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heterogeneity in direct metaanalysis to reduce blood loss.2 Similarly, IV and topical TXA were found to reduce the risk of transfusion compared to placebo by 60% and 71%, respectively.2 Network metaanalysis of low dose IV (< 20mg/kg or ≤ 1g), high dose IV (≥ 20mg/kg or > 1g), high dose topical (> 1.5g), oral, and combined IV/topical TXA reduced the risk for blood loss compared to placebo.2 Correspondingly, network meta-analysis demonstrated low dose IV, high dose IV, high dose topical, low dose topical, and combined IV/topical TXA to significantly reduce the risk of transfusion.2 Due to a lack of studies directly comparing oral TXA with placebo, no conclusions could be derived in the direct meta-analysis.2 Network meta-analysis was performed to provide an indirect comparison of oral TXA, which demonstrated significantly reduced blood loss compared to placebo.2 Although oral TXA was shown to be equivalent regarding risk of transfusion to all other formulations of TXA in the network meta-analysis, oral TXA did not reduce the risk of transfusion compared to placebo. The inconsistency is the result of the network relying on indirect comparisons and a limited number of studies. Similar limitations were observed for lower doses (≤ 1.5g) of topical TXA in the network meta-analysis.2 In the analysis, low dose topical TXA did not significantly reduce blood loss but did reduce the risk of transfusion compared to placebo.2 Total Knee Arthroplasty Intravenous and topical TXA consistently demonstrated in direct meta-analysis the ability to reduce blood loss during the perioperative episode of a primary TKA. 3 Topical and oral TXA reduced the risk of transfusion by 66% and 61% for each respective formulation of TXA when compared to placebo.3 Intravenous TXA administered as a single dose either before or after incision, reduced the risk of transfusion by either 81% or 55% compared to placebo.3 When multiple doses of IV TXA were administered, the observed reduction in transfusion was 75% compared to placebo.3 Subsequent network meta-analysis demonstrated low dose IV, high dose IV, low dose topical, high dose topical, and oral TXA as well as combinations of IV/topical and IV/oral TXA to reduce blood loss and risk of transfusion during the perioperative episode of a TKA. 3 Guideline Question 2: For patients undergoing primary TJA, what method of administration of TXA, compared to a different method of administration, reduces the risk of transfusion and/or reduces blood loss? Response/Recommendation: The analysis of studies did not identify a clearly superior method, or combinations of methods, for the administration of TXA. All methods of administration effectively demonstrate equivalent efficacy at reducing calculated blood loss and the risk of transfusion during the perioperative episode of a primary TJA. Strength of Recommendation: Strong Rationale: The direct meta-analysis of 31 high quality studies provided no evidence to favor any specific method of TXA to reduce the risk of blood loss and need for transfusion during the perioperative episode of primary hip and knee arthroplasties.2, 3 Subsequent network meta-analysis included a more expansive comparison between the methods of TXA administration with no evidence to clearly support a superior method of administration. 4, 5 Total Hip Arthroplasty Intravenous and topical TXA have been compared together in multiple randomized clinical trials, which through direct meta-analysis showed no difference in the risk of transfusion.2 Network meta-analysis provided the opportunity to perform direct and indirect comparisons between low dose IV (< 20mg/kg or ≤ 1g), high dose IV (≥ 20mg/kg or > 1g), low dose topical (≤ 1.5g), high dose topical (> 1.5g), oral, and combined IV/topical TXA.2 In terms of the ability to reduce blood loss, no method of TXA administration was found to provide a significantly different outcome.2 Similar results in the network meta-analysis were observed for risk of transfusion with the exception that a combination of IV and topical TXA was equivalent to oral TXA but superior to low dose IV, high dose IV, low dose topical, and high dose topical TXA. 2 However, the inconsistent result regarding combined IV/topical TXA likely represents bias from a limited number of studies and not superiority to other methods of TXA administration. Total Knee Arthroplasty Direct comparisons were performed between IV TXA and topical, oral, or combined IV/topical TXA, which found no difference in the risk of transfusion.3 Similar to the network meta-analysis of THA, direct and indirect comparisons were performed between low dose IV, high dose IV, low dose topical, high dose topical, and oral TXA as well as combinations of IV/topical and IV/oral TXA that resulted in no difference in their blood sparing properties. 3 The significant differences between methods of TXA administration were observed in respect to the risk of transfusion being higher for low dose IV TXA compared to high dose IV or combined IV/topical TXA, which could represent a dose response or the limited number of studies. 3 Guideline Question 3: For patients undergoing primary TJA, does the dose amount of IV or topical TXA affect the risk of transfusion and/or reduction in blood loss? Response/Recommendation: Within the context of the TXA doses used in primary TJA, the dose amount of TXA was not
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