Neuroprotection of the Brain During Cardiopulmonary Bypass

Abstract

Background and Purpose-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 (Pϭ0.028) and changes in 3 individual tests (PϽ0.05). 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. (Stroke. 1998;29:2357-2362.)

Comparison of Microembolism Detected by Transcranial Doppler and Neuropsychological Sequelae of Carotid Surgery and Percutaneous Transluminal Angioplasty

“…Because of the potential for all neuropsychological tests to show learning with repetition, a greater improvement in neuropsychological scores on this analysis will reflect a combination of greater learning and less deficit. 21,22 The sum of all the standardized change scores between before the procedure and 6 weeks after the procedure and between before the procedure and 6 months after the procedure was then correlated with the following: (1) the number of presumed solid microembolic signals detected during the procedure (ie, the number of microembolic signals detected during dissection during CEA or catheter movement and balloon deflation during PTA); (2) total ischemic time; and (3) ipsilateral cerebral reactivity before the procedure.…”

Pharmacological agents as cerebral protectants during deep hypothermic circulatory arrest in adult thoracic aortic surgery

“…However, the therapeutic range of some glutamate receptor antagonists is very narrow and there may be receptor upregulation with neurological injury on withdrawal of the agents. Arrowsmith et al [22] have shown a possible neuroprotective effect of remacemide, a glutamate antagonist, during coronary artery bypass in 171 patients. However, there currently exists insufficient evidence to support the clinical use of this drug.…”

Cerebral Microembolization during Primary Total Hip Arthroplasty and Neuropsychologic Outcome: A Pilot Study

“…We used intraoperative transcranial Doppler (TCD) to measure cerebral microemboli load [4,52]. Monitoring was continuous, beginning before the operation started, ie, before the skin incision, and continuing until no microembolus had been detected for 2 minutes and when the patient was returned to the supine position after THA.…”