Pediatric Anesthesia and Neurodevelopment

  • Wald, Samuel, MD, MBA, FASA
| Jun 13, 2011

The US Food and Drug Administration is examining the evidence concerning the effect of anesthetic agents on the developing brain. Data from animal and human studies may indicate a link between anesthetic exposure and behavioral/cognitive deficits, but not yet with conclusive evidence. Exposure in animals to N-methyl-D-aspartate (NMDA) antagonists and gamma-Aminobuytric acid (GABA) agonists during critical stages of brain development induces apoptosis of neurons that may have long-term effects, but apoptosis does not definitely mean a learning deficit will later evolve. Even with a growing number of studies, the conclusions have not all been consistent. Some results have even led to conflicting conclusions, as is the case with the study of ketamine. The specifics (duration of exposure, agents, age window), and extent of the potential deficits (long versus short term), still require further exploration. According to most of the existing evidence, the harmful effects are related to the length of exposure.

There are even fewer human studies on this topic, and thus still less conclusive evidence at this time. Only a handful of studies have been published so far, with a number of collaborative research projects underway from multiple organizations, including Pediatric Anesthesia Neuro-Development Assessment (PANDA), The Effects of Anaesthesia on Neurodevelopmental Outcome and Apnoea in Infants (GAS), and SmartTots studies ( The retrospective data that we do have suggests that the risk of anesthesia in the developing brain may be increased in children three years and younger and potentially with multiple exposures. One problem with accurately interpreting the evidence is that many children who require anesthesia at a young age may have a confounding diagnosis such as prematurity. This makes it difficult to pinpoint the etiology of a later diagnosis of a learning or behavioral deficit. One of the most recent clinical studies compared a birth cohort in children who underwent hernia repair before age three. Children who had anesthesia and surgery, even once were twice as likely to be diagnosed later in life with a disorder of behavior or development.

What is certain is that parents will ask about the effects of anesthetics on their children. Traditionally, the risk benefit discussion has centered on the organ effects, ranging from short-term complications such as emergence delirium or sore throat and hypoxia, rather than neurocognitive ones and behavior disorders as the result of anesthesia exposure. Today, there is still no definitive evidence, and although we may wish to offer a better explanation, all that can be said is that it is still under investigation and that anesthesiologists across the globe are diligently working for an answer.  


DiMaggio C, Sun LS, Kakavoulu A, Byrne MW, Li G, A Retrospective Cohort Study of the Association of Anesthesia and Hernia Repair Surgery With Behavioral and developmental Disorders in Young Children, JNSA 2009;21:286-291.

Glass NL, Malvia S, Anesthesia in Children-Limitation of the Data on Neurotoxicity, NEJM, April 14, 2011;364(15)1466-1467.

Kuehn NM, FDA Considers Data on potential Risks of Anesthesia Use in Infants, Children, JAMA May 4, 2011;303(17):1749-1751.

Rappaport B, Mellon RD, Simone A, Woodcock J, Defining Safe Use of Anesthesia in Children, NEJM April 14, 2011;364(15):1387-1390.

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