Median effective dose (ED50) of ciprofol combined with alfentanil for suppressing cervical dilation responses during hysteroscopy: a prospective Dixon up-and-down study

BACKGROUND: Cervical dilation during hysteroscopy induces significant nociceptive stimulation that may provoke somatic response and compromise procedural conditions. The optimal induction dose of ciprofol combined with alfentanil for suppressing cervical dilation responses remains unclear. This study aimed to determine the median effective dose (ED50) of ciprofol using the Dixon up-and-down method and to estimate ED95 using logistic regression. METHODS: In this prospective dose-finding study, adult patients undergoing elective hysteroscopy received alfentanil 7.4 μg/kg followed by ciprofol at sequentially adjusted doses (initial dose 0.40 mg/kg; step size 0.025 mg/kg). A positive response (failure) was defined as the occurrence of any somatic movement (body movement, perioral twitching, frowning, or restlessness) during cervical dilation. A negative response (success) was defined as complete absence of movement. Enrollment continued until seven crossover pairs were obtained. ED50 was calculated using the Dixon-Mood method. ED95 and 95% confidence intervals were estimated using logistic regression. RESULTS: Thirty-two patients were included. The ED50 determined by the Dixon-Mood method was 0.397 mg/kg. Model-based regression analysis yielded an ED50 of 0.397 mg/kg (95% CI: 0.366-0.428 mg/kg) and an ED95 of 0.521 mg/kg (95% CI: 0.389-0.652 mg/kg). Two patients (6.3%) required transient jaw-thrust intervention; no assisted ventilation or serious adverse events occurred. CONCLUSION: When combined with alfentanil 7.4 µg/kg, ciprofol provided dose-dependent suppression of cervical dilation responses during hysteroscopy, with an ED50 of 0.397 mg/kg and a model-based ED95 of 0.521 mg/kg.