Smart Tots Consensus Statement: From print to patient bedside
Reviewed by Joseph Cravero, MD
Dr. Sidanthem Suresh opened the conference by addressing the issue of possible neurocognitive effects of exposure to sedation and anesthesia. He reviewed the history of the SmartTots program that is a collaborative effort between the International Anesthesia Research Society, the Society for Pediatric Anesthesia, the American Society of Anesthesiologists, multiple other pediatric-focused organizations, and the FDA.
He noted the original statement from the FDA several years ago, warning of the possible risk to children and pregnant mothers after exposure to anesthesia drugs and how this was a bombshell for the fields of pediatric sedation and pediatric anesthesia. This warning was based on multiple studies that documented neuroapoptosis and neurocognitive deficits in animal models after exposure to anesthesia. He also noted that essentially all the drugs used for sedation and anesthesia have been implicated. All of this is now required as part of the package insert for all of these drugs.
How should we advise our healthcare partners? As opposed to the animal studies, clinical studies in humans (at this point) do not indicate that limited exposures for limited periods of time are a problem. Having pointed this out, Dr. Suresh noted that delaying elective procedures until children are over three years of age seems appropriate. He pointed out that, because this is a complex and uncertain area, information and counseling should be available to parents.
Dr. Suresh's current SmartTots research grant recipients were outlined and he encouraged more research by investigators in the Society for Pediatric Sedation. He noted the difference between animal physiology and human physiology. He used this to explain the discordance between the studies that have been done in animals and the implications for humans – the differences in exposure and outcomes are large – hard to know what animal studies mean for humans.
Dr. Suresh asked the question as to whether or not we should consider alternative methods for sedation? He reviewed the specific evidence for apoptosis in rat models. He also mentioned the data that confirms apoptosis issues in primate models. He noted the most sensitive period is during rapid brain growth. Injury appears to have a definite dose-response effect. There also appears to be some gender influences. Sedation/anesthesia with tissue damage appear to worsen the apoptosis effect. In comparing isoflurane, ketamine and propofol, propofol has been found to be least toxic at either fetal or newborn ages. Multiple exposures seem to be more of a problem than a one time exposure. In terms of behavior or histological findings – multiple exposures remain more of a problem. Funding organizations are most interested in studies that focus research on long-term behavior changes rather than immediate histological changes.
In terms of clinical studies Dr. Suresh then reviewed all of the clinical data that is available on the topic, and it is not consistent. Data from the Mayo Clinic showed that multiple exposures to anesthesia are the problem – not single exposure. New York state data revealed that odds ratio of developing a learning disorder was significantly greater for those who received multiple anesthetics. A study from the Netherlands in twins found no difference in outcome in twins where one received anesthesia and the other did not – regardless of age of exposure. A Danish study of children undergoing hernia repair showed no difference in academic performance in adolescence for patients who received anesthesia in infancy. An Australian study looking at neuropsych testing, after young exposure to anesthesia, found no difference in late academic performance.
Dr. Suresh also reviewed the general anesthesia vs. spinal anesthesia study and the lack of findings regarding neuropsych problems at two years after the exposure or non-exposure of newborns to general anesthesia. He also reviewed data from the PANDA study that looked at the performance prospectively after anesthesia in twins – no findings of neurocognitive effect.
Dr. Suresh summarized with the point that the most concern for neurocognitive injury is implicated for patients who have long duration or multiple exposures to anesthesia.
He reviewed upcoming studies – particularly looking at dexmedetomidine as a potentially protective medication. He noted that data on dexmedetomidine at this point is not uniform – variability in outcomes exist.
Dr. Suresh concluded by noting that we are still trying to figure out the best strategies for applying preclinical data to clinical issues. Stay tuned.