Intranasal midazolam for procedural distress in children in the emergency department: a systematic review and meta-analysis.

Objectives: Intranasal (IN) midazolam is the most common anxiolytic for children in the emergency department (ED), but evidence of benefit is conflicting. We synthesized the evidence on IN midazolam for procedural distress in children undergoing ED painful procedures.

Methods: We included trials involving painful ED procedures in children 0-18 years involving IN midazolam. Primary outcome was procedural distress. We summarized results using Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," and "unfavorable" (p < 0.05), supporting IN midazolam or comparator, respectively, or "indeterminate" (unable to judge). Where possible, we pooled results using meta-analysis. Methodologic quality of evidence was evaluated using Cochrane Collaboration's risk of bias tool and GRADE system.

Results: We included 41 trials (n = 2973 participants). Thirty trials involved intravenous insertion. IN midazolam was superior to placebo (RR = 7.2; 95% CI: 3.43, 15.25; 3 trials; I² = 0%). However, 56-90% of the IN midazolam group resisted the procedure. Focusing on the three trials that used validated measures, IN midazolam was "neutral" versus IN ketamine and either "neutral" or "unfavorable" versus IN dexmedetomidine. There was no difference in the proportion of children with a satisfactory distress score between IN midazolam and oral midazolam (RR = 1.1; 95% CI: 0.74, 1.73; 2 trials; I² = 53%), IN ketamine (RR = 1.1; 95% CI: 0.91, 1.25; 6 trials; I² = 0%), or IN dexmedetomidine (RR = 0.4; 95% CI: 0.17, 1.05; 3 trials; I² = 84%). Ten trials involved laceration repair. IN midazolam was "favorable" versus placebo; however, both groups scored in the anxious range. There was no difference in distress between IN midazolam and oral midazolam (SMD = 0.01; 95% CI:-0.32, 0.34; 2 trials; I² = 0%) (Fig. 3E) [64,65]. Using validated instruments, IN midazolam was "unfavorable" versus IN dexmedetomidine but "favorable" versus oral diazepam and placebo.

Conclusions: There is limited methodologically rigorous evidence that IN midazolam is better than placebo for IV insertion and laceration repair. At the doses studied, preliminary evidence suggests that IN dexmedetomidine may be superior to IN midazolam for both IV insertion and laceration repair.