Femoral-Canal Administration of Tranexamic Acid in Tourniquet-Assisted Total Knee Arthroplasty: A Prospective Randomized Trial.

Background: This study compared femoral-canal administration of tranexamic acid (TXA), which is a modified intraosseous regional administration (IORA) technique, with intravenous (IV) TXA and combined IORA+IV-TXA across prosthesis designs in tourniquet-assisted, manual total knee arthroplasty (TKA). Methods: This single-center study comprised 2 consecutive prospective, randomized, placebo-controlled, triple-blind cohorts: a previously reported cruciate-retaining (CR) cohort followed by a posterior-stabilized (PS) cohort. Within each cohort, patients undergoing primary, unilateral, manual TKA were randomized to IORA-TXA, IV-TXA, or IORA+IV-TXA. The primary outcome was total blood loss (TBL). Secondary outcomes included transfusion, inflammatory and coagulation markers, pain, knee function, and complications. Pooled and prosthesis-stratified analyses were performed, including treatment-by-prosthesis interaction testing. Results: Among 202 randomized participants (mean age, 69.1 years [SD, 6.5]; 162 women [80%]; CR, 97; PS, 105), TBL differed significantly among groups. Compared with IV-TXA (578.7 ± ±277.4 mL), TBL was lower with IORA-TXA (429.2 ± 293.9 mL, p = 0.010) and IORA+IV-TXA (354.3 ± 252.1 mL, p < 0.001). The treatment-by-prosthesis interaction for TBL was not significant (p = 0.289). Transfusion occurred in 1 participant in the IV-TXA group and none in the IORA-TXA or IORA+IV groups. Statistically significant differences were observed in the selected early inflammatory and clinical outcomes, primarily involving the combined regimen; however, these differences did not translate into clinically meaningful differences in pain scores, range of motion, or KOOS-JR scores by 90 days. No statistically detectable differences in complications were observed. Conclusions: In tourniquet-assisted manual TKA, femoral-canal IORA-TXA reduced TBL compared with IV-TXA, and IORA+IV-TXA showed the lowest mean TBL. These findings should be interpreted within the pre-tourniquet-release IV-TXA protocol; evidence was insufficient to establish corresponding reductions in transfusion or clinically meaningful functional benefits by 90 days. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.