Anesthesia and the Young Brain
In recent years, several studies have found that brain cells in newborn mice die after spending hours under anesthesia. If similar effects are occurring in human newborns, it could have significant implications for pediatric surgery and critical care medicine. But do the animal studies fully correlate to human development? Andreas Loepke, MD, PhD, a researcher and a staff anesthesiologist at Cincinnati Children’s, is working to find out.
Loepke spends much of his clinical time working with very young children who need open heart surgery, a type of surgery known for its risk of potential cognitive impairment. He became interested in studying the potential toxic effects of anesthetics after finding evidence that some agents might limit postsurgical impairment. But the new studies were reporting that all common forms of anesthesia have neurotoxic effects in mice.
“I didn’t want to give kids a neurotoxicant as a neuroprotectant,” Loepke says. However, the deeper he gets into the research, the narrower that potential window of damage appears to be.
Earlier studies predicted that the toxic effects of anesthesia could occur in children up to age 3. But more recent studies indicate that the risk, if any, may be limited to children who have surgery just after birth – and possibly even to those born prematurely.
“In small rodents, the damage peaks at seven days of age and wanes to near zero at 14 days of age,” Loepke says. “But even that is controversial . The question remains: at what time in development does this correlate to the human brain? Some of the more recent research states that what we see in small rodents is a very premature state… more similar to mid-gestation stages for the human brain.”
Assessing the Real Damage
In mice, a six-hour exposure to anesthesia can kill about 2 percent of the developing neurons. However, during normal human development we lose nearly 50 percent of all brain neurons from the prenatal stage to adolescence.
“We are born with an overabundance of neurons. So we do not know if the anesthesia is affecting neurons that would have died anyway,”
Loepke says.
In hopes of resolving some of the uncertainties, Loepke is taking a closer look at what kinds of cells are killed by anesthetics.
“The brain has billions of cells. We can see that some cells die after anesthesia, but we also see hundreds of cells around them that do not die,” Loepke says. “We trying to figure out what is different about the cells that are affected versus those that are not.”
In one recent finding, Loepke reports that staining neurons with the marker NeuN reveals that 98 percent of affected cells are post-mitotic neurons. These are fully mature cells rather than progenitor cells – which could indicate that long–term risks from anesthesia are minimal.
“My current thinking is that the human brain should be more capable than the rodent brain to recover from these injuries,” Loepke says.
An Issue to Watch
Loepke says anesthesiologists and critical care physicians need to closely follow the issue as the research continues. But one thing is clear: anesthesia remains necessary.
“Newborns receive anesthesia because they need surgery for life-threatening conditions,” he says. “Studies have clearly shown that undertreated pain in children can have long-term harmful effects on brain development.”
