Do platelet activating factor antagonists reduce cerebral injury after cardiac surgery?

BACKGROUND. There is only one previous report of a neuroprotective agent for patients undergoing CABG. Platelet activating factor (PAF) antagonists reduce cerebral injury in experimental models of cerebral ischaemia but there is no confirmatory evidence in clinical practice METHODS 150 patients undergoing CABG in a single centre were randomized by minimization in a double-blind. placebo-controlled, parallel group study into three groups to receive placebo infusion, 10 mg or 100mg lexipafant over 24 hours. Patients were assessed on a standardized battery of nine neuropsychological tests before surgery, prior to hospital discharge, and three months post-operatively. Serial samples of S100b were obtained in all patients RESULTS Patient groups were similar with respect to age, sex, body surface area (BSA) and urgency of operation. The PAF antagonist was well tolerated without any adverse side effects. Most neuropsychological tests deteriorated at 5 days with a return to or improvement over baseline performance in all except one test at three months in each group. All groups showed a rise in S100 to maximum levels at 1 hour after surgery followed by decline to basal levels at 24 hours. The three groups did not differ with respect to changes from baseline for either neuropsychological tests or S100. At no specific time point was there a significant difference between the absolute or change scores between the groups on any of the tests. Conclusions: Neuropsychological impairment is less frequent and less severe than that observed a decade ago. Despite considerable experimental evidence that PAF antagonists reduce brain injury this was not observed in the clinical setting.