As early as 1999, research began showing that general anesthetic drugs, once assumed to have no lasting effects after elimination from the body, may potentially impact brain development, prompting concerns about their safety in infants and young children. In response, the FDA partnered with the International Anesthesia Research Society to launch SmartTots, a 16-year public–private collaboration that unified researchers, funded key studies, and advanced understanding of pediatric anesthetic neurotoxicity. After hundreds of studies and multiple major clinical trials—including GAS, PANDA, and MASK—it was found that a single, brief exposure to anesthesia in early childhood is not associated with significant long-term cognitive harm, though uncertainties remain regarding multiple or prolonged exposures. Despite challenges such as limited funding, SmartTots successfully mobilized a global research community, informed FDA safety communications, and established a model for future collaborative efforts to address critical questions in anesthesiology.
Cooper, Thomas EJD; Rappaport, Bob A. MD; Orser, Beverley A. OOnt, MD, PhD, FRCPC, FCAHS, FRSC
Anesthesia & Analgesia December 2025