Fentanyl concentrations in ligated femoral blood in the presence and absence of NPS benzodiazepine drugs. A review of over 1250 benzo-dope / fentanyl toxicity cases in Alberta, Canada.

The drug combination referred to as 'benzo dope' has become prevalent in recent years, with an increasing number of fentanyl-related deaths reporting the concomitant presence of one or more benzodiazepine drug, such as etizolam, flualprazolam and flubromazepam. The central nervous system (CNS) depressant effects of these benzodiazepine drugs can exacerbate respiratory and CNS depressant effects resulting from the use/misuse of potent opioids such as fentanyl. This combined and enhanced drug-induced toxicity can pose a significant threat to life. Over a three-year period (2020-2022), the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada issued 2812 case reports with fentanyl detected; of these cases, approximately 45% (1261) were positive for at least one benzodiazepine drug. This study presents concentrations of both fentanyl and benzodiazepine drugs in post mortem blood collected from a visualized, ligated femoral vein. The study demonstrates that the blood concentration of fentanyl in benzo-dope case reports is considerably higher than in cases where no benzodiazepine drug was detected.The median concentration of fentanyl in femoral blood for cases that also contained a benzodiazepine drug was 12.4 ng/mL (2020), 11.9 ng/mL (2021) and 14.0 ng/mL (2022). The median concentration of fentanyl in femoral blood for cases that did not contain a benzodiazepine drug was 8.5 ng/mL (2020), 7.0 ng/mL (2021) and 7.2 ng/mL (2022). The percent differences between the groups were similar with those observed from quantitative analysis of drug powders from unrelated police seizures in Alberta, Canada, suggesting the observed differences in blood fentanyl concentration may be due to the use of a drug substance with a higher concentration of fentanyl.Furthermore, the reported concentration of the benzodiazepine drug(s) is low, such that the role/contribution, if any, that this drug may have played in the decedents' death should be questioned and carefully considered by the certifying medical examiner/coroner.

The distribution and redistribution of carfentanil in post mortem samples.

This article compares 290 post mortem case reports that were positive for carfentanil. All the cases were submitted to, and analyzed by, the toxicology department of the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada. This study highlights the varied distribution of carfentanil in the body after death as a result of misadventure, i.e., these are accidental drug overdose cases. Post mortem samples were collected from more than one anatomical site and analysed for carfentanil using a validated liquid chromatography-tandem mass spectrometry method. Ante-mortem samples were available in 15 of these cases and were also analysed. Post mortem mean blood carfentanil concentrations were found to be 0.362 µg/L (femoral), 0.442 µg/L (iliac), 0.484 µg/L (cardiac) and 0.692 µg/L (subclavian). The mean vitreous humor carfentanil concentration was 0.238 µg/L; the mean urine carfentanil concentration was found to be 0.697 µg/L. Little difference was found between ligated and 'blindstick' femoral blood carfentanil concentrations. Whilst carfentanil can readily be detected in both vitreous humor and urine samples neither were found to correlate with blood concentrations, limiting their use in interpretation. This study demonstrates the importance of multi-site sample collection and subsequent analysis for a thorough post mortem toxicological investigation. The study also highlights the risks and limitations associated with the interpretation of post mortem analytical results concerning carfentanil.