Abstract |
This study investigated the pharmacokinetics of midazolam and its main metabolite, 1-hydroxymethylmidazolam glucoronide, during long-term i.v. infusion in 39 mechanically ventilated ICU patients of whom 6 were in acute renal failure (ARF). The mean infusion rate of midazolam was similar (9.4 vs 8.7 mg/h) in the control patients and those with ARF. The renal clearance of 1-hydroxymethylmidazolam glucuronide was much lower in the ARF group than in the control group (3.9 vs 136 ml/min). Consequently, its plasma elimination half-life after discontinuation was also greatly prolonged, but this shouldn't cause very prolonged sedative effects since this metabolite is much less active than the parent drug. However, the half-life of midazolam itself was also significantly longer in patients with ARF than in the control group (13.2 vs 7.6 h). Apparently, this was caused by a combination of a slightly lower total clearance and a higher volume of distribution. Therefore, regular reassessment of the degree of sedation and appropriate adaptation of the infusion rate of midazolam are recommended in ICU patients with ARF.
|
Authors | J J Driessen, T B Vree, P J Guelen |
Journal | Acta anaesthesiologica Belgica
(Acta Anaesthesiol Belg)
Vol. 42
Issue 3
Pg. 149-55
( 1991)
ISSN: 0001-5164 [Print] Belgium |
PMID | 1767626
(Publication Type: Journal Article)
|
Chemical References |
- Glucuronates
- 1-hydroxymethylmidazolam
- Midazolam
|
Topics |
- Acute Kidney Injury
(blood)
- Critical Illness
- Female
- Glucuronates
(blood)
- Humans
- Infusions, Intravenous
- Male
- Midazolam
(administration & dosage, analogs & derivatives, blood, pharmacokinetics)
- Middle Aged
- Respiration, Artificial
|