Quantitative efficacy of topical administration of tranexamic acid on postoperative bleeding in total knee arthroplasty

Topical tranexamic acid (TXA) is used in patients undergoing total knee arthroplasty to reduce perioperative blood loss. However, the optimal dosing regimen remains undetermined. The aim of the present study was to quantitatively evaluate the effect of topical TXA on the reduction of postoperative drainage, and identify the dosing regimen factors affecting the efficacy of topical TXA.Model-based meta-analysis was used to evaluate the efficacy of topical TXA and the dosing regimen factors influencing clinical efficacy. Data from a systemic literature search was identified and used to build a time-effect model for placebo and TXA in treating perioperative blood loss.Fourteen studies containing 16 TXA-control groups of drainage volume data were included for MBMA modelling. The model described the postoperative drainage-time profiles adequately. According to the model estimation, TXA can finally reduce the postoperative drainage by about 41.7%, and 10.9 h was needed to reach 50% of the maximal drainage volume. Covariate analysis indicated that both dose and contact time alone did not correlate well with clinical efficacy. However, when considered together, they can dramatically improve fitting of the data. Simulation showed that increasing dose or contact time extensively would produce a plateau-like effect: 2-3 g TXA with contact time of 1-2 h would yield >60% reduction in the drainage volume.Dose and contact time together determined the efficacy of TXA. Extensively large dose or long contact time seems unnecessary. These findings may further guide the clinical practice on the topical TXA regimen optimization.