Tranexamic Acid Attenuates Inflammatory Response in Cardiopulmonary Bypass Surgery Through Blockade of Fibrinolysis: A Case Control Study Followed by a Randomized Double-Blind Controlled Trial

Introduction: Extracorporeal circulation induces haemostatic alterations which lead to inflammatory response (IR) and postoperative bleeding. Tranexamic acid (TA) reduces fibrinolysis and blood loss after cardiopulmonary bypass (CPB). However, its effects on IR and vasoplegic shock (VS) are not well known and this was the main objective of this study.

Methods: A case-control was carried out to determine factors associated with IR after CPB. Secondly, patients undergoing elective CPB surgery were randomly assigned to receive 2g of TA or placebo (0.9% saline) before and after intervention. We performed an intention-to-treat analysis, comparing the incidence of IR and VS. We also analyzed several biological parameters related with inflammation, coagulation and fibrinolysis systems. We used SPSS-12.2 for statistical purposes.

Results: In the case control study, 165 patients were studied, 20.6% fulfilled IR criteria and the use of TA proved an independent protective variable (OR 0.38; 95%CI: 0.18-0.81; P<0.01). The clinical trial was interrupted. Fifty patients were randomly assigned to receive TA (24) and placebo (26). Incidence of IR was 17% in the TA group vs 42% in the placebo group (P=0.047). In the TA group, we observed a significant reduction in the incidence of vasoplegic shock (P=0.003), the use of norepinephrine (P=0.029) and time on mechanical ventilation (P=0.018). These patients showed a significantly lower D-dimer, PAI-1 and creatine-kinase levels, and a trend toward a lower levels of STNFR and IL-6, within the first 24-hr after CPB.

Conclusion: The use of tranexamic acid attenuates the development of inflammatory response and vasoplegic shock after CPB.