Efficacy and Safety of Nalbuphine Compared With Analgesics for Moderate to Severe Postoperative Pain: A Systematic Review and Network Meta-Analysis
Author(s)
Rong-Sheng Chen, .1, He-Yu Chen, Sr., PharmD2, Ping-Hsuan Hsieh, PhD3.
1National Defense Medical Center, Taipei, Taiwan, 2National Defense Medical Center, Taipei City 11490, Taiwan, 3National Defense Medical Center, Taipei City, Taiwan.
1National Defense Medical Center, Taipei, Taiwan, 2National Defense Medical Center, Taipei City 11490, Taiwan, 3National Defense Medical Center, Taipei City, Taiwan.
OBJECTIVES: Postoperative pain is a common and challenging form of acute pain, particularly at moderate to severe intensity. Although opioids such as morphine are effective, their adverse effects often limit clinical use. Nalbuphine has been proposed as a safer alternative, but its comparative efficacy and safety remain unclear. This study aimed to systematically evaluate nalbuphine’s analgesic performance and safety profile compared with other analgesics.
METHODS: A systematic search of electronic databases was conducted up to March 2025 (PROSPERO: CRD420251004070). Eligible studies comparing nalbuphine with other analgesics for postoperative pain were included. Risk of bias was assessed using the RoB 2.0 and ROBINS-I tools. Pain outcomes were assessed across 0 to 8, 8 to 24, and 24 to 48 hours using standardized mean differences, and efficacy was ranked using surface under the cumulative ranking values. Subgroup analyses by surgical type were also performed.
RESULTS: Twenty-six studies (21 RCTs and 5 observational studies) comprising 6,223 patients were included, with 14 monotherapy and 12 combination therapy comparisons. The 0 to 8 hours postoperative interval included the most studies (n = 12), where nalbuphine showed moderate analgesic efficacy, ranking below morphine and above sufentanil and ketorolac. Other intervals followed a similar ranking pattern. Subgroup analyses suggested the analgesic efficacy of nalbuphine was more favorable in gynecological and abdominal surgeries than in orthopedic procedures. Nalbuphine also had significantly lower rates of nausea (RR = 0.442, 95% CI: 0.253 to 0.774), vomiting (RR = 0.428, 95% CI: 0.278 to 0.659), and pruritus (RR = 0.066, 95% CI: 0.009 to 0.484) than morphine.
CONCLUSIONS: Nalbuphine provides moderate efficacy in postoperative pain control with a favorable safety profile, particularly in surgeries associated with visceral pain. Although it is less potent than morphine, nalbuphine may be a valuable clinical alternative when minimizing opioid-related adverse effects is an important consideration.
METHODS: A systematic search of electronic databases was conducted up to March 2025 (PROSPERO: CRD420251004070). Eligible studies comparing nalbuphine with other analgesics for postoperative pain were included. Risk of bias was assessed using the RoB 2.0 and ROBINS-I tools. Pain outcomes were assessed across 0 to 8, 8 to 24, and 24 to 48 hours using standardized mean differences, and efficacy was ranked using surface under the cumulative ranking values. Subgroup analyses by surgical type were also performed.
RESULTS: Twenty-six studies (21 RCTs and 5 observational studies) comprising 6,223 patients were included, with 14 monotherapy and 12 combination therapy comparisons. The 0 to 8 hours postoperative interval included the most studies (n = 12), where nalbuphine showed moderate analgesic efficacy, ranking below morphine and above sufentanil and ketorolac. Other intervals followed a similar ranking pattern. Subgroup analyses suggested the analgesic efficacy of nalbuphine was more favorable in gynecological and abdominal surgeries than in orthopedic procedures. Nalbuphine also had significantly lower rates of nausea (RR = 0.442, 95% CI: 0.253 to 0.774), vomiting (RR = 0.428, 95% CI: 0.278 to 0.659), and pruritus (RR = 0.066, 95% CI: 0.009 to 0.484) than morphine.
CONCLUSIONS: Nalbuphine provides moderate efficacy in postoperative pain control with a favorable safety profile, particularly in surgeries associated with visceral pain. Although it is less potent than morphine, nalbuphine may be a valuable clinical alternative when minimizing opioid-related adverse effects is an important consideration.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
PT38
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Surgery, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)