Intended for healthcare professionals

Clinical Review State of the Art Review

Does general anesthesia affect neurodevelopment in infants and children?

BMJ 2019; 367 doi: (Published 09 December 2019) Cite this as: BMJ 2019;367:l6459
  1. Mary Ellen McCann, associate professor of anesthesia (pediatrics), senior associate in anesthesiology12,
  2. Sulpicio G Soriano, professor of anesthesia, endowed chair in pediatric neuroanesthesia12
  1. 1Department of Anesthesia, Harvard Medical School, Boston, MA, USA
  2. 2Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, MA, USA
  1. Correspondence to S Soriano Sulpicio.Soriano{at}


General anesthesia has been unequivocally linked to abnormal development of the central nervous system, leading to neurocognitive impairments in laboratory models. In vitro and in vivo studies have consistently shown that exposure to GABA agonists (eg, volatile anesthetics, midazolam, and propofol) or NMDA antagonists (eg, ketamine, isoflurane, and nitrous oxide) produces dose dependent and developmental age dependent effects on various neuronal transmission systems. Exposure to these drugs increases neuronal cell death in juvenile animals including rats, mice, and non-human primates. The possibility of anesthetic induced neurotoxicity occurring in children has led to concerns about the safety of pediatric anesthesia. A spectrum of behavioral changes has been documented after general anesthetic exposure in young children, including emergence delirium, which may be evidence of toxicity. Most clinical studies are retrospective; specifics about medications or monitoring are unavailable and many of the outcomes may not be sensitive to detect small neurocognitive deficits. Some of these retrospective studies have shown an association between anesthesia exposure at a young age and neurocognitive deficits, but others have not. Practitioners and families should be reassured that although general anesthetics have the potential to induce neurotoxicity, very little clinical evidence exists to support this.


  • Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors

  • Contributorship statement MEM and SGS contributed equally to the conception, design, interpretation, drafting, and revising the manuscript and approving the final version.

  • Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none.

  • Further details of The BMJ policy on financial interests are here:

  • Provenance and peer review: commissioned; externally peer reviewed.

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