Efficacy and Safety of Oliceridine for Patient-Controlled Intravenous Analgesia in Elderly Patients Undergoing Laparoscopic Radical Resection Surgery for Gastrointestinal Malignant Tumors: A Prospective Randomized Controlled Non-Inferiority Clinical Trial.

Background: Opioid-related adverse events are common with sufentanil-based patient-controlled intravenous analgesia after laparoscopic gastrointestinal cancer surgery in older adults. Oliceridine, a G protein-biased μ-opioid receptor agonist, may provide effective analgesia with fewer adverse events. Methods: In this single-center, randomized, double-blind, non-inferiority trial (Tangdu Hospital, Xi'an, China), patients aged ≥60 years undergoing elective laparoscopic radical resection for gastrointestinal malignant tumors were allocated 1:1 to postoperative patient-controlled intravenous analgesia containing oliceridine (0.4 mg/kg) or sufentanil (2 μg/kg), combined with ketorolac and tropisetron, for 48 hours. The primary endpoint was the cumulative area under the curve for resting 0-10 visual analogue scale pain scores over 0-48 hours. The non-inferiority margin was prespecified as 20% of the mean AUC in the sufentanil group (18.3 points), a threshold based on prior studies and deemed clinically acceptable. Results: Of 90 randomized patients, 88 received the study drug and were included in the analyses (44 per group); two patients were excluded as they never received the intervention. In the per‑protocol analysis, the cumulative resting pain area under the curve was 73.02±22.59 with sufentanil and 72.55±23.54 with oliceridine (between-group difference 0.48; 95% CI -9.30 to 10.26), meeting non-inferiority. A modified intention‑to‑treat analysis including all 88 treated patients yielded identical results, confirming robustness. Movement-evoked pain area under the curve was similar (difference 1.77; 95% CI -8.72 to 12.27). Respiratory depression occurred in 1/44 (2.27%) with oliceridine versus 8/44 (18.18%) with sufentanil, and hypotension in 5/44 (11.36%) versus 13/44 (29.55%). Conclusion: In elderly patients undergoing laparoscopic gastrointestinal cancer surgery, oliceridine provided non-inferior analgesia to sufentanil while significantly lowering the incidence of respiratory depression and hypotension. These findings suggest that oliceridine may be a preferred opioid option for PCIA when respiratory and hemodynamic safety are critical concerns. Trial Registration: ChiCTR2400090780.