The Efficacy and Safety of Remimazolam for the Management of Emergence Agitation: A Randomized, Double-Blind, Placebo-Controlled Study

Xiaoxing Lu^1,2Meiyan Zhou²Yao Lu^2,3Jia Sun²Kexin Mao^2,3Yangzi Zhu^2,3Rongguo Wang²Yong Cao^4*Liwei Wang^1,2,3*

• ¹Soochow University Medical College, Suzhou, Jiangsu Province, China
• ²Xuzhou Central Hospital, Xuzhou, China
• ³Xuzhou Medical University, Xuzhou, Jiangsu Province, China
• ⁴Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou, Jiangsu Province, China

Emergence agitation (EA) is a common postoperative complication characterized by confusion, disorientation, and restless behavior that can lead to self-harm, the removal of medical devices, and other adverse events. This randomized, double-blind, placebo-controlled study was designed to assess the efficacy and safety of a novel benzodiazepine, remimazolam, in the management of EA.A total of 219 adults experienced EA ( Riker Sedation-Agitation Scale SAS score ≥ 5) after otolaryngological surgery were randomly assigned (1:1:1 ratio) to receive one of the following three treatments: 2.5 mg remimazolam, 5.0 mg remimazolam, or placebo. The primary endpoint was the treatment success rate of EA, which was defined as an SAS score of <5 within 15 minutes after administration without the need for rescue sedation and no recurrence after 15 minutes. Secondary outcomes included rescue propofol dosage, EA duration, and the post-anesthesia care unit (PACU) discharge time. Adverse events were also monitored. The results demonstrated that both remimazolam groups (77.5% for 2.5 mg and 85.9% for 5.0 mg) had significantly higher treatment success rates compared to the placebo group (44.3%) (both P < 0.001). Additionally, they required less rescue propofol, had shorter EA durations, and faster PACU discharge times (all P < 0.001).Furthermore, the 2.5 mg group showed a lower incidence of hypoxia (7.0%) and hypotension (14.1%) compared to the placebo group (22.9% for hypoxia, 31.4% for hypotension) (P = 0.024 and 0.042, respectively). Exploratory analysis indicated that, for patients with dangerous agitation (SAS=7), only the 5.0 mg group (83.3%) had a significantly higher treatment success rate than the placebo group (0%) (P < 0.001). Our findings suggest that remimazolam is a promising option for managing EA in the PACU. For the entire study population, the 2.5 mg dose strikes an optimal balance between efficacy and safety. In patients with dangerous agitation, a 5.0 mg dose of remimazolam may offer potential benefits. These findings hold significant implications for guiding future therapeutic strategies for AE.