Postmortem Toxicology Results Research Articles

Intoxications involving methoxyacetylfentanyl and U-47700: a study of 3 polydrug fatalities

Novel synthetic opioids (NSOs) represent an emerging group of novel psychoactive substances, acting as agonists at the opioid receptors. NSOs include fentanyl-related compounds, e.g. methoxyacetylfentanyl (MeACF), and non-fentanyl analogs, e.g. “U compounds” including U-47700. Here we present three cases of death involving MeACF and U-47700, with particular reference to preliminary data on pharmacokinetics and tissue distribution.After a complete post-mortem examination, general unknown screenings and analysis of drugs of abuse were performed on postmortem samples by immunoassays, gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry. To quantify the analytes of interest in post-mortem blood and tissues, the standard addition method was used. A toxicological significance score (TSS), weighing the role of the NSO in each death case, was assigned.Case 1 died at the hospital after consumption of U-47700, methadone (serum levels: 2,600 ng/ml and 37 ng/ml), tilidine and benzodiazepines. In case 2, U-47700 (204 ng/ml) together with methadone (290 ng/ml), flubromazepam (480 ng/ml) and diazepam (300 ng/ml) were detected in peripheral blood. In case 3, methoxyacetylfentanyl (266 ng/ml), furanylfentanyl (4.3 ng/ml) 4-ANPP (15 ng/ml) and alprazolam (69 ng/ml) were quantified in femoral blood. In all cases, the NSO likely contributed to the death (TSS = 3).NSOs appear to be often consumed in the setting of polydrug intoxications, especially in combination with other opioids and benzodiazepines, which often exert synergistic effects. The standard addition method remains the most reliable in post-mortem analysis and toxicological results should always be evaluated together with circumstantial and autopsy data.

Postmortem redistribution of amphetamines and benzodiazepines in humans: Important variables that might be influencing the central blood / peripheral blood ratio

IntroductionThe primary objective of postmortem forensic toxicology is to determine if toxicological substances detected in bodily material of victims have contributed to the death of the victim. Interpretation of postmortem drug concentrations is hindered by the fact that time and site dependent variations in postmortem drug concentrations occur, as a result of postmortem redistribution (PMR). An often-used marker for the occurrence of PMR, is the cardiac blood concentration/peripheral blood concentration ratio (C/P ratio) of a drug. In this study, we investigated the relationship between 13 variables and the C/P ratios of amphetamines and benzodiazepines. MethodToxicological results of all postmortem cases that were positive for amphetamines (amphetamine, MDMA, MDA) and/or benzodiazepines (diazepam, desmethyldiazepam, temazepam, oxazepam, midazolam, α-hydroxymidazolam) investigated by the Netherlands Forensic Institute between January 1 2010 and July 31 2020 were reviewed. A total of 112 amphetamine positive cases (224 paired specimen) and 179 benzodiazepine positive cases (358 paired specimen) were selected. The C/P ratios were determined for all selected cases. Ratios were compared between subgroups by performing either a Mann-Whitney U test or a Kruskal-Wallis test followed by post-hoc Mann-Whitney U test. ResultsAfter dividing cases in quartiles based on their amphetamine concentration in femoral blood, the amphetamine C/P ratio was significantly lower in cases with a high amphetamine concentration (quartile 4) compared to cases with a low amphetamine concentration (quartiles 1 and 2) with median C/P ratios of 1.6, 2.4 and 2.2, respectively (p-value<0.001 and p-value=0.001, respectively).The MDA C/P ratio was significantly higher in cases where trauma was the cause of death compared to cases where intoxication was the cause of death with median C/P ratios of 3.3 and 1.6, respectively (p-value<0.001). The MDA C/P ratio was also significantly lower in cases where resuscitation was attempted compared to cases where no resuscitation was attempted with median C/P ratios of 1.6 and 2.4, respectively (p-value=0.003). However, a significant dependency between the variables cause of death and attempted resuscitation was observed.No significant differences in benzodiazepine C/P ratios were observed between subgroups of any of the investigated variables. However, the low p-value of BMI suggests a potential difference in midazolam C/P ratio between BMI subgroups (p-value=0.027). ConclusionWhen interpreting postmortem toxicological results, it might prove useful to take the above-mentioned variables into account.

