Newly published research from the Department of Geriatrics and Gerontology at the Rowan University School of Osteopathic Medicine explains why up to half of older adults who undergo general anesthesia develop postoperative delirium - the sudden onset of confusion, aggression or agitated behavior that could progress to dementia. The findings indicate that older patients who are undergoing surgery may benefit from a less-potent, slower-acting anesthetic.
Working with animal models, the research team tested two inhaled anesthetics - Sevoflurane and Isoflurane. Sevoflurane is one of the commonly used inhaled anesthetics for inducing general anesthesia because it acts more quickly and has a shorter recovery time. But, the researchers found that Sevoflurane caused increased disruption of the blood-brain barrier, the cellular structure that regulates the entry and removal of various blood components in the brain. Isoflurane, however, failed to demonstrate similar levels of blood-brain barrier breach.
"Our research has shown that when the blood-brain barrier breaks down, various plasma components, such as immunoglobulin, gain access into the brain and selectively bind to pyramidal neurons," said Nimish K. Acharya, PhD, the study's lead author. "This may disrupt normal neuronal activity and could cause the onset the symptoms that define postoperative delirium."
The selective binding of those autoantibodies to the pyramidal neurons that dominate the cerebral cortex occurred in animals treated with both inhaled anesthetics. However, older animals treated with Sevoflurane showed a "dramatic and significant increase in the density and extent of vascular leak" caused by a disruption in the blood-brain barrier. By contrast, older animals exposed to Isoflurane failed to show any significant age-related differences in either the density or extent of vascular leaks.
"Extrapolating this data to humans suggests that older patients who will be exposed to inhaled anesthetics during surgery would benefit from a less potent anesthetic that would presumably pose less risk of blood-brain barrier compromise and minimize the risk of subsequent postoperative delirium," said the study's corresponding author, Robert Nagele, PhD, director of the Biomarker Discovery Center and a professor of Medicine at the Rowan University School of Osteopathic Medicine.
The authors of the study suggest that more research is needed to identify other anesthetics for use in surgery that would be less disruptive to the blood-brain barrier and less likely to lead to postoperative complications such as delirium, cognitive decline and dementia.
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