Anesthetic-related neurotoxicity and the developing brain: shall we change practice?

Millions of human infants receive general anesthetics for surgery or diagnostic procedures every year worldwide, and there is a growing inquietude regarding the safety of these drugs for the developing brain. In fact, accumulating experimental evidence together with recent epidemiologic observations suggest that general anesthetics might exert undesirable effects on the immature nervous system. The goal of this review is to highlight basic science issues as well as to critically present experimental data and clinical observations relevant to this possibility. By acting on a plethora of ligand-gated ion channels, general anesthetics are powerful modulators of neural activity. Since even brief interference with physiologic activity patterns during critical periods of development are known to induce permanent alterations in brain circuitry, anesthetic-induced interference with brain development is highly plausible. In line with this hypothesis, compelling experimental evidence, from rodents to primates, suggests increased neuroapoptosis and associated long-term neurocognitive deficits following administration of these drugs at defined stages of development. Recent epidemiologic studies also indicate a potential association between anesthesia/surgery and subsequently impaired neurocognitive function in humans. It is, however, important to note that extrapolation of experimental studies to human practice requires extreme caution, and that currently available human data are hindered by a large number of potentially confounding factors. Thus, despite significant advances in the field, there is still insufficient evidence to determine whether anesthetics are harmful to the developing human brain. Consequently, no change in clinical practice can be recommended.