Postmortem redistribution of cocaine and its metabolites, benzoylecgonine and ecgonine methyl ester in humans: Important variables that might be influencing the central blood / peripheral blood ratio

IntroductionA big challenge in forensic toxicology is the correct interpretation of the results of quantitative analyses in postmortem cases. Postmortem drug concentrations not necessarily reflect the drug concentrations at the time of death, due to postmortem changes in drug concentrations caused by postmortem redistribution (PMR). Cardiac blood is more prone to PMR related concentration changes than peripheral blood. Because of this difference in susceptibility to PMR related concentration changes, the ratio of cardiac blood concentration/peripheral blood concentration (C/P) of a drug is an often-used marker of PMR. In this study, we investigated the relationship between different potentially significant variables and the C/P ratios of cocaine, benzoylecgonine (BE) and ecgonine methyl ester (EME) in humans. The aim was to elucidate the mechanisms involved in PMR of these substances and potentially provide guidelines aiding forensic toxicologists in the interpretation of postmortem quantitative results of cocaine and its metabolites. To differentiate between postmortem concentration changes due to redistribution versus degradation of cocaine, the relationships between these variables and metabolite/cocaine ratios were investigated as well. MethodToxicological results of all postmortem cases that were positive for cocaine, BE and/or EME investigated by the Netherlands Forensic Institute between January 1st 2010 and July 31st 2020 were reviewed. The C/P ratios, BE/cocaine ratios and EME/cocaine ratios were determined for all selected cases. Cocaine, BE and/or EME were quantified in both femoral blood and cardiac blood in a total of 148 cases. Ratios were compared between subgroups by performing either a Mann-Whitney U test or a Kruskal-Wallis test followed by post-hoc Mann-Whitney U test. ResultsA statistically significant difference in C/P ratio of EME was observed between trauma and non-trauma cases with median C/P ratios of 2.03 and 1.57, respectively (p value=0.001). A statistically significant difference in EME/cocaine ratio was observed between the BMI subgroups 18.5 – 25.0 kg/m2 and> 25 kg/m2 with median EME/cocaine ratios of 3.79 and 1.58, respectively (p-value<0.001). ConclusionPostmortem cocaine concentrations should be interpreted with caution, considering the occurrence of both PMR and postmortem degradation. When interpreting postmortem toxicological results in cocaine-related fatalities, it might prove useful to take the above-mentioned variables into account.

The relationship between chronic disease and drugs/toxins-how important is negative disease-drug synergy?

The interaction of diseases with drugs and toxins may result in significantly worse outcomes in a forensic context when i) chronic diseases cause toxicity by increasing drug levels due to reduced renal clearance or slowed hepatic breakdown, and ii) drugs exacerbate underlying lethal mechanisms. In other words, 'negative disease-drug synergy' may result in increased drug toxicity and/or greater organ dysfunction despite the use of standard dosages. This is yet another confounding factor to be considered in the interpretation of postmortem toxicological results, as underlying illness and disease states may significantly alter drug availability and physiological responses.

