Developmental neurotoxicity of sedatives and anesthetics: a concern for neonatal and pediatric critical care medicine?

Objective: To evaluate the currently available evidence for the deleterious effects of sedatives and anesthetics on developing brain structure and neurocognitive function.
Design: A computerized, bibliographic search of the literature regarding neurodegenerative effects of sedatives and anesthetics in the developing brain.
Measurements and Main Results: A growing number of animal studies demonstrate widespread structural damage of the developing brain and long-lasting neurocognitive abnormalities after exposure to sedatives commonly used in neonatal and pediatric critical care medicine. These studies reveal a dose and exposure time dependence of neuronal cell death, characterize its molecular pathways, and suggest a potential early window of susceptibility in humans. Several clinical studies document neurologic abnormalities in neonatal intensive care unit graduates, usually attributed to comorbidities. Emerging human epidemiologic data, however, do not exclude prolonged or repetitive exposure to sedatives and anesthetics in early childhood as contributing factors to some of these abnormalities.
Conclusions: Neuronal cell death after neonatal exposure to sedatives and anesthetics has been clearly demonstrated in developing animal models. Although the relevance for human medicine remains speculative, the phenomenon's serious implications for public health necessitate further preclinical and clinical studies. Intensivists using sedatives and anesthetics in neonates and infants need to stay informed about this rapidly emerging field of research.