Effect of oliceridine versus morphine on the quality of early recovery after thoracoscopic surgery: a randomized, controlled clinical trial

Thoracic surgery is frequently accompanied by severe pain. Although opioids remain the primary choice for effective analgesia in acute moderate-to-severe pain, their use is limited by adverse effects. Oliceridine, a novel G protein-biased μ-receptor agonist, has demonstrated a potentially improved safety compared to traditional opioid medications. Therefore, we investigated a short-course regimen of oliceridine for postoperative analgesia to evaluate its effects on early recovery quality in patients undergoing video-assisted thoracoscopic surgery (VATS). A total of 100 patients (ages 18-75 years) scheduled for elective thoracoscopic surgery were enrolled and randomly assigned to either the oliceridine group or the morphine group (n = 50 per group). Standardized anesthesia protocols were implemented. At the conclusion of surgery, patients received an intravenous loading dose of either oliceridine (1.5 mg) or morphine (4 mg). Supplemental analgesia (oliceridine 0.5 mg or morphine 1 mg) was administered as needed in the post-anesthesia care unit (PACU). The primary outcome measure was time to extubation. Secondary outcome measures included time to alertness recovery, Numerical Rating Scale (NRS) pain scores, requirement for analgesic rescue, adverse events during PACU stay, Quality of Recovery-15 (QoR-15) scores at 24 h postoperatively, time to first oral intake, time to first ambulation, and incidence of 24-h gastrointestinal adverse events. A total of 95 patients completed the study (Oliceridine group: n = 46, Morphine group: n = 49). Compared with the Morphine group, the Oliceridine group demonstrated a shorter time to extubation (12 ± 4 min vs. 20 ± 8 min, mean difference -7.6 min,95% CI -10.4 – -4.9, P < 0.001); faster alertness recovery (18 ± 5 min vs. 29 ± 10 min, P < 0.001); and lower NRS pain scores at 5 min post-extubation (3 points vs. 5 points, P < 0.001); a lower proportion of patients requiring analgesic rescue (45.7% vs. 77.6%, P = 0.001); fewer overall adverse events occurred during PACU stay (19.6% vs. 38.8%, P = 0.04). However, no statistically significant differences were observed between the two groups in postoperative recovery metrics assessed at 24 h, including QoR-15 scores, time to first oral intake, time to first ambulation, and gastrointestinal adverse events (P > 0.05). Oliceridine demonstrated significant early recovery benefits compared to morphine in VATS patients, including faster extubation, quicker return of alertness, superior immediate analgesia, and fewer PACU adverse events. These advantages, however, were restricted to the immediate postoperative period and did not extend to 24-h recovery metrics. Therefore, while oliceridine is a potential option for optimizing early recovery pathways, its longer-term efficacy and role require further investigation. Randomized controlled trial; Chinese Clinical Trial Registration, ChiCTR2500096716 (Date 05/02/2025). This study was reported in accordance with the CONSORT guidelines (Consolidated Standards of Reporting Trials).