Aprotinin but not epsilon-aminocaproic acid decreases interleukin-10 after cardiac surgery with extracorporeal circulation: randomized, double-blind, placebo-controlled study in patients receiving aprotinin and epsilon-aminocaproic acid

Abstract

Background: Extracorporeal circulation induces a systemic inflammatory response, which may adversely affect organ function. One manifestation of this response is increased fibrinolysis. Antifibrinolytic drugs such as aprotinin and epsilon-aminocaproic acid have been effective in reducing fibrinolysis and blood loss after extracorporeal circulation; however, the effects of antifibrinolytic drugs on proinflammatory and anti-inflammatory mediators are not known. This study examined the effects of aprotinin and epsilon-aminocaproic acid on plasma levels of proinflammatory [interleukin-6 (IL-6)] and anti-inflammatory [interleukin-10 (IL-10)] cytokines during and after extracorporeal circulation.

Methods and results: Seventy-two patients undergoing coronary artery bypass grafting with extracorporeal circulation were randomly assigned in a double-blind study to receive high-dose aprotinin, epsilon-aminocaproic acid, or saline placebo. Plasma levels of IL-6 and IL-10 were measured at 5 time points before, during, and after extracorporeal circulation. In all 3 groups, both IL-6 and IL-10 rose significantly after institution of extracorporeal circulation and remained elevated through the first postoperative day. Compared with saline, aprotinin significantly reduced IL-10 (P=0.02) and peak IL-6 (P=0.02) after extracorporeal circulation. In contrast, none of the reductions in IL-6 and IL-10 by epsilon-aminocaproic acid achieved statistical significance. Both aprotinin and epsilon-aminocaproic acid decreased blood loss compared with saline, but there was no significant difference in the number of patients receiving blood products among the treatment groups.

Conclusions: These data suggest that aprotinin and epsilon-aminocaproic acid differ in their effects on the inflammatory response to extracorporeal circulation. Aprotinin but not epsilon-aminocaproic acid appears to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6 and IL-10. Further studies will be required to determine if these cytokine alterations translate to changes in clinical outcomes.