title: Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints.
abstract: BACKGROUND
  Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin).
  
  
  METHODS
  Studies were included if they reported at least one clinically relevant outcome (mortality, rethoracotomy, proportion of patients receiving a transfusion, or perioperative myocardial infarction) in addition to perioperative blood loss. In addition, a separate meta-analysis was done for studies concerning complicated cardiac surgery.
  
  
  RESULTS
  We identified 72 trials (8409 patients) that met the inclusion criteria. Treatment with aprotinin decreased mortality almost two-fold (odds ratio 0.55 [95% CI 0.34-0.90]) compared with placebo. Treatment with aprotinin and with lysine analogues decreased the frequency of surgical re-exploration (0.37 [0.25-0.55], and 0.44 [0.22-0.90], respectively). These two treatments also significantly decreased the proportion of patients receiving any allogeneic blood transfusion. By contrast, the use of desmopressin resulted in a small decrease in perioperative blood loss, but was not associated with a beneficial effect on other clinical outcomes. Aprotinin and lysine analogues did not increase the risk of perioperative myocardial infarction; however, desmopressin was associated with a 2.4-fold increase in the risk of this complication. Studies in patients undergoing complicated cardiac surgery showed similar results.
  
  
  CONCLUSIONS
  Pharmacological strategies that decrease perioperative blood loss in cardiac surgery, in particular aprotinin and lysine analogues, also decrease mortality, the need for rethoracotomy, and the proportion of patients receiving a blood transfusion.
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands. m.m.levi@amc.uva.nl
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: M E
authors.initials: ME
authors.lastname: Cromheecke
authors.forename: E
authors.initials: E
authors.lastname: de Jonge
authors.forename: M H
authors.initials: MH
authors.lastname: Prins
authors.forename: B J
authors.initials: BJ
authors.lastname: de Mol
authors.forename: E
authors.initials: E
authors.lastname: Briët
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000614:Aminocaproates / Q000009:adverse effects / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007611:Aprotinin / Q000009:adverse effects / Q000627:therapeutic use; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001803:Blood Transfusion; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D003894:Deamino Arginine Vasopressin / Q000009:adverse effects / Q000627:therapeutic use; D006490:Hemostatics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology; D010919:Placebos; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012086:Reoperation; D013908:Thoracotomy; D014148:Tranexamic Acid / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000614:Aminocaproates; D000933:Antifibrinolytic Agents; D006490:Hemostatics; D010919:Placebos; D014148:Tranexamic Acid; D007611:Aprotinin; D003894:Deamino Arginine Vasopressin