Midazolam and its metabolites in brain death diagnosis.
OBJECTIVE
There is only limited knowledge on the pharmacokinetics of midazolam and its active metabolites in potential organ donors. Before establishing the diagnosis of brain death, drugs interfering with the neurological assessment have to be washed out. National guidelines advise a waiting time of 12 hours. The aim of our study was to evaluate whether it is sufficient to rely on a calculated waiting time.


METHODS
As examples of typical pharmacokinetics of midazolam and its metabolites, we followed the concentration over time in four potential organ donors with immunoassays and high-performance liquid chromatography (HPLC).


CONCLUSIONS
In each of the 4 patients studied, the elimination of midazolam and/or midazolam metabolites was delayed. As long as brain death diagnosis requires that drugs interfering with the clinical assessment must be at levels below the therapeutic range, monitoring of midazolam and metabolites appears mandatory.
Meinitzer
A
A
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz, Austria.
Zink
M
M
März
W
W
Baumgartner
A
A
Halwachs-Baumann
G
G
D000759:Adjuvants, Anesthesia / Q000097:blood / Q000493:pharmacokinetics; D000328:Adult; D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics; D001926:Brain Death / Q000175:diagnosis*; D002851:Chromatography, High Pressure Liquid; D020719:Glucuronides / Q000097:blood; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics; D008874:Midazolam / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D014019:Tissue Donors
D000759:Adjuvants, Anesthesia; D018686:Anesthetics, Intravenous; D020719:Glucuronides; D006993:Hypnotics and Sedatives; C040081:1-hydroxymethylmidazolam; D008874:Midazolam