Inducible nitric oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy.

BACKGROUND AND PURPOSE: Cognitive dysfunction occurs in 9% to 23% of patients during the first month after carotid endarterectomy (CEA). A 4-basepair (AAAT) tandem repeat polymorphism (either 3 or 4 repeats) has been described in the promoter region of inducible nitric oxide synthase (iNOS), a gene with complex roles in ischemic injury and preconditioning against ischemic injury. We investigated whether the 4-repeat variant (iNOS(+)) affects the incidence of cognitive dysfunction after CEA. METHODS: One-hundred eighty-five CEA and 60 spine surgery (control) subjects were included in this nested cohort analysis. Subjects underwent a battery of 7 neuropsychometric tests before and 1 day and 1 month after surgery. Multivariate logistic regression analyses were performed to determine if the iNOS promoter variant was independently associated with the incidence of cognitive dysfunction at 1 day and 1 month. Further, all right-hand-dominant CEA subjects were grouped by operative side and performance on each test was compared between iNOS(+) and iNOS(-) groups. RESULTS: Forty-four of 185 CEA subjects had at least 1 iNOS promoter allele containing 4 copies of the tandem repeat (iNOS(+)). iNOS(+) status was significantly protective against moderate/severe cognitive dysfunction 1 month after CEA. Right-hand-dominant iNOS(+) CEA subjects undergoing left-side CEA performed significantly better than iNOS(-) subjects on a verbal learning test and those undergoing right-side CEA performed significantly better on a test of visuospatial function. CONCLUSIONS: We demonstrate an iNOS promoter polymorphism variant provides protection against moderate/severe cognitive dysfunction 1 month after CEA. Further, this protection appears to involve cognitive domains localized ipsilateral to the operative carotid artery.

Neurocognitive performance in hypertensive patients after spine surgery.

BACKGROUND: Cognitive dysfunction is fairly common after noncardiac surgery and may be related to intraoperative blood pressure management. The authors present an analysis of risk factors for cognitive deterioration after spine surgery in older patients, with particular emphasis on intraoperative blood pressure in normotensive and hypertensive patients. METHODS: This is a post hoc cohort analysis of 45 patients enrolled before undergoing lumbar laminectomy or microdiscectomy. The patients underwent a battery of 5 neuropsychometric tests preoperatively, and 1 day and 1 month postoperatively. Computerized anesthesia records were used to obtain intraoperative mean arterial pressure (MAP) data. Simple linear regressions between intraoperative MAP and postoperative cognitive performance were performed, and multivariate linear regression models of postoperative cognitive performance were constructed to analyze potential risk factors for cognitive decline after surgery. RESULTS: Twenty-one normotensive patients (mean age, 62.4 yr) and 24 hypertensive patients (mean age, 67.9 yr) were included in this analysis. There was a significant positive relationship between minimum intraoperative MAP values and 1-day cognitive performance by simple linear regression in hypertensive (P = 0.003), but not normotensive, patients. In multivariate linear regression analysis of cognitive performance, there was a significant interaction between hypertension and minimum intraoperative MAP at 1 day and 1 month. CONCLUSIONS: In hypertensive patients, there was a significant relationship between minimum intraoperative MAP and decline in cognitive function 1 day and 1 month after surgery. A prospective controlled trial of intraoperative blood pressure control, especially during induction of anesthesia when MAP values typically drop, is needed to confirm these findings.

A study of cognitive dysfunction in patients having carotid endarterectomy performed with regional anesthesia.

BACKGROUND: In previous studies, we found that approximately 25% of patients having carotid endarterectomy with general anesthesia (CEA general) develop cognitive dysfunction compared with a surgical control Group 1 day and 1 mo after surgery. In this study, we tested the hypothesis that patients having CEA with regional anesthesia (CEA regional) will develop significant cognitive dysfunction 1 day after surgery compared with a control group of patients receiving sedation 1 day after surgery. We did not study persistence of dysfunction. METHODS: To test this hypothesis, we enrolled 60 patients in a prospective study. CEA regional was performed with superficial and deep cervical plexus blocks in 41 patients. The control group consisted of 19 patients having coronary angiography or coronary artery stenting performed with sedation. A control group is necessary to account for the "practice effect" associated with repeated cognitive testing. The patients from the CEA regional group were enrolled at New York Medical Center and the control group at Columbia-Presbyterian Medical Center. The cognitive performance of all patients was evaluated using a previously validated battery of neuropsychometric tests. Differences in performance, 1 day after compared with before surgery, were evaluated by both event-rate and group-rate analyses. RESULTS: On postoperative day 1, 24.4% of patients undergoing CEA regional had significant cognitive dysfunction, where "significant" was defined as a total deficit score > or =2 SD worse than the mean performance in the control group. CONCLUSIONS: Patients undergoing CEA regional had an incidence of cognitive dysfunction which was not different than patients having CEA general as previously published and compared with a contemporaneously enrolled group.