Anesthetics produce postsurgical memory deficits by activating a5GABAa receptors in brain

From University of Toronto Media Room:

University of Toronto researchers discover why anesthetics cause prolonged memory loss

Posted on November 3, 2014

Toronto, ON – Researchers at the University of Toronto’s Faculty of Medicine have shown why anesthetics can cause long-term memory loss, a discovery that can have serious implications for post-operative patients.

Until now, scientists haven’t understood why about a third of patients who undergo anesthesia and surgery experience some kind of cognitive impairment—such as memory loss—at hospital discharge. One-tenth of patients still suffer cognitive impairments three months later.

Anesthetics activate memory-loss receptors in the brain, ensuring that patients don’t remember traumatic events during surgery. Professor Beverley Orser and her team found that the activity of memory loss receptors remains high long after the drugs have left the patient’s system, sometimes for days on end.

Animal studies showed this chain reaction has long-term effects on the performance of memory-related tasks.

“Patients — and even many doctors — think anesthetics don’t have long-term consequences. Our research shows that our fundamental assumption about how these drugs work is wrong,” says Orser, a Professor in the Departments of Anesthesia and Physiology, and anesthesiologist at Sunnybrook Health Sciences Centre.

In the study — led by PhD candidate Agnes Zurek — the team gave healthy male mice a low dose of anesthetic for just 20 minutes and found that receptor activity was increased for a week afterwards. These results suggest the same effect can impact a patient’s learning and memory during a time when they are receiving critical information about their care.

“There’s a lot going on after surgery, which can alter our ability to think clearly. Loss of sleep, new environments and medications can all impact a patient’s mental function. Anesthetics likely compound these issues,” says Orser.

She recommends physicians and family members carefully monitor patients after surgery for any signs of memory loss. “Patients should write everything down or have a second pair of ears with them after surgery. For high-risk groups, physicians need to inform patients about these possible side effects and help manage the impact on recovery and overall health,” says Orser.

The likelihood of a patient experiencing cognitive impairment depends on their age, health, type of surgery and the anesthetic, with chances increasing for more intricate procedures. The incidence is highest in the elderly or those undergoing major surgery such as cardiopulmonary bypass.

“Anesthetics don’t put you to sleep—they induce a pharmacological coma. We shouldn’t take these drugs lightly,” Prof. Orser cautions.

Read more.

From an earlier article by Grant MacArthur published at the Herald Sun in Melbourne in May of this year:

SCIENTISTS are racing to develop a new generation of anaesthetics amid revelations one in 10 major surgery patients suffers long-term memory loss.

Prof Beverly Orser from the University of Toronto said the chance of cognitive impairment followed all types of surgery, but risk grew the longer an operation lasted, the deeper an anaesthetic was and the age of the patient.

While the biggest danger of permanent memory loss faces the elderly, US authorities have launched a large study into the high rates of learning difficulties among children who have undergone repeated anaesthetics.

“Roughly one in three patients show a decline in cognitive dysfunction at the time of hospital discharge, one in 10 show a deficit that persists at three months,” Prof Orser today told the Australian and New Zealand College of Anaesthetists annual meeting in Singapore.

“It’s a big problem, the incidents are high, but unfortunately we don’t have a real clear insight into the underlying mechanisms and no treatment.”

After finding the activity of a receptor in the brain associated with memory called a5GABAa increased following anaesthetic, Prof Orser’s Canadian team developed a new drug to block the receptor and were able to prevent the long-term memory loss suffered by anaesthetised mice.

[…]

Assoc Prof Evered released research showing a third of patients over 65 experiencing temporary memory issues after surgery go on to suffer dementia within seven-and-a-half years — compared with just 10 per cent in the general population.

“There is a proportion who actually don’t recover to their preoperative level of cognition,” Assoc Prof Evered said.

Read more.

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