Intraoperative Methadone for Postoperative Pain Control in Living Donor Hepatectomy

Postoperative pain control is often suboptimal, with many patients experiencing inadequate relief or side effects. Methadone, a long-acting μ-opioid agonist and NMDA antagonist, provides stable analgesia and reduces postoperative opioid requirements when administered as a single intraoperative dose. However, its use has not been studied in living donor hepatectomy patients.

We conducted a retrospective review of a quality improvement initiative involving 50 living donor hepatectomy patients treated from 2023 to 2025. 32 received usual opioid care and 18 received methadone, stratified into high-dose (≥ 0.2 mg/kg lean body weight) and low-dose (< 0.2 mg/kg) groups. The primary outcome was postoperative morphine milligram equivalents (MMEs) consumed during the hospital stay. Secondary outcomes included intraoperative MME, total MME, ICU and hospital length of stay, bowel recovery, and safety events.

Mean age was 39.4 years, 70% female and 72% white. Most patients (66%) underwent a minimally invasive, robotic surgical approach. Methadone was administered to 36%. Intraoperative opioid exposure was significantly higher in methadone groups compared with usual care (p < 0.0001), but postoperative opioid requirements did not increase. There was a trend toward lower postoperative morphine equivalents in patients receiving higher methadone doses (156.7 ± 152.8 vs. 260.4 ± 112.3, p = 0.09). No adverse events occurred; length of stay and bowel recovery were similar across groups.

Intraoperative methadone administration in living donor hepatectomy appears safe and demonstrated a trend toward reduced postoperative MME use at higher doses of ≥ 0.2 mg/kg lean body weight. These findings warrant further prospective evaluation.