Intravenous methadone for pain management in cardiac surgery: a randomised controlled trial with plasma concentration analysis*

Abstract

Introduction: Postoperative pain after cardiac surgery remains significant despite the administration of opioids. Methadone may improve pain control and decrease the need for postoperative opioids. Randomised controlled trials, however, are limited and the effects of cardiopulmonary bypass on methadone pharmacokinetics are unclear. The aims of this study were to compare methadone and morphine in cardiac surgery, measuring methadone concentrations and correlating them with pain control. Methods: Patients undergoing cardiac surgery that required cardiopulmonary bypass were allocated randomly to receive either 0.2 mg.kg-1 methadone or 0.2 mg.kg-1 morphine (based on actual body weight, maximum 20 mg for both drugs). Postoperative pain was assessed at 15 min and 8 h, 12 h, 24 h, 48 h and 72 h after tracheal extubation, by analysis of morphine consumption and pain scores. Opioid-related adverse events were evaluated. Postoperative blood samples were collected for 96 h to measure plasma methadone concentrations. Results: In total, 80 patients were analysed (40 allocated to the methadone group, 40 allocated to the morphine group). Patients allocated to the methadone group had significantly reduced 24-h and total postoperative morphine requirements compared to those allocated to the morphine group (median (IQR [range]) 9 (5–16 [0–40]) mg vs. 24 (17–43 [4–54]) mg (p < 0.001) at 24 h and 35 (23–52 [5–66]) mg vs. 11 (7–20 [0–44]) mg (p < 0.001) total). Patients allocated to the methadone group had lower pain scores at rest (β -2.24, standard error 0.49, p < 0.001) and on coughing (β -2.16, standard error 0.50, p < 0.001). There was no difference in the incidence of opioid-related adverse effects between the two groups. Plasma methadone concentration decreased during cardiopulmonary bypass but remained above the minimum effective analgesic concentration for approximately 24 h after administration (mean (SD) 51 (24.7) ng.ml-1 at baseline to 30 (10.7) ng.ml-1 at 24 h). Discussion: Intra-operative methadone reduces postoperative analgesia requirements without increasing the incidence of opioid-related adverse events.