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

Abstract

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.

A Cohort Study of Strabismus Rates Following Correction of the Unicoronal Craniosynostosis Deformity: Conventional Bilateral Fronto-Orbital Advancement Versus Fronto-Orbital Distraction Osteogenesis

“…FODO's shorter operative time, even with addition of the second procedure for device removal, represents an advantage given the recent trend towards decreasing anesthetic exposure during the first several years of life. 12 It was also associated with less estimated blood loss, and lower blood product transfusion with a trend toward a decrease in hospital stay. Fronto-orbital distraction osteogenesis mediated reconstruction allows surgery to be performed at an earlier age which may be beneficial in order to ameliorate issues associated with increased intracranial pressure, including the poorly understood effects it may have on neuropsychological outcomes.…”

“…The data presented in this study supports a favorable perioperative profile for the correction of UCS with both treatment modalities. FODO's shorter operative time, even with addition of the second procedure for device removal, represents an advantage given the recent trend towards decreasing anesthetic exposure during the first several years of life 12 . It was also associated with less estimated blood loss, and lower blood product transfusion with a trend toward a decrease in hospital stay.…”

Comparing Results of Syndactyly Operated Children Younger and Older Than 1 Year

“…Since the late 1990s, different studies correlating anesthetics with neurotoxicity and neurocognitive sequelae in animal models have been carried out. 13 Data obtained in animal and in vitro studies showed that under experimental conditions, all general anesthetics, including γ-aminobutyric acid agonists and N-methyl-D-aspartate antagonists, have immediate neuroanatomical consequences, 14 such as apoptotic neurodegeneration. 15 However, extrapolating animal research results to humans is still a challenge.…”

“…Patients with syndactyly usually require surgical intervention at an early age, and much is discussed about the potential implications of exposure to anesthetic agents in childhood. Since the late 1990s, different studies correlating anesthetics with neurotoxicity and neurocognitive sequelae in animal models have been carried out 13 . Data obtained in animal and in vitro studies showed that under experimental conditions, all general anesthetics, including γ-aminobutyric acid agonists and N -methyl- d -aspartate antagonists, have immediate neuroanatomical consequences, 14 such as apoptotic neurodegeneration 15 .…”

Pediatric eosinophilic esophagitis: a review for the clinician

“…Researchers have focused on the development of less invasive tools to evaluate esophagus inflammation, since upper endoscopy is an invasive and expensive procedure, even requiring general anesthesia in children and conscious sedation in most adult patients. Moreover, in 2016, the Food and Drug Administration issued a safety warning states 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”, caused increase concerns over anesthetic exposure at a young age leading to anesthetic-induced neurotoxicity [ 99 , 100 ]. Since then, more caution has been used to do repeated EGD under anesthesia.…”