Laboratory animals exposed to most anesthetic and sedative drugs early in life show changes to the brain and nervous system that can interfere with memory and learning. There is not enough data to support or refute the possibility that similar effects could occur in young children exposed to anesthetics. This project will advance the knowledge and understanding of the effects of anesthetics on the developing brain through a series of preclinical studies, the results of which will ultimately inform the design of one or more major clinical trials. It will also provide a steady stream of information for healthcare providers and the public on new developments and research findings in this area and the implications for clinical practice and public health. The project is designed to accomplish the following objectives: (1) Provide the administrative, management, and strategic support for the SmartTots Public-Private Partnership (PPP) to assist the FDA and its stakeholders in achieving the goals of the Pediatric Anesthesia Safety Initiative (PASI). (2) Provide the scientific infrastructure and expert support for the creation and execution of a series of projects under the SmartTots PPP aligned with achieving the goals of the PASI. (3) Determine the research direction, identify the preclinical and clinical endpoints, contract for, and oversee a series of studies to advance the preclinical and clinical knowledge about the effects of anesthetics and sedatives on the developing brain. (4) Coordinate the translation of research outcomes for future studies, clinical practice, and an understanding of the implications for public health.
Non-clinical studies in juvenile animal models have demonstrated an association of exposure to some anesthetics and sedatives with memory and learning deficits and other neurodegenerative changes in the central nervous system. Insufficient human data exist to support or refute the possibility that similar effects could occur in children. Two recent studies provide reassurance that a single, short- duration exposure may be safe for young children, but many young children who receive anesthesia don't fall into the categories addressed by those studies. Additional well-designed studies are needed to determine whether the animal findings are applicable to children. Approximately 2 million children in the United States younger than 5 years undergo general anesthesia/deep sedation each year. Any potential neurocognitive risks from pediatric anesthesia present a major public health issue. This project will advance the knowledge in this area and provide much-needed information for healthcare providers and the public.
