N Engl J Med 2011 (DOI: 10.1056/NEJMp1102155, published in March 2011)

 

Link for fulltext: www.nejm.org/doi/full/10.1056/NEJMp1102155

 

 

Anesthetic agents are commonly used for a variety of medical procedures in infants and children, but little is known about their effects on the developing brain. A growing body of data from studies in animals suggests that under certain circumstances, such as prolonged anesthesia, these drugs could adversely affect neurologic, cognitive, and social development of neonates and young children. We believe that these findings should be of concern to the scientific and medical communities.

Over the past decade, studies in rodents have found that exposure to anesthetic agents during sensitive periods of brain development (i.e., the brain growth spurt) results in widespread neuronal apoptosis and functional deficits later in development. So far, agents that either antagonize N-methyl-D-aspartate (NMDA) receptors or potentiate the neurotransmission of γ-aminobutyric acid (GABAergic agents) have been implicated, and no safe doses of these agents or safe durations of administration have been defined.

More recent investigations in nonhuman primates have extended these findings. Studies conducted by the National Center for Toxicology Research (NCTR) of the Food and Drug Administration (FDA) have demonstrated that exposure to ketamine — the prototypical NMDA-receptor antagonist — resulted in increased neuronal cell death in nonhuman primates.