General anesthetics in children: neurotoxic or neuroprotective?

  • Jéssica Farias Rebouças
  • Gylmara Bezerra de Menezes Silveira
  • Maria de Fátima Vasques Monteiro
  • Sara Araújo de Morais
  • Hermes Melo Teixeira Batista


Introduction: general anesthetics are involved in neuroprotection in adults after ischemic events and cognitive impairment, thus, they also may be associated with learning disorders in children exposed to them before three years of age.

Objective: Describe about the neurotoxic effects of general anesthetics in experimental animals and children.

Method: This is a systematic review, performed from search in databases and on PubMed using the keywords "neurotoxicity" and "general anesthetics," and "general anesthetics," "neurotoxicity", "children", "young child "and" pediatric ".

Results: The search resulted in 185 articles. Out of these, 78 met our inclusion criteria. We found that there was a significant evidence of neurotoxicity induced by general anesthetics in experimental animals that were just born, resulting in late and permanent cognitive deficits. This effect was associated with multiple exposures, exposure length of time and combination of drugs. However, some studies found cognitive impairment after a single exposure to anesthetic.

Conclusion: There is insufficient evidence to state that general anesthetics are neurotoxic and have the potential to trigger learning and behavior disabilities in children. However, we suggest caution in indicating surgery in children under three years old, analyzing risk-benefit and inserting the family in the decision process.


Keywords: Neurotoxicity, Neuroprotection, Cognitive Impairment, Children, General Anesthesics





[1] Hudson AE, Hemmings Jr HC. Are anaesthetics toxic to the brain? British J of Anaesth. 2011;107(1):30-7
[2] Chiao S, Zuo Z. A double-Edge Sword: Volatile Anesthetic Effects on the Neonatal Brain. Brain Sci. 2014;4:273-94
[3] Viana JT. Tratado de Anestesiologia, SAESP. 7 ed. São Paulo: Editora Atheneu, 2011;(1)3-13
[4] Garcia PS, Kolesky SE, Jenkins A. General Anesthetic Actions on GABAA Receptors. Current Neuropharmacology, 2010.8:2-9
[5]. Bai X, Twaroski D, Bosnjak ZJ. Modeling anesthetic developmental neurotoxicity using human stem cells. Semin Cardiothorac. Vasc. Anesth. 2013;17(4)
[6] Davidson AJ. Anesthesia and neurotoxicity to the developing brain: the clinical relevance. Pediatric Anesth. 2010;21:716-21
[7] Jevtovic-Todorovic V, Absalom AR, Blomgren K, Brambrink A, Crosby G, Culley DJ, Fiskum G, Giffard RG, Herold KF, Loepke AW, Ma D, Orser BA, Planel E, Slikker Jr W, Soriano SG, Stratman G, Vutskits L, Xie Z and Hemmings Jr. HC. Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar. British J of Anaesth. 2013;11(2):143-51
[8] Silva AJ, Neves, LAT, Frônio JS, Ribeiro LC. Factors related to motor developmental delay of newborns. Journal of Human Growth and Development. 2014; 24(3):320-7
[9] Boutin C, Vachiéry-Lahaye F, Alonso S, Louart G, Bouju A, Lazarovici S, Perrigault PF, Capdevila X, Jaber S, Colson P, Jonquet O, Ripart J, Lefrant JY, Muller L. Anaesthetic management of brain-dead for organ donation: impact on delayed graft function after kidney transplantation. Ann Fr Anesth Reanim. 2012 ;31(5):427-36
[10] Batista HMT, Silveira GBM, Sampaio LA, Araújo MFG, Ferreira NAS, Bezerra IMP, Rolim MMM, Valenti VE, Benevides BS, Abreu LC. Are General anesthetics neurotoxic?. International Archives of Medicine. 2015;8(53):1-7
[11] Hofacer RD, Deng M, Ward CG, Joseph B, Hughes EA, Jiang C, Danzer SC, Loepke AW. Cell Age-Specific Vulnerability of Neurons to Anesthetic Toxicity. Annals of Neurology. 2013.
[12] Lei X, Guo Q, Zhang J. Mechanistic Insights into Neurotoxicity Induced by Anesthetics in the Developing Brain. Int. J. Mol. Sci. 2012;13:6772-99
[13] Wei H. The Role of Calcium Dysregulation in Anesthetic-Mediated Neurotoxicity. Anesth Analg. 2011;113(5):972-4
[14] Pearn ML, Hu Y, Niesman IR, Patel HH, Drummond JC, Roth DM, Akassoglou K, Patel PM, Head BP. Propofol Neurotoxicity is Mediated by p75 Neurotrophin Receptor Activation. Anesthesiology . 2012;116(2):352-61
[15] Reddy SV. Effect of general anesthetics on the developing brain. J Anaesth. Clin Pharmacol. 2012;28(1):6-10
[16] Sanders RD, Hassell J, Davidson AJ, Robertson NJ, Ma D. Impact of anaesthetics and surgery on neurodevelopment: an update. British J. of Anaesth. 2013;110(s1):i53-i72
[17] Lin EP, Soriano SG, Loepke AW. Anesthetic Neurotoxicity. Anesthesiology Clin. 2014;32:133-55
[18] Gomez VRV, Bazon MR. Association between child maltreatment indicators and developmental problems in early childhood education. Journal of Human Growth and Development. 2014;24(2):214-20
[19] Bittner EA. Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer's disease. Can J Anaesth. 2011;58(2):216-23
[20] Deng M, Hofacer RD, Jiang C, Joseph B, Hughes EA, Jia B, Danzer SC, Loepke AW. Brain regional vulnerability to anaesthesia-induced neuroapoptosis shifts with age at exposure and extends into adulthood for some regions. British J. of Anaesth. 2014;15
[21] Stratmann G. Neurotoxicity of Anesthetic Drugs in the Developing Brain. Anesth Analg. 2011;113(5):1170-9
[22] Ward CG, Loepke AW. Anesthetics and sedatives:Toxic or protective for the developing brain? Pharmacol. Res. 2012;65:271-4
[23] Pinheiro RC, Martinez CMS, Fontaine AMGV. Visual motor integration and overall cevelopment of preterm and at term children at the beginning of schooling. Journal of human Growth and Development. 2014;24(2):181-7
[24] Zhu C, Gao J, Karlsson N, Li Q, Zhang Y, Huang Z, Li H, Kuhn HG, Blomgren K. Isoflurane anesthesia induced persistent, progressive memory impairment, caused a loss of neural stem cells, and reduced neurogenesis in young, but not adult, rodents. J. of Cereb. Blood Flow Met. 2010; 30:1017-30
[25] Li J, Xiong M, Nadavaluru PR, Zuo W, Ye JH, Eloy JD, Bekker A. Dexmedetomidine attenuates Neurotoxicity Induced by Prenatal Propofol Exposure. J Neurosurg Anesthesiol. 2015;
[26] Ma D, Rajakumaraswamy N, Maze M. α2-Adrenoceptor agonists: shedding light on neuroprotection? British Med Bul. 2005;71:77-92
[27] Yoles E, Wheeler LA, Schwartz M. α2-Adrenoceptor agonists Are Neuroprotective in a Rat Model of Opitc Nerve Degeneration. Invest. Opht Vis of Science. 1999;40(1):65-73
[28] Amrock LG, Starner ML, Murphy KL, Baxter MG. Long