Clinical trial to determine whether the timing of tranexamic acid administration influences perioperative bleeding in total knee arthroplasty

The ideal timing of tranexamic acid administration in total knee arthroplasty with tourniquet remains unclear. Our primary objective was to prove if administering it before surgical incision, instead of before releasing the tourniquet, reduces postoperative bleeding. A second objective was to determine whether a second dose reduces post-operative bleeding.A prospective, double-blind clinical trial was performed on 212 patients scheduled for total knee arthroplasty. They were randomised into 4 groups. Tranexamic acid was administered before the surgical incision in "pre-induction groups" (1 and 2), and just before the tourniquet release in "pre-release groups" (3 and 4). Groups 2 and 4 received a second dose 3h post-surgery. Main outcome was postoperative bleeding (visible blood loss and calculated total bleeding). Secondary outcomes were haemoglobin variations, complications and transfusion rate.The mean calculated total bleeding was 1563ml (95%CI: 1445-1681) in preinduction groups versus 1576ml (95%CI: 1439-1713) in pre-release groups (P=0.9); 1579ml (95%CI: 1452-1706) in single-dose groups versus 1559ml (95%CI: 1431-1686) in double-dose groups (P=0.82). One patient was transfused. The mean haemoglobin at discharge was 10.4g/dl (95%CI: 10.2-10.7) in singledose groups versus 10.8 (95%CI: 10.6-11.1) in double-dose groups (P=0.06).There were no differences in bleeding or transfusion regarding the time of tranexamic acid administration. The second dose had not impact on outcomes.EudraCT 2016-000071-24.