Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints

Lancet. 1999 Dec 4;354(9194):1940-7. doi: 10.1016/S0140-6736(99)01264-7.

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.

Findings: 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.

Interpretation: 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.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Aminocaproates / adverse effects
  • Aminocaproates / therapeutic use
  • Antifibrinolytic Agents / adverse effects
  • Antifibrinolytic Agents / therapeutic use
  • Aprotinin / adverse effects
  • Aprotinin / therapeutic use
  • Blood Loss, Surgical / prevention & control*
  • Blood Transfusion
  • Cardiac Surgical Procedures* / adverse effects
  • Deamino Arginine Vasopressin / adverse effects
  • Deamino Arginine Vasopressin / therapeutic use
  • Hemostatics / adverse effects
  • Hemostatics / therapeutic use*
  • Humans
  • Myocardial Infarction / etiology
  • Placebos
  • Postoperative Hemorrhage / prevention & control*
  • Randomized Controlled Trials as Topic
  • Reoperation
  • Thoracotomy
  • Tranexamic Acid / adverse effects
  • Tranexamic Acid / therapeutic use
  • Treatment Outcome

Substances

  • Aminocaproates
  • Antifibrinolytic Agents
  • Hemostatics
  • Placebos
  • Tranexamic Acid
  • Aprotinin
  • Deamino Arginine Vasopressin