Comparison of intravenous nalbuphine and sufentanil on the median effective effect-site concentration of propofol to attenuate the response to cervical dilation during hysteroscopy: a double-blind, dose-response study.

Background: Nalbuphine, a synthetic opioid receptor agonist, exhibits comparable analgesic activity to morphine while demonstrating superior safety. Recent reports suggest that it is more effective than sufentanil in relieving uterine contraction pain. The objective of our study was to investigate the role of nalbuphine in reducing effect-site propofol concentration (Ce_prop) required to suppress response to cervical dilation in 50% of patients (EC₅₀) undergoing hysteroscopy.

Methods: Ninety patients having monitored anesthesia care for hysteroscopy were randomized to receive 0.15 mg·kg^-1, 0.2 mg·kg^-1 intravenous nalbuphine or 0.15 μg·kg^-1 intravenous sufentanil, followed by a target controlled infusion (TCI) of propofol. The initial target effect-site propofol concentration (Ce_prop) was 3.5 μg·ml^-1 which was increased or decreased in subsequent patients by steps of 0.5 μg·ml^-1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ce_prop that produced an effective response in 50% of patients (EC₅₀). Probit analysis was applied as a backup and sensitivity test.

Results: The calculated EC₅₀ of propofol in nalbuphine Group of 0.2 mg·kg^-1 (3.57 [95% CI 3.36 to 3.79] μg·ml^-1) were lower compared to propofol in nalbuphine Group of 0.15 mg·kg^-1 (4.04 [95% CI 3.85 to 4.22] μg·ml^-1) and sufentanil Group of 0.15 μg·kg^-1 (4.07 [95% CI 3.88 to 4.25] μg·ml^-1) (P = 0.002). Differences between EC₅₀ values for propofol in nalbuphine Group of 0.15 mg·kg^-1 and sufentanil Group of 0.15 μg·kg^-1 were not statistically significant. Minutely propofol requirement was also lower in 0.2 mg·kg^-1 nalbuphine Group (0.22 [0.19 to 0.27] mg·kg^-1·min^-1) compared with 0.15 mg·kg^-1 nalbuphine Group (0.30 [0.25 to 0.33] mg·kg^-1·min^-1) and 0.15 μg·kg^-1 sufentanil Group (0.27 [0.24 to 0.37] mg·kg^-1·min^-1) (P = 0.020).

Conclusions: During hysteroscopic surgery, when compared with sufentanil, 0.2 mg·kg^-1 nalbuphine significantly reduced the EC₅₀ for propofol to inhibit cervical dilation response and the propofol requirement, and did not delay the emergence from anesthesia. Whether 0.2 mg·kg^-1 nalbuphine could improve perioperative prognosis is worthy of further studies.

Trial registration: The study was then registered on August 9th, 2023 at the Chinese Clinical Trial Registry which participates in the World Health Organization International Clinical Trials Registry Platform (Identifier: ChiCTR2300074513) before enrolling the first participant and written informed consent was obtained by each patient.