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

Abstract

Summary 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.

A Double-Blind Clinical Trial to Determine the Effect of Oral Zolpidem and Midazolam on the Level of Preoperative Anxiety in Children Undergoing Eye Examination Under General Anesthesia

“…The patients were divided into two groups, one group received 0.5 mg/kg oral midazolam and the other 0.25 mg/kg oral zolpidem. They found that the effects of zolpidem and midazolam on anxiety were not significantly different (14). Our findings are in line with the results of the above study and show the effectiveness of oral zolpidem.…”

“…The drug was given to the patients at a relatively low dose to prevent excessive sedation that might mask the symptoms of anxiety and would not be obvious to others, including researchers collecting information. Therefore, the dose of drug was set to a value less than similar studies (6,13,14).…”

“…A double-blind study was conducted by Hanna et al in 2018. It was reported that the effect of midazolam was well accepted. However, there are cases where this medicine is not effective.…”

Pharmacological strategies to reduce perioperative anxiety in children – a narrative review

“…Toddlers (1-3 years old) possibly require a higher dose (1mgkg -1 ) whereas 0,75mgkg -1 seems sufficient for >95% of children more than 3 years old 5,12,13 . Most studies use 0,5mgkg -1 as a 'golden standard' [14][15][16][17][18][19][20][21][22][23][24][25][26] and this is believed to be the most effective dose with least side effects 27 . Some authors endeavor higher doses of oral midazolam.…”

“…Mask-acceptance scores were significantly (p=0,03) worse in the zolpidem-group. Five participants in the zolpidem group (n=42) showed minor adverse reactions: double vision, visual hallucinations, dysphoria, involuntary tongue movements and excessive sleepiness 14 .…”