Postmortem Concentration and Redistribution of Diazepam, Methadone, and Morphine with Subclavian and Femoral Vein Dissection/Clamping

Abstract

Postmortem redistribution (PMR) concerns blood drug concentration variations after death, depending on many factors such as sampling site and technique. In our study, we focused on sampling method. 30 cases were sampled, each at cardiac, subclavian, femoral, and popliteal sites. Targeted substances were diazepam, methadone, and morphine. Blind stick and dissection/clamping techniques were concomitantly performed at subclavian and femoral sites. Subclavian and femoral concentrations were compared according to technique used. To assess the influence of sampling technique on PMR, central/peripheral ratios were calculated depending on sampling method. Results show that drug concentrations tend to be lower when drawn from a clamped subclavian or femoral vein whereas ratios including subclavian and/or femoral blood concentration are influenced according to the technique used. In conclusion, clamping a subclavian or femoral vessel before sampling tends to result in lower drug concentrations and may influence ratios, suggesting the importance of isolating vessels from thoraco-abdominal viscera.

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

“…With subclavian sampling, there are publications suggesting that the subclavian vein should not be considered a strictly central site, but rather an intermediate one (16,26), but we did not find any study addressing adequately the issue of subclavian sampling techniques. Consequently, we evaluated the sampling method in a recent study and our results showed that diazepam and methadone concentrations were lower when drawn from either clamped subclavian or femoral vein, whereas subclavian morphine mean concentrations tend to be lower when drawn from a clamped subclavian vein, but not for femoral sampling (14,27). Hence, we suggested that clamping vessels and isolating them from heart or abdominal blood may result in lower concentrations depending on the drug.…”

Postmortem Metabolomics: Strategies to Assess Time-Dependent Postmortem Changes of Diazepam, Nordiazepam, Morphine, Codeine, Mirtazapine and Citalopram

“…However, neither of these ratios have been found to demonstrate a clear relationship to a drugs’ physicochemical properties that are, as mentioned above, thought to influence the occurrence/extent of PMR. Thus, the prediction power of such approaches is very limited [ 4 , 5 , 6 ]. In addition, PMR of some drugs (of abuse) was previously modelled by quantitative structure-activity relationship (QSAR) methods.…”

Postmortem metabolomics: Correlating time‐dependent concentration changes of xenobiotic and endogenous compounds

“…However, postmortem phenomena such as diffusion processes, degradation or drug neo‐formation (driven by microorganisms) can lead to artificial postmortem modifications of drug concentrations. Grouped under the term postmortem redistribution (PMR), this can pose challenges in forensic case interpretation 2,3 . Only a limited number of studies have been conducted so far that systematically study time‐dependent postmortem drug concentration changes on authentic human cases (e.g.…”

“…However, neither of these ratios were found to have a clear relationship to a drug’s physicochemical properties (e.g. volume of distribution, pKa, or protein binding affinity) that are thought to influence PMR, thus the prediction power is very limited 2,12–14 . Additionally, quantitative structure–activity relationship (QSAR) methodology was used previously to model the PMR of various xenobiotics.…”