Circadian rhythms on the median effective dose (ED50) of ciprofol in hysteroscopy: a prospective, double-blind, dose-response study

Background: Recent studies indicate that the pharmacokinetics and pharmacodynamics of sedative-hypnotics, such as propofol, may be influenced by circadian rhythms and the timing of surgery. Ciprofol, a short-acting intravenous sedative derived from propofol, is frequently utilized for sedation during non-tracheal intubation, general anesthesia, and in intensive care settings. This study aimed to evaluate circadian rhythm’s effect on the median effective dose (ED50) of ciprofol sedation during hysteroscopy. Methods: A total of 290 female patients undergoing hysteroscopy were randomly assigned to either a daytime group (8:00–18:00) or a nighttime group (20:00–8:00). Each group received one of four doses of ciprofol (0.3, 0.4, 0.5, 0.6 mg/kg) or 2.0 mg/kg propofol, followed by continuous infusion. As required, a bolus was administered. ED50 was determined through probit regression analysis and induction requirements, emergence times, duration of stay in the Post-Anesthesia Care Unit (PACU), pain levels assessed using a numeric rating scale, Ramsay sedation scale scores, and any intraoperative or postoperative adverse events were recorded. Results: The ED50 of ciprofol was determined to be 0.29 mg/kg for the nighttime group and 0.36 mg/kg for the daytime group. The nighttime group exhibited lower induction requirements (p = 0.031), longer emergence times (8.0 vs. 6.0 minutes; p < 0.001), and extended PACU stays (30.0 vs. 28.0 minutes; p = 0.040). Furthermore, Ramsay sedation scores were lower in the nighttime group (p = 0.002). Conclusions: For women undergoing hysteroscopic procedures, nighttime surgery significantly decreased the ED50 of ciprofol needed to suppress the response to cervical dilation and lowered the induction requirements compared to daytime surgery. Additionally, nighttime surgery was, however, associated with longer emergence times, extended PACU stays, and lower postoperative Ramsay sedation scale scores. Clinical Trial Registration: We registered with the Chinese Clinical Trial Registration Center (ChiCTR2400087340, 25 July 2024).

Ciprofol; Circadian rhythm; Propofol; Cervical dilation; Hysteroscopy

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