Intraoperative Intravenous Methadone Versus Non-Methadone Opioid Analgesia in Instrumented Spinal Fusion: A GRADE-Guided Systematic Review and Meta-Analysis

Background: Instrumented spinal fusion is among the most painful surgical procedures. Methadone, a long-acting μ-opioid receptor agonist with N-methyl-D-aspartate receptor antagonism, may provide more sustained analgesia than shorter-acting intraoperative opioids. Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched through August 2026 for randomized trials in adults or adolescents undergoing instrumented spinal fusion that compared intraoperative intravenous methadone with a shorter-acting intraoperative opioid. Random-effects meta-analysis, the Cochrane Risk of Bias 2 tool, GRADE, and published minimal clinically important differences (MCIDs) were used. Results: Five trials (364 participants; three in adults and two in adolescents) were included. Methadone reduced pain intensity at 24 h (MD −1.06, 95% CI −2.03 to −0.09; three trials), 48 h (MD −1.52, 95% CI −2.36 to −0.67), and 72 h (MD −1.04, 95% CI −1.91 to −0.17; two adult trials each); point estimates approximated the 1-point MCID, but confidence intervals included clinically unimportant differences. Opioid consumption was lower at 24 h (SMD −0.50, 95% CI −0.79 to −0.21; four trials; I2 = 0%), corresponding to relative reductions of 17% to 52% in the individual trials, but not at 48 h. Vomiting did not differ (RR 1.10, 95% CI 0.72 to 1.70). Respiratory events were rare, inconsistently defined, and not pooled. Certainty was moderate for 24-h opioid consumption and low or very low for all other outcomes. Conclusions: In adults undergoing instrumented spinal fusion, a single intraoperative dose of intravenous methadone may modestly reduce postoperative pain at 24 h and opioid consumption, but the clinical importance of these effects is uncertain; the evidence in adolescents is limited to two small trials, and adverse events were insufficiently reported. Methadone should be regarded as an optional, monitored component of multimodal analgesia rather than routine practice until larger trials powered for safety and longer-term opioid use are available.