A Comparison of the Effect of Remimazolam and Midazolam on Recovery and Preserved Memory Function for Patients with Dental Extraction Anxiety

Quan Jing,1,* Weijia Wang,2,* Limeng Wu,1 Lejunzi Wang,2 Boru Yuan,2 Yan Wang,2 Chengbin Wang,3 Lin Liu,4 Lei Guan,5 Riyue Yu,6 Yuelun Zhang,7 Daniel I Sessler,8,9 Yuguang Huang,2 Kuo Wan,1 Lijian Pei2 1Department of Stomatology, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Department of Anesthesiology, Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Stomatology, Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Anesthesiology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Stomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 7Medical Research Center, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 8Center for Outcomes Research and Department of Anesthesiology, UTHealth, Houston, TX, USA; 9Outcomes Research Consortium®, Houston, TX, USA*These authors contributed equally to this workCorrespondence: Lijian Pei, Department of Anesthesiology, Peking Union Medical College Hospital, Dongdan District, No. 1, Shuaifuyuan, Beijing, 100730, People’s Republic of China, Tel +86 18612672127, Fax +86 10 69155581, Email [email protected] Kuo Wan, Department of Stomatology, Peking Union Medical College Hospital, Dongdan District, No. 1, Shuaifuyuan, Beijing, 100730, People’s Republic of China, Tel +86 15811185513, Email [email protected]: Remimazolam is an ultrashort-acting benzodiazepine, which has been indicated to be effective in endoscopic surgery and general anaesthesia. Research on its use in outpatient dental procedures remains limited. This triple-blinded randomized clinical trial was designed to determine whether the quality of postoperative recovery is better with continuous intravenous remimazolam administration compared with midazolam administration for impacted wisdom tooth extraction in patients with dental anxiety.Patients and Methods: This study was a randomized, parallel triple-blinded, superiority trial conducted between 30 April 2022 and 24 June 2024. Participants aged ≥ 18 years who exhibited dental anxiety and who were eligible for impacted wisdom tooth extraction in an outpatient setting were included in this study. Participants were randomly assigned at a 1:1 ratio to receive either a continuous intravenous infusion of remimazolam or midazolam. The primary outcome was the time to recover full alertness. The secondary outcome was postoperative anterograde amnesia.Results: A total of 150 participants were randomized in this study, with 75 patients assigned to the remimazolam group and 75 patients assigned to the midazolam group. The time to complete alertness was significantly shorter in the remimazolam group than in the midazolam group (3.0 ± 3.6 min vs 4.7 ± 5.2 min, mean difference, − 1.9 min; 95% CI, − 3.3min to − 0.4 min; P = 0.013). The odds of immediate and delayed anterograde amnesia were much reduced with remimazolam administration compared with midazolam administration (immediate: 0.14, 95% CI, 0.05 to 0.34, delayed: 0.07, 95% CI, 0.03 to 0.15, both P < 0.001).Conclusion: For patients with dental anxiety, remimazolam offers not only faster recovery, but also a much better restoration of memory function compared with midazolam.Trial Registration: https://clinicaltrials.gov/study/NCT05350085.Plain Language Summary: This study compared the effects of two sedatives—remimazolam (an ultrashort-acting benzodiazepine) and midazolam—in 150 outpatients with dental anxiety undergoing wisdom tooth extraction. In this randomized, triple-blinded trial, patients received either continuous intravenous remimazolam (n = 75) or midazolam (n = 75). The results showed that remimazolam not only led to significantly faster recovery (3.0 ± 3.6 min vs 4.7 ± 5.2 min to full alertness, p = 0.013) but also substantially reduced both immediate and delayed anterograde amnesia (p < 0.001) compared to midazolam. In other words, postoperative memory function—whether immediate or delayed—was better preserved with remimazolam. These findings suggest that remimazolam offers quicker recovery and fewer memory disturbances for outpatients, making it a superior choice for outpatient sedation procedures.Keywords: antegrade amnesia, benzodiazepine, outpatient surgery, procedure sedation, remimazolam, besylate