Remimazolam vs. propofol for induction and maintenance of general anesthesia: A systematic review and meta-analysis of emergence agitation risk in surgical populations

Introduction: The association between remimazolam and emergence agitation (EA) remains unclear. This meta- analysis aimed to compare the relative risk of developing EA when using remimazolam vs. propofol in induction and maintenance of general anesthesia. Method: We searched PubMed, clinicaltrials.gov, Web of Science, Cochrane Library, and Embase databases to identify studies meeting the inclusion criteria. The primary outcome was the incidence of EA. Secondary outcomes included the incidence of postoperative delirium (POD) within 7 days after surgery, emergence time, extubation time, length of post-anesthesia care unit (PACU) stay, and adverse events. Results: A total of 19 randomized controlled trials with 3031 patients were included in the meta-analysis. There was no statistically significant difference in the incidence of EA (RR = 0.82; 95 % confidence interval [CI], 0.41-1.65; p = 0.585) between remimazolam and propofol. Likewise, there were no significant intergroup differences in POD incidence, extubation time, emergence time, or length of PACU stay. Remimazolam exhibited superior hemodynamic stability, with a significantly reduced incidence of postinduction hypotension and intraoperative hypotension compared with propofol, while maintaining comparable safety profiles in terms of postoperative nausea and vomiting (PONV), intraoperative awareness, and hypoxemia. Subgroup analysis revealed that without routine postoperative antagonist administration, remimazolam was associated with prolonged extubation and length of PACU stay relative to propofol. In contrast, following antagonizing with flumazenil, the extubation and emergence times of the remimazolam group were shorter than those of the propofol group, while comparable PACU discharge time was maintained. Conclusion: The use of remimazolam for the induction and maintenance of general anesthesia does not lead to a higher occurrence of EA in adult patients undergoing surgery, relative to propofol. However, in patients with ASA III-IV, remimazolam may be linked to a greater risk of POD than propofol.