Anesthesia and Neurodevelopment in Children

Abstract

RECENT animal studies have suggested that anesthetics may be toxic to the immature developing brain.1–3 In rodents, γ-aminobutyric acid receptor agonists and N -methyl-d-aspartic acid receptor antagonists, including ketamine, isoflurane, midazolam, and nitrous oxide, induce dose- and age-dependent neuronal apoptosis and neuronal cell death in vitro ,1,2 with the most prominent effects being observed at postnatal day 7, which interestingly is also the peak period for synaptogenesis. Ketamine produces similar age- and dose-dependent neurotoxicity in nonhuman primates.3 Alarmingly, these in vitro findings were shown to have long-term functional consequences resulting in deficits in memory, learning, attention, and motor function in adult rats after neonatal exposure to anesthetics.2 Comparable data are not yet available in nonhuman primates. Although the dose and duration of anesthetic exposure used in most laboratory studies are substantially higher than those used in children, these findings are nevertheless of serious concern.4,5 Moreover, recent work indicates that neurotoxicity could indeed occur with doses within the human range.6