Fatal concentrations of antidepressants and antipsychotics in post-mortem blood

The objective was to compare the summary statistics for fatal antidepressant and antipsychotic drug concentrations mined by different approaches from post-mortem (PM) toxicological data. Reference concentrations of drugs play a major part in the interpretation of PM toxicology results. However, PM drug concentrations are not necessarily the same as those at the time of death, and consequently standard tables of clinical plasma concentration data are of limited value. Compilations of PM concentrations collected from literature sources are often heterogeneous in terms of the sampling site, the analytical methods used, and the number of cases involved. However, there are also published summary statistics for drug concentrations in PM femoral venous blood, based on extensive databases from centralized laboratories with well-established and high-quality working practices. The present study establishes concentration distributions for a number of antidepressant and antipsychotic drugs, specified as a principal finding in fatal poisoning (principal finding approach). These levels are then compared with those obtained using two previous approaches: according to the all-causes-of-death (Ketola RA, Drug Test Anal, 2019, 11, 1326–1337) or according to the grouped causes of death, aka “the Druid approach”, where the reference information is subdivided into poisonings by one specific substance only, multi-substance poisonings and non-poisoning controls (Reis M, J Anal Toxicol, 2007, 31, 254-264; Söderberg C, Forensic Sci Int, 2016, 266, 91-101). Summary statistics for fatal antidepressant and antipsychotic drug concentrations in PM femoral venous blood were generated according to the principal drug finding. In most cases, also other drugs were implicated in the cause of death. The data were mined between 2000–2020 from the national PM toxicology database, maintained by the Finnish Institute for Health and Welfare, in which all results of the toxicological analyses in medico-legal investigations and information from the respective death certificates are collected. From this material, those antidepressant and antipsychotic drugs that had been quantitatively analysed at least 10 times were selected. Concentration percentiles (10th, 50th, 90th, 95th, 97.5th) were calculated for 16 different antidepressant ( N = 1999) and for 7 different antipsychotic drugs ( N = 1134), defined as principal findings of fatal poisoning by forensic pathologists. For instance, for the antidepressant amitriptyline the respective concentrations were 0.66, 2.0, 8.3, 13 and 25 mg/L, and for the antipsychotic levomepromazine (methotrimeprazine) 0.40, 1.5, 5.3, 10 and 16 mg/L. A comparison with other data mining approaches will be presented in visual form. A clear correspondence was found between, for example, the 90th percentile concentration level of the present principal finding approach and the 97.5th percentile concentration level of the all-causes-of-death approach. Similarly, a correspondence was found between, for example, the median concentration level of the present principal finding approach and the median concentration level of the multi-substance poisoning group in the Druid approach. The novel data presented in this study followed by a systematic comparison with data from previous studies helps rationalize the use of reference concentrations from various sources in the interpretation of potential poisoning deaths. Further data mining for additional drugs will be markedly easier in the principal finding approach than in the Druid approach, provided that the principal findings are specified in advance in the database as is in our case. Despite the proven usefulness of reference concentrations, interpretation must always be made on a case-by-case basis, taking into account e.g. background information, autopsy findings, and substance interactions. A forensic toxicologist must have the evidence-based PM concentration information at his or her disposal when assisting a forensic pathologist in determining the cause of death or being called to testify in court.

Summary statistics for drugs and alcohol concentration recovered in post-mortem femoral blood in Western Switzerland

In post-mortem investigations of fatal intoxication, it is challenging to determine which drug(s) were responsible for the death, and which drugs did not. This study aims to provide post-mortem femoral blood drug levels in lethal intoxication and in post-mortem control cases, where the cause of death was other than intoxication. The reference values could assist in the interpretation of toxicological results in the routine casework.To this end, all post-mortem toxicological results in femoral blood from 2011 to 2017 in Western Switzerland were considered. A full autopsy with systematic toxicological analysis (STA) was conducted in all cases. Results take into account the cause of death classified into one of four categories (as published by Druid and colleagues): I) certified intoxication by one substance alone, IIa) certified intoxication by more than one substance, IIb) certified other causes of death with incapacitation due to drugs, and III) certified other causes of death without incapacitation due to drugs.This study includes 1 990 post-mortem cases where femoral blood was analysed. The material comprised 619 women (31%) and 1 371 men (69%) with a median age of 50 years. The concentrations of the 32 most frequently recorded substances as well as alcohol are discussed. These include 6 opioids and opiates, 3 antidepressants, 6 neuroleptics and hypnotics, 1 barbiturate, 11 benzodiazepines (and related drugs), 2 amphetamine-type stimulants, cocaine, paracetamol, and tetrahydrocannabinol (THC).The most common substances that caused intoxication alone were morphine, methadone, ethanol, tramadol, and cocaine. The post-mortem concentration ranges for all substance are categorized as I, IIa, IIb, or III. Statistical post-mortem reference concentrations for drugs are discussed and compared with previously published concentrations. This study shows that recording and classifying cases is time-consuming, but it is rewarding in a long-term perspective to achieve a more reliable information about fatal and non-fatal blood concentrations.

