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.
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.


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.
Greilich
P E
PE
Dallas Veterans Affairs Medical Center: Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, USA.
Okada
K
K
Latham
P
P
Kumar
R R
RR
Jessen
M E
ME
D015119:Aminocaproic Acid / Q000008:administration & dosage*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D007611:Aprotinin / Q000008:administration & dosage*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005112:Extracorporeal Circulation / Q000009:adverse effects; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D011184:Postoperative Period; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
D000933:Antifibrinolytic Agents; D015850:Interleukin-6; D015842:Serine Proteinase Inhibitors; D016753:Interleukin-10; D007611:Aprotinin; D015119:Aminocaproic Acid