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Making Adjustments

Anesthesia may trigger cognitive deficits, neuroinflammation

Children who undergo repeated surgeries that require general anesthesia before age four may be at an increased risk for learning disabilities, say HMS scientists at Massachusetts General Hospital.

In the March online issue of Anesthesiology, the researchers report an animal study indicating that age, the specific anesthetic agent used, and the number of doses delivered combine to induce impairments in learning and memory accompanied by inflammation of brain tissue. In a separate report in the same issue of the journal, the team presents findings that the offspring of mice that received a specific anesthetic gas during pregnancy also showed the effects of neuroinflammation and impaired learning.

“We found that different anesthetic drugs—sevoflurane and desflurane—had different effects on neuroinflammation and on learning and memory function in young mice,” says the studies’ corresponding author, Zhongcong Xie, an HMS associate professor of anaesthesia and director of the Geriatric Anesthesia Research Unit at Mass General.

The researchers found that, when comparing two test groups of young mice, those that received a single two-hour dose of either sevoflurane or desflurane showed neither neuroinflammation nor cognitive impairment. Three doses of the respective drugs, however, caused inflammation and impairment in the mice that received sevoflurane, but not in those that received desflurane. In addition, the researchers also determined two strategies that reduced the negative effects of sevoflurane: pre-anesthesia treatment with an anti-inflammatory drug and placement of the young animals in an environment enriched with ladders, wheels, and mazes.

The second study exposed a group of pregnant female mice to a single two-hour dose of sevoflurane two-thirds of the way through gestation. When assessed a month after birth, offspring of sevoflurane-exposed females showed evidence of impaired learning and memory and elevated levels of inflammatory markers, compared with a control group. As in the first study, placing the anesthetic-exposed pregnant mice and then their offspring into an enriched environment appeared to reduce both the neuroinflammatory and behavioral effects of sevoflurane.

“Six million children undergo surgery each year in the United States,” says Xie. “We hope our findings will promote more research into anesthesia neurotoxicity in the developing brain.