Community overdose surveillance: Comparing substances collected from the death scene investigation to toxicology results

BackgroundRecent overdose trends are characterized by increased toxicological detection of stimulants with opioids, yet it is unclear whether these substances are mixed prior to consumption or purposefully used simultaneously. MethodsPostmortem toxicology data were collected in Marion County, Indiana, from 45 fatal overdose cases involving heroin, fentanyl, methamphetamine, or cocaine. Substances found by death scene investigators at the scene of the fatal overdose (57 samples) were tested using high-pressure liquid chromatography mass-spectrometry (LC–MS) technology. We compared toxicology and LC–MS results to understand whether substances contributing to overdose were found in combination or separately at the scene of the overdose. ResultsComparing toxicology reports with LC–MS results from substances found at the scene of overdose deaths involving opioids and stimulants reveal that deaths are largely the result of the co-use of opioids and stimulants, rather than use of stimulants combined with opioids. ConclusionsCollecting and testing physical samples from fatal overdose scenes and comparing these to post-mortem toxicology results is a new way to examine polydrug use patterns. This community overdose surveillance method can be used to improve overdose prevention and response efforts.

Comparisons between suicide in persons with serious mental illness, other mental disorders, or no known mental illness: Results from 37 U.S. states, 2003–2017

BackgroundSuicide is a leading cause of death in persons with schizophrenia and other serious mental illnesses (SMI), however, little is known about the characteristics and circumstances of suicide decedents with SMI in the US compared to those with other or no known mental illness. MethodsThis study was a retrospective analysis of suicide deaths in individuals aged ≥18 years from the National Violent Death Reporting System, 2003–2017. Odds ratios compared sociodemographic and clinical characteristics, cause of death, precipitating circumstances, and post-mortem toxicology results. All analyses were stratified by gender. ResultsOf the 174,001 suicide decedents, 8.7% had a known SMI, 33.0% had other mental disorders, and 58.2% had no known mental illness. Relative to persons with other mental disorders, SMI decedents were younger and more likely to have previous suicide attempts and co-occurring drug use. Problems with intimate partners, poor physical health, and recent institutional release were the most common precipitating circumstances for SMI decedents. Firearms were the most common suicide method for males with SMI. Although 67.0% male and 76.0% of female SMI decedents were currently in treatment, toxicology results suggest many were not taking antipsychotic or antidepressant medications at the time of death. ConclusionsPersons with SMI are over-represented in suicide deaths. Efforts to improve treatment of co-occurring substance use disorders, continuity of care following hospitalization, medication adherence, and to reduce access to firearms are important suicide prevention strategies.

The importance of sample size with regard to the robustness of postmortem reference values

Evaluating postmortem toxicological results is a challenging task due to multiple factors affecting blood concentrations after death. In order to improve the diagnostic accuracy in cases of suspected fatal intoxication different compilations of postmortem reference drug concentrations are often used. However, it is not clear what constitutes a reliable postmortem reference value.The current study presents reference concentrations for 13 substances from seven substance groups according to a standardized protocol. The reference concentrations were gathered from 3767 autopsy cases and subdivided into intoxications by one substance only (Group A, n=611), multi-substance intoxications (Group B, n=1355) and postmortem controls, in which incapacitation by drugs were excluded (Group C, n=1801). In particular, this study presents statistical information about the precision and conformity change with various sample sizes.Based on the present data >10 detections are usually needed, for the substances examined, to differentiate between intoxication cases and controls. Repeated samplings show that the median of small samples (N=≤5) has a high variation (normalized interquartile range 138–75%) and that a high number of detections (N=>20) in each group are needed to reduce the variation.

