Concomitant Use of Intravenous Remimazolam With Inhalation Anesthesia and Subsequent Emergence Delirium in Children: A Systematic Review and Meta-Analysis

Emergence delirium (ED) is a typical postoperative complication in pediatric anesthesia, especially with inhalational agents. Remimazolam, a short-acting benzodiazepine, shows potential for reducing the occurrence of ED. Given limited evidence of its use in pediatric anesthesia, we evaluated the efficacy and safety of remimazolam by conducting a systematic review and meta-analysis. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and International Clinical Trials Registry Platform (ICTRP) databases were explored for studies on remimazolam in pediatric anesthesia. The studies included were randomized controlled trials (RCTs), prospective and retrospective cohort studies, case series, and case reports. Eligible patients were pediatric patients as American Society of Anesthesiologists Physical Status I or II who underwent sevoflurane-based general anesthesia. Primary outcomes included ED and emergence time. Study quality was assessed using the Risk of Bias 2 tool, and evidence certainty was evaluated by the Grading of Recommendations, Assessment, Development, and Evaluation approach. Random-effects meta-analyses estimated pooled risk ratios (RRs). Three RCTs (n = 310) were included. A 0.2 mg/kg remimazolam bolus may result in a large reduction in ED (RR 0.26, 95% confidence intervals (CIs) 0.16 to 0.44, I² = 0%; low certainty, three studies). Continuous infusion showed similar effects (RR 0.22, 95% CIs 0.08 to 0.60, low certainty, one study). Emergence times varied by dosage and administration method, with continuous infusion associated with prolonged emergence times (mean difference 5.7 minutes, 95% CIs 3.67 to 7.73, low evidence, one study). Evidence certainty ranged from very low to low, with the 0.2 mg/kg bolus rated very low. The concomitant use of intravenous remimazolam with inhalation anesthesia may reduce the ED in pediatric patients. However, evidence on emergence times remains inconclusive. Anesthetists could potentially use remimazolam to reduce the ED in children after inhalation anesthesia, but further investigation regarding its efficacy and safety across diverse populations is warranted.