Research and GrantsResearch Priorities | Grants | SmartTots Funded Studies | Related Research Projects
Anesthesia Use in Children: Concerns and the Need for Research
For several years the FDA’s National Center for Toxicological Research (NCTR), as well as investigators at several universities, have been conducting research to study the effects of anesthetics on the nervous systems of developing animals. This research continues to demonstrate that exposure to some anesthetics and sedatives cause memory and learning difficulties and other harmful changes in the central nervous systems of some laboratory animals. Currently, inadequate data exist to prove or disprove whether similar effects occur in children. SmartTots was launched to facilitate and support studies of existing anesthetic drugs and their effects on childhood development, as well as the impact of drug type, dosage amounts and number of exposures. Information from these research studies will help to determine if particular anesthetic drugs pose hazards to young children, to design the safest anesthetic regimens (dose and duration), and potentially foster the development of new anesthetic drugs. The early research in animals has raised concerns about some anesthetic drugs. Further investigation is needed to determine if there is a risk to infants and children, particularly those younger than four years of age. To date, although research is ongoing, the results are not yet conclusive. Dangers to infants and children from anesthesia are still unproven at this point. More research is needed and SmartTots seeks to facilitate the funding of well controlled clinical studies that will ultimately yield definitive answers.
Insufficient human data currently exist to determine whether anesthetics induce neurotoxicity in the developing brain. Current research is focused on determining whether volatile anesthetics administered during periods of rapid brain growth are neurotoxic to the developing human brain, and whether they cause long-term difficulties in learning and behavior. Thus far, implicated anesthetic agents include NMDA receptor antagonists, such as ketamine, and GABA agonists, such as sevoflurane.
Key Research Questions
As determined by our Scientific Advisory Board, SmartTots will fund research focused primarily on three fundamental areas:
- What is the spectrum of general anesthetic agents, sedatives, surgical procedures, and/or opiates that cause developmental neurotoxicity? What are the doses, durations, and frequencies of exposure? What are the most vulnerable periods of development?
- Are there short- and long-term neurocognitive, emotional, behavioral, and/or social outcomes resulting from exposure to anesthetic agents?
- What approaches can be taken to prevent or mitigate developmental anesthetic neurotoxicity?
Related Research Projects
Oregon Health & Science University: Ansgar Brambrink, MD, PhD National Center for Toxicological Research (NCTR) Pediatric Anesthesia NeuroDevelopment Assessment (PANDA Study) Mayo Clinic Research: MASK (Mayo Safety in Kids) Study GAS Study
Oregon Health & Science University: Ansgar Brambrink, MD, PhD
Project: Long-Term Outcome of Single vs. Triple Anesthesia Exposure of Infant Monkeys Dr. Brambrink proposes using their newly established infant non-human primate (NHP) model to simulate the human condition of general anesthesia in a highly controlled environment and, supported by a team of expert neuroscientists at the Oregon National Primate Research Center, will investigate long-term functional and morphologic consequences of single vs. triple anesthesia exposure of infant NHPs. Dr. Brambrink’s study is supported by the IARS Frontiers in Anesthesia Research Award. Related Publications:
National Center for Toxicological Research (NCTR)
Pediatric Anesthesia NeuroDevelopment Assessment (PANDA Study)
- Report of the third PANDA symposium on “Anesthesia and Neurodevelopment in Children”
- Feasibility and pilot study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project
- Pediatric anesthesia and neurodevelopmental impairments: a Bayesian meta-analysis
- Long-term Differences in Language and Cognitive Function After Childhood Exposure to Anesthesia
Mayo Clinic Research: MASK (Mayo Safety in Kids) Study
Additional grant opportunities will be announced as funding becomes available.
