Efficacy and safety of methadone in the analgesic management of patients undergoing thoracic surgery: a systematic review

Abstract

Postoperative pain remains a significant challenge in thoracic and cardiac surgeries, particularly in light of the potential adverse effects associated with the use of short-acting opioids. In this context, methadone has been considered as an alternative analgesic due to its unique pharmacological properties and its potential role within multimodal analgesia strategies. Accordingly, this study aims to systematically evaluate the efficacy and safety of methadone as an analgesic agent in the intraoperative and/or postoperative period in adult patients undergoing thoracic surgery, compared with other opioids traditionally used for perioperative pain management. This study consists of a systematic literature review conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search and selection of articles were performed in the PubMed/MEDLINE, Embase, Scopus and Web of Science databases, following predefined eligibility criteria. Extracted data were organized into a standardized table including study characteristics, investigated populations, interventions, comparators, and main reported outcomes. A total of 848 records were initially identified from PubMed, Web of Science, Embase, and Scopus. After screening, eligibility assessment, and manual reference searching, eight studies met all inclusion criteria and were included in the review. The studies comprised 2,271 patients undergoing major cardiac and thoracic surgeries, including coronary artery bypass grafting, valvular surgery, esophagectomy, and thoracotomy. Methadone was mainly administered intravenously as a single intraoperative dose and was mainly compared with morphine, fentanyl, or conventional multimodal analgesic protocols. Most studies demonstrated a significant reduction in postoperative opioid consumption within the first 24 to 72 hours in the methadone groups, frequently associated with a longer time to first rescue analgesia. Pain scores were either lower or comparable to control groups, with reduced need for additional opioids. No consistent increase in serious adverse events, including respiratory depression or arrhythmias, was observed. Overall, the findings indicate a clinically relevant opioid-sparing effect of methadone with an acceptable safety profile in cardiac and thoracic surgery. Further studies are required to better evaluate the analgesic efficacy and safety profile of methadone in this clincal context.