Efficacy and Safety Comparison of Ulinastatin Versus Flurbiprofen Axetil for Preemptive Analgesia in Reducing Opioid Burden After Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND

Total knee arthroplasty (TKA) poses a significant challenge for acute pain. Opioid-based analgesia carries substantial risks, whereas non-steroidal anti-inflammatory drugs (NSAIDs) have adverse effects and ceiling effects. Ulinastatin may be a novel treatment option with improved efficacy and safety.

PURPOSE: To compare the efficacy and safety of single preoperative administration of ulinastatin (UTI), flurbiprofen axetil (FA), and control (saline) in reducing opioid consumption and adverse events in TKA.

PATIENTS AND

METHODS

In this prospective, double-blind, placebo-controlled trial, 150 TKA patients were randomized to receive intravenous UTI (30 IU), FA (100 mg), or saline 15 minutes before skin incision. Standardized postoperative analgesia utilizes patient-controlled intravenous analgesia (PCIA) to maintain visual analog scale (VAS) scores ≤30 mm. The primary outcome was cumulative morphine consumption within 72 h postoperatively, while the secondary outcomes included adverse reactions and inflammatory factor levels (IL-6 and IL-10).

RESULTS

The final analysis included 149 patients. Median 72-hour morphine consumption was significantly lower with UTI (29.00 [22.50-33.50] mg) than with FA (40.00 [27.50-60.50] mg) and the control (54.40 [46.40-82.80] mg, P < 0.001). VAS scores showed no intergroup differences (P > 0.05). UTI reduced total adverse reactions (24.5%) versus FA (48.0%, P = 0.015) and control (52.0%, P = 0.005), specifically lowering vomiting (4.1 vs 20.0%), gastrointestinal discomfort (6.1 vs 26.0%), and delirium (4.1 vs 30.0%). UTI suppressed IL-6 and IL-10 elevation better than control (ΔIL-6:0.00 vs 1.63 pg/mL, P = 0.003; ΔIL-10:2.20 vs 19.92 pg/mL, P < 0.001).

CONCLUSION

Single preoperative UTI significantly reduced postoperative morphine consumption (~48%) and adverse reaction risks compared with FA and control by modulating the balance of proinflammatory and anti-inflammatory factors (IL-6 and IL-10). UTI provides an efficient and safe alternative, supporting its inclusion in enhanced recovery after surgery (ERAS) analgesia strategies.