High-dose aprotinin modulates the balance between proinflammatory and anti-inflammatory responses during coronary artery bypass graft surgery

Objective: To rule out the effect of high-dose aprotinin in respect to the balance of proinflammatory and anti-inflammatory mediators induced by cardi opulmonary bypass (CPB). Design:Randomized, double-blind, placebo-controlled study. Setting: University-affiliate cardiac center. Participants: Twenty patients scheduled for coronary artery bypass graft su rgery. Interventions: In group A patients (n = 10), high-dose aprotinin was admini stered (2 x 10(6) KIU pre-CPB, 2 x 10(6) KIU in prime, 500,000 KIU/hr durin g CPB). In group C patients (n = in), placebo was used instead. Proinflamma tory interleukin (IL)-6, anti-inflammatory IL-1-receptor antagonist, and cl inical parameters were measured 8 times perioperatively. The values are pre sented as mean +/- SEM. Measurements and Main Results: Four hours after CPB, IL-6 concentration rea ched the maximum value, being significantly lower in group A patients as co mpared with group C patients (615 +/- 62 pg/mL v 1409 +/- 253 pg/mL; p = 0. 019). On the first postoperative day, the concentration of IL-6 in group A patients remained lower (219 +/- 24 pg/mL v 526 +/- 123 pg/mL; p = 0.015). In contrast, IL-1-receptor antagonist concentration was higher in group A p atients as compared with group C patients after CPB (13,857 +/- 4264 pg/mL v 5675 +/- 1832 pg/mL; p = 0.03). Total postoperative blood loss was lower in group A patients as compared with group C patients (648 +/- 64 mi v 1284 +/- 183 mi; p = 0.002). Conclusions: High-dose aprotinin treatment reduced the inflammatory reactio n and postoperative blood loss. The anti-inflammatory reaction was signific antly enhanced in these patients, which suggests that the physiologic react ion of the organism to reduce the deleterious effects from CPB is more pron ounced by using high-dose aprotinin. Copyright (C) 2000 by W.B. Saunders Co mpany.