A pharmacokinetic study of midazolam in paediatric patients undergoing cardiac surgery.

Midazolam 0.3 mg kg-1 was given as a single dose to three groups of children undergoing cardiac surgery to determine its pharmacokinetic profile in this situation. The first group, undergoing closed heart surgery, received the midazolam during the operation. The other groups underwent cardiopulmonary bypass (CPB) with and without complete circulatory arrest. Mean clearance was 512 ml kg-1 h-1 and mean elimination half-lives were 3.3 h following CPB, with a tendency to a higher clearance in those children who had not undergone bypass. In a subsequent part of the study, 10 children received an infusion of midazolam 0.05 mg kg-1 h-1, in combination with intermittent doses of morphine, in the postoperative period. Mean plasma midazolam concentrations consistent with adequate sedation were 80-100 ng ml-1 during the infusion. One child who had not undergone CPB had very low plasma concentrations of midazolam with the same rate of infusion, consistent with the tendency for higher clearance in this group in the bolus pharmacokinetic study.