Memory Loss Caused by Surgical Anesthetics Could Be Prevented

A new study indicates that memory loss after anesthesia could be prevented by blocking inhibitory α5 subunit-containing γ-aminobutyric acid subtype A (α5GABAA) receptors, thought to contribute to the memory deficits.

Researchers at Mount Sinai Hospital (Toronto, Canada) pretreated mice with L-655,708 (an α5GABAA receptor-selective inverse agonist), or with a vehicle. They were then exposed to isoflurane for one hour. The mice were then conditioned in fear-associated contextual and cued learning paradigms, either 1 or 24 hours later. In addition, the effect of L-655,708 on the immobilizing dose of isoflurane was studied. Motor coordination, sedation, anxiety, and the concentration of isoflurane in the brain at 5 minutes, 1 hour, and 24 hours after isoflurane administration were also examined.

The researchers found that motor and sensory function recovered within minutes after termination of isoflurane administration. In contrast, a robust deficit in contextual fear memory persisted for at least 24 hours. Administration of L-655,708 completely prevented the memory deficits without changing the immobilizing dose of isoflurane. The researchers therefore suggest that an isoflurane interaction at α5GABAA receptors contributes to memory impairment during the early postanesthesia period. The study was published in the November 2010 issue of Anesthesiology.

"In practical terms, our study suggests the need to reevaluate and study the assumption that patients will remember important information given to them after surgery,” said lead author Beverley A. Orser, M.D., Ph.D. "Until such studies are performed, it seems prudent to use strategies such as written information or sharing information with family members to ensure that instructions are learned and remembered.”

Memory blockade is an essential component of the anesthetic state. However, postanesthesia memory deficits represent an undesirable and poorly understood adverse effect. The memory impairment is an especially common occurrence in the elderly, with around 47% of elderly patients who underwent general anesthesia for minor surgical procedures exhibiting memory deficits for at least 24 hours after surgery. Some of these deficits can linger, as cognitive impairment, including memory loss, is present in 31% - 47% of patients at the time of hospital discharge.

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