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.

The use of desmopressin as a hemostatic agent: A concise review

“…In 1997, Laupacis and Fergusson [53] published another metaanalysis showing that desmopressin was ineffective in reducing blood loss in cardiac surgery. Another metaanalysis of randomized controlled trials studying the role of desmopressin in cardiac surgery was per- formed by Levi et al [54] in 1999, in which 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 (mortality, repeat thoracotomy, proportion of patients receiving transfusion). Moreover, desmopressin was associated with a 2.4-fold increase in the risk of myocardial infarction.…”

Antifibrinolíticos e cirurgia cardíaca com circulação extracorpórea

“…However, despite of this tendency, in-hospital mortality in this meta-analysis was always lower in the aprotinin group. Comparing patients who received aprotinin, regardless of the dose, with the placebo group, the in-hospital mortality was twice as high in the placebo group 82 . It is important to stress that the scientific value of the mortality evaluation would be higher if the follow-up were not restricted to the hospitalization period.…”

“…In another meta-analysis, undertaken by Levi et al 35 , comparing TA and EACA together, as lysine analogues, to placebo, demonstrated a tendency for decreased prevalence of MI in the group treated with lysine analogues than in the placebo group.…”

“…Em quatro horas, 80% do fármaco já foi eliminado. A aprotinina teve o seu emprego comprovado como fármaco poupador de sangue em vários ensaios clínicos com distribuição aleatória de pacientes e três metanálises [33][34][35] . Inclusive em pacientes com alto risco para sangramento, a aprotinina demonstrou ser efetiva para reduzir sangramento e transfusões em cirurgia cardíaca com CEC [36][37][38] .…”

“…In 4 hours, 80% of the drug has already been eliminated. The use of aprotinin as a blood-sparing drug has been demonstrated in several clinical studies, with random distribution of patients, and 3 meta-analyses [33][34][35] . It has been demonstrated that aprotinin is effective in reducing bleeding and blood transfusions in cardiac surgeries with CPB, even in patients with increased risk of bleeding [36][37][38] .…”