Intraoperative methadone in adult laparoscopic surgery: a systematic review and meta-analysis of randomized trials

Opioids are routinely used for pain control in laparoscopic procedures. Methadone, a long-acting opioid, has unclear efficacy in this context. Therefore, we aim to compare intraoperative methadone vs. short-acting opioids or placebo for laparoscopic surgeries.

We searched PubMed, Scopus, Embase, and Cochrane for eligible Randomized Controlled Trials (RCTs) up to June 2025. Outcomes were cumulative opioid use at 24-hours (primary endpoint), the incidence of respiratory depression, postoperative nausea/vomiting, and hypoxia; intraoperative propofol use; emergence time; Post-Anesthesia Care Unit (PACU) length of stay and opioid use; pain scores at 30 and 60-minutes and at 24-hours (h). We used a random-effects model, Cochrane risk-of-bias analyses, certainty-of-evidence assessment, trial sequential analyses, and minimal clinically important differences to assess clinical impact.

7 RCTs (591 patients) were included. Compared to short-acting opioids, methadone was significantly associated with a reduction in postoperative hypoxia (RR = 0.24; 95% CI 0.06-0.91; p = 0.03), PACU opioid use (RR = 0.69; 95% CI 0.53-0.90; p < 0.01), pain scores at 30 (MD = -1.21; 95% CI -1.91 to -0.51; p < 0.01) and at 60-minutes (MD = -0.41; 95% CI -0.80 to -0.03; p = 0.03), and cumulative opioid use at 24h (MD = -1.62; 95% CI -2.75 to -0.50; p < 0.01). There were no differences between groups in the remaining outcomes.

Intraoperative methadone in laparoscopic procedures was associated with a statistically significant reduction in pain scores, hypoxia, and opioid requirements. However, the reduction in opioid requirements did not reach clinical significance, and most effects were small, heterogeneous, and supported by limited-certainty evidence. Evidence regarding respiratory adverse events remains limited because of the small number of trials and participants.