General anesthetic – used to put surgery patients out cold – may work a little too well, researchers from the University of Toronto have found.
While the drugs prevent patients from remembering traumatic events during surgery, a new study conducted on mice suggests anesthesia-induced cognitive impairments may persist long after the drugs have left the system.
Memory receptors in the hippocampus region of the brain are "exquisitely sensitive to anesthetic drugs," said the study's co-author, Dr. Beverley Orser, a professor at the University of Toronto and anesthesiologist at Sunnybrook Health Sciences Centre.
"One of the assumptions we've always worked on is that once the drugs are eliminated, the function of those receptors goes back to normal," she said. "But that never fit with the clinical picture, because we knew that patients who'd undergone anesthesia during surgery exhibited these memory deficits."
Memory loss after surgery affects more than 35 per cent of young adults and 40 per cent of elderly patients at the time of hospital discharge. Three months after surgery, about 6 per cent of young adults and 13 per cent of elderly patients continue to suffer from memory loss and cognitive problems – the kind that interfere with the ability to remember names, locate a car in a parking lot, or find a set of keys.
The procedure with the highest rate of memory loss is cardiac surgery, likely because it is so invasive and results in "a huge inflammatory insult" that increases sensitivity to anesthetic, Orser said.
She added that cognitive impairments after surgery are not due to anesthesia alone. Contributing factors may include the illness itself, inflammation triggered by surgery, opioid pain killers, stress and sleep deprivation during recovery. But based on the findings of the mouse study, published Monday in the Journal of Clinical Investigation, "we now know that the drugs themselves – acting on the very receptors we want them to act on – are contributing to memory loss," Orser said.
The researchers injected mice with anesthesia in doses low enough to sedate the mice but not render them unconscious. Although the mice had only brief exposure to anesthetic, just 20 minutes, they showed cognitive impairments that persisted for at least a week. "What that means in patients, we don't know," said Orser, but she described a week in a mouse's life as "a very long time."
The Canadian Anesthesiologists' Society declined to comment on the study. Anesthesiology departments at the University of British Columbia, University of Calgary and University of Montreal did not respond to interview requests by deadline.
To gather more information on human subjects, researchers at Sunnybrook are recruiting patients to complete cognitive tests before and after surgery, with the aim to document any changes.
Meanwhile, Orser and colleagues are looking for ways to minimize the potential cognitive side effects of general anesthetic. A drug called dexmedetomidine works on a different type of receptor than drugs used for general anesthetic, Orser said. In the mouse study, it was not associated with prolonged memory loss. Although dexmedetomidine is less effective as an anesthetic, it could potentially be used for procedures in which sedation is sufficient, or in addition to general anesthetic to "allow us to reduce the dose of the anesthetic we use," she said.
The Canadian Centre for Health Information was unable to provide statistics on the number of surgeries requiring general anesthetic performed in Canada each year, since data on anesthesia in the Physician Services Benefit Rates Report are excluded "due to uncertainties about the interprovincial comparability of the data," according to the 2012-'13 report.
Orser emphasized that the mouse research is preliminary, and cautioned patients against reconsidering vital surgery because of possible cognitive problems. "This is not to scare people, but to better prepare patients," she said. After surgery, patients should be ready to write everything down, have a friend or relative in the hospital to provide a second pair of ears, "and be aware that you may not be as bright as you normally are," she said.
The good news is that mice in the study eventually recovered their cognitive functioning, Orser said.
But she added, "these are very powerful drugs," and general anesthesia is not the same as going to sleep – "it's a pharmacological coma," she said.
With that in mind, patients undergoing elective surgery, such as a tummy tuck, may decide they can live with that extra roll after all.