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Intraoperative methadone alters 72-hour postoperative morphine use after hip fracture surgery in older adults

Intraoperative methadone alters 72-hour postoperative morphine use after hip fracture surgery in old…
Photo by Nathan Rimoux / Unsplash
Key Takeaway
Consider intraoperative methadone may shift, not uniformly reduce, 72-hour opioid use and may lengthen stay after hip fracture surgery.

This randomized trial compared a single intraoperative dose of methadone (0.10 mg/kg) with placebo in 129 patients aged 60 years or older undergoing hip fracture surgery. The primary outcome was postoperative morphine consumption, measured in 24-hour intervals over 72 hours. Secondary outcomes included pain scores, time to mobilization, time to discharge, and adverse and serious adverse events.

Postoperative morphine consumption over 72 hours differed significantly between groups by likelihood-ratio test (P = 0.02). Model-based estimates indicated lower morphine consumption with methadone at 0-24 hours (LSM 7.1 [SE 1.2] vs 10.1 [SE 1.7] mg) and at 24-48 hours (4.1 [SE 0.8] vs 5.3 [SE 0.9] mg). In the 48-72 hour window, the model suggested lower morphine consumption in the placebo group (3.2 [SE 0.6] vs methadone 4.6 [SE 0.9] mg), so the overall effect was a redistribution rather than a uniform reduction across the full 72 hours.

Most secondary outcomes were similar between groups, except for time to hospital discharge, which was longer with methadone (LSM 5.6 vs 4.5 days; mean difference -1.3 days, 95% CI -2.3 to -0.4; P < 0.01). Harms appeared comparable, but the low event rate precluded formal analysis, so specific adverse event rates and discontinuations were not reported in the abstract.

The authors conclude that a single intraoperative dose of methadone significantly alters postoperative morphine consumption over 72 hours after hip fracture surgery without major safety concerns. Clinicians weighing this approach should consider the front-loaded opioid-sparing effect against the signal for longer hospital stay and the limited power to characterize harms.

Study Details

Study typeRct
Sample sizen = 129
EvidenceLevel 2
Follow-up720.0 mo
PublishedApr 2026
View Original 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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