Midazolam infusion for basal sedation in intensive care: absence of accumulation.
This study was designed to: (1) determine plasma midazolam concentrations producing adequate sedation in ICU patients; (2) establish an intravenous regimen to provide continuous sedation and rapid recovery after discontinuation of infusion. Initially, 13 ICU patients were given midazolam as a bolus injection, 0.20 mg.kg-1 over 30 s in order to define the midazolam plasma concentration corresponding to an adequate level of sedation. The optimal level was reached in a mean time of 61 +/- 26 min and the mean corresponding midazolam plasma concentration was 163 +/- 62 ng.ml-1. Estimations of the main pharmacokinetic parameters (elimination half life: 230 +/- 102 min, total body clearance: 520 +/- 283 ml.min-1, total volume of distribution: 2.23 +/- 1.15 l.kg-1) showed no marked differences with normal patients. From those variables, an infusion regimen (loading dose and maintenance rate) to provide long term (24 to 80 h) sedation was derived in 9 patients. The mean loading dose was 0.33 +/- 0.18 mg.kg-1 over 30 min and the mean continuous infusion dose was 0.06 +/- 0.02 mg.kg-1.h-1. The mean midazolam plasma concentration during infusion was 215 +/- 61 ng.ml-1, and the mean midazolam plasma concentration at the end of infusion was 199 +/- 93 ng.ml-1. The level of sedation was considered as optimal in most patients throughout the study. After discontinuation of infusion, the mean time for normalization of the mental state was 97 min.
Michalk
S
S
Département d'Anesthésie et de Réanimation Chirurgicale, Hôpital Bichat, Paris, France.
Moncorge
C
C
Fichelle
A
A
Huot
O
O
Servin
F
F
Farinotti
R
R
Desmonts
J M
JM
D000328:Adult; D000368:Aged; D003422:Critical Care; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged
D006993:Hypnotics and Sedatives; D008874:Midazolam