Efficacy and Safety of Nalbuphine Compared with Other Analgesics for Moderate-to-severe Postoperative Pain: A Systematic Review and Network Meta-analysis

Background: Postoperative pain is a common and challenging form of acute pain, especially at moderate to severe intensity. While opioids are effective, their adverse effects limit clinical use. Nalbuphine has been proposed as a safer alternative, but its comparative efficacy and safety remain unclear. Aim: This study aimed to systematically evaluate the analgesic efficacy and safety of nalbuphine versus other analgesics. Methods: A systematic search of electronic databases was conducted through March 2025. Studies comparing nalbuphine with other analgesics for postoperative pain were included. Risk of bias (RoB) was assessed using RoB 2.0 and ROBINS-I. Pain outcomes were analyzed across 0–8, 8–24, and 24–48 h intervals using the standardized mean differences. Efficacy was ranked using surface under the cumulative ranking values. Subgroup analyses were performed by surgical type. Results: Twenty-six studies (21 randomized clinical trials and 5 observational) involving 6223 patients were included. Fourteen studies compared monotherapy and 12 examined combination therapy. In the 0–8 h interval ( n = 12), nalbuphine showed moderate analgesic efficacy, ranking below morphine but above sufentanil and ketorolac. Similar trends were seen at later intervals. Subgroup analyses showed greater efficacy in gynecological and abdominal surgeries compared to orthopedic ones. Compared with morphine, nalbuphine was associated with significantly lower rates of nausea (risk ratio [RR] = 0.442), vomiting (RR = 0.428), and pruritus (RR = 0.066). Conclusion: Nalbuphine offers moderate analgesic efficacy with a more favorable safety profile than morphine, especially in surgeries involving visceral pain. It may be a valuable option when minimizing opioid-related adverse effects is a clinical priority.