抄録
The objectives of this study were to evaluate the risk of the accumulation of midazolam and its active metabolites in critically ill patients in an intensive care unit (ICU) being treated by continuous hemodiafiltration (CHDF) using a polymethyl methacrylate (PMMA) and/or a polysulfone (PS) membrane and the influence of CHDF on the pharmacokinetics of midazolam in these patients. The serum and ultrafiltration liquid concentrations of midazolam and its active metabolites were measured by high-performance liquid chromatography to study the pharmacokinetics of midazolam and its active metabolites in seven patients with renal failure who were being treated by CHDF using a PMMA and/or a PS membrane. There was no progressive accumulation of midazolam or 1-hydroxymidazolam, though high levels of 1-hydroxymidazolam glucuronide were noted. The extraction rates for these 3 substances by CHDF using a PMMA and a PS membrane were 1.3%, 3.0% and 13.4%, and 5.0%, 4.8 % and 74.4%, respectively. A positive correlation was observed between the 1-hydroxymidazolam glucuronide concentration and serum creatinine concentration for CHDF using the PMMA membrane (r2=0.8223), while there was no correlation between these concentrations when the PS membrane was used (r2=0.0361). These results show that CHDF using a PMMA membrane did not affect the elimination of 1-hydroxymidazolam glucuronide but it was affected when the PS membrane was used. The risk of accumulation of 1-hydroxymidazolam glucuronide and the need for prolonged sedation should be therefore be taken into account in drug dose adjustment for patients undergoing CHDF.
