Intravenous methadone in perioperative acute and chronic pain management in Chinese adult cardiac surgical patients: a protocol for pilot randomised controlled trial

Abstract

Abstract Background Postoperative pain is significant in cardiac surgical patients. Perioperative analgesia with intermittent administration of opioids can result in significant fluctuations in serum opioid concentrations. Methadone should provide a rapid onset and long-term pain relief upon a single intravenous dose at induction of anaesthesia, and may reduce chronic postsurgical pain (CPSP) in cardiac surgical patients. The feasibility of using intravenous methadone in Chinese cardiac surgical patients, and its effect on acute and chronic pain management after cardiac surgery will be evaluated. Methods A single-centre, prospective, randomized-controlled pilot study. Adult cardiac surgical patients will be randomized to receive either methadone 0.2mg/kg (maximum dose 20mg) or equipotent dose of morphine at induction of anaesthesia. Patient-controlled analgesia morphine protocol, oral paracetamol and dihydrocodeine will be given for postoperative analgesia. Venous blood sampling for plasma methadone concentration will be obtained at regular intervals from study drug infusion to 96 hours after administration. The primary outcomes will be the recruitment and attrition rate, complications from methadone, and the perceived trial feasibility. Secondary outcomes include time weaned to spontaneous breathing trial, morphine consumption within 24 hours and 72 hours after surgery, time to first morphine rescue, postoperative pain score, patient satisfaction, length of stay in ICU and hospital. Side effects of opioids including sedation, nausea and vomiting, and time to first bowel opening will be recorded. CPSP will be assessed with Neuropathic Pain Scale and Pain Catastrophizing Scale at 3 and 6 months after surgery. Discussion There have not been many randomized controlled trials describing the use of intravenous methadone in cardiac surgical patients, and none in Chinese population. Results from this study will lay the foundation for future large-scale studies on intravenous methadone use in cardiac surgery, which has the potential to improve the quality of recovery by optimizing acute and chronic pain management. This is also the first study to demonstrate perioperative changes in plasma concentration of methadone in cardiac surgery. Ethics and dissemination The Joint CUHK-NTEC Clinical Research Ethics Committee approved the study protocol (CREC Ref. No.: 2022.636-T). The findings will be presented at scientific meeting, peer-reviewed journals and to study participants. Trial registration number NCT05913284 Trial registration URL https://clinicaltrials.gov/study/NCT05913284