Clinical forensic toxicological approach for the brain death drug screening

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Nippon Medical School
• Principal Investigator: HAYASHIDA Makiko Nippon Medical School, Faculty of Medicine, Assistant professor, 医学部, 講師 (60164977)
• Co-Investigator(Kenkyū-buntansha): NIHIRA Makoto Nippon Medical School, Faculty of Medicine, Associate professor, 医学部, 助教授 (40089636) ; OHNO Youkichi Nippon Medical School, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (70152220) ; YAMAMOTO Yasuhiro Nippon Medical School, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (70125079) ; YOKOTO Hiroyuki Nippon Medical School, Faculty of Medicine, Associate professor, 医学部, 助教授 (60182698)
• Project Period (FY): 2003 – 2005
• Keywords: brain death diagnosis / drug / benzodiazepines / LC-MS / GC-MS / tissue / screening / blood concentration / スクリーニング / 薬物濃度

Research Abstract

The brain death drug screening (BDDS) was examined on many sides using various samples. In The LC/ESI/MS screening for the verapamil, midazolam, diazepam, flunitrazepam, and active metabolites was optimized. In addition of GC-MS general screening method propofol, droperidol, vecuronium and thiamylal were also considered The BDDS was carried out about 24 in the patient who entered the critical care medical center (CCMC) of an immunoassay positive results. In addition to the general drug screen, it checked that it was effective to carry out a BDDS. Midazolam and its active metabolites have a depressant effect on respiration and consciousness level, and therefore their effects should be considered in all patients for whom brain death testing is contemplated. The concentrations of midazolam and its active metabolites were measured in CCMC patients on a ventilator during and after continuous intravenous infusion of midazolam. Three days after cessation of midazolam infusion, the concentrations of midazolam decreased to below the therapeutic range in all patients, although the concentrations of 1-hydroxymidazolam glucuronide remained extremely high in a patient who showed deteriorating renal function. When it is impossible to confirm factors consistent with irreversible brain death, such as the lack of cerebral blood flow, until 3 days after cessation of midazolam infusion, monitoring of the concentration of these substances should be carried out in all patients in whom suspicion exists prior to the evaluation of brain death. The BDDS method was employed for the investigation of two autopsy cases under the influence of benzodiazepines. Although the blood concentrations did not of lethal dose independently, it suggested that the victim was under severe pharmaco-dynamic influence in tissue distribution. It was shown that the BDDS established by this research is useful on clinical forensic toxicology.