David Faraoni1, Christophe Cacheux, Caroline Van Aelbrouck, Brigitte E Ickx, Luc Barvais, Jerrold H Levy. 1. From the Department of Anaesthesiology, Queen Fabiola Children's University Hospital (DF), Department of Anaesthesiology, Erasme University Hospital (CC, CVA, BEI, LB), Free University of Brussels, Brussels, Belgium and Department of Anaesthesiology and Intensive Care, Duke University School of Medicine, Durham, North Carolina, USA (JHL).
Abstract
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. TRIAL REGISTRATION: EudraCT number: 2010-024104-99.
RCT Entities:
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. TRIAL REGISTRATION: EudraCT number: 2010-024104-99.
Authors: Dominik F Draxler; Kah Yep; Gryselda Hanafi; Anoushka Winton; Maria Daglas; Heidi Ho; Maithili Sashindranath; Lisa M Wutzlhofer; Andrew Forbes; Isaac Goncalves; Huyen A Tran; Sophia Wallace; Magdalena Plebanski; Paul S Myles; Robert L Medcalf Journal: Blood Adv Date: 2019-05-28