2019 Mark Coventry Award: A multicentre randomized clinical trial of tranexamic acid in revision total knee arthroplasty

Abstract

Aims Tranexamic acid (TXA) is proven to reduce blood loss following total knee arthroplasty (TKA), but there are limited data on the impact of similar dosing regimens in revision TKA. The purpose of this multicentre randomized clinical trial was to determine the optimal regimen to maximize the blood-sparing properties of TXA in revision TKA. Patients and Methods From six-centres, 233 revision TKAs were randomized to one of four regimens: 1 g of intravenous (IV) TXA given prior to the skin incision, a double-dose regimen of 1 g IV TXA given both prior to skin incision and at time of wound closure, a combination of 1 g IV TXA given prior to skin incision and 1 g of intraoperative topical TXA, or three doses of 1950 mg oral TXA given two hours preoperatively, six hours postoperatively, and on the morning of postoperative day one. Randomization was performed based on the type of revision procedure to ensure equivalent distribution among groups. Power analysis determined that 40 patients per group were necessary to identify a 1 g/dl difference in the reduction of haemoglobin postoperatively between groups with an alpha of 0.05 and power of 0.80. Per-protocol analysis involved regression analysis and two one-sided t-tests for equivalence. Results In total, one patient withdrew, five did not undergo surgery, 16 were screening failures, and 25 did not receive the assigned treatment, leaving 186 patients for analysis. There was no significant difference in haemoglobin reduction among treatments (2.8 g/dl for single-dose IV TXA, 2.6 g/dl for double-dose IV TXA, 2.6 g/dl for combined IV/topical TXA, 2.9 g/dl for oral TXA; p = 0.38). Similarly, calculated blood loss (p = 0.65) and transfusion rates (p = 0.95) were not significantly different between groups. Equivalence testing assuming a 1 g/dl difference in haemoglobin change as clinically relevant showed that all possible pairings were statistically equivalent. Conclusion Despite the higher risk of blood loss in revision TKA, all TXA regimens tested had equivalent blood-sparing properties. Surgeons should consider using the lowest effective dose and least costly TXA regimen in revision TKA. Cite this article: Bone Joint J 2019;101-B(Supple 7):10–16

Is There a Synergistic Effect of Topical Plus Intravenous Tranexamic Acid Versus Intravenous Administration Alone on Blood Loss and Transfusions in Primary Total Hip and Knee Arthroplasties?

“…With the growing data on the efficacy and safety of TXA, the routine use of TXA in primary and revision procedures has been widely adopted by arthroplasty surgeons [19]. However, there is little to no consensus on the most effective and safest route and dosage of perioperative TXA [6,[16][17][18][19][20][21][22][23]26]. In one of the largest single-institution studies analyzing the efficacy and safety of TXA utilization in elective primary THA and TKA, the present study shows that both a double IV TXA and a combined single IV and topical TXA dose result in a similarly low total blood loss of~300 mL and drop in Hgb of~2 g/dL, low transfusion rate of~2%, and low in-Table 3 Univariate analysis of total calculated blood loss, blood transfusions, and complications in patients undergoing primary TKA who received 2 doses of IV TXA (double IV) compared with one dose of IV and one dose of topical TXA (1 IV þ 1 topical).…”

“…We can speculate that a single dose of TXA is approaching, if not reaching, the plateau in which TXA can effectively minimize perioperative blood loss. Data in further support of this include a multicenter RCT by Fillingham et al [17] analyzing various dosing regimens of TXA in patients undergoing revision TKA (single IV, double IV, combined IV/topical, and oral), which did not show a difference in change in Hgb, calculated blood loss, or transfusion rates for any of these dosing regimens. Finally, in a double-blinded RCT of 100 patients undergoing primary TKA with combined IV and topical TXA administration, Tsukada et al [26] did not find any further reduction in the total blood loss in patients randomized to 3 additional postoperative doses of 1-g IV TXA compared with those who received 3 additional doses of saline.…”

“…Furthermore, there is growing evidence that TXA has only antifibrinolytic properties without thrombogenic properties [5] and is clinically safe [12][13][14][15], even in higher-risk patients. However, although several dosages of intravenous (IV), topical, and oral administrations have been studied, there is currently no consensus on the optimal TXA administration or combination [6][7][8][16][17][18][19]. Although there have been some limited studies on the potential synergistic effect of the administration of both IV and topical TXA [20][21][22][23], the data remain mixed.…”

Role of tranexamic acid to reduce blood loss and transfusion of allogeneic blood in the field of surgery

“…25,26 Despite the higher risk of blood loss and need for transfusion following revision total knee arthroplasty, lowest effective dose and least costly regimen should be used due to similar effect in the management of blood loss with all TXA dosing regimens. 27 Efficacy of TXA in gynecology and obstetrics i). C-Section: Bouthors et al reported that the tranexamic acid reduces the intraoperative bleeding as well as minimize postpartum volume, duration of surgery, and transfusion need but not the hysterectomy rate.…”

Are we scientifically ready to adopt tranexamic acid as a routine in arthroplasty?

“…Single or multiple dose IV administrations of 10 to 30 mg/kg TXA before and/or after the procedure, topical administration of 1 to 3 g TXA in 50 mL of saline at the end of the procedure, multi-dose 650 mg tablets of oral TXA, and combination of these are the commonly reported administration modalities. [11,12,15,16] Furthermore, the literature has not shown an increased risk of VTE in low-risk patients while there are no reliable data on high-risk patients with positive VTE history.…”