No drug has been demonstrated to provide at once appropriate sedation, safety and lack of disturbance of the measured parameters during cardiac catheterization in infants. The main objective of this trial was to estimate the dose of midazolam, administered rectally, that would provide a 90% rate of adequate sedation in infants during cardiac catheterization. A double blind, continual reassessment method using a Baye formula has been employed. The single doses studied ranged from 0.1 to 0.6 mg/kg. Sixteen infants, age 1 to 21 months entered the study and were administered midazolam rectally, 15 minutes before cardiac catheterization starts. The treatment was considered as a success when the sedation score was ≥ 4, in a six-point scale, during the 30 to 60 minute time-duration after dosing. The numerous consecutive failures lead to the allocation of the higest dose (0.6 mg/kg) within the dose-range to 15 out of 16 patients. At the end of the trial, the estimate probability failure of the 0.6 mg/kg dose was 81% (78.51 to 83.96%, 95% CI). The time to reach a score ≥ 4 was longer than expected and the median duration-time at score ≥ 4 was shorter (15 min) than expected (30 min). These data might be related to a delayed absorption and low rectal bioavailability. Higher doses or different routes of administration may shorten the time to reach the expected sedation and expand the duration of sedation but the safety of doses higher than 0.6 mg/kg administered rectally has not be evaluated. Haemodynamic parameters remained unchanged during the study. The four interpretable individual curves that plot sedation versus plasma concentration, shows counterclockwise hysteresis.
Funded in part by Delegation à la Recherche Clinique-Assistance Publique-Hôpitaux de Paris and Produits Roche-FRANCE.
