Thiopental Sodium

This research is designed to investigate the sedative effects of naringenin (NAR) and diazepam against thiopental sodium‐induced sleeping mice. NAR (5 and 10 mg kg), diazepam (DZP) (2 mg kg), flumazenil (FLN) (0.1 mg kg), and their combinations are administered intraperitoneally to mice. After 30 min, sleep is induced with intraperitoneal thiopental sodium (20 mg kg), and sleep latency and duration are measured. In silico analysis investigates the role of GABA receptors. NAR significantly reduces sleep latency and prolongs sleep duration in a dose‐dependent manner, with the combination of NAR‐10 and DZP‐2 showing a synergistic effect. The combination of the antagonist (FLN) (NAR‐10 and FLN‐0.1) indicates that latency increases and sleep duration decreases compared to NAR‐10 alone. Furthermore, in silico docking studies corroborates these results, demonstrating a significant binding affinity of NAR (−8.3 kcal mol), which is comparable to the standard ligand DZP (−8.7 kcal mol) and FLN (−7.0 kcal mol) for the GABAA (6X3X) receptor, indicating a GABAergic mechanism. Pharmacokinetics and toxicity evaluations confirm NAR's potential as a safe therapeutic agent, with a high LD50 (2000 mg kg) and minimal toxicity. These findings highlight NAR's potential as a GABAergic sedative agent, requiring further research before being used clinically to treat sleep disorders.

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.

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.

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.

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.