ED95 of Ciprofol Combined with Esketamine or Sufentanil in Elderly Patients Undergoing Endoscopic Submucosal Dissection: A Dose-Finding and Randomized Controlled Trial

Background: This study aimed to estimate the 95% effective dose (ED95) of ciprofol when combined with esketamine or sufentanil in elderly patients undergoing endoscopic submucosal dissection (ESD), and to explore the associated clinical and safety profiles of these sedation strategies. Methods: This study was conducted in two phases. In Phase 1, 44 patients aged 65– 80 years undergoing ESD were randomized to receive ciprofol combined with esketamine (group E) or sufentanil (group S). Dixon’s up-and-down method was used to characterize the dose-response relationship of ciprofol, and ED95 values were derived as model-based estimates. In Phase 2, 68 patients were randomized to group E or group S. Phase 2 was designed as an exploratory randomized comparison, and intraoperative parameters, hemodynamic variables, and postoperative outcomes were recorded. Results: Based on model-based analysis, the estimated ED95 of ciprofol combined with esketamine was 0.276 mg/kg (95% CI: 0.264– 0.349), while that combined with sufentanil was 0.244 mg/kg (95% CI: 0.236– 0.282). No significant differences were observed between the two groups in the proportion of patients requiring rescue sedation or analgesia ( P > 0.05). Induction time was shorter in group E than in group S ( P = 0.039). During the procedure, group E showed lower incidences of hypoxia and hypotension and less fluctuation in mean arterial pressure (MAP) and heart rate (HR) compared with group S ( P < 0.05). In contrast, the time to full alertness was longer in group E than in group S ( P = 0.012). Conclusion: Ciprofol combined with esketamine or sufentanil showed different clinical and hemodynamic profiles in elderly patients undergoing ESD. These findings were derived from an exploratory analysis and should be interpreted as strategy-specific rather than evidence of superiority. The longer time to full alertness with esketamine indicates a potential trade-off. Trial Registration: Chictr.org.cn; identifier: ChiCTR2500102341. Keywords: ciprofol, esketamine, sufentanil, endoscopic submucosal dissection, elderly