A low body mass index did not establish a validated correction for postmortem midazolam concentration. A Dutch retrospective study found different cardiac-to-femoral ratio patterns across BMI groups, but the comparison did not meet the study’s corrected significance threshold, and the low-BMI group contained only three cases.
What did the study measure?
de Groot and colleagues reviewed Netherlands Forensic Institute casework from January 2010 through July 2020. The benzodiazepine dataset included 179 cases with a studied compound quantified in both cardiac and femoral blood. Midazolam itself had 58 paired results; the larger dataset was not 179 independent midazolam pairs.
Femoral blood was collected by syringe after targeted dissection, before internal examination. Central blood was collected from the right atrium or inferior vena cava with the heart in place. Tubes contained sodium fluoride and sodium heparin. Samples were frozen at −20°C and analyzed within three months of collection.
These were two postmortem collection sites, not paired measurements before and after death. The cardiac/peripheral ratio, abbreviated C/P, described their concentration relationship at autopsy.
Midazolam differed from the other benzodiazepines
Across 58 midazolam cases, the median C/P ratio was 2.3, mean 5.4 and range 0.59–91. Diazepam, by comparison, had a median ratio of 1.1 across 73 cases. These descriptive findings caution against treating every benzodiazepine as having an identical site-distribution pattern.
Midazolam’s median femoral concentration was 0.017 mg/L, compared with 0.060 mg/L in cardiac blood. Those two group medians are not an individual’s paired result and should not be used to calculate a personal correction.
What happened in the BMI comparison?
| BMI | Cases | Median C/P ratio | Range |
|---|---|---|---|
| Below 18.5 kg/m² | 3 | 0.72 | 0.59–0.79 |
| 18.5–25.0 kg/m² | 19 | 2.5 | 1.1–12 |
| Above 25.0 kg/m² | 35 | 2.2 | 0.64–91 |
The overall BMI comparison yielded p = 0.027. The investigators had adjusted for multiple testing and required p < 0.0038 for the midazolam group. The result therefore remained a potential signal rather than a statistically significant finding under their specified analysis.
The authors acknowledged that this conservative correction could overlook real associations. That limitation supports further investigation; it does not turn an exploratory signal into a proven effect or resolve the uncertainty created by three low-BMI observations.
Adipose storage was a proposed explanation
The authors proposed that differences in predeath adipose accumulation and subsequent redistribution might explain the pattern. They did not directly measure each person’s adipose drug reservoir or experimentally assign body composition. No individual predeath concentration was available to establish how much that person’s blood changed.
Routine screening was followed by quantitative UPLC–MS/MS. For midazolam, the reported calibration limits were 0.001–0.3 mg/L, with accuracy deviation −10%, precision 6% and recovery 81%. Analytical performance supports specimen measurement; it does not validate the proposed biological mechanism.
How should an individual finding be reviewed?
Preserve the collection site, timing, BMI, medication history and both measured concentrations. A C/P ratio below one does not prove absence of postmortem change, and dividing a result by 0.72 or 2.3 would not recover a validated concentration during life. The study established neither a dose formula nor an impairment or cause-of-death threshold.
Exposure provenance is a separate question: midazolam can also reflect emergency treatment before death.
Primary source
de Groot ADE, Borra LCP, van der Hulst R, et al. Postmortem redistribution of amphetamines and benzodiazepines in humans: Important variables that might be influencing the central blood / peripheral blood ratio. Forensic Science International. 2023;353:111876. doi:10.1016/j.forsciint.2023.111876.
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