Tegileridine vs. sufentanil for postoperative analgesia in general surgery: A prospective, randomized, controlled, non-inferiority trial.

OBJECTIVE: Tegileridine, a novel G protein-biassed μ-opioid receptor agonist, may offer effective postoperative analgesia with fewer opioid-related adverse effects. This study evaluated its analgesic efficacy, safety and impact on surgical stress response vs. sufentanil for patient-controlled intravenous analgesia (PCIA) in general surgery patients. METHODS: In this single-centre, double-blind, non-inferiority trial, 120 adults scheduled for elective laparoscopic cholecystectomy, appendectomy or inguinal hernia repair were randomized 1:1 to 48-h PCIA with tegileridine (5 mg) or sufentanil (200 μg), both with tropisetron 10 mg. The primary outcome was 24-h area under the curve (AUC) for resting visual analogue scale (VAS) pain scores, with a non-inferiority margin of 10.6 points·h. Secondary outcomes included pain scores, PCIA usage, adverse events, recovery and plasma cortisol and interleukin-6 (IL-6). RESULTS: All 120 patients completed the study. Mean 24-h resting VAS-AUC was 102.3 ± 25.6 points·h (tegileridine) vs. 105.8 ± 27.1 points·h (sufentanil). Upper 97.5% confidence limit for the difference was 9.8 points·h, below the 10.6 margin (p < .001). Tegileridine significantly reduced postoperative nausea and vomiting (p = .007) and accelerated gastrointestinal recovery (p < .001). Postoperative cortisol and IL-6 elevations were significantly attenuated at 6 and 24 h (p < .001). No significant differences were observed for other adverse events or satisfaction. CONCLUSION: Tegileridine provides non-inferior analgesia to sufentanil FOR PCIA after general surgery, with reduced PONV, faster gastrointestinal recovery and blunted stress response, supporting its potential role in enhanced recovery protocols. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500114360).