Effect of two doses of tranexamic acid on fibrinolysis evaluated by thromboelastography during cardiac surgery A randomised, controlled study

BACKGROUND Tranexamic acid is used to decrease bleeding and transfusions during cardiac surgery. However, dosing based on pharmacokinetic data to optimally inhibit fibrinolysis is unknown. With increasing concerns regarding seizures associated with higher doses, lower dosing schemes may be important. OBJECTIVE To determine the effect of two dosing schemes compared with placebo on fibrinolysis and clinical outcomes. DESIGN A double-blind, randomised, controlled, pilot trial. SETTING Single tertiary centre. PATIENTS Cardiac surgery patients requiring cardiopulmonary bypass. INTERVENTION Patients were randomised to receive a 30 mg kg(-1) bolus and continuous infusion of 16 mg kg(-1) h(-1) (Group HIGH), a 5 mg kg(-1) bolus followed by 5 mg kg(-1) h(-1) (Group LOW) or Sodium chloride (Placebo). MAIN OUTCOME MEASURE Fibrinolysis was evaluated by thromboelastography and D-dimers. Secondary endpoints were blood loss, transfusion requirement and side effects. RESULTS Thirty-three patients were included. Significant fibrinolysis was defined by LY30 more than 7.5% based on thromboelastography and was not observed after cardiopulmonary bypass in any groups. After protamine administration, LY30 differences between groups were 0.7 [95% confidence interval (95% CI) -0.04 to 1.4] between Groups HIGH and Placebo, -0.08 (95% CI -0.82 to 0.66) between Groups HIGH and LOW, and 0.78 (95% CI 0.02 to 1.5) between Groups LOW and Placebo. A significant increase in D-dimers was observed in the Group Placebo compared with the two treatment groups. There were no differences in bleeding or transfusion requirement. CONCLUSION In this dose-finding study, there were no differences in fibrinolysis or clinical outcomes among the two tranexamic acid schemes and placebo. Any difference in fibrinolytic inhibition requires a larger adequately powered study.