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

2026/04/16 by Kevin Heebøll Nygaard, Nikolaj Schmidt, Lasse Eriksen +4 · 1 voice
Medicine · #Pain Management and Opioid Use #Opioid Use Disorder Treatment #Anesthesia and Pain Management

paper · pdf · doi:10.2340/17453674.2025.44754

openalex publication_date 2026/04/16 · openalex created_date 2026/04/17 · openalex updated_date 2026/08/01

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.

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