The efficacy and safety of remimazolam versus propofol on emergence agitation in children undergoing root canal therapy when combined with sevoflurane: a randomized controlled trial

Background: The combination of intravenous and inhalational anesthesia has been proven to be an effective anesthetic method for pediatric root canal therapy (RCT). Propofol, though commonly used, has significant injection pain, respiratory and circulatory depression, and risk of propofol infusion syndrome. Remimazolam, with organ-independent clearance, may offer advantages. The effects of combining remimazolam with sevoflurane remain uncertain and require further investigation. This study aimed to compare the effect of remimazolam versus propofol on emergence agitation (EA) in children undergoing RCT under sevoflurane anesthesia.

Methods: It was a prospective, observer-blind randomized controlled trial. Between April 2023 and April 2024, patients aged 2 to 7 years with American Society of Anesthesiologists (ASA) physical statuses of 1 or 2, scheduled for RCT in The First Affiliated Hospital of Zhengzhou University were screened for eligibility. Eligible children were allocated at random into two groups (1:1), namely a remimazolam group and a propofol group (control group). The rate of occurrence of EA [defined as a pediatric anesthesia emergence delirium (PAED) score ≥12] was the primary outcome was observed at 0, 5, 10, 20, and 30 min after emergence from anesthesia. Secondary outcomes included the incidence of intraoperative bradycardia, tachycardia, and hypotension, PAED and Aono scores, extubation time and full recovery time, post-anesthesia care unit (PACU) discharge time, the incidence of adverse events from the start of anesthesia to PACU discharge, and family satisfaction.

Results: Baseline characteristics were comparable between groups. Compared with the control group, the proportion of EA in the PACU was less in the remimazolam group {12 out of 61 cases, 19.67% vs. 25 out of 61 cases, 40.98%; relative risk [95% confidence interval (CI)]: 0.48 (0.26–0.84), P=0.01}. The intention-to-treat (ITT) analysis confirmed that remimazolam significantly reduced the incidence of EA compared with propofol [19.05% vs. 41.27%; relative risk (95% CI): 0.46 (0.25–0.81), P=0.007], consistent with the per-protocol analysis. The remimazolam group also had lower PAED scores {6 [3–9.5] vs. 8 [6–13], P=0.002}. However, the time to full awakening was significantly longer in the remimazolam group {37 [30–44] vs. 30 [22.5–35.5], P<0.001}. In terms of extubation time and PACU discharge time, there were no differences between the groups, and the same for the incidences of intraoperative bradycardia, tachycardia, and hypotension. Family satisfaction was higher in the remimazolam group {10 [9–10] vs. 9 [8–10], P=0.03}.

Conclusions: When combined with sevoflurane, the simultaneous administration of remimazolam significantly reduced the incidence of EA in children undergoing RCT compared with propofol. But it also prolonged full awakening time, this trade-off should be considered in clinical decision-making.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300075012).