The effects of aprotinin and steroids on generation of cytokines during coronary artery surgery

Objectives: To compare the efficacy of aprotinin and methylprednisolone in reducing cardiopulmonary bypass (CPB)-induced cytokine release, to evaluate the effect of myocardial cytokine release on systemic cytokine levels, and to determine the influence of cytokine release on perioperative and postop erative hemodynamics. Design: Prospective, randomized clinical trial. Setting: University teaching hospital and clinics. Participants: Thirty patients undergoing elective coronary artery bypass gr aft surgery. Interventions: Patients were randomly allocated into groups tr eated with aprotinin (n = 10) or methylprednisolone (n = 10) or into an unt reated control group (n = 10). Aprotinin-treated patients received aprotini n as a high-dose regimen (6 x 10(6) KIU), and methylprednisolone-treated pa tients received methylprednisolone (30 mg/kg intravenously) before CPB. Measurements and Main Results: Patients were analyzed for hemodynamic chang es and alveolar-arterial PO2 difference (AaDO(2)) until the first postopera tive day. Plasma levels of proinflammatory cytokines (tumor necrosis factor [TNF]a, interleukin [IL]-1 beta, IL-6, and IL-8) were measured in peripher al arterial blood immediately before the induction of anesthesia, 5 minutes before CPB, 3 minutes after the start of CPB, 2 minutes after the release of the aortic cross-clamp, 1 hour after CPB, 6 hours after CPB, and 24 hour s after CPB; and in coronary sinus blood immediately before CPB and 2 minut es after the release of the aortic cross-clamp. The hemodynamic parameters did not differ among the groups throughout the study. After CPB, AaDO(2) si gnificantly increased (p < 0.05) in all groups. A significant decrease in A aDO(2) was observed in aprotinin-treated patients at 24 hours after CPB com pared with the other groups (p < 0.05). TNF-a level from peripheral arteria l blood significantly increased in control patients 1 hour after CPB (p < 0 .01) and did not significantly increase in methylprednisolone-treated patie nts throughout the study. In all groups, IL-6 levels increased after the re lease of the aortic cross-clamp and reached peak values 6 hours after CPB. At 6 hours after CPB, the increase in IL-6 levels in methyl prednisolone-tr eated patients was significantly less compared with levels measured in cont rol patients and aprotinin-treated patients (p < 0.001). In control patient s, IL-8 levels significantly increased 2 minutes after the release of the a ortic cross-clamp (p < 0.05), and peak values were observed 1 hour after CP B (p < 0.01). IL-8 levels in control patients were significantly higher com pared with patients treated with aprotinin and patients treated with methyl prednisolone 1 hour after CPB (p < 0.05). Conclusion: This study showed that methylprednisolone suppresses TNF-<alpha >, IL-6, and IL-8 release; however, aprotinin attenuates IL-8 release alone . Methylprednisolone does not produce any additional positive hemodynamic a nd pulmonary effects. An improved postoperative AaDO(2) was observed with t he use of aprotinin. Copyright (C) 2001 by W.B. Saunders Company.