| Summary: | 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. === Medicine, Faculty of === Anesthesiology, Pharmacology and Therapeutics, Department of === Graduate
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