Pharmacological prevention of the deleterious effects of cardiopulmonary bypass.
Indomethacin is a known immune modulator that inhibits cyclooxygenase. Studies indicate that ketoconazole, a selective lipoxygenase and thromboxane A(2) 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.
Hassantash
Seyed A
SA
Modarres Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. sahassan@pol.net
Omrani
Gholam R
GR
Givtaj
Nozar
N
Afrakhteh
Maryam
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003029:Coagulants / Q000494:pharmacology / Q000627:therapeutic use*; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007654:Ketoconazole / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000097:blood / Q000209:etiology / Q000517:prevention & control* / Q000601:surgery; D011446:Prospective Studies; D012086:Reoperation; D012121:Respiration, Artificial; D013997:Time Factors; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003029:Coagulants; D003176:Complement C3; D003181:Complement C4; D007136:Immunoglobulins; D002097:C-Reactive Protein; D007654:Ketoconazole; D007213:Indomethacin