title: Mortality associated with administration of high-dose tranexamic acid and aprotinin in primary open-heart procedures: a retrospective analysis.
abstract: BACKGROUND
  Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding. Because of safety concerns, aprotinin was withdrawn from the market in 2007. Since then, tranexamic acid (TXA) has become the antifibrinolytic treatment of choice in many heart centers. The safety profile of TXA has not been extensively studied. Therefore, the aim of this study was to evaluate safety and efficiency of TXA compared with aprotinin in cardiac surgery.
  
  
  METHODS
  Since July 1, 2006, TXA has been administered at a dose of 50 mg/kg tranexamic acid before cardiopulmonary bypass (CPB) and 50 mg/kg into the priming fluid of the CPB. Prior to this, all patients were treated with aprotinin at a dose of 50,000 KIU per kilogram body weight. Safety was evaluated with mortality, biomarkers, and the diagnosis of myocardial infarction, ischemic stroke, convulsive seizures, and acute renal failure in the intensive care unit (ICU), intermediate care unit (IMCU), and hospital stay. Efficiency was evaluated by the need for transfusion of blood products and total postoperative blood loss.
  
  
  RESULTS
  After informed consent, 893 patients were included in our database (557 consecutive patients receiving aprotinin and 336 patients receiving TXA). A subgroup of 320 patients undergoing open-heart procedures (105 receiving TXA and 215 receiving aprotinin) was analyzed separately. In the aprotinin group, a higher rate of late events of ischemic stroke (3.4% versus 0.9%; P = 0.02) and neurologic disability (5.8% versus 2.4%; P = 0.02) was found. The rate of postoperative convulsive seizures was increased in tendency in patients receiving TXA (2.7% versus 0.9%; P = 0.05). The use of TXA was associated with higher cumulative drainage losses (PANOVA < 0.01; Ptime < 0.01) and a higher rate of repeated thoracotomy for bleeding (6.9% versus 2.4%; P < 0.01). In the subgroup of patients with open-chamber procedures, mortality was higher in the TXA group (16.2% TXA versus 7.5% aprotinin; P = 0.02). Multivariate logistic regression identified EURO score II and CPB time as additional risk factors for this increased mortality.
  
  
  CONCLUSIONS
  The use of high-dose TXA is questioned, as our data suggest an association between higher mortality and minor efficiency while the safety profile of this drug is not consistently improved. Further confirmatory prospective studies evaluating the efficacy and safety profile of TXA are urgently needed to find a safe dosage for this antifibrinolytic drug.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany. michael.sander@charite.de
authors.forename: Michael
authors.initials: M
authors.lastname: Sander
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Spies
authors.forename: Viktoria
authors.initials: V
authors.lastname: Martiny
authors.forename: Christoph
authors.initials: C
authors.lastname: Rosenthal
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Wernecke
authors.forename: Christian
authors.initials: C
authors.lastname: von Heymann
mesh_terms: D000368:Aged; D000933:Antifibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007611:Aprotinin / Q000009:adverse effects / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000706:statistics & numerical data; D006348:Cardiac Surgical Procedures / Q000379:methods* / Q000401:mortality; D002315:Cardiopulmonary Bypass / Q000379:methods / Q000401:mortality; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D011183:Postoperative Complications / Q000453:epidemiology / Q000401:mortality; D012189:Retrospective Studies; D012307:Risk Factors; D014148:Tranexamic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D007611:Aprotinin