Perioperative Stroke, Encephalopathy, and Central Nervous System Dysfunction

Abstract

The leading cause of mortality in adult populations throughout the world is atherosclerosis, which results in cardiovascular and cerebrovascular complications and consumes substantive health care resources. The impact of atherosclerosis on patients undergoing surgery is also considerable, given the multiple stresses occurring during, and especially following, the surgical procedures, thereby precipitating vascular morbidity. Perioperative cerebrovascular morbidity and mortality occur in approximately 10% of the 600,000 patients who undergo cardiac surgery annually, consuming approximately $13 billion, which is expended on in-hospital, intensive care unit (ICU), and long-term specialized care for these neurological complications of stroke, encephalopathy, and cognitive dysfunction. Furthermore, risk of these outcomes will continue to increase as the surgical population ages. Principal among the etiologies of focal stroke and encephalopathy appear to be perioperative hypotension and precipitation of macroemboli and microemboli. As a result, new detection techniques for these events have been instituted, including (1) continuous hemodynamic monitoring, for detection of hypotensive episodes; (2) transesophageal echocardiography, for detection of aortic atherosclerosis, a potential source for emboli; and (3) transcranial Doppler sonography, for detection of cerebral emboli, as well as determination of cerebral blood flow. Recent large-scale multicenter studies have identified risk factors and indices for perioperative central nervous system (CNS) morbidity. Regarding therapy, a number of pharmacological approaches are currently under consideration; principal among these approaches are agents that can modulate the excitotoxic response, including glutamate receptor antagonists (NMDA, AMPA, metabotrophic), calcium channel blockers, free radical scavengers, and agents that modify the inflammatory white cell response. Although a number of laboratory, animal, and smaller clinical trials have been conducted, only one large-scale multicenter program to date has been conducted to assess the efficacy of adenosine modulation. These data, collected in more than 4,000 patients undergoing cardiac surgery, suggest that in addition to mitigation of myocardial injury, stroke also may be modulated by enhancing adenosine concentration in the area of cerebral ischemia. However, these preliminary findings must be validated in appropriately powered clinical trials. Finally, postoperative stroke and encephalopathy consume substantive resources, resulting in prolonged length-of-stay (17 days in-hospital 10 days for patients suffering Q-wavc infarction, vs 7 days for patients having no adverse outcome) and prolonged length-of-stay in the ICU following surgery (5 vs 3 vs 2 days, respectively). Hospital costs increase by approximately 3- to 4-fold in patients who suffer CNS outcomes following surgery. In conclusion, perioperative CNS morbidity and mortality is a critical problem that affects a substantial portion of the surgical population and consumes considerable health care resources. Over the next several years, attention must be focused on this important problem, and clinical and research resources should be redirected toward the solution of perioperative CNS morbidity.