The median effective dose (ED50) of remimazolam combined with esketamine for conscious sedation in patients with dental anxiety undergoing outpatient dental surgery: a prospective, dose-finding study.
TL;DR
The ED50 provides a preliminary reference for initial dose selection in this clinical setting and requires validation in larger studies, but the wide confidence interval of the ED95 limits its clinical utility and requires validation in larger studies.
Abstract
Background
Dental anxiety presents a significant barrier to treatment. Conscious sedation is widely used to alleviate anxiety. Although remimazolam has demonstrated its efficacy and advantages for outpatient dental procedures, research on the effective dose of remimazolam combined with esketamine remains limited. Thus, the purpose of our research was to estimate the effective dose of remimazolam with esketamine for conscious sedation in patients with dental anxiety undergoing outpatient dental surgery.
Methods
The study enrolled outpatients with dental anxiety aged 18-65 years who received dental operations and were classified under ASA grades I-II. Using the modified Dixon up-and-down method, each patient was first administered by infusing esketamine 0.1 mg/kg, followed by an assigned dose of remimazolam. The initial dose of remimazolam was 0.1 mg/kg, with a dose gradient of 0.01 mg/kg. Sedation success was defined as achieving a MOAA/S score of 3-4 within 5 min after the initial loading dose, without requiring additional remimazolam. The primary outcome was the ED50 of remimazolam and its 95% confidence interval (CI). Secondary outcomes included security indicators, patient satisfaction and memory of the procedure, dentist satisfaction, duration of treatment, and discharge time.
Results
The study achieved 10 transition points (from sedation success to failure) with a total enrollment of 32 individuals. The ED50 and ED95 of remimazolam with 0.1 mg/kg esketamine, for conscious sedation during outpatient dental surgery, were 0.069 mg/kg (95% CI: 0.050-0.080 mg/kg) and 0.099 mg/kg (95% CI: 0.085-0.200 mg/kg), respectively. No circulatory and respiratory adverse events requiring intervention were observed during anesthesia induction.
Conclusions
For outpatient dental procedures in patients with dental anxiety, the ED50 and ED95 of remimazolam with esketamine for conscious sedation were 0.069 mg/kg and 0.099 mg/kg, respectively. The ED50 provides a preliminary reference for initial dose selection in this clinical setting. However, the wide confidence interval of the ED95 limits its clinical utility and requires validation in larger studies. TRIAL REGISTRATION This study was registered in the Chinese Clinical Trial Registry (ChiCTR2500104775; first registered on 23/06/2025).