Anesthetic neurotoxicity in the newborn and infant

Purpose of review: Every year, millions of children undergo anesthesia. Emerging evidence from experimental in-vitro and in-vivo models supports a role for neuropathologic injury and neurobehavioral deficits at older age after early exposure to various anesthetic regimens. Clinical studies have sought to identify a phenotype of developmental anesthesia neurotoxicity in humans, but the current evidence is limited to data from retrospective studies with their associated confounders. Experimental models have been used to further define the injury and to help identify potential mechanisms of this neurotoxicity. Recent findings: A recent clinical trial from an Australian birth cohort suggests a single anesthesia exposure as a neonate or infant may increase the risk for language and abstract reasoning deficits later in life, though residual data confounders may remain. Several ongoing clinical trials like Mayo Safety in Kids, Pediatric Anesthesia NeuroDevelopment Assessment, and General Anesthesia and Apoptosis Study will likely offer more clear answers in the future. In the interim, experimental models have described roles for neuroinflammation, mitochondrial damage from reactive oxygen species, and the presence of several neuronal morphology changes from anesthesia exposure. Additionally, several potential neuroprotective agents and strategies have been tested in the laboratory. Summary: Whether anesthesia-associated neurotoxicity affects the developing human brain and whether this leads to clinically measurable deficits remains unclear.