A comparison of midazolam and zolpidem as oral premedication in children, a prospective randomized double-blinded clinical trial

Background: Anxiety associated with pediatric surgery can be stressful. Midazolam is a well-accepted anxiolytic in this setting. However, there are cases in which this medication is not effective. Zolpidem is a short-acting nonbenzodiazepine hypnotic drug that is administered orally and has quick onset of action (~15 minutes), and 2-3 hour duration.

Aims: Based on the theory that impaired perception following oral zolpidem administration would suppress the development of anxiety, we sought to compare zolpidem to midazolam for pediatric preoperative anxiety.

Methods: This prospective randomized double-blinded clinical trial was designed to compare the effectiveness of oral midazolam and zolpidem for anxiety premedication. Eighty ASA class I-II pediatric patients between 2 and 9 years old, surgery >2 hours, and at least 23 hours postoperative admission were included in the study. Randomization was done with 0.5 mg/kg midazolam or 0.25 mg/kg zolpidem administered orally. The primary outcome measure was between group difference in patient anxiety at the time of separation using the Modified Yale Preoperative Anxiety Scale. Secondary outcomes included emergence delirium and mask acceptance at induction.

Results: There was no significant difference in Modified Yale Preoperative Anxiety Scale scores at separation between midazolam (median/interquartile range = 26.7/23.3-36.6) and zolpidem (median/interquartile range = 30.0/23.3-56.6) groups, difference 0.01 (95% CI -3E^-5 , 3E^-2 ; P = 0.07). Mask acceptance score was significantly better in the midazolam group. There was no significant difference in emergence delirium scores between groups.

Conclusion: This study demonstrates that zolpidem, as dosed, was similar to midazolam with regard to anxiety scoring, and inferior with regard to mask acceptance scores.