The rise of suicides using a deadly dose of barbiturates in Amsterdam and Rotterdam, the Netherlands, between 2006 and 2017

IntroductionThe three ‘advised’ suicide methods are helium asphyxiation, voluntarily stop eating and drinking and the use of a deadly dose of medication such as barbiturates. The aim of this study was to analyse the number of suicides resulting from barbiturate overdose and examine the influence of publications and internet on this suicide method in the two larger cities of the Netherlands. MethodsData of suicides by medication and drugs overdose were extracted from the electronic registration systems of the forensic physicians of the district of Amsterdam and Rotterdam over the period 1 January 2006–31 December 2017. We analysed whether or not the number of suicides using barbiturate overdose has significantly risen since 2013. This was the year ‘right-to-die-organisations’ informed individuals about this method and a book was published describing this as a humane death. In addition, a regression analysis was used to examine which factors predict a suicide resulting from barbiturate overdose. ResultsA total of 553 overdose suicides were identified and 91 suicides resulting from barbiturate overdose were included for further evaluation. During 2013–2017 there were significantly (p < 0.00) more suicides resulting from barbiturate overdose compared to 2007–2012.Individuals using barbiturate overdose to die by suicide were significantly (p < 0.00) older than those using other medication and drugs (65 years compared to 55 years respectively). 48% of these cases were male. In barbiturate suicides, information sources (books or information on the internet, p < 0.01) and the presence of family during suicide (p < 0.00) occurred significantly more often than in suicides resulting from other medication and/or drugs overdose. The odds for barbiturate suicides were 4.8 higher (CI 2.6–9.2) after 2013 compared to before 2013 after correction for age, sex, city and postmortem toxicology results. DiscussionOur data showed a rise in suicides resulting from barbiturate overdose whereas the total number of inhabitants and suicides resulting from medication overdose has remained more or less constant. Easy access of information or medication through the internet and ‘right-to-die-organisations’ may have directly impacted the rise in suicides resulting from an overdose of barbiturates. To our knowledge this is the first study analysing the rise of barbiturate suicides and the influence of media in published literature.

The use of contextual information in forensic toxicology: An international survey of toxicologists' experiences

Cognitive bias is a well-documented automatic process that can have serious negative consequences in a variety of settings. For example, cognitive bias within a forensic science setting can lead to examiners' judgements being swayed by details that they have learned while working on the case, and which go beyond the physical evidence being examined. Although cognitive bias has been studied in many forensic disciplines, such as fingerprints, bullet comparison, and document examination, knowledge of cognitive bias within forensic toxicology is lacking. Here, we address this knowledge gap by assessing the reported use of contextual information by an international group of forensic toxicologists attending the 54th conference of The International Association of Forensic Toxicologists (TIAFT) in Brisbane in 2016. In a first study, participants read a set of simple post-mortem toxicology results (two drug concentrations in blood) and then indicated what information they would normally use when interpreting these results in their day-to-day casework. Using a questionnaire, we then surveyed the familiarity of toxicologists with contextual bias and captured any suggested bias-minimizing procedures for use in forensic toxicology laboratories. Thirty-six participants from 23 different countries and with a range of 1–35 years' forensic toxicology reporting experience volunteered. Analysis of their responses showed that the majority of participants reported using some contextual information in their interpretation of these post-mortem toxicology results (range = 3–15 pieces of information, median ± SD = 11 ± 3), the most common being the deceased's history of prescription or illicit drug use. More than three-quarters of participants reported being familiar with the concept of contextual bias, although few (n = 9) worked in laboratories that had a formal policy covering it. Over half of participants knew of at least one bias-minimizing procedure specifically for forensic toxicology casework, but only a quarter (overall) reported using bias-minimizing procedures in their laboratories. Our results provide substantial evidence that although practising forensic toxicologists are familiar with contextual bias, many report that they still engage in behaviours that could lead to cognitive bias (e.g., through the use of contextual information, through lack of explicit policies or bias-minimizing procedures). We anticipate that our work will form the basis of further research involving a larger sample of participants and examining other potentially relevant factors such as sex/gender, country and accreditation of laboratories.

