and 0.953 mg/L) and injuries caused by gunshot wounds in two cases (peripheral blood concentrations of 0.045 and 0.031 mg/L). One case involving NEP described an individual who exhibited classic CNS‐stimulant induced erratic behavior before being found dead. These cases enhance the forensic literature regarding specific NPS like NEP and provide contextual reference for professionals considering the significance of NEP in toxicological interpretation.     

Pig-mentation: postmortem iris color change in the eyes of Sus scrofa

Experienced forensic pathologists and examiners may be familiar with the phenomenon of postmortem iris color change; however, only Knight, Simpson's forensic medicine, Arnold, London, 1997; Ref. 1 and Saukko and Knight, Knight's forensic pathology, 3rd ed., Arnold, London, 2004; Ref. 2 have referred to it in the literature, and to date, there have been no published scientific research studies on this taphonomic artifact. A controlled experiment was conducted of postmortem changes to isolated Sus scrofa eyes. The eyes (n = 137) were separated into three groups and each sample was observed for 3-day postmortem at a different temperature. In addition, a Sus scrofa head was obtained to observe postmortem changes of eyes in situ. All isolated blue eyes in the experiment, at room temperature and higher, changed to brown/black within 48 h. The in situ blue eye, at room temperature, turned brown/black within 72 h. If iris color consistently changes postmortem in humans, then this taphonomic artifact must be incorporated into victim identification protocol, including disaster victim identification software, and autopsy reports to prevent inaccurate victim identification and inappropriate exclusion from the identification process.     

Teens and Spice: A Review of Adolescent Fatalities Associated with Synthetic Cannabinoid Use

Synthetic cannabinoids (SCs) are commonly abused by adolescents with reported past year (2013) use in high school students between 3 and 10%. Standard adolescent postmortem toxicology does not include routine SC analysis, and thus, the true burden of fatalities related to SCs is unknown. A retrospective case review of two cases included scene investigation, interviews, autopsy, and toxicology. SCs were confirmed by liquid chromatography–tandem mass spectrometry (LC?MS/MS). Review of the eight adolescent SC‐associated fatalities in the literature revealed five of eight cases had no other discernible cause of death on autopsy. Compounds detected included PB‐22 (1.1 ng/mL), JWH‐210 (12 ng/mL), XLR‐11 (1.3 ng/mL), JWH‐122, AB‐CHMINACA (8.2 ng/mL), UR‐144 (12.3 ng/mL), and JWH‐022 (3 ng/mL). With synthetic drug use on the rise, forensic experts should have a high index of suspicion for the possibility of SC intoxication in adolescent fatalities with no other discernible cause of death.     

The Toxicology of Methadone‐Related Death in Infants Under 1 Year: Three Case Series and Review of the Literature

Methadone‐related fatalities occur rarely in infants under 1 year, with five confirmed cases in the literature. The interpretation of pediatric postmortem toxicology relies on adult data; however, infants have crucial physiological differences that may impact interpretation of results. Retrospective case review included scene investigation, interviews, autopsy, and NIH/CDC Sudden Unexplained Infant Death Investigation Reporting Form. Methadone levels were confirmed by liquid chromatography/tandem mass spectrometry (LC‐MS/MS). The fatal blood methadone levels in this case series ranged from 69 to 700 ng/mL. This review of the literature adds toxicological findings of three methadone‐related infant fatalities and reviews the current literature on methadone‐related death in infants under 1 year. With opioid use on the rise in today's society, forensic experts should have a high index of suspicion for the possibility of intentional or unintentional poisoning in infants.     

Measurement of Postmortem 1,5‐anhydroglucitol in Vitreous Humor for Forensic Diagnosis

In forensic diagnosis, postmortem blood glucose is known to be susceptible to change after death. However, the 1,5‐anhydroglucitol (1,5‐AG) concentrations in plasma and cerebrospinal fluid (CSF) reflect the mean blood glucose level for a short period of time. In this study, we compared the postmortem 1,5‐AG concentrations in vitreous humor and CSF in 47 subjects to evaluate the utility of this concentration in the vitreous humor for forensic diagnosis. The postmortem 1,5‐AG concentrations in vitreous humor (mean±SD: 20.2 ± 8.7 μg/mL) and CSF (16.8 ± 8.7 μg/mL) did not differ significantly and showed a strong correlation (r² = 0.87, p < 0.01). These results suggest that the vitreous humor 1,5‐AG concentration provides useful information on the antemortem blood glucose level, in addition to the HbA1c value and the CSF 1,5‐AG concentration.     

