Pharmacological Prevention of the Deleterious Effects of Cardiopulmonary Bypass

Abstract

Indomethacin is a known immune modulator that inhibits cyclooxygenase. Studies indicate that ketoconazole, a selective lipoxygenase and thromboxane A₂ synthetase inhibitor, can prevent activation of the inflammatory cascade by inhibition of proinflammatory mediators. This study was designed to determine if ketoconazole or indomethacin could reduce the adverse effects of extracorporeal circulation. As a double-blind prospective study, 76 patients were randomized into 3 groups according to preoperative medication: indomethacin, ketoconazole, and placebo groups, with 25, 26, and 25 patients, respectively. Four types of parameters were evaluated preoperatively and up to 24 hr after cardiac surgery in all patients: inflammatory (complement C3 and C4, C-reactive protein, immunoglobulins); hematologic; coagulation; and physiologic (blood loss, fluid and blood components received, weight gain, and duration of ventilation). Statistical analyses showed similar patient profiles in each group. Complement C4 decreased in all groups postoperatively, but significantly less in the indomethacin group (p < 0.01). Ketoconazole reduced postoperative bleeding (p < 0.0001) as well as the incidence of re-operation for bleeding (p = 0.05). It was concluded that indomethacin decreases complement (specifically C4) consumption during cardiopulmonary bypass, and ketoconazole may reduce postoperative bleeding by limiting coagulation abnormalities in cardiac surgery patients.