The Use of Methadone in Adult Cardiac Surgery: A Systematic Review With Narrative Synthesis

Methadone is a long-acting opioid with multifaceted analgesic properties that is under increasing investigation as an intraoperative analgesic in cardiac surgery. A systematic search of United States National Library of Medicine Database (MEDLINE) and Excerpta Medica Database (EMBASE) databases identified publications investigating the use of intraoperative methadone in adult cardiac surgical patients. The risk of bias and quality of evidence of these studies were assessed, and data from these reports were extracted and presented in a narrative format. Sixteen eligible publications were included. Although the quality of the studies was moderate to high, the certainty of the evidence is low due to the limited available data regarding optimal dosing strategies, timing of administration in relation to cardiopulmonary bypass, and long-term safety outcomes. The composite data suggest that a single dose of intraoperative methadone results in less postoperative pain and opioid consumption postoperatively without any increased risk for QTc prolongation or respiratory depression. Doses of 0.1 to 0.3 mg/kg are reported in the cardiac surgery literature; however, there is evidence of a dose-response relationship with methadone's analgesic benefits and increased deliriogenic side effects. Studies using 0.1 mg/kg reveal equivocal analgesia, whereas the studies administering ≥0.2 mg/kg consistently report lower postoperative pain scores and opioid consumption compared to short-acting intravenous (IV) opioids. Crucially, the use of cardiopulmonary bypass significantly impacts methadone's plasma concentrations and must be considered when determining the optimal dose and timing of administration. Further, recent observational studies offer valuable insight into methadone's role in multimodal enhanced recovery after cardiac surgery protocols. Additional trials are needed to refine methadone usage in this population.