Combination of Intravenous and Intra‐Articular Application of Tranexamic Acid and Epsilon‐Aminocaproic Acid in Primary Total Knee Arthroplasty: A Prospective Randomized Controlled Trial

Abstract

Objective There were limited randomized controlled trials (RCTs) of epsilon‐aminocaproic acid (EACA) versus tranexamic acid (TXA) in total knee arthroplasty (TKA). The aim of the study was to compare the efficacy and safety of TXA and EACA in the combination of intravenous (IV) and intra‐articular (IA) administration on reducing blood loss in patients following primary TKA. Methods From January 2020 to January 2021, a total of 181 patients undergoing a primary unilateral TKA were enrolled in this prospective randomized controlled trial. Patients in the TXA group (n = 90) received 20 mg/kg of intravenous TXA preoperatively, 1 g of intra‐articular TXA intraoperatively, and three doses of 20 mg/kg intravenous TXA at 0, 3, 6 h postoperatively. Patients in the EACA group (n = 91) received 120 mg/kg of intravenous EACA preoperatively, 2 g of intra‐articular EACA intraoperatively, and three doses of 40 mg/kg intravenous EACA at 0, 3, 6 h postoperatively. The primary outcomes were total blood loss (TBL), transfusion rates and drop of hemoglobin (HB) level. The secondary outcomes included postoperative hospital stays and postoperative complications. The chi‐square tests and Fisher's exact tests were utilized to compare categorical variables, while the independent‐samples t‐tests and Mann–Whitney tests were used to compare continuous variables. Results The patients who received TXA averaged less TBL than the patients who received EACA (831.83 ml vs 1065.49 ml, P = 0.015), and HB drop in TXA group was generally less than that of EACA group on postoperative day 1 and 3 (20.84 ± 9.48 g/L vs 24.99 ± 9.40 g/L, P = 0.004; 31.28 ± 11.19 vs 35.46 ± 12.26 g/L, P = 0.047). The length of postoperative stays in EACA group was 3.66 ± 0.81 day, which is longer than 2.62 ± 0.68 day in TXA group (P < 0.001). No transfusions were required in either group. The risk of nausea and vomiting in TXA group was significantly higher than that in EACA group (11/90 vs 0/91, P < 0.01). Conclusion Although the TBL and HB drop were slightly greater in EACA group, these results were not clinically important, given that no transfusions were required. EACA could be an alternative to TXA, especially for patients with severe nausea and vomiting after using TXA postoperatively. Further studies are needed to adjust dosage of EACA to make better comparison of the two drugs.

Comparison of efficacy between tranexamic acid and epsilon-aminocaproic acid for total knee arthroplasty: A meta-analysis of randomized controlled trials

“…Country TXA EACA Dose of TXA Dose of EACA Outcomes Study Boese, 2017 [18] USA 98 96 Intravenous 1g before the tourniquet was deflated and 1g at the time of wound closure Intravenous 7g before the tourniquet was deflated and 7g at the time of wound closure 1,4,5,6,7 RCT Bradley, 2019 [13] USA 73 72 Intravenous 10 mg/kg before the tourniquet was deflated and 3h later Intravenous 5g before incision and 1g at the time of wound closure 2,5,6,7 RCT Camarasa, 2006 [19] Spain 35 32 Intravenous 10 mg/kg before the tourniquet was deflated and 3h later 100 mg/kg before tourniquet deflation followed by continuous perfusion (1g h during 3h) 2,3,5,6,7 RCT Guerreiro, 2021 [20] Brazil 30 30 1 g of TXA (0.05 g/ml) was applied intraarticularly 4 g of EACA (0.2 g/ml) was applied intraarticularly 2,3,4,5,6,7 RCT Morales-Avalos, 202 [21] Mexico 46 46 Oral at 2 h before surgery and 6 and 12 h after surgery Oral at 2 h before surgery and 6 and 12 h after surgery 1,2,3,4,5,6,7 RCT Zheng, 2022 [12] China 90 91 20 mg/kg of intravenous TXA preoperatively, 1 g of intra-articular TXA intraoperatively, and 3 doses of 20 mg/kg intravenous TXA at 0, 3, There were no significant differences in the need for transfusion between the TXA and EACA groups (RR, 0.27; 95% CI, 0.06 to 1.28; P = .100; Fig. 4).…”

“…A total of 739 (TXA:372; EACA:367) patients were enrolled in the studies, the information of the included studies is summarized in Table 1. [12,13,[18][19][20][21] They are all RCT studies and the methodological bias of 4 study was low and other 2 studies were unclear (Figs. 2 and 3).…”

“…[11] Several randomized controlled trials (RCT) have compared TXA to EACA in TKA. [12,13] Many of these trials contained relatively small cohorts, and demonstrated inconsistent outcomes. This uncertainty leads to the determination of which antifibrinolytic agent to adopt by the preference of the surgeons.…”