Frontiers in Pharmacology
Effective doses of propofol and oliceridine fumarate for painless hysteroscopy: a two-phase dose-finding study using Dixon’s up-and-down method
By Jinming Chen, Yunhao Shao, Hao Sun and 1 others.
Abstract
Background Painless hysteroscopy is widely performed in gynecological practice, yet achieving an optimal balance between anesthetic safety and patient comfort remains challenging. Combining propofol with oliceridine may mitigate respiratory depression and injection pain associated with conventional regimens, though the effective doses for this combination have not been established. This study sought to identify the optimal dose combination of propofol and oliceridine for use in painless hysteroscopy. Methods Fifty-one women scheduled for elective painless hysteroscopy were enrolled in this prospective, two-phase dose-finding study. In Phase I, all patients received a fixed 1 mg dose of oliceridine at induction; propofol was subsequently titrated from an initial 2 mg/kg using Dixon’s up-and-down sequential method in 0.1 mg/kg intervals. Probit regression modeling was used to derive propofol ED50 and ED95, with 95% confidence intervals (CIs) obtained via the delta method; isotonic regression served as sensitivity analysis. In Phase II, propofol was fixed at the Phase I ED50, and oliceridine was titrated from 1 mg in 0.1 mg increments, with ED50 and ED95 determined identically. An effective response was defined as no body movement, no frowning, and a Ramsay Sedation Score ≥5 during cervical dilation and hysteroscope insertion. Secondary outcomes included Nociception Level Index (NOX), Cerebral State Index (CSI), hemodynamic parameters, and adverse events. Results The ED50 and ED95 of propofol were 1.818 mg/kg (95% CI: 1.696–1.940) and 2.223 mg/kg (95% CI: 1.840–2.605), respectively. For oliceridine, the corresponding ED50 was 0.663 mg (95% CI: 0.605–0.720) and ED95 was 0.813 mg (95% CI: 0.692–0.934). Pearson goodness-of-fit tests confirmed adequate model fit for both phases (propofol: P = 0.755; oliceridine: P = 0.899), and isotonic regression yielded ED50 estimates within 3% of probit-derived values. Hemodynamic parameters remained stable throughout sedation, with no serious adverse events observed. Conclusion The propofol-oliceridine appears to be a feasible option for painless hysteroscopy, with an acceptable safety profile provided that continuous airway monitoring is maintained. The ED50 and ED95 values observed in this study offer preliminary dosing guidance for outpatient practice. Clinical Trial Registration www.chictr.org.cn/showproj.html?proj=241260 , identifier ChiCTR2500102118.



