THE DOSE-RESPONSE RELATIONSHIP OF TRANEXAMIC ACID

Background: Prophylactic administration of the antifibrinolytic drug t ranexamic acid decreases bleeding and transfusions after cardiac opera tions. However, the best dose of tranexamic acid for this purpose rema ins unknown. This study explored the dose-response relationship of tra nexamic acid for hemostatic efficacy after cardiac operation. Methods: In prospective, randomized, double-blinded fashion, 148 patients unde rgoing cardiac operation with extracorporeal circulation were divided into six groups: a placebo group and five groups receiving tranexamic acid in loading doses before incision (range 2.5 to 40 mg.kg(-1)) and one-tenth the loading dose hourly for 12 h. The mass of blood collecte d by chest tubes over 12 h represented blood loss. Allogeneic transfus ions within 12 h and within 5 d of surgery were tallied. Results: The six groups presented similar demographics. Patients receiving placebo had increased postoperative D-dimer concentration compared to groups r eceiving tranexamic acid. Patients receiving at least 10 mg.kg(-1) tra nexamic acid followed by 1 mg.kg(-1).h(-1) bled significantly less (36 5, 344, and 369 g.12 h(-1), respectively, for those three groups) comp ared with patients who received placebo (552 g, P < 0.05). Tranexamic dose did not affect transfusions. Only initial hematocrit affected whe ther a patient received an allogeneic transfusion within 5 days of ope ration (odds ratio 2.08 for each 3% absolute decrease in hematocrit). Conclusions: Prophylactic tranexamic acid, 10 mg.kg(-1) followed by 1 mg.kg(-1).h(-1), decreases bleeding after extracorporeal circulation. Larger doses do not provide additional hemostatic benefit.