Grants and Funded Studies
2013 Research Grants Recipients
Lena Sun, MD - $200,000 Grant
Columbia University Medical Center Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) Study Dr. Lena S. Sun, E.M. Papper Professor of Pediatric Anesthesiology, Professor of Anesthesiology & Pediatrics and Chief of Division of Pediatric Anesthesiology at Columbia University Medical Center, leads the effort as the Principal Investigator of the multi-site PANDA (Pediatric Anesthesia and Neuro-Development Assessment) study to pursue the important research question of whether anesthetic exposure has detrimental effects in the developing human brain. SmartTots funding is supporting the completion of this ongoing study on the effects of a single episode of early childhood anesthesia exposure before age 3 years on long-term neurocognitive function and behavior in healthy children. The PANDA study will provide the first set of neurocognitive and behavior data in healthy children that are prospectively collected and directly assessed. The study is expected to provide the needed evidence for informed discussions with providers and parents as well as guidance for clinical decision-making. Update: In early 2015 Dr. Sun reported having successfully recruited 117 sibling pairs to participate in the study. She also obtained 23 completed anesthesia records in the exposed cohort to analyze whether low-flow versus high-flow sevoflurane anesthesia (based on fresh gas flow relative to minute ventilation) is associated with differences in results of neurocognitive testing. It is anticipated that the study will be complete and results reported by June 2016.
Jeffrey Sall, PhD, MD - $200,000 Grant
Jeffrey Sall, PhD, MD – $200,000 Grant
University of California San Francisco Recognition Memory Following Early Childhood Anesthesia Dr. Jeffrey Sall, Hamilton Associate Professor at UCSF School of Medicine, Department of Anesthesia and Perioperative Care, is utilizing the SmartTots grant funding to conduct a research study which is examining the limits or boundary conditions of early childhood anesthesia exposure that lead to cognitive deficits. This project will determine how the duration of anesthesia exposure and the age of the child at the time of exposure affect recognition memory deficits.
Update: During 2015, the study was more than 50% complete and continuing to make progress, actively partnering with academic centers around the country to recruit and test subjects. Once complete, the results will provide guidance to clinicians and parents when deciding to perform certain procedures and will give future researchers an important outcome measure that is easily testable.
Robert Block, PhD - $100,000 Grant
Prior Funded Studies
2012 Research Grants Recipients
Robert Block, PhD – $100,000 Grant
University of Iowa, Iowa City, Iowa General Anesthesia During Human Infancy and Brain Development Dr. Block aimed to evaluate the hypothesis that exposure to general anesthesia and surgery during infancy affects brain and cognitive development as reflected in measures of brain tissue volume and composition and white matter integrity, memory-related regional brain activation, and cognitive test performance. Adolescents who were exposed to anesthesia during infancy are compared to unexposed, but otherwise matched, control subjects. Patients will have been exposed to anesthesia during operations that would not normally, in themselves, be associated with subsequent central nervous system problems or risk factors; and both patients and controls will be individuals in whom no such problems or risk factors during infancy can be identified. Update: By the middle of 2014, Dr. Block’s study analysis found that there were lower white matter volumes and diminished white matter integrity in patients, relative to controls. He also reported finding trends toward differences in brain activity associated with long-term memory and working memory processes in patients, relative to controls. Dr. Block intends to complete the analyses of the present study, publish the results, and seek funding from NIH for a substantially larger-scale study to replicate and extend the results. His new research would involve studying more patients with a broader age range of exposure to anesthesia and comparing patients who were exposed for more vs. less invasive procedures, in addition to unexposed controls.
Caleb Ing, MD - $100,000 Grant
Columbia University Medical Center, New York, New York Anesthetic Exposure Duration and Effects on Cognitive and Language Ability Dr. Ing and colleagues are conducting research to determine the relationship between anesthetic exposure before the age of three and long-term neurocognitive deficits using a battery of directly administered neuropsychological assessments. The results of this study will help determine the association between anesthetic exposure and long-term deficits. This will be a critical piece of information that will help parents and physicians weigh the risks and benefits of exposure to anesthesia and whether to delay certain types of elective surgery. Update: As of March 2015, Dr. Ing and team reported two important research findings, they determined that in their cohort, specific neuropsychological outcome measures related to language and abstract reasoning were able to determine differences in children exposed to anesthesia, while academic achievement tests could not. His team was also able to determine that initial exposure to anesthesia after age 3 had no measurable effects on language and abstract reasoning, suggesting that there may be distinct windows of vulnerability for different neurodevelopmental domains in children.
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