title: Neuroprotection during cardiac surgery: a randomised trial of a platelet activating factor antagonist.
abstract: OBJECTIVE
  To assess platelet activating factor (PAF) antagonists, potent neuroprotective agents in experimental cerebral dysfunction, in clinical practice.
  
  
  METHODS
  Double blind, minimised, placebo controlled trial of low and high dose PAF antagonist (lexipafant).
  
  
  METHODS
  Cardiac surgery unit.
  
  
  METHODS
  150 patients undergoing coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass.
  
  
  METHODS
  Randomisation to placebo, low dose (10 mg) or high dose (100 mg) lexipafant.
  
  
  METHODS
  Incidence of impairment on four established cognitive tests, undertaken before, five days, and three months after CABG, examined by three methods for defining impairment.
  
  
  RESULTS
  The three groups were similar with respect to preoperative and intraoperative factors. Observed levels of cognitive impairment were less than had been predicted from previous studies. There was no difference in the groups in cognitive change scores at five days or three months. Group mean analysis showed significant time factors for all four tests but not for interactions or for the lexipafant group. A composite cognitive index, based on the aggregate of four normally distributed tests, showed a significant effect for timing of the test but not for the lexipafant group or interaction. Age, but not duration of bypass, was the most important determinant of postoperative cognitive impairment.
  
  
  CONCLUSIONS
  The neuroprotective PAF antagonist lexipafant did not differentially reduce the level of cognitive impairment after CABG as determined by power estimates derived from published studies. The strongest predictors of cognitive impairment were age and timing of the test after operation.
authors.affiliation: Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, UK. david.taggart@orh.anglox.nhs.uk
authors.forename: D P
authors.initials: DP
authors.lastname: Taggart
authors.forename: S M
authors.initials: SM
authors.lastname: Browne
authors.forename: D T
authors.initials: DT
authors.lastname: Wade
authors.forename: P W
authors.initials: PW
authors.lastname: Halligan
mesh_terms: D003072:Cognition Disorders / Q000517:prevention & control*; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
chemical_list: D007093:Imidazoles; D018696:Neuroprotective Agents; D010972:Platelet Activating Factor; D007930:Leucine; C103289:lexipafant