Midazolam for sedation before procedures in adults and children: a systematic review update

Midazolam is used for sedation before diagnostic and therapeutic medical procedures by several routes including oral, intravenous, intranasal and intramuscular. This is an update of a Cochrane review published in 2016, which aimed to determine the evidence on the effectiveness of midazolam for sedation when administered before a diagnostic or therapeutic procedure in adults and children. We searched CENTRAL, MEDLINE, Embase and two trials registers up to May 2020 together with reference checking to identify additional studies. We imposed no language restrictions. Randomized controlled trials of midazolam in comparison with placebo or other medications used for sedation were included. Two authors independently extracted data and assessed risk of bias for each included study. Eight new trials were included in this update, which resulted in changed conclusions for the intravenous midazolam versus placebo, oral midazolam versus chloral hydrate and oral midazolam versus placebo comparisons. Effect estimates for all outcomes within the intravenous midazolam versus placebo (7 trials; 633 adults and 32 children) are uncertain due to concerns about imprecision and risk of bias. Midazolam resulted in a higher level of sedation than placebo (mean difference (MD) 1.05; 95% confidence interval (95% CI) 0.69 to 1.41; 1 study; 100 adults). There was no difference in anxiety (RR 0.43, 95% CI 0.09 to 1.99; I = 75%; 2 studies; 123 adults). Risk of difficulty performing procedures was lower in the midazolam group (RR 0.5; 95% CI 0.29 to 0.86; I = 45%; 3 studies; 191 adults and 32 children). There was no difference in discomfort (RR 0.51; 95% CI 0.25 to 1.04; I = 0%; 2 studies; 190 adults). Five trials with 336 children were included in the oral midazolam versus chloral hydrate comparison. Midazolam was less likely to result in moderate sedation (RR 0.30, 95% CI 0.11 to 0.82; I = 64%; 2 studies, 228 participants). This effect estimate is highly uncertain due to concerns about the risk of bias, imprecision and inconsistency. There was no difference in ratings of anxiety (SMD - 0.26; 95% CI - 0.75 to 0.23; I = 0%; 2 studies; 68 participants). Midazolam increased risk of incomplete procedures (RR 4.01; 95% CI 1.92 to 8.40; I = 0%; 4 studies, 268 participants). This effect estimate is uncertain due to concerns about the risk of bias. There were four trials with 359 adults and 77 children included in the oral midazolam versus placebo comparison. Midazolam reduced ratings of anxiet