Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial

BACKGROUND: Laparoscopic hysterectomy is often carried out as day-stay surgery. Minimising postoperative pain is therefore of utmost importance to ensure timely discharge from hospital. Methadone has several desirable pharmacological features, including a long elimination half-life. Therefore, a single intraoperative dose could provide long-lasting pain relief. METHODS: Patients scheduled to undergo laparoscopic hysterectomy were randomly allocated to receive methadone (0.2 mg kg(−1)) or morphine (0.2 mg kg(−1)) intraoperatively, 60 min before tracheal extubation. Primary outcomes were opioid consumption (oral morphine equivalents in milligrams) at 6 and 24 h. Secondary outcomes included pain intensity at rest and during coughing, patient satisfaction, postoperative nausea and vomiting, and adverse events up to 72 h after completion of surgery. RESULTS: The postoperative median opioid consumption was reduced in the methadone group compared with the morphine group at 6 h (35.5 [0–61] mg vs 48 [31–74.5] mg; P=0.01) and 24 h (42 [10–67] mg vs 54.5 [31–83] mg; P=0.03). On arrival at the PACU, pain at rest was significantly lower in patients receiving methadone (numeric rating scale: 3 [2–5] vs 5 [3–6]), whereas pain scores at rest and coughing were not significantly different throughout the rest of the observation period. No differences in other secondary outcomes were found. CONCLUSIONS: In this randomised, blinded, controlled trial, opioid consumption was reduced during the first 24 postoperative hours in patients receiving methadone without causing an increase in adverse events. The difference observed might be considered as small and of limited clinical relevance. CLINICAL TRIAL REGISTRATION: NCT03908060; EudraCT no. 2018-004351-20.