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

Lemaire, Éric; Schmidt, Carl J.; Denooz, Raphaël; Charlier, Corinne; Boxho, Philippe

doi:10.1111/1556-4029.13061

Cited by 16 publications

(8 citation statements)

References 38 publications

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“…Secondly, ICB/FB and SB/FB mean ratios are consistently less than the corresponding ICB/PB and SB/PB for all targeted substances, suggesting that PMR is more apparent when comparing central sites with the popliteal versus the femoral site. Third, FB/PB mean ratios are statistically greater than 1 for all drugs and their metabolites, suggesting that popliteal blood may be less prone to PMR, which we reported previously .…”

Section: Discussionsupporting

confidence: 65%

“…We studied popliteal blood concentrations of diazepam, methadone, and morphine and showed that sampling from this site results in drug concentrations lower than those in cardiac, subclavian, and even femoral sampling. This suggests that popliteal blood is less prone to PMR, probably because of its distance from the trunk and isolation from many of the factors that alter postmortem drug concentrations .…”

mentioning

confidence: 99%

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

Lemaire

Schmidt

Dubois³

et al. 2017

Journal of Forensic Sciences

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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.

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Section: Discussionsupporting

confidence: 65%

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confidence: 99%

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

Lemaire

Schmidt

Dubois³

et al. 2017

Journal of Forensic Sciences

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“…This further adds to the uncertainty of the actual blood concentration parameter used in pharmacokinetic equations. Femoral blood is considered to be the ‘least affected’ by postmortem redistribution [22], but recent studies suggest that popliteal blood may be a ‘better’ sample to use than femoral blood [23,24]. However, any postmortem sample is liable to be affected by postmortem redistribution.…”

Section: Postmortem Changes and Their Influence On Pharmacokinetic Parametersmentioning

confidence: 99%

Just say no to postmortem drug dose calculations

Maskell

2021

Journal of Forensic Sciences

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For years, a number of professional groups have warned forensic and clinical toxicologists against calculating an administered dose of a drug based on postmortem blood drug concentrations. But to date, there has been limited information as to how unreliable these dose calculations may actually be. Using amitriptyline as a model drug, this study used empirically determined pharmacokinetic variables for amitriptyline from clinical studies coupled with clinical overdoses (where the individual survived), and death case studies (ascribed to amitriptyline toxicity) in which the dose of amitriptyline was known. Using these data, standard pharmacokinetic equations, and general error propagation, it was possible to estimate the accuracy of calculated doses of amitriptyline, compared with the doses that were consumed. As was expected in postmortem cases, depending on the pharmacokinetic equation used, the accuracy (mean +128% to +2347%) and precision (SD ± 383% to 3698%) were too large to allow reliable estimations of the dose of amitriptyline consumed prior to death based on postmortem blood drug concentrations. This work again reinforces that dose calculations from postmortem blood drug concentrations are unreliable.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Brockbals

Staeheli

Kræmer

et al. 2020

Drug Testing and Analysis

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Postmortem redistribution (PMR) describes the artificial postmortem concentration changes of xenobiotics that may pose major challenges in forensic toxicology. Only a few studies have systematically investigated time‐dependent postmortem drug concentration changes so far and the a posteriori estimation of the occurrence of PMR is not yet possible. In this context, the general concept that postmortem biochemical changes in blood might parallel drug redistribution mechanisms seems promising. Thus, the current study investigated the possible correlations between time‐dependent postmortem concentration changes of xenobiotic and endogenous compounds; exemplified for authentic morphine (n = 19) and methadone (n = 11) cases. Peripheral blood samples at two time‐points postmortem were analyzed for morphine and methadone concentrations and an (un)targeted postmortem metabolomics approach was utilized to combine targeted quantitative analysis of 56 endogenous analytes and untargeted screening for endogenous compounds (characterizing 1174 features); liquid and gas chromatography–mass spectrometry was used respectively. Individual statistically significant correlations between morphine/methadone and endogenous compounds/features could be determined. Hence, the general applicability of the proposed concept could successfully be confirmed. To verify the reproducibility and robustness of the correlating behavior, a larger dataset must be analyzed next. Once a marker/set of markers is found (e.g. robust correlation with specific xenobiotic or xenobiotic class), these could be used as surrogates to further study the time‐dependent PMR in a broader variety of cases (e.g. independent of a xenobiotic drug present). A crucial next step will also be the attempt to create a statistical model that allows a posteriori estimation of PMR occurrence of xenobiotics to assist forensic toxicologists in postmortem case interpretation.

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

Cited by 16 publications

References 38 publications

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

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

Just say no to postmortem drug dose calculations

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

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