Neuroprotection of the brain during cardiopulmonary bypass: a randomized trial of remacemide during coronary artery bypass in 171 patients.
OBJECTIVE
Neuropsychological impairment may follow coronary artery bypass surgery as a result of peroperative cerebral microembolism. The hypothesis that remacemide, an NMDA receptor antagonist, would provide protection against such ischemic damage has been tested in a randomized trial.


METHODS
One hundred seventy-one patients undergoing 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 microembolic events detected by transcranial Doppler ultrasonography of the middle cerebral artery. A battery of 9 neuropsychological tests was administered before and 8 weeks after surgery.


RESULTS
The proportion of patients showing a decline in performance of 1 SD or more in 2 or more tests was reduced in the treated group (9% versus 12%), but this was not statistically significant. On the other hand, overall postoperative change (reflecting learning ability in addition to reduced deficits) was more favorable in the remacemide group, which demonstrated significantly 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 matched, including for the burden of microembolic events.


CONCLUSIONS
This is the first study to show statistically significant drug-based neuroprotection during cardiac surgery. In addition to offering improvement in cerebral outcome for such at-risk patients, it supports the hypothesis that drugs acting on the excitotoxic mechanism of ischemic cerebral damage can be effective in humans.
Arrowsmith
J E
JE
Departments of Anaesthesiology, Neurology, Psychiatry and Behavioural Sciences and Cardiothoracic Surgery, University College London Hospital and Medical School, London, UK.
Harrison
M J
MJ
Newman
S P
SP
Stygall
J
J
Timberlake
N
N
Pugsley
W B
WB
D000081:Acetamides / Q000008:administration & dosage*; D000293:Adolescent; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000502:physiology*; D002536:Cerebral Arteries / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009483:Neuropsychological Tests; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial
D000081:Acetamides; D018696:Neuroprotective Agents; C067553:remacemide