A lower postmortem MDA cardiac-to-femoral ratio in resuscitated cases did not prove that resuscitation caused the difference. In a Dutch casework study, attempted resuscitation and cause of death were associated with one another, preventing a clean separation of their possible influences.
The evidence came from retrospective autopsy records
de Groot and colleagues reviewed Netherlands Forensic Institute investigations from January 2010 through July 2020. Their amphetamine-group dataset contained 112 cases with a studied compound quantified in both femoral and central blood. There were 35 MDA pairs, 39 MDMA pairs and 75 amphetamine pairs; these analyte counts were not separate, mutually exclusive populations.
The authors assumed MDA in these 35 cases had formed in vivo as a metabolite after MDMA exposure. That was their interpretation of the case material, rather than an experimentally established administration history for every person.
Femoral blood was drawn after targeted dissection before internal examination. Central blood came from the right atrium or inferior vena cava with the heart in situ. Samples collected in sodium-fluoride/sodium-heparin tubes were stored at −20°C and analyzed within three months.
What did the resuscitation comparison show?
For MDA, 14 cases with attempted resuscitation had a median cardiac/peripheral ratio of 1.6, range 0.93–2.7. Seventeen cases without attempted resuscitation had a median of 2.4, range 1.0–5.3. The comparison yielded p = 0.003, below the study’s multiple-testing threshold of 0.0045 for the amphetamine group.
Those 31 cases were the available resuscitation comparison, not all 35 MDA cases. A lower median ratio describes the sampled groups. It does not reveal whether cardiac concentration fell, femoral concentration rose, both changed, or different predeath distributions were present.
Why did cause of death matter?
MDA ratios also differed by cause-of-death category. Six trauma-death cases had a median ratio of 3.3, compared with 1.6 in 23 intoxication-death cases. The reported post-hoc comparison was p < 0.001. Trauma and cause of death were themselves associated.
The investigators also found an association between cause of death and attempted resuscitation, with χ² = 9.2 and p = 0.026. Resuscitated and nonresuscitated cases therefore differed in relevant circumstances beyond the intervention being examined.
This is why the two findings cannot be joined into the claim that CPR reduces MDA redistribution. The records did not provide a randomized intervention, matched pre-CPR and post-CPR sampling, or an isolated estimate of resuscitation’s causal effect.
The proposed mechanisms remained possibilities
The authors discussed how trauma could rupture tissues, mix fluids or change barriers. Resuscitation could potentially increase or decrease a site ratio depending on drug reservoirs and timing. These were possible explanations; the study did not experimentally demonstrate which mechanism produced an individual MDA result.
The findings were also compound-specific. The study did not find corresponding statistically significant resuscitation differences for amphetamine or MDMA. The MDA observation should not be expanded into a general rule for stimulants or every resuscitated decedent.
Analytical confirmation did not remove the confounding
Routine screening was followed by quantitative UPLC–MS/MS. MDA’s reported calibration interval was 0.005–1 mg/L, with accuracy deviation −11%, precision 5% and recovery 84%. The ratio itself was dimensionless because both blood measurements used the same concentration units.
Reliable identification and quantitation address what was present in the specimens. They do not make the observational groups interchangeable or establish predeath impairment.
What does this mean for a case review?
Keep the resuscitation history alongside injury pattern, collection details, postmortem interval and the two original concentrations. No validated CPR adjustment factor or reverse calculation to a concentration during life resulted from this study. Detection and a site ratio do not independently establish cause of death.
For another distinction in paired-data interpretation, see why ratios of group averages are different from individual paired ratios.
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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