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A fixed 1-month course of oral oxycodone after total knee arthroplasty produces small improvements in day 1 pain and length of hospital stay that are statistically significant but below clinically meaningful thresholds.

In a triple-blind randomized controlled trial, 190 adults undergoing primary total knee arthroplasty received either immediate-release oral oxycodone (5 mg twice daily) or placebo for 1 month, in addition to a standardized multimodal nonopioid regimen. Oxycodone reduced day 1 pain by 0.48 cm on a 10-cm VAS (P=0.015) and length of stay by 0.2 days (P=0.047), but these differences did not reach the minimal clinically important difference (MCID) of 1.0 cm for pain. No significant differences were observed for pain at day 7 or 30, or for functional outcomes, sleep quality, or satisfaction.

Last updated: Aug 20, 2026•1 RCTs•📖 Read as article →

Evidence Score

Evidence Score44/100
Human RCT★★☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Effect of 1-Month Oral Oxycodone on Postoperative Pain Following Total Knee Arthroplasty.

observational

Poursalehian M, Kalantar SH, Razzaghof M, Tajvidi M, Esmaeili S, Nafisi M, Razzaghi A, Mansournia MA, Farajidavar H, Hashemipour F, Firoozabadi MA, Mortazavi SMJ · JB & JS open access (2026)

Participants: N/A
Duration: 1 month treatment, 6 months follow-up
Intervention: Immediate-release oral oxycodone 5 mg twice daily for 1 month, added to standard multimodal analgesia (acetaminophen, celecoxib, pregabalin)
Outcome: Knee pain on Visual Analog Scale (VAS) at postoperative days 1, 7, and 30; hospital length of stay; KOOS; Oxford Knee Score; Pittsburgh Sleep Quality Index (PSQI); patient satisfaction; adverse events
Effect Size: Mean difference in day 1 VAS pain = 0.48 cm (95% CI 0.06-0.92); length of stay difference = 0.2 days
Population: Adults undergoing primary total knee arthroplasty (TKA) with optimized multimodal nonopioid analgesia

Result:

PubMed: 42598736DOI: 10.2106/JBJS.OA.26.00170

Mechanism Graph

Oxycodone binds to mu-opioid receptors in the central nervous system
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This reduces transmission of pain signals from the surgical site
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The effect is most pronounced in the immediate postoperative period (day 1)
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Result: small reduction in early pain and hospital stay, but not clinically meaningful overall

Limitations

  • ⚠Single-center study may limit generalizability
  • ⚠The 0.48 cm pain difference did not reach the MCID of 1.0 cm, so clinical relevance is questionable
  • ⚠Two placebo recipients died of myocardial infarction before the 6-month visit, though not attributed to study drug
  • ⚠The study was phase-II, possibly underpowered for some secondary outcomes

Frequently Asked Questions

Does oxycodone improve pain after knee replacement?▼

It provides a small, statistically significant reduction in pain on the first day after surgery (0.48 cm on a 10-cm VAS), but this is below the minimal clinically important difference of 1.0 cm, so it is not considered clinically meaningful.

What is the recommended dose of oxycodone after TKA?▼

The study used 5 mg immediate-release oxycodone twice daily for 1 month, but the authors recommend individualized prescribing rather than routine scheduled use.

Does oxycodone affect sleep quality after knee replacement?▼

No significant difference was found in Pittsburgh Sleep Quality Index (PSQI) scores at 1 or 6 months compared to placebo.

Is oxycodone safe to use for a month after TKA?▼

Minor adverse events were similar between groups, and no serious events were attributed to the study drug, but the study was not powered to detect rare serious events.

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References

  1. 1.Poursalehian M, Kalantar SH, Razzaghof M, Tajvidi M, Esmaeili S, Nafisi M, Razzaghi A, Mansournia MA, Farajidavar H, Hashemipour F, Firoozabadi MA, Mortazavi SMJ. "Effect of 1-Month Oral Oxycodone on Postoperative Pain Following Total Knee Arthroplasty.." JB & JS open access, 2026. PMID: 42598736 DOI: 10.2106/JBJS.OA.26.00170
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.