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Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically
M Levi1, M E Cromheecke, E de Jonge
1Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands. m.m.levi@amc.uva.nl
Insights
Pharmacological strategies like aprotinin and lysine analogues significantly reduce mortality and rethoracotomy rates in cardiac surgery patients. These agents also decrease the need for blood transfusions, improving patient outcomes.
Area of Science:
- Cardiology
- Pharmacology
- Critical Care Medicine
Background:
- Excessive bleeding is a significant complication in cardiac surgery, increasing morbidity and mortality.
- Previous trials showed pharmacological agents reduce blood loss but often lacked power for clinical outcomes.
- A meta-analysis was conducted on aprotinin, lysine analogues, and desmopressin for perioperative bleeding reduction.
Purpose of the Study:
- To evaluate the efficacy of three pharmacological strategies in reducing perioperative bleeding in cardiac surgery.
- To assess the impact of these strategies on clinically relevant outcomes, including mortality and transfusion rates.
Main Methods:
- Meta-analysis of 72 randomized controlled trials involving 8409 patients.
- Inclusion criteria required reporting of clinical outcomes (mortality, rethoracotomy, transfusion, myocardial infarction) alongside blood loss.
- Separate analysis for studies on complicated cardiac surgery.
Main Results:
- Aprotinin nearly halved mortality (OR 0.55) and, with lysine analogues, reduced rethoracotomy rates (OR 0.37-0.44).
- Both aprotinin and lysine analogues significantly decreased allogeneic blood transfusion requirements.
- Desmopressin showed minimal blood loss reduction without clinical benefit and increased myocardial infarction risk (OR 2.4).
Conclusions:
- Pharmacological agents, particularly aprotinin and lysine analogues, effectively reduce perioperative blood loss in cardiac surgery.
- These agents are associated with decreased mortality, rethoracotomy, and transfusion rates.
- Desmopressin is not recommended due to lack of clinical benefit and increased risk of myocardial infarction.
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.
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