Intraoperative single-dose methadone significantly affects postoperative morphine consumption in older patients with a hip fracture: the MetaHip randomized controlled trial

Clinical Snapshot

Key Findings

• P Value: Primary endpoint P = 0.02; hospital discharge P < 0.01

• Effect Size: Methadone group: 7.1 mg vs placebo 10.1 mg at 0-24 hours; 4.1 mg vs 5.3 mg at 24-48 hours

• Primary Outcome: Postoperative morphine consumption over 72 hours differed significantly between groups

• Nnt Or Sensitivity: Approximately 30% reduction in early postoperative morphine consumption

• Confidence Interval: Hospital discharge difference: -2.3 to -0.4 days

Clinical Application

Single intraoperative dose is practical and feasible in standard anaesthetic practice Relevant to Australian orthogeriatric services; methadone is PBS-listed; aligns with ANZCA pain management guidelines for older adults Older adults (≥60 years) undergoing hip fracture surgery in Australian hospitals

Abstract

BACKGROUND AND PURPOSE: Effective pain management in older patients with a hip fracture is critical for postoperative recovery. Our primary objective was to compare intraoperative methadone with placebo on postoperative morphine consumption over 72 hours. METHODS: Patients aged ≥ 60 years with hip fractures were randomized to receive methadone (0.10 mg/kg) or placebo intraoperatively. The primary outcome was postoperative morphine consumption measured in 24-hour intervals over 72 hours. Secondary outcomes included pain scores, time to mobilization, and discharge. Harms were assessed as adverse and serious adverse events. RESULTS: 129 patients were included. The primary endpoint analysis demonstrated that postoperative morphine consumption over 72 hours differed significantly between groups (likelihood-ratio test, P = 0.02). Model-based estimates suggested lower morphine consumption in the methadone group at 0-24 hours (least square mean [LSM] 7.1 [SE 1.2] vs placebo 10.1 [SE 1.7] mg) and at 24-48 hours (4.1 [SE 0.8] vs placebo 5.3 [SE 0.9] mg). At 48-72 hours, the model suggested lower morphine consumption in the placebo group (3.2 [SE 0.6] vs methadone 4.6 [SE 0.9] mg). Secondary outcomes were similar between groups, except that time to hospital discharge was longer in the methadone group (LSM 5.6 vs 4.5 days; mean difference -1.3 days, 95% confidence interval -2.3 to -o.4; P < 0.01). Harms appeared comparable, although the low event rate precluded formal analysis. CONCLUSION: A single intraoperative dose of methadone significantly alters postoperative morphine consumption over 72 hours after hip fracture surgery, without major safety concerns.

References

1. 1.Nygaard, K. H., Schmidt, N. H., Eriksen, L., Petersen, S. R., Strøm, T., Specht, K., & Schønnemann, J. O. (2025). Intraoperative single-dose methadone significantly affects postoperative morphine consumption in older patients with a hip fracture: the MetaHip randomized controlled trial. Acta Orthopaedica. https://doi.org/10.2340/17453674.2025.44754