RESUMEN
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 30âmgâ kg(-1) bolus and continuous infusion of 16 âmg âkgâ(-1) h(-1) (Group HIGH), a 5âmgâ kg(-1) bolus followed by 5âmgâ kg(-1) âh(-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. TRIAL REGISTRATION: EudraCT number: 2010-024104-99.