Pharmacological Strategies to Decrease Excessive Blood Loss in Cardiac Surgery: Meta‐analysis of Clinically Relevant Endpoints*

Abstract

SUMMARY 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 randomized, 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.