Background: Opioids remain the mainstream therapy for post-surgical pain. The choice of opioids administered by patient-controlled intravenous analgesia (PCIA) for thoracoscopic lung surgery is unclear. This study compared 3 opioid analgesics for achieving satisfactory analgesia with minimal emesis (SAME). Methods: This randomized clinical trial enrolled patients scheduled for thoracoscopic lung surgery randomized to receive 1 of 3 opioids for PCIA: oxycodone (group O), hydromorphone (group H), and sufentanil (group S). The primary outcome was the proportion of subjects achieving SAME, i.e., no-to-mild pain (pain score < 4/10) with minimal nausea/ vomiting (PONV score < 2/4) when coughing during the pulmonary rehabilitation exercise in the first 3 postoperative days. Results: Of 555 enrolled patients, 184 patients in group O, 186 in group H and 184 in group S were included in the final analysis. The primary outcome of SAME was significantly different among group O, H and S (41.3% vs 40.3% vs 29.9%, P = 0.043), but no difference was observed between pairwise group comparisons. Patients in groups O and H had lower pain scores when coughing on the second day after surgery than those in group S, both with mean differences of 1 (3(3,4) and 3(3,4) vs 4(3,4), P = 0.009 and 0.039, respectively). The PONV scores were comparable between three groups (P > 0.05). There were no differences in other opioid-related side effects, patient satisfaction score, and QoR-15 score among three groups. Conclusions: Given clinically relevant benefits detected, PCIA with oxycodone or hydromorphone is superior to sufentanil for achieving SAME as a supplement to multimodal analgesia in patients undergoing thoracoscopic lung surgery. Trial registration: This study was registered at (ChiCT R2100 045614, 19/04/2021).
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