PROLONGED SEDATION DUE TO ACCUMULATION OF CONJUGATED METABOLITES OF MIDAZOLAM

被引:220
作者
BAUER, TM
RITZ, R
HABERTHUR, C
HA, HR
HUNKELER, W
SLEIGHT, AJ
SCOLLOLAVIZZARI, G
HAEFELI, WE
机构
[1] UNIV BASEL HOSP,DEPT INTERNAL MED,DIV CLIN PHARMACOL,CH-4031 BASEL,SWITZERLAND
[2] UNIV BASEL HOSP,DEPT INTERNAL MED,DIV INTENS CARE,CH-4031 BASEL,SWITZERLAND
[3] UNIV BASEL HOSP,DEPT NEUROL,CH-4031 BASEL,SWITZERLAND
[4] UNIV ZURICH HOSP,CARDIOVASC THERAPY RES UNIT,CH-8091 ZURICH,SWITZERLAND
[5] F HOFFMANN LA ROCHE & CO LTD,CH-4002 BASEL,SWITZERLAND
来源
LANCET | 1995年 / 346卷 / 8968期
关键词
D O I
10.1016/S0140-6736(95)91209-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Midazolam is a short-acting benzodiazepine routinely used in intensive-care medicine. Conjugates of its main metabolite, alpha-hydroxymidazolam, have been shown to accumulate in renal failure but have not previously been related to the prolonged sedative effects commonly observed in critically ill patients. We report five patients with severe renal failure who had prolonged sedation after administration of midazolam. In all five patients, the comatose state was immediately reversed by the benzodiazepine-receptor antagonist flumazenil. Serum concentration monitoring showed high concentrations of conjugated alpha-hydroxymidazolam when concentrations of the unconjugated metabolite and the parent drug were below the therapeutic range. In-vitro binding studies showed that the affinity of binding to the cerebral benzodiazepine receptor of glucuronidated alpha-hydroxymidazolam was only about ten times weaker (affinity constant 16 nmol/L) than that of midazolam (1 . 4 nmol/L) or unconjugated alpha-hydroxymidazolam (2 . 2 nmol/L). Conjugated metabolites of midazolam have substantial pharmacological activity. Physicians should be aware that these metabolites can accumulate in patients with renal failure.
引用
收藏
页码:145 / 147
页数:3
相关论文
共 14 条