Intraoperative Methadone Versus Epidural Analgesia for Perioperative Pain Management in Major Abdominal and Thoracic Surgery: A Retrospective Single-Center Study

<b>Background</b>: Adequate analgesia is essential for enhanced recovery following major abdominal and thoracic surgery. Intravenous methadone has emerged as an alternative analgesic modality to traditional epidural analgesia. This study compares intravenous methadone with epidural analgesia in postoperative pain. <b>Methods</b>: We retrospectively analyzed adult patients who underwent laparotomy or non-cardiac thoracotomy between January 2019 and December 2022 and who had either general anesthesia with epidural analgesia or intravenous methadone. Co-primary outcomes were mean numeric rating scale (NRS) pain scores and cumulative opioid consumption from extubation until the end of postoperative day 2. Pain scores were obtained regularly from routine postoperative assessments documented in the electronic health record and were not recorded at predefined postoperative hours. Secondary outcomes related to analgesia, recovery, and clinical outcomes were examined. <b>Results</b>: We analyzed 796 adults (mean age 58 ± 15 years, 52% male, 68% ASA III-IV), of which 691 (87%) underwent laparotomy and 105 (13%) underwent non-cardiac thoracotomy. Patients receiving methadone had a higher postoperative NRS score (0.4 points, 95% CI 0.23 to 0.62, <i>p</i> < 0.001), with a mean NRS of 2.1 ± 1.4 points in the methadone group and 1.6 ± 1.2 points in the epidural group. The postoperative opioid consumption (morphine equivalent dose) was lower in the methadone group (23 ± 31 vs. 29 ± 43 mg, -7.2 mg, 95% CI -12.6 to -1.79, <i>p</i> = 0.009). Methadone was associated with earlier mobilization (-0.13 days, 95% CI -0.24 to -0.01, <i>p</i> = 0.030). Epidural patients had greater need for escalation of laxatives (26% vs. 15%, <i>p</i> = 0.016), while time to extubation was shorter (8.4 min, 95% CI 6.2 to 10.5, <i>p</i> < 0.001). No differences were observed in maximum NRS, oxygen demand, blood product transfusions, major adverse cardiac and cerebrovascular events, or length of stay. <b>Conclusions</b>: Methadone was associated with higher, clinically non-relevant postoperative pain scores and a clinically non-relevant reduction of postoperative opioid use.