An assessment of the effects of general anesthetics on developing brain structure and neurocognitive function

Anesth Analg. 2008 Jun;106(6):1681-707. doi: 10.1213/ane.0b013e318167ad77.


Background: Neuronal cell death after general anesthesia has recently been documented in several immature animal models. Worldwide, volatile anesthetics are used in millions of young children every year during surgical procedures and imaging studies. The possibility of anesthesia-induced neurotoxicity during an uneventful anesthetic in neonates or infants has led to serious questions about the safety of pediatric anesthesia. However, the applicability of animal data to clinical anesthesia practice remains uncertain. In the present review, we assess the evidence for the effects of commonly used anesthetics on neuronal structure and neurocognitive function in newborn humans and animals.

Methods: Medical databases, including Medline, Cinahl, and Pubmed, abstract listings of the American Society of Anesthesiologists, International Anesthesia Research Society, Society for Pediatric Anesthesia, and Society for Neuroscience Annual Meetings, and personal files were queried regarding anesthesia-induced neurotoxicity.

Results: A growing number of studies in immature animal models demonstrate degenerative effects of several anesthetics on neuronal structure. A few studies reveal cognitive impairment in adult animals after neonatal anesthesia. There are no prospective studies evaluating neurocognitive function in children after neonatal exposure to anesthetics. However, several retrospective reviews demonstrate temporary neurological sequelae after prolonged anesthetic exposure in young children and larger studies identify long-term neurodevelopmental impairment after neonatal surgery and anesthesia.

Conclusions: The evidence for anesthesia-induced neurodegeneration in animal models is compelling. Although this phenomenon has not been prospectively studied in young children, anecdotal data point toward the possibility for neurological impairment after surgery and anesthesia early in life. Given the serious implications for public health, further investigations of this phenomenon are imperative, both in laboratory animals and in young children.

Publication types

  • Review

MeSH terms

  • Anesthetics, General / toxicity*
  • Animals
  • Animals, Newborn
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Brain / growth & development
  • Brain / pathology
  • Cell Death / drug effects
  • Child Behavior / drug effects
  • Child, Preschool
  • Cognition / drug effects*
  • Disease Models, Animal
  • Evidence-Based Medicine
  • Humans
  • Infant
  • Infant, Newborn
  • Neurons / drug effects*
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Risk Assessment
  • Species Specificity


  • Anesthetics, General
  • Neuroprotective Agents