Preemptive Intravenous Nalbuphine for the Treatment of Post-Operative Visceral Pain: A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Introduction: Post-operative visceral pain is common in early postoperative period after laparoscopic surgery. As a kappa opioid receptor agonist, the antinociceptive effects of nalbuphine in visceral pain are consistent across a multitude of experimental conditions irrespective of species. We hypothesized that preemptive nalbuphine can decrease the visceral pain for patients with incisional infiltration of ropivacaine after laparoscopic cholecystectomy.

Methods: In a multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial, 2094 participants scheduled for laparoscopic cholecystectomy were randomly assigned to receive nalbuphine (Nal group, n = 1029) or placebo (Con group, n = 1027). The Nal group received intravenous nalbuphine 0.2 mg·kg^-1 and the Con group received saline in a similar way. The primary endpoint was the effect of nalbuphine on post-operative visceral pain intensity scores within 24 h postoperatively. The total amount of analgesic as well as complications were recorded.

Results: A total of 1934 participants were analyzed. Nalbuphine reduced the visceral pain both at rest (β = - 0.1189, 95% CI - 0.23 to - 0.01, P = 0.037) and movement (β = - 0.1076, 95% CI - 0.21 to - 0.01, P = 0.040) compared with placebo. Patients in the Nal group required less frequent supplemental analgesic administration during the first 24 h after surgery. There were fewer patients in the Nal group who experienced nausea and vomiting (PONV) (P = 0.008).

Conclusions: Preemptive nalbuphine administered at a dose of 0.2 mg·kg^-1 was safe and effective at reducing the postoperative visceral pain and supplemental analgesic use in patients undergoing laparoscopic cholecystectomy.

Trial registration: Chinese Clinical Trial Registry; ChiCTR1800014379.