Methadone for Enhanced Postoperative Analgesia in Intermediate-Risk Noncardiac Surgery: A Multicentre Randomized Controlled Trial (MELODY Trial)
Alexandre P. Joosten
Summary
Postoperative pain control remains suboptimal for a large proportion of surgical patients and is frequently associated with slower recovery and higher reliance on opioids after surgery. Current intraoperative analgesic approaches predominantly use short-acting opioids, whose rapid pharmacokinetics can lead to variable drug exposure and inconsistent control of nociceptive stimuli. Methadone has a different pharmacologic profile, combining prolonged μ-opioid receptor activity with N-methyl-D-aspartate receptor antagonism, allowing sustained analgesia following a single intraoperative administration and potentially enhancing postoperative recovery. The MELODY trial is a multicentre, randomized, patient-blinded clinical study designed to compare a single intravenous dose of methadone given at induction with conventional short-acting opioid-based anesthesia in adults undergoing intermediate-risk noncardiac surgery. The primary aim is to evaluate whether this strategy leads to improved quality of recovery on the first postoperative day.
Description
Acute postoperative pain remains insufficiently controlled in a substantial proportion of surgical patients, with more than half reporting moderate-to-severe pain after surgery. Standard intraoperative opioid strategies rely on short-acting agents such as fentanyl or hydromorphone, which are associated with rapid clearance and fluctuating plasma concentrations that may contribute to variability in nociceptive control and increased postoperative opioid requirements. Methadone offers a pharmacologic profile that may address these limitations. It provides prolonged analgesic effect due to its lo…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria * Age ≥18 years * Elective intermediate-risk noncardiac surgery under general anesthesia * ASA physical status I-III * Expected hospital stay ≥24 hours * Ability to provide informed consent Exclusion Criteria * Severe hepatic dysfunction (Child-Pugh C) * Severe renal impairment (eGFR \<30 mL/min/1.73 m²) * Known allergy to methadone or opioids * Pregnancy or breastfeeding * Chronic opioid use or opioid use disorder * Planned use of epidural or regional analgesia * Inability to complete study assessments
Interventions
- DrugIntravenous Methadone
Intervention Description - Intravenous Methadone A single intravenous dose of methadone (0.25 mg/kg based on ideal body weight) administered at induction of anesthesia to provide sustained intraoperative and early postoperative analgesia. Additional short-acting opioids are discouraged but may be administered if clinically required. A supplemental dose of methadone (2 mg) may be given at emergence in case of significant nociceptive signs.
- DrugShort-acting Opioids Intraoperative analgesia
ntervention Description - Short-acting Opioids Intraoperative analgesia using short-acting opioids (e.g., fentanyl and/or hydromorphone) administered at induction and throughout surgery according to clinician judgment and institutional practice. This approach reflects usual care, with dosing and timing determined pragmatically based on intraoperative needs.
Location
- UCIIrvine, California