Effectiveness and safety of intraosseous regional administration versus intravenous tranexamic acid in primary total knee arthroplasty: a randomized, triple-blind, placebo-controlled trial

Background: Tranexamic acid (TXA) is widely used in total knee arthroplasty (TKA) to reduce blood loss. Intraosseous regional administration (IORA) has been shown to increase local drug concentrations while potentially reducing systemic drug-related complications. Researches on the application of IORA-TXA in TKA remain limited. This study aimed to describe a novel IORA technique in TKA and evaluate whether IORA-TXA, alone or combined with intravenous TXA (IV-TXA), reduces perioperative total blood loss (TBL) without increasing complications compared to IV-TXA alone. Methods: In this prospective, randomized, triple-blind controlled trial, 97 patients undergoing elective primary manual unilateral TKA with tourniquet TKA were allocated into: Group A (1.0 g IORA-TXA), Group B IV-TXA (15 mg/kg IV-TXA), or Group C (Combined use of the above two protocols). All patients were followed at least three months. Primary outcomes were TBL and transfusion rate. Secondary outcomes included coagulation indicators, inflammatory markers, knee function, patient-reported outcome measures (PROMs), and complications. Results: The mean TBL was 430.7 ± 243.4 mL in Group A, 503.6 ± 277.5 mL in Group B, and 314.4 ± 222.6 mL in Group C. TBL in Group C was less than Group B (P = 0.020). No difference in TBL was found between the Group A and the other two groups (P > 0.05). No cases of transfusion were found. C-reactive protein in Group C was significantly lower than Group B on postoperative days 3 (P = 0.049). On postoperative day (POD) 14, Group B reported significantly higher VAS scores compared with Groups A (P = 0.023) and C (P < 0.001), whereas flexion contracture in Group C was significantly less than in Groups A (P = 0.003) and B (P = 0.034). No significant differences in complication rates were observed. Conclusions: This study is the first to evaluate IORA-TXA in TKA. In manual primary TKA with femoral canal opening, IORA-TXA showed hemostatic efficacy and safety comparable to IV-TXA and reduced pain at POD14. The combination of IORA- and IV-TXA further reduced total blood loss, and showed a lower CRP levels at POD 3 as well as reductions in pain scores and flexion contracture at POD14, without increasing complications. These findings suggest IORA-TXA as an effective and safe strategy in primary manual TKA.