Authors (including presenting author) :
Henry MK WONG(1), Sandra LC CHIU(2), WT WONG(2), SK WO(3), JZ ZUO(3), PY CHEN(1), XD LIU(2), Sylvia SW AU(1), Randolph HL WONG(4)
Affiliation :
(1)Department of Anaesthesia, Pain and Perioperative Medicine, Prince of Wales Hospital, New Territories, Hong Kong
(2)Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong
(3)School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
(4)Division of Cardiothoracic Surgery, Department of Surgery, Prince of Wales Hospital, New Territories, Hong Kong
Introduction :
Postoperative pain after cardiac surgery is significant, despite opioid use. Opioids have limitations, including tolerance and side effects. Methadone, with its long duration of action and unique properties, may offer improved pain control and reduce opioid consumption.
Objectives :
Evidence from clinical trials is limited, and the impact of cardiopulmonary bypass on methadone pharmacokinetics is unclear. This study aims to compare the efficacy and safety of methadone to morphine in cardiac surgery, assess methadone plasma concentrations, and investigate the relationship between plasma levels and pain control. Findings will inform the optimal use of methadone in cardiac surgery and contribute to enhanced recovery. Single dose administration reduces persistent postoperative opioid use after discharge.
Methodology :
Patients undergoing cardiac surgery with cardiopulmonary bypass (n=86) were randomized to receive either methadone (0.2mg/kg) or morphine (0.2mg/kg) on induction. Postoperative pain assessments were done at 15min, 8, 12, 24, 48, and 72h after extubation, including pain scores at rest and on exertion, and postoperative analgesic requirements. Opioid-related adverse events such as nausea, vomiting, bowel movements were evaluated. Blood samples were taken until 96h after study drug administration.
Result & Outcome :
Postoperative morphine requirements at 24h after extubation were reduced by 63% from a median (IQR) of 24 (17.0 to 43.0)mg in morphine group to 9 (5.0 to 15.8)mg in methadone group (P < 0.001). Total postoperative morphine requirements were 69% lower in patients receiving methadone throughout the study period (median [IQR] 11 [7.0 to 20.0]mg vs 35 [23.0 to 52.0]mg; P < 0.001). Reductions in pain scores at rest were observed at 24h after extubation (median [IQR] 1 (0 to 2) vs 0 (0-1), P = 0.027), and pain scores on coughing were also reduced at 12h (median [IQR] 4 (2.3-5.0) vs 3 (1.3-4.0), P = 0.037), together with better satisfaction to pain management at all time points up to 72h after surgery (median 80 to 90 vs median 70 to 80; all P < 0.001 to 0.003). No difference in opioid-related side effects was observed. Plasma methadone concentration decreased by 37% during cardiopulmonary bypass. The plasma level remained above the minimum effective analgesic concentration (MEAC) for approximately 24h after administration, with persistent analgesia observed until approximately 80h after administration.
Intraoperative methadone (0.2mg/kg) resulted in reduced postoperative analgesia requirements, improved pain scores and greater patient satisfaction without increased opioid-related adverse events up to 72 hours after tracheal extubation. Plasma methadone concentration analysis supported the extended analgesia of methadone beyond the MEAC
