Anesthetic-Induced Developmental Neurotoxicity: Cognitive Sequelae of Early Exposure

Preclinical studies showing widespread neuronal apoptosis and long-term behavioral deficits when exposed to common anesthetics raised concerns for anesthetic-induced neurotoxicity in pediatric patients during periods of rapid synaptogenesis. N-methyl-D-aspartate receptor antagonists have been shown in animal studies to disrupt activity-dependent plasticity, hinder mitochondrial function, and induce epigenetic dysfunction. These studies have led to regulatory warnings and investigation into the potential long-term cognitive and neurodevelopmental consequences in children who have been exposed to anesthesia before the age of three. Human data, including cohort studies and randomized controlled trials, such as the General Anesthesia versus Spinal Anesthesia trial and the Pediatric Anesthesia Neurodevelopmental Assessment studies have found that a single, brief, exposure to anesthesia in infancy is not associated with any measurable deficits in intelligence. However, multiple, prolonged exposures can be associated with dysfunctions in learning, behavior, and social communication but remains a question due to confounding variables across studies. The current literature does not support the delay of medically necessary procedures in pediatric populations due to potential anesthetic toxicity. Continuing research aims to delineate mechanisms of injury, identify vulnerable populations, and develop mitigation strategies such as alternative agents and neuroprotective adjuvants.