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Coronary artery bypass surgery with cardiopulmonary bypass carries a significant risk of perioperative brain injury. At least 1% to 5% will suffer a stroke, and at 3-months postoperatively approximately 30% are reported to have cognitive impairment assessed by neuropsychologic testing. In off-pump surgery cardiopulmonary bypass is not used and instrumentation on the ascending aorta is reduced. The main aim of this study was to assess if off-pump surgery reduces intraoperative cerebral embolization.This was a prospective and randomized study of two comparable groups with regard to age, sex, years of education, preoperative cognitive functioning, and surgical characteristics. Fifty-two patients (29 off-pump) were monitored by the use of transcranial Doppler ultrasound for cerebral microembolization during surgery. Preoperative and postoperative clinical, cerebral magnetic resonance imaging, and neuropsychologic examinations were also carried out.There was a significant reduction in the number of cerebral microemboli during off-pump compared with on-pump surgery (16.3 [range 0 to 131] versus 90.0 [range 15 to 274],p< 0.0001). No significant difference with regard to the incidence of neuropsychologic performance (decline in 29% off-pump, 35% on-pump) or neuroradiologic findings at 3 months was found, and there was no association between the number of cerebral microemboli and cognitive outcome.This study clearly demonstrates that off-pump surgery leads to a reduction in intraoperative cerebral microembolization. A significant reduction in the number of off-pump patients with cognitive decline or ischemic brain lesions on cerebral magnetic resonance imaging could not be demonstrated in this relatively small patient population.