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

Background: Opioid stewardship is a priority after total knee arthroplasty (TKA). Although scheduled, outpatient oxycodone adds clinically meaningful benefit to contemporary multimodal, nonopioid analgesia remains uncertain. Methods: We conducted a phase-II, single-center, triple-blind, randomized, placebo-controlled trial. Adults undergoing primary TKA received immediate-release oral oxycodone (5 mg twice daily) or matching placebo for 1 month in addition to a standardized multimodal regimen (acetaminophen, celecoxib, pregabalin). The primary outcome was knee pain on the Visual Analog Scale (VAS) on postoperative days 1, 7, and 30. Secondary outcomes were hospital length of stay, Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), Pittsburgh Sleep Quality Index (PSQI), patient satisfaction, and adverse events through 6 months. Analyses followed the intention-to-treat principle. Results: Between July 2023 and July 2024, 190 patients were randomized (95 per group); 2 placebo recipients died of myocardial infarction before the 6-month visit. Baseline characteristics were balanced. On postoperative day 1, the mean VAS pain was 6.7 ± 1.5 (mean ± SD) with oxycodone and 7.2 ± 1.5 with placebo (mean difference, 0.48 cm; 95% confidence intervals, 0.06-0.92; P = 0.015); the difference did not reach the minimal clinically important difference (MCID) (1.0 cm). No between-group differences were observed on day 7 or day 30. Length of stay was reduced by 0.2 days (1.7 vs. 1.9 days, P = 0.047), a statistically significant but clinically modest difference. KOOS, OKS, PSQI, and patient satisfaction were comparable at 1 or 6 months. Minor adverse events were similar between groups; no serious events were attributed to the study drug. Conclusions: In patients undergoing primary TKA with optimized multimodal, nonopioid analgesia, a fixed 1-month course of oral oxycodone produced small improvements in day 1 pain and length of hospital stay that were statistically significant but below established MCID thresholds. These findings support individualized prescribing through shared decision making rather than routine scheduled oxycodone use after TKA. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.