Yuwei Qiu, Y. Zhang, Chengya Huang, Kun Liu, Jingxiang Wu
Purpose: Tegileridine, a new highly selective biased μ-opioid receptor agonist, demonstrated a favorable profile in relief of moderate-to-severe pain, but comparative data with other μ-opioid receptor agonists are sparse. We aimed to compare the analgesic efficacy of tegileridine to oliceridine with morphine as the active control in patients undergoing minimally invasive esophagectomy (MIE). Patients and Methods: We conducted a preliminary randomized trial involving patients having moderate-to-severe pain after MIE. Patients were randomized 2:2:1 to receive a loading dose of 0.75 mg tegileridine, 1.5 mg oliceridine, or 3 mg morphine, followed by a patient-controlled analgesia pump composed of the corresponding same agent over a 48-hour period. The primary endpoint was the time-weighted sum of the resting pain-intensity difference over 24 hours (rSPID 24h ). Results: A total of 75 patients were randomized and finally analyzed (n = 15 in morphine group, n = 30 in tegileridine and oliceridine groups). Neither the time-weighted rSPID 24h nor motion-SPID 24h (mSPID 24h ) was statistically different among the three groups. The numerical rating pain scale (NRS) at rest or during movement was significantly less in patients receiving tegileridine compared to oliceridine ( P < 0.01) within postoperative 48 hours, and there was no statistical significance between tegileridine and morphine ( P > 0.05). The sum of total pain relief demonstrated a similar tendency that morphine and tegileridine were better than oliceridine at postoperative 24h ( P = 0.057) and 48h ( P = 0.033). Conclusion: Tegileridine showed comparable or slightly superior analgesic efficacy to oliceridine for moderate-to-severe pain following MIE. These findings support that tegileridine may provide promising profiles for postoperative pain management. Keywords: thoracic surgery, acute pain, postoperative analgesia, biased μ-opioid receptor agonist, opioid-related adverse events