INDOMETHACIN AND KETOCONAZOLE IN THE PROPHYLAXIS OF THE DELETERIOUS EFFECTS OF CARDIOPULMONARY BYPASS IN ADULT CARDIAC SURGERY

Objective: Cardiopulmonary bypass is associated with complications-having substantial adverse clinical implications, most of which are due to undesired activation of immune and coagulation vicious cycle. Indomethacin has been knownas an immune modulator by illhibiting cyclo-oxygenase. Studies indicate that ketoconazole can prevent activation of inflammatory cascade by inhibition of proinflammatory mediators. This study was designedto determineif ketoconazole,a selective lipooxygenase and thromboxane A2 synthetase inhibitor, or indomethacin would decrease the trigger for activation of the qestructive effectsof extracorporeal circulation.
Methods: As a double blind prospective study 76 patients were randomized into three groups according to the medication received preoperatively; the indomethacin,ketoconazole, and control groups with 25, 26, and 25 patients in each group, respectively. Three groups of parameters were evaluated preoperatively up to 24 hours in all patients: 1) inflammatory, (C3, C4, CRP, immunoglobulins);2) hematologic, and coagulation; and 3) physiologic (amount of bleeding, fluid and blood components received, weight gain, and duration of respiratory support required postoperatively.
Results: Statistic analysis showed similar patient profile. Complement 4 decreased in all groups postoperatively but significantly less in the indomethacin group (p<0.01). Ketoconazole lessened postoperative bleeding (p<0.0001) and a lower incidenceof reoperation for bleeding(p=0.05). There was a favorable trend for other inflammatory, coagulation,pnd physiologic parameters in the two medicated groups, however they did not reach statistical significance.
Conclusion: Indomethacin decreases complement (specifically C4) consumption during CPB. Ketoconazole may cause less postoperative bleeding by lessening coagulation abnormalitiesin cardiac surgery patients. Further studies with larger number of patients are needed to better evaluate the significanceof our findings.