Comparison of pre-mortem and post-mortem blood concentrations of analgesic and sedative drugs in intensive care patients

Background

Patients in the intensive care unit (ICU) often receive analgesic and sedative drugs. There is limited knowledge about the resulting drug concentrations in blood in the critically ill patient, and how these concentrations change after death. In this single-centre prospective study of deceased patients from a general ICU, the aim was to describe blood concentrations and post-mortem redistribution for ten common analgesic and sedative drugs.

Methods

We included 46 patients who died during intensive care. Blood samples were collected pre-mortem (before death), peri-mortem (within one hour after death) and post-mortem (through aortic arch sampling at the morgue or during clinical or forensic autopsy). Samples were analysed for clonidine, dexmedetomidine, fentanyl, ketamine, ketobemidone, morphine, midazolam, paracetamol, propofol and thiopental.

Results

Post-mortem redistribution was significant for fentanyl, with a mean concentration increase from 3.1 ng/g to 5.2 ng/g (p = 0.002). There was no correlation between neither cumulative fentanyl dose nor post-mortem interval and post-mortem concentration changes. For the other drugs, the changes during the post-mortem interval were not significant. Median peri-mortem concentrations were 2.3–9 times higher than observed concentrations in a larger cohort of living ICU patients.

Conclusion

In conclusion, of the investigated drugs, only fentanyl showed a predominant positive post-mortem redistribution, whereas for the other drugs, post-mortem changes were unpredictable. We also conclude that concentrations from the living may not be comparable to those obtained even shortly after death. These concentration differences, as well as the observed post-mortem changes, can influence toxicological interpretation.