Studies in animal models provide compelling evidence that commonly used anesthetic agents (e.g., isoflurane, midazolam, nitrous oxide) enhance neuronal cell death in the immature brain, in some studies at doses lower than those required to achieve a surgical plane of anesthesia. The clinical implications of these data are controversial. Some observational studies suggest worse neurodevelopmental outcomes among children exposed to anesthetic agents in infancy, but the optimal study design for addressing this question is a randomized trial due to the potential biases inherent in observational studies. With collaborators in Australia/New Zealand, Europe, Canada, and at 9 other sites in the U.S., we are conducting a prospective, multi-site, randomized, controlled, equivalence trial comparing children’s neurodevelopment following receipt of general or regional awake anesthesia for inguinal herniorrhaphy, The primary hypothesis is that Full-Scale IQ at 5 years of age is equivalent in children who received general anesthesia or regional awake anesthesia. Secondary endpoints include scores on assessments of memory/learning, language, attention/executive functions, visuospatial skills, social perception, and processing speed. Equivalence will be accepted if the 2-sided 95% confidence interval of the adjusted treatment group difference in mean Full-Scale IQ lies within -5 and +5 points.
