Prophylactic Midazolam and Clonidine for Emergence from Agitation in Children After Emergence From Sevoflurane Anesthesia: A Meta-analysis

Abstract Background Emergence agitation (EA) after emergence from sevoflurane anesthesia is a common phenomenon in children. The efficacy of prophylactic midazolam or clonidine in preventing EA is controversial. Objective We performed a meta-analysis of clinical trials of the 2 drugs to evaluate their ability to prevent EA in pediatric patients after emergence from sevoflurane anesthesia. Methods A comprehensive literature search was conducted to identify clinical trials that observed the effect of midazolam and clonidine on preventing EA in children after their emergence from sevoflurane anesthesia. All data were examined using the Mantel-Haenszel model to calculate the pooled odds ratio (OR) and 95% CI. I2 was used to assess heterogeneity. Subgroup analysis was used to assess the effects of preoperative analgesics, routes of administration, and dose, and funnel plots were used to check publication bias. Results After a comprehensive literature search, we found 12 papers that met the criteria for inclusion in this analysis, with a total of 447 children in the midazolam group and 767 children in the clonidine group. We found that both midazolam and clonidine decreased the incidence of EA (OR = 0.45 [95% CI, 0.29–0.70], P = 0.0004, I2 = 46%; and OR = 0.24 [95% CI, 0.13–0.43], P < 0.00001, I2 = 48%, respectively). Subgroup analysis indicated that preoperative analgesia may decrease the effect of midazolam against EA, whereas for clonidine, neither the route of administration (intravenous or caudal) nor the dose affected the results. Funnel plots did not detect publication bias in the midazolam group, but a bias was detected in the clonidine group. Conclusions This meta-analysis suggests that prophylactic administration of midazolam or clonidine could significantly decrease the incidence of sevoflurane-induced EA in pediatric patients.