Do Anesthetic Drugs Harm Neonates? A Global Perspective

There is still much to be discovered regarding the effects of anesthetics on the developing and immature human brain and the mechanisms behind this effect. Given that N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid A (GABA_A) receptors modulate brain development and growth, it is biologically plausible that if anesthetics, which exert their actions via these same receptors, are administered during the period of rapid brain development, they may adversely affect long-term neurocognitive development. Numerous studies in neonatal animals have demonstrated both short- and long-term neurological deficits. However, evidence from animals does not necessarily portend similar outcomes in humans. Moreover, neurocognitive outcome studies in humans have yielded conflicting evidence. Despite these results, repeated controversial and alarming statements that children who receive general anesthesia may sustain adverse neurological outcomes have been issued repeatedly by federal agencies based primarily on preclinical animal studies and weak human evidence. In the absence of alternatives to the current general anesthetics and the possible risks associated with delaying most surgeries, choosing which anesthetics are least likely to cause long-term neurocognitive outcomes in humans is a daunting challenge. Knowing that the underlying disease processes, surgical interventions, and trauma, as well as other perioperative factors, significantly impact the neurocognitive outcome, isolating the effects of anesthetics on these outcomes becomes even more challenging. Whether we can ever determine the effects of anesthetics themselves on neurocognitive outcomes in human infants and children remains before us.