Increased Presence of Fentanyl in Cocaine-Involved Fatal Overdoses: Implications for Prevention.

After remaining stable from 2010 to 2014, the rate of cocaine-involved overdose death increased sharply from 2015 to 2016. This study aims to determine the contribution of opioids, and fentanyl in particular, to the increase in cocaine-involved overdose death from 2015 to 2016. Using New York City death certificate data linked to medical examiner toxicology data, we identified all overdose deaths where post-mortem toxicology results were positive for cocaine from 2010 to 2016. We analyzed cocaine-involved overdose deaths by co-occurring substances. Age-adjusted rates per 100,000 residents were calculated for 6-month intervals from 2010 to 2016. Data suggest that increased deaths involving opioids, specifically fentanyl, accounted for most of the increase in cocaine-involved deaths from 2015 to 2016.

Characteristics of Opioid-Related Deaths in Ontario, Canada: Leveraging the Drug and Drug/Alcohol Related Death (DDARD) Database

IntroductionReview of post-mortem toxicological results is the gold standard for identifying whether a death is opioid-related. The Drug and Drug/Alcohol Related Death (DDARD) database contains abstracted information from the Office of the Chief Coroner of Ontario, for all opioid-related deaths that occurred in Ontario, Canada between 1991 and 2016.&#x0D; Objectives and ApproachThe DDARD, which contains manner of death and drug concentrations from post-mortem toxicology results for opioids-related deaths in Ontario, was linked to the data repository housed at ICES. The objective of this project was to examine demographic characteristics and the type of opioid contributing to opioid-related deaths in FY2015/16. Individuals identified within DDARD who died from an opioid-related cause were linked to demographic, hospitalization and prescription drug databases to report on age, gender, neighbourhood income quintile, past health services utilization for opioid-toxicity, alcohol use disorders (AUD), mental health emergency department (ED) visits, and opioid(s) present at time of death.&#x0D; ResultsWe identified 737 opioid-related deaths in FY2015/16, the majority of which involved men (n=497; 67.4%), those living in lower socioeconomic status areas (n=395; 53.6%), and those residing in urban regions (n=655; 88.9%). Nearly half (n=325; 44.1%) of opioid-related deaths occurred among those aged 45 to 65 years. We found 9.5% (n=70) of individuals had a previous hospital visit for opioid toxicity, 25.4% (n=187) had previously diagnosed AUD, and 42.5% (n=313) had a previous mental health ED visit. Overall, 250 (33.9%) individuals had an active opioid prescription at time of death with oxycodone (n=92; 36.8%) the most commonly dispensed. Among those who didn’t have an active opioid prescription at time of death (n=484; 66%), fentanyl (n=184; 37.8%) was the most commonly found opioid on post-mortem toxicology.&#x0D; Conclusion/ImplicationsThis project demonstrates how data obtained through chart abstractions can be used to enhance existing administrative health datasets. Given the concern around the safety of opioids, it is important to examine the characteristics and type of opioid(s) involved at time of opioid-related death in order to develop targeted preventative strategies.

Older women who died by suicide: suicide means, sociodemographic and psychiatric risk factors, and other precipitating circumstances.

Data are from the 2005 to 2015 US National Violent Death Reporting System (N = 12,401 female decedents aged 50 years and over). We used three logistic regression models, with overdose versus firearms, overdose versus hanging/suffocation, and overdose versus "other" means as the dependent variables, to examine associations between suicide means and sociodemographic and risk/precipitating factors. χ2 tests were used to examine positive toxicology of prescription and illicit drugs by suicide means. Compared to firearm users, overdose users were younger and had higher odds of having had previous suicide attempts/intent disclosures, mental disorders (e.g. depression/dysthymia: AOR = 1.18, 95% CI = 1.05-1.34), and substance abuse other than alcohol, but lower odds of having had relationship problems and any crisis. Compared to hanging/suffocation, overdose declined (AOR = 0.95, 95% CI = 0.93-0.97) during the study period and was less prevalent among Hispanic and Asian women and those with job/finance/housing problems. Toxicology reports showed that 47%, 43%, and 45% of overdose users were antidepressant, opiate, and benzodiazepine positive, respectively. Firearm users had the lowest rates of positive toxicology results for these drugs. Suicide prevention should include limiting access to large quantities of prescription medications and firearms for those at risk of suicide. More effective mental health/substance abuse treatment and chronic illness management support are also needed.

