Ranking high on the list of a mom and dad's nightmares is being told their small child needs surgery.
Questions by the dozens run through their heads: Does my child really need the operation? Will the operation take care of the problem? How long will recovery take? Another question they ought to be asking is: Does anesthesia affect my child's developing brain?
Because more than a million children in the U.S. under the age of 4 need anesthesia for surgery each year, the Food and Drug Administration (FDA) and other health organizations have teamed up to answer this question.
Studies yield mixed results
Previous scientific studies in young animals have shown that commonly used anesthetics can be harmful to the developing brain. However, results have been mixed in children. Some studies of infants and young children undergoing anesthesia have reported long-term deficits in learning and behavior, while other studies have not.
These conflicting results make it obvious that more research is needed to understand fully the risks anesthesia may pose to very young patients.
To close these research gaps, FDA and the International Anesthesia Research Society (IARS) started an initiative called SmartTots (Strategies for Mitigating Anesthesia-Related neuroToxicity in Tots). SmartTots seeks to ensure that children under age 4 will be as safe as possible when they need anesthesia. Studies have shown that this is a period of significant brain development in young children.
"Our hope is that research funded through SmartTots will help us design the safest anesthetic regimens possible," says Bob Rappaport, M.D., director of the Division of Anesthesia, Analgesia and Addiction Products at FDA. "This research can potentially foster the development of new and safer anesthetic drugs for use in pediatric medicine."
According to SmartTots steering committee co-chair James Ramsay, M.D., young children usually do not undergo surgery unless the procedure is vital to their health. "Therefore, postponing a necessary procedure may itself lead to significant health problems and may not be an option for the majority of children," Ramsey says.
SmartTots was launched in 2010 in part to fund research that would build on the work done at FDA and several universities.
Since 2003, Merle Paule, Ph.D., director of the Division of Neurotoxicology at FDA's National Center for Toxicological Research (NCTR), and colleagues have been exploring the effects of ketamine -- an anesthetic commonly used on children-on the brains and learning ability of young rhesus monkeys.
"Earlier research has shown that exposing young rat pups to ketamine caused learning problems when they became adults, but we wanted to see what would happen with primates," said Paule. Primates, such as the rhesus monkey used in this research, more closely resemble humans in physiology and behavior.
"The learning of concepts such as matching (see a triangle, match it with another triangle from among other symbols) took much longer in the ketamine-treated monkeys And even after basic concepts were learned, the ketamine-exposed animals performed less accurately than animals in the control group," Paule says.
The same holds true for the test monkeys even today, Paule says. Six years after their ketamine treatment, they're still showing below-normal brain function.
Children and ketamine
What might that mean for young children who have been exposed to ketamine or other anesthetics during surgery?
"We can't know with certainty at this time," says Rappaport, a member of the steering committee that coordinates, manages and oversees the SmartTots initiative. "We need to definitively answer the questions of whether anesthetic use in children poses a risk to their development and, if so, under what circumstances."
FDA and other health-related organizations recognize the importance of learning more on this topic. For example, do other forms of anesthesia similarly affect the brain's ability to, learn and remember? How long might these deficits last?
SmartTots Paves the Way
The SmartTots partnership is working to mobilize the scientific community around this issue, stimulate dialogue among leaders in the anesthesia community and work to raise funding for the necessary research ahead.
As part of these efforts, SmartTots issued a consensus statement that's been endorsed by organizations including the FDA, American Academy of Pediatrics, the American Society of Anesthesiologists and the European Society of Anaesthesiology in December, 2012. The statement acknowledged that, in the absence of conclusive evidence, it would be unethical to withhold sedation and anesthesia when necessary.
SmartTots is funding research underway at Columbia University and the University of Iowa on the effects of anesthesia on infant brain development, and on cognitive and language ability. All research first undergoes approval by an Institutional Review Board (IRB), a committee formally designated to approve, monitor, and review biomedical and behavioral research involving humans. The top priority of IRBs is to protect human subjects from physical or psychological harm.
In the meantime, Ramsay says parents and other caretakers should talk to their pediatrician or other health care professionals about the risks and benefits of procedures requiring anesthetics and weigh them against the known health risks of not treating certain conditions.