NEUROPROTECTION OF THE BRAIN DURING CARDIOPULMONARY BYPASS - A RANDOMIZED TRIAL OF REMACEMIDE DURING CORONARY-ARTERY BYPASS IN 171 PATIENTS

Background and Purpose-Neuropsychological impairment may follow corona ry artery bypass surgery as a result of peroperative cerebral microemb olism. The hypothesis that remacemide, an NMDA receptor antagonist, wo uld provide protection against such ischemic damage has been tested in a randomized trial. Methods-One hundred seventy-one patients undergoi ng coronary artery bypass surgery by a single cardiothoracic surgical team were randomized to receive remacemide (up to 150 mg every 6 hours ) or placebo from 4 days before to 5 days after their bypass procedure . Peroperative monitoring included an estimate of the number of microe mbolic events detected by transcranial Doppler ultrasonography of the middle cerebral artery. A battery of 9 neuropsychological tests was ad ministered before and 8 weeks after surgery. Results-The proportion of patients showing a decline in performance of 1 SD or more in 2 or mor e tests was reduced in the treated group (9% versus 12%), but this was not statistically significant. On the other hand, overall postoperati ve change (reflecting learning ability in addition to reduced deficits ) was more favorable in the remacemide group, which demonstrated signi ficantly greater improvement in a global z score (P=0.028) and changes in 3 individual tests (P<0.05). The 2 patient groups were well matche d, including for the burden of microembolic events. Conclusions-This i s the first study to show statistically significant drug-based neuropr otection during cardiac surgery. In addition to offering improvement i n cerebral outcome for such at-risk patients, it supports the hypothes is that drugs acting on the excitotoxic mechanism of ischemic cerebral damage can be effective in humans.