An Examination of the Postmortem Redistribution of Fentanyl and Interlaboratory Variability,

Fentanyl is a synthetic opioid agonist used for pain control. Often administered as a transdermal patch, it is an interesting drug for study of postmortem redistribution. We hypothesized that fentanyl concentrations would increase over time after death, as measured in blood drawn on the day prior to autopsy and in blood drawn at the time of autopsy in ten cases where fentanyl patches were identified at the scene. Concentrations were compared, and heart blood to femoral blood ratios were calculated as markers of postmortem redistribution. Fentanyl concentrations measured in peripheral blood drawn the day of autopsy (peripheral blood 2 [PB2]) were higher than those drawn the day prior to autopsy (peripheral blood 1 [PB1]) with a mean ratio (PB2/PB1) of 1.80. The ratio of heart blood concentrations (HB) to femoral blood concentrations drawn at autopsy (PB2) had a mean ratio (HB/PB2) of 1.08. Some cases had blood from the same source analyzed at two different laboratories, and concentrations of fentanyl in those samples showed inter‐ and intralaboratory differences up to 25 ng/mL. Postmortem fentanyl concentrations may be affected by antemortem factors, postmortem redistribution, and laboratory variability. Forensic pathologists must use caution in interpreting fentanyl levels as part of death investigation.     

Fatal Overdose of Gamma‐hydroxybutyrate Acid After Ingestion of 1,4‐Butanediol

We report a case of fatal intoxication from 1,4‐butanediol (1,4‐BD), which was ingested by a young and “naïve” gamma‐hydroxybutyrate (GHB) consumer during a party with the co‐ingestion of alcohol, cannabis, and methylene‐dioxy‐methamphetamine. The following drug concentrations were found using gas chromatography coupled with mass spectrometry on autopsy samples and on a cup and a glass found at the scene: 20,350 mg/L (bottle) for 1,4‐BD; 1020 mg/L (femoral blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L (vitreous humor) for GHB. The concentration of GHB is difficult to interpret in forensic cases due to the possibility of an endogenous production of GHB. The variable tolerance of the user may also modify the peri‐ and postmortem GHB concentrations. This case underscores the need to have many different sources of toxicology samples analyzed to avoid the hypothesis of endogenous production of GHB.     

The influence of site of collection on postmortem morphine concentrations in heroin overdose victims

When assaying for postmortem morphine concentration, significant site sampling variability exists between central and peripheral sampling sites and even within sampling regions of the body. To study the variation, 76 suspected heroin overdoses were identified. Each had femoral artery (FA) and vein (FV), left and right ventricle and pooled heart blood samples obtained at autopsy. Forty-four tested positive for morphine. Morphine concentrations were determined by gas chromatography/mass spectrometry, with sampling site differences reported as log-transformed ratios and compared by signed rank test.The mean FA to FV ratio for total morphine was 1.2 (range 0-4.5). The ratio for left heart to right heart total morphine was 1.1 (range 0.4-3.2). Left ventricular to FV total morphine ratio was 2.0 (range 0.6-6.9). In these opioid overdose deaths, FA and FV morphine concentrations are usually similar, although up to 4.5-fold differences were noted. Centrally obtained morphine concentrations are on average twice as high compared with peripheral morphine concentrations. Left and right ventricular morphine concentrations were usually similar, although up to 3.2-fold differences were noted (left side higher).     

Involvement of Amphetamines in Sudden and Unexpected Death

Abstract:  In the present study, the effects of amphetamine-class drugs were examined in cases reported to the Victorian coroner from 2001 to 2005 to determine if death can occur from the use of amphetamine-class drugs alone. A total of 169 cases were reviewed where a forensic autopsy detected amphetamine(s) in the blood. Pathology, toxicology, and police reports were analyzed in all cases to ascertain the involvement of amphetamine-class drugs in these deaths. In Victoria, methamphetamine (MA) is the principal abused amphetamine-class followed by methylenedioxymethamphetamine (MDMA). There were six cases in which a cerebral hemorrhage caused death and three cases in which serotonin syndrome was established as being caused by the interaction of MDMA and moclobemide. There were 19 cases in which long-term use of amphetamines was associated with heart disease. There were three cases where amphetamine-class drugs alone were regarded as the cause of death, of which two cases exhibited high levels of MDMA and lesser amounts of MA and/or amphetamine. There were no cases in which significant natural disease was absent and death was regarded as caused by the use of MA. There was no correlation between blood concentration of drug and outcome.