Abstract / Summary
Postoperative pain can be effectively managed using opioid-based patient-controlled intravenous analgesia (PCIA). However, this analgesic approach is commonly associated with side effects, such as postoperative nausea and vomiting, pruritus, constipation, postoperative ileus, urinary retention, sedation, and respiratory depression, all of which may interfere with early postoperative recovery. Nalbuphine is a κ-receptor agonist with partial μ-receptor antagonism and may complement the μ-opioid receptor agonist sufentanil, potentially maintaining analgesic efficacy while reducing certain opioid-related adverse effects, particularly opioid-induced pruritus and possibly postoperative nausea and vomiting. Nevertheless, respiratory depression and gastrointestinal adverse effects may still occur because nalbuphine is itself an opioid analgesic. We evaluated the efficacy and safety of PCIA with nalbuphine plus sufentanil after thoracoscopic lung surgery. A total of 128 adult patients scheduled for elective thoracoscopic pulmonary resection were enrolled in this single-center, prospective, randomized controlled trial. Participants were randomly assigned in a 1:1 ratio to receive sufentanil PCIA (control) or nalbuphine plus sufentanil PCIA (experimental) ( n = 64 per group). All patients received ultrasound-guided thoracic paravertebral block (PVB). The primary endpoint was the area under the curve (AUC) of the numerical rating scale (NRS) for pain during activity (coughing) during the first 24 postoperative hours. A noninferiority margin of 11.86 AUC units was prespecified. Secondary endpoints included NRS pain scores at prespecified time points, PCIA use, QoR-15 scores, postoperative nausea and vomiting (PONV), sedation assessed using the Ramsay scale, respiratory depression, and recovery milestones. Baseline characteristics were comparable between groups. Noninferiority of nalbuphine plus sufentanil PCIA was demonstrated for the 24-h activity-related NRS AUC, the prespecified primary endpoint. The upper bound of the 95% confidence interval was below the prespecified noninferiority margin. When compared with sufentanil alone, the experimental group had a lower activity-related NRS pain score at 24 h and a lower incidence of PONV at both 4 h and 8 h after surgery (all P <0.05). QoR‑15 scores and quantitative cough-intensity scores at 24 h were higher in the experimental group. Respiratory depression was uncommon and occurred mainly in the postanesthesia care unit. No respiratory depression event required assisted ventilation or naloxone. Among patients undergoing thoracoscopic lung surgery and receiving PVB, nalbuphine plus sufentanil PCIA provided non‑inferior overall analgesia over the first 24 postoperative hours and was associated with reduced early PONV and improved early recovery‑related outcomes. This regimen may support ERAS goals by balancing analgesia, tolerability and functional recovery. The nalbuphine plus sufentanil PCIA regimen evaluated in this trial has informed postoperative analgesic practice for selected patients undergoing thoracoscopic lung surgery; nevertheless, analgesic selection remains individualized according to patient characteristics, surgical factors, and safety considerations. Trial registration The study protocol was reviewed and approved by the Ethics Committee/Institutional Review Board of Qingdao Municipal Hospital (Approval No. 2024-KY-078; Date: 2024-12-26). The trial was also registered on the National Health Insurance Information Platform for Medical Research (registration number MR-37-25-006869, https://www.medicalresearch.org.cn/login ) on November 5, 2024. Written informed consent was obtained from every subject prior to study participation.