Postmortem distribution and redistribution of synthetic cathinones

Synthetic cathinones are powerful psychostimulants that have been associated with fatal intoxications. Because of changes that take place following death, postmortem toxicology results require careful interpretation. The purpose of this study was to evaluate the distribution of synthetic cathinones in postmortem specimens in a series of 50 cathinone-positive fatalities. Liquid chromatography–quadrupole time-of-flight-mass spectrometry was used to quantitatively identify cathinones in central blood (n = 51), peripheral blood (n = 31), urine (n = 33), liver (n = 22), vitreous humor (n = 1) and stomach contents (n = 1). The distribution of cathinones and the potential for postmortem redistribution was assessed. Among the 50 cases investigated, a total of nine synthetic cathinones (α-PVP, ethylone, methylone, butylone, MDPV, methedrone, pentylone, 4-MEC, and MDPBP) were identified in 139 specimens. The number of specimens per case ranged from one to six. In cases that included central blood or liver, together with a peripheral blood source, the central/peripheral (C/P) or liver/peripheral (L/P) ratio was calculated to estimate the potential for postmortem redistribution (n = 21 C/P; n = 11 L/P). Methylone and ethylone appeared to exhibit the greatest potential for postmortem redistribution, producing C/P ratios of 4.0 (1.5–6.1) and 2.9 (0.5–9.2), respectively. In contrast, the C/P ratio for α-PVP was 1.1 (0.5–1.9). Differences in C/P ratios between methylone and α-PVP were statistically significant (α = 0.05). Although synthetic cathinones may exhibit low to moderate postmortem redistribution, significant variability exists due to site- and time-dependent factors. This, in combination with their overall instability, necessitates careful interpretation of postmortem toxicology results.

Heroin and fentanyl overdoses in Kentucky: Epidemiology and surveillance

BackgroundThe study aims to describe recent changes in Kentucky's drug overdose trends related to increased heroin and fentanyl involvement, and to discuss future directions for improved drug overdose surveillance. MethodsThe study used multiple data sources (death certificates, postmortem toxicology results, emergency department [ED] records, law enforcement drug submissions, and prescription drug monitoring records) to describe temporal, geographic, and demographic changes in drug overdoses in Kentucky. ResultsFentanyl- and heroin-related overdose death rates increased across all age groups from years 2011 to 2015 with the highest rates consistently among 25–34-year-olds. The majority of the heroin and fentanyl overdose decedents had histories of substantial exposures to legally acquired prescription opioids. Law enforcement drug submission data were strongly correlated with drug overdose ED and mortality data. The 2016 crude rate of heroin-related overdose ED visits was 104/100,000, a 68% increase from 2015 (62/100,000). More fentanyl-related overdose deaths were reported between October, 2015, and September, 2016, than ED visits, in striking contrast with the observed ratio of >10 to 1 heroin-related overdose ED visits to deaths. Many fatal fentanyl overdoses were associated with heroin adulterated with fentanyl; <40% of the heroin overdose ED discharge records listed procedure codes for drug screening. ConclusionsThe lack of routine ED drug testing likely resulted in underreporting of non-fatal overdoses involving fentanyl and other synthetic drugs. In order to inform coordinated public health and safety responses, drug overdose surveillance must move from a reactive to a proactive mode, utilizing the infrastructure for electronic health records.

Frequency of Pathological Changes in Lungs of Bodies with Positive Postmortem Toxicology Results for Narcotics and Psychotropic Substances

Frequency of Pathological Changes in Lungs of Bodies with Positive Postmortem Toxicology Results for Narcotics and Psychotropic Substances

Nitrobenzodiazepines: Postmortem brain and blood reference concentrations

Reference concentrations are needed to evaluate postmortem toxicology results and usually femoral blood is the specimen of choice. However, brain tissue has been suggested as a viable alternative specimen, since postmortem blood concentrations can be difficult to interpret due to postmortem redistribution, among other factors. Here we present reference concentrations of postmortem brain and femoral blood of the nitrobenzodiazepines clonazepam, flunitrazepam, and nitrazepam that are of particular interest since they commonly are converted to their corresponding 7-aminometabolites in the postmortem situation. The drugs and metabolites were quantified in both matrices using LC–MS-MS in 69 cases. In 63 cases the compounds were judged not to have been of significance for the death (C cases), whereas they were considered to have been a contributing factor in 6 cases (B cases). No cases were observed with a nitrobenzodiazepine being the sole cause of death (A cases). The brain–blood ratios for clonazepam and nitrazepam were 5.5 and 4.7, respectively, while the brain–blood ratios for the 7-aminometabolites ranged from 0.4 to 0.5. Flunitrazepam only occurred as the 7-aminometabolite. A positive correlation between brain and blood concentrations was found with Spearman’s rank correlation coefficients (rs) ranging from 0.77 to 0.96. The measured femoral blood concentrations agree with literature values, but only few brain concentrations were available for comparison. The drug–metabolite ratios for clonazepam and nitrazepam were 10–12 times higher in brain than in blood. The pre-analytical variation in brain of 5.9% was fairly low, suggesting that brain tissue is a useful alternative to blood. The reported brain and femoral blood concentrations serve as reference values in postmortem investigations.

Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature.

To interpret postmortem toxicology results, reference concentrations for non-toxic and toxic levels are needed. Usually, measurements are performed in blood, but because of postmortem redistribution phenomena this may not be optimal. Rather, measurement in the target organ of psychoactive drugs, the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral blood and brain tissue in 104 cases. BZDs were judged to be unrelated to the cause of death in 88 cases and contributing to death in 16 cases. No cases were found with cause of death solely attributed to BZD poisoning. All BZDs investigated tended to have higher concentrations in brain than in blood with median brain-blood ratios ranging from 1.1 to 2.3. A positive correlation between brain and blood concentrations was found with R(2) values from 0.51 to 0.95. Our reported femoral blood concentrations concur with literature values, but sparse information on brain concentration was available. Drug-metabolite ratios were similar in brain and blood for most compounds. Duplicate measurements of brain samples showed that the pre-analytical variation in brain (5.9%) was relatively low, supporting the notion that brain tissue is a suitable postmortem specimen. The reported concentrations in both brain and blood can be used as reference values when evaluating postmortem cases.

Fibromyalgia: Comorbidity or a psychosomatic symptom of depression leading to the abuse of opioids?

Introduction: We conducted a retrospective study at the Wayne County Medical Examiner Office, which examined decedents diagnosed with Fibromyalgia, a disorder of unknown etiology characterized by widespread chronic musculoskeletal pain, concomitant with fatigue, sleep disturbances, and psychological distress. Material & Methods: Over a seventeen year period a total of 54 cases from our database met this criterion. Other criteria in the study included cause and manner of death, post-mortem toxicology results, major autopsy findings, and medical history. Results: Our study revealed that the cause of death in approximately two-thirds of the cases was due to drug intoxication. The most frequent post-mortem toxicology finding was Opioids, such as Morphine, Hydrocodone, Oxycodone, Fentanyl, and Codeine. The most common manner of death was accident. Almost 90% of the decedents were Caucasian females, which contrasted with the demographic diversity of Wayne County, Michigan. Additional findings revealed that the average age was 47 years, and the average Body Mass Index (BMI) could be categorized as obese. Nearly 67% of the cases had a medical history of depression. Conclusion: Our findings suggest that Fibromyalgia might be a psychosomatic symptom of depression rather than comorbidity. Therefore, physicians should further inquire about, and consider treating, depression in patients with chronic musculoskeletal pain while completely avoiding the use of opioids, for opioids have a greater risk of being abused and resulting in death in such patients, as found in our study.