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Clinical forensic toxicological approach for the brain death drug screening

Research Project

Project/Area Number 15590591
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Legal medicine
Research InstitutionNippon 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
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsbrain death diagnosis / drug / benzodiazepines / LC-MS / GC-MS / tissue / screening / blood concentration / スクリーニング / 薬物濃度 / MS(液体クロマト質量分析) / MS(ガスクロマト質量分析)
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.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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