ED50 and ED95 of Remimazolam Combined with Sufentanil for Sedation During Ultrasound-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids: A Prospective Dose-Finding Study.

Background: Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids requires conscious sedation to ensure patient comfort while preserving responsiveness for real-time feedback. Remimazolam, an ultra-short-acting benzodiazepine, has faster onset, predictable clearance, and lower respiratory depression risk than midazolam or propofol, making it ideal for conscious sedation. Nevertheless, its optimal maintenance dosage combined with sufentanil remains undetermined. This study was designed to explore the ED50 and ED95 of remimazolam for targeted sedation during the operation. Methods: A total of 40 eligible patients were enrolled in this prospective dose-escalation study. Sedation was induced with remimazolam (0.1 mg/kg) and sufentanil (0.1 μg/kg), both infused over > 30 seconds, followed by continuous infusion of sufentanil (0.3 μg/kg/h) and remimazolam at an initial maintenance dose of 0.1 mg/kg/h. The maintenance dose of remimazolam was adjusted using the Dixon up-and-down sequential allocation method with a 0.02 mg/kg/h stepwise change. Effective sedation was defined as a Ramsay Sedation Scale score ≥ 2 at four or more intraoperative time points without the need for rescue sedation. Probit regression was used to calculate ED50 and ED95, and perioperative safety indicators and satisfaction degrees were recorded. Results: The estimated ED50 and ED95 of remimazolam were 0.064 (95% CI: 0.025-0.086) mg/kg/h and 0.102 (95% CI: 0.089-0.128) mg/kg/h, respectively. All operations were accomplished smoothly with fast postoperative recovery. The incidences of postoperative nausea and vomiting were 30.0% and 22.5% respectively. High satisfaction was achieved among patients, surgeons and anesthesiologists, and no severe adverse reactions occurred. Conclusion: The continuous infusion dose of remimazolam ranging from 0.06 to 0.10 mg/kg/h combined with sufentanil can provide satisfactory conscious sedation with quick recovery in USgHIFU treatment. Since single antiemetic prophylaxis fails to effectively reduce postoperative nausea and vomiting, further researches are essential to establish optimized multimodal antiemetic strategies for this sedative regimen. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2400084538), Registration Date: May 20, 2024.