The Use of Methadone and Ketamine for Intraoperative Pain Management in Cardiac Surgery: A Retrospective Cohort Study

Objectives: To evaluate whether the addition of ketamine to intraoperative methadone is associated with superior postoperative pain management and decreased opioid consumption compared with methadone alone in cardiac surgery patients.

Design: A retrospective cohort study.

Setting: A large academic medical system comprising four sites.

Participants: A total of 6,856 patients who underwent cardiac surgery with cardiopulmonary bypass and received intraoperative methadone between 2018 and 2023 were included. Patients were divided into two groups: those who received both methadone and ketamine (Group M+K; n = 5,696) and those who received methadone alone (Group M; n = 1,160).

Interventions: Intraoperative administration of methadone with or without ketamine. Some patients also received additional opioids such as hydromorphone and fentanyl.

Measurements and main results: The primary outcomes were daily total oral morphine equivalents (OMEs) until postoperative day (POD) 7 and the time to first postoperative opioid administration. The secondary outcome was daily postoperative pain scores until POD 7. Exploratory outcomes included delirium and intensive care unit length of stay. The median time to first postoperative opioid administration was longer in Group M+K (7.2 hours) compared with Group M (5.0 hours) (hazard ratio = 0.88, 95% confidence interval: [0.82, 0.95]). Total OMEs were significantly lower in Group M+K on POD 0 (ß = -2.24; 95% confidence interval: [-3.2, -1.3]), with no significant differences beyond POD 0. No significant differences were found in pain scores or exploratory outcomes.

Conclusions: Adding ketamine to methadone prolonged the time to first opioid consumption postoperatively but showed no benefits beyond POD 0. Future studies should consider protocolized dosing to optimize pain control.