Etizolam Blood Concentrations in 191 Forensic Cases in Ontario, Canada (2019-2020).

Although not used clinically in North America, etizolam has been identified in forensic samples as an illicit 'designer' benzodiazepine. As a central nervous system depressant, analysis for etizolam has probative value in both death investigations and forensic cases where incapacitation or human psychomotor performance is relevant. This report examines toxicological findings and demographic data in a series of authentic forensic cases analyzed between November 2019 and December 2020 in which etizolam was quantified by liquid chromatography-tandem mass spectrometry analysis. Blood concentrations were determined in 191 individuals aged 1-75 years. In living individuals (i.e., impaired driving and sexual assaults), etizolam concentrations ranged from <5 to 767 ng/mL which overlapped with the range of <5 to 260 ng/mL reported in death investigations. In all but one case, other drugs were detected in combination with etizolam. Fentanyl was the most common co-occurring drug and was present in 164 cases (86%). Additional case details are provided for cases of forensic interest: two deaths involving children <3 years of age, two deaths involving body packing and an individual arrested for drug-impaired driving with, to our knowledge, the highest reported etizolam concentration to date.

Strategic Decision-Making by a Forensic Toxicology Laboratory in Response to an Emerging NPS: Detection, Quantitation and Interpretation of Carfentanil in Death Investigations in Ontario, Canada, July 2017 to June 2018.

The proliferation of novel psychoactive substances (NPS) and the current opioid epidemic creates challenges for a toxicology laboratory. Methods capable of detecting and quantitating emerging compounds must be established despite limited information on toxicologically relevant concentrations. This paper will (i) describe how a publicly funded forensic laboratory reacted to the emergence of carfentanil as a public safety concern and (ii) contribute to the existing forensic literature by presenting a series of deaths involving carfentanil between July 2017 and June 2018. The Centre of Forensic Sciences is the primary provider of forensic toxicology testing in medicolegal death investigations in the province of Ontario. When carfentanil was first identified in the illicit drug supply, routine screening methods used by this laboratory were not sufficiently sensitive to detect the drug at concentrations expected in blood samples. Previously validated, multi-target liquid chromatography-tandem mass spectrometry (LC-MS-MS) quantitative methods already in use by the laboratory did show improved detectability for carfentanil. Thus, an existing LC-MS-MS method was adapted to include carfentanil, achieving improved sensitivity while also providing quantitation in suspected drug-related deaths. This approach had the added benefit that the LC-MS-MS method selected for modification was used in all death investigations requiring toxicology analysis in Ontario, thereby providing an opportunity for surveillance. Using this method, 4,953 cases were analyzed with carfentanil detected at a concentration greater than the limit of detection (0.05 ng/mL) in 160 decedents. Postmortem blood carfentanil concentrations ranged from less than 0.1 to 9.2 ng/mL. Of the 160 carfentanil-positive cases, 156 were classified as either mixed drug toxicity or carfentanil overdose. The approach described enabled this laboratory to efficiently implement a quantitative test for carfentanil in all death investigations, providing a useful template for modifying existing methods when a new psychoactive substance becomes available in the population.

A review of alcohol-impaired driving: the role of blood alcohol concentration and complexity of the driving task.

The operation of a motor vehicle requires the integrity of sensory, motor, and intellectual faculties. Impairment of these faculties following the consumption of alcohol has been studied extensively through laboratory, closed-course and on-road driving, and epidemiological studies. The scientific literature was reviewed critically, with a focus on low-to-moderate blood alcohol concentrations (BAC ≤ 0.100%), to identify the most reliable determinants of alcohol-impaired driving. Variables such as age, gender, driving skill, and tolerance were shown to have limited impact on impairment. It was concluded the most relevant variables are BAC and complexity of the driving task. The scientific literature provides a high degree of confidence to support the conclusion that a BAC of 0.050% impairs faculties required in the operation of a motor vehicle. Whether impairment is apparent depends upon the complexity of the driving task, which applies to both study design and actual driving.

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.

Does hyperthyroidism increase risk of death due to the ingestion of ecstasy?

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive amphetamine derivative widely used for recreational purposes. Deaths caused by acute drug intoxication with MDMA are rare but can often involve a severe hyperthermic episode. The factors underlying the increased risk of some ecstasy users to a fatal drug reaction are not known. We present a case report of a 24-year-old woman who developed fatal hyperthermia with multi-organ complications following MDMA use and was found at autopsy to have diffuse thyroid hyperplasia (Graves' disease). An antemortem blood MDMA concentration of 0.68 mg/L was measured in a sample obtained on admission to hospital. Although a cause and effect cannot be established, as the thyroid hormone is a major regulator of thermogenesis, we suggest that hyperthyroidism predisposed the subject to ecstasy-induced hyperthermia and that a pre-existing defect affecting temperature status could be one factor in explaining some ecstasy intoxication deaths.

Fentanyl-related deaths in Ontario, Canada: toxicological findings and circumstances of death in 112 cases (2002-2004).

In order to characterize fentanyl-related deaths in the province of Ontario, Canada, a retrospective study of all cases in which fentanyl was quantitated in blood was conducted for the time period between 2002 and 2004. A total of 112 fentanyl-related deaths were identified. Decedents ranged in age from 4 to 93 years and comprised 63 men and 49 women. A variety of routes of administration of the drug were identified: transdermal application of Duragesic patches, intravenous injection of patch contents or fentanyl citrate solution, oral/transmucosal administration, and volatilization and inhalation of Duragesic systems. Blood fentanyl concentrations were determined for all modes of drug administration and are provided. There were 54 cases in which death was attributed solely to fentanyl intoxication; the mean blood concentration was 25 microg/L (range: 3.0-383 microg/L). This concentration range overlapped with blood fentanyl concentrations measured among cases where the presence of the drug was considered incidental. For example, a mean blood concentration of 12 microg/L was observed among 12 cases of natural death (range: 2.7-33 microg/L). Detailed case reports of six individuals are also included and provide additional insight into the use of this drug for both therapeutic and illicit means.