The Role of Methadone in Postoperative Analgesia in Esophagectomy Patients–A Retrospective Study

<b>Background:</b> Effective pain control is key to recovery after esophagectomy. Methadone may enhance analgesia and reduce opioid needs. Its role in thoracic surgery is not well defined. <b>Methods:</b> This single-center retrospective cohort study included 206 patients who underwent esophagectomy from 2017 to 2023. A total of 66 received intraoperative methadone, and 140 served as controls. The primary outcome was cumulative postoperative opioid use in morphine milligram equivalents (MMEs) at 12, 24, 36, 48, and 72 h. Secondary outcomes included pain scores, time to first opioid, and opioid-related side effects. <b>Results:</b> Demographics were similar between groups. Intraoperative opioid use was lower in the methadone group (49.9 ± 31.0 vs. 76.1 ± 39.6 MME, <i>p</i> < 0.001). Postoperatively, MME use was significantly lower in the methadone group at all time points: 12 h (38.4 ± 48.1 vs. 56.4 ± 53.5; <i>p</i> = 0.017), 24 h (76.7 ± 81.2 vs. 122.4 ± 109.7; <i>p</i> < 0.001), 36 h (103.8 ± 106.2 vs. 176.9 ± 156.9; <i>p</i> < 0.001), 48 h (139.4 ± 135.6 vs. 229.6 ± 210.7; <i>p</i> < 0.001), and 72 h (173.5 ± 173.5 vs. 304.0 ± 286.1; <i>p</i> < 0.001). Time to first opioid was longer (225.6 ± 296.5 vs. 41.6 ± 69.8 min, <i>p</i> < 0.001). Pain scores were similar in the first 72 h; at two weeks, they were lower with methadone (0.69 ± 1.42 vs. 1.43 ± 2.55, <i>p</i> = 0.009). Side effect rates were similar. <b>Conclusions:</b> Intraoperative methadone is associated with reduced postoperative opioid use without increasing side effects.