Behind the Black Box: The Evidence for the U.S. Food and Drug Administration Warning about the Risk of General Anesthesia in Children Younger than 3 Years.

On December 14, 2016, the U.S. Food and Drug Administration issued a Drug Safety Communication warning "that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children's brains." Health care professionals were urged to "balance the benefits of appropriate anesthesia in young children and pregnant women against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required in children under 3 years." Surgeons must have an understanding of the evidence that led to the U.S. Food and Drug Administration warning and recommendations to appropriately weigh these risks and counsel their patients. In this article, the authors summarize the preclinical and clinical data that led to the U.S. Food and Drug Administration warning, discuss ongoing clinical studies, and provide strategies to reduce the risk of general anesthesia in patients younger than 3 years.