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General anesthesia and cognitive impairment Butterfield, Noam Nahum Douglas


This thesis describes clinical and laboratory studies of the relationship between general anesthesia and cognitive impairment. Clinical studies investigated whether anesthetics with faster elimination pharmacokinetics would improve recovery in patients at high-risk of developing short-term cognitive impairment. Animal experiments investigated the relationship between general anesthesia, age, and long-term cognitive impairment. Carotid endarterectomy patients are at high risk of developing postoperative cognitive impairment because of advanced age, comorbidities, and potential surgical complications. Early postoperative neurological assessment is necessary to avoid irreversible neurological complications, but may be delayed by residual anesthesia. The inhalational anesthetic desflurane is more rapidly cleared from the body than isoflurane, which may lead to earlier recovery. Patients randomly received either anesthetic. Emergence times and cognitive recovery, tested at 30 minutes (Minimental status exam), and at 4 and 24-hours postoperatively (comprehensive neuropsychological assessment), were not significantly different. Depressed patients who receive electroconvulsive therapy (ECT) are at high risk of developing postictal cognitive impairment because of preexisting cognitive deficits and effects of ECT. Cognitive impairment can reduce patient compliance, promote premature discontinuation of effective treatments, distress family members, and delay discharge. The parenteral anesthetic propofol is more rapidly cleared from the body than thiopental, and may reduce cognitive impairment after ECT. Patients received thiopental or propofol alternating over six consecutive ECTs. Propofol was associated with less cognitive impairment (similar neuropsychological battery as in carotid study) 45 minutes after ECT. Long-term postoperative cognitive impairment in elderly patients has been attributed to general anesthesia. Clinical studies are limited in their ability to separate the effects of anesthesia from surgery. Hence, experiments were conducted in young (3-month) and aged (18- and 27-month) mice to test whether general anesthesia, administered 3 hours after training on psychomotor and spatial memory tasks, would impair cognitive performance tested approximately 24 hours later. Isoflurane or propofol anesthesia was repeated throughout training. Even with repeated administrations, general anesthesia did not cause long-term cognitive impairment in mice in any experimental condition. In summary, anesthetics with faster elimination times can improve short-term cognitive recovery in some cases (i.e. ECT patients), but in other cases (i.e. carotid endarterectomy patients), the choice of anesthetic may be less important than disease or surgical related factors. Results from the animal experiments suggest that general anesthesia does not cause long-term cognitive impairment in the elderly.

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