title: Effect of two doses of tranexamic acid on fibrinolysis evaluated by thromboelastography during cardiac surgery: a randomised, controlled study.
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.
  
  
  METHODS
  A double-blind, randomised, controlled, pilot trial.
  
  
  METHODS
  Single tertiary centre.
  
  
  METHODS
  Cardiac surgery patients requiring cardiopulmonary bypass.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  EudraCT number: 2010-024104-99.
authors.affiliation: 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).
authors.forename: David
authors.initials: D
authors.lastname: Faraoni
authors.forename: Christophe
authors.initials: C
authors.lastname: Cacheux
authors.forename: Caroline
authors.initials: C
authors.lastname: Van Aelbrouck
authors.forename: Brigitte E
authors.initials: BE
authors.lastname: Ickx
authors.forename: Luc
authors.initials: L
authors.lastname: Barvais
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000933:Antifibrinolytic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016063:Blood Loss, Surgical / Q000517:prevention & control; D002315:Cardiopulmonary Bypass / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D011479:Protamines / Q000008:administration & dosage; D013916:Thrombelastography / Q000379:methods*; D014148:Tranexamic Acid / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; D011479:Protamines; C036309:fibrin fragment D; D014148:Tranexamic Acid