Cardiovascular drugs did not share a single postmortem concentration pattern in a paired hospital-to-mortuary study. Atenolol and verapamil had statistically significant increases, while diltiazem’s median ratio was below one. Neither result supplied a universal correction to a concentration during life.
What specimens were compared?
Mantinieks and colleagues compiled 811 hospital-death coronial cases from Victoria, Australia, during 2009–2017, reporting 42 drugs and metabolites with at least ten paired results each. The cardiovascular drugs had separate, much smaller denominators.
Earlier clinical material could be whole blood, plasma or serum. The institute generally selected specimens closest to hospital admission, not necessarily closest to death. Approximately 35% of earlier specimens overall were plasma or serum.
Postmortem material was approximately 2–5 mL of femoral blood obtained by leg puncture at mortuary admission, preserved with 1% w/v sodium fluoride and potassium oxalate, stored at 4°C and typically analyzed within 24 hours. Earlier specimens were typically stored at −20°C after receipt.
The five drugs had different paired distributions
| Drug | Pairs | Median ratio | Range | Paired p-value |
|---|---|---|---|---|
| Atenolol | 35 | 1.8 | 0.23–5.9 | 0.002 |
| Verapamil | 25 | 1.5 | 0.07–3.8 | 0.04 |
| Propranolol | 11 | 1.4 | 0.06–42 | >0.05 |
| Sotalol | 11 | 1.3 | 0.22–2.8 | >0.05 |
| Diltiazem | 13 | 0.69 | 0.09–5.4 | >0.05 |
The study used a significance level of 0.05. Thus only atenolol and verapamil had significant paired increases among these drugs. A median above one did not automatically mean a significant result; diltiazem’s median below one did not establish a significant decrease.
The atenolol group had median earlier and postmortem concentrations of 0.20 and 0.29 mg/L. Verapamil medians were 0.15 and 0.17 mg/L. These concentration medians must remain separate from the median of individual ratios. Dividing group medians does not reproduce that statistic.
Hospital treatment was an unresolved influence
The authors could not reliably establish whether these drugs were administered in hospital. A substance might have been incompletely absorbed at the first collection, or administered after it. Missing medication records prevented isolation of postmortem redistribution from the whole interval’s other influences.
For atenolol, the median earlier-collection-to-death interval was 22 hours and the median death-to-postmortem-collection interval 20 hours. For verapamil, the corresponding intervals were 27 and 18 hours. These were not experiments holding the predeath concentration constant while varying only postmortem time.
Diltiazem’s lower median did not prove hydrolysis
The authors discussed potential in-vitro hydrolysis to desacetyldiltiazem as an explanation for the lower diltiazem ratio. That was a possible mechanism, not a measured causal allocation in these 13 people. The wide ratio range also included later values above earlier ones.
Unequal partitioning between plasma or serum and whole blood, individual pharmacokinetics and unknown last-dose times complicated interpretation. Blind femoral puncture was another acknowledged sampling limitation. Bodies were not obviously traumatized, burned or decomposed, limiting extrapolation to those circumstances.
Analytical measurement did not establish causation
The investigation used validated LC–MS/MS procedures and referred to earlier analytical publications. It did not provide a complete drug-specific numerical validation table for these five agents. No absent analytical limit should be supplied by assumption.
The study did not validate a lethal threshold, impairment rule or administered-dose estimate. Preserve both specimen types, concentrations, units and collection times. A ratio of 1.8 or 0.69 cannot simply be applied to a new person to recover a known concentration at death.
For another matrix-sensitive comparison from this research, see pholcodine ratios with mixed earlier specimen types versus whole blood.
Primary source
Mantinieks D, Gerostamoulos D, Glowacki L, et al. Postmortem Drug Redistribution: A Compilation of Postmortem/Antemortem Drug Concentration Ratios. Journal of Analytical Toxicology. 2021;45:368–377. doi:10.1093/jat/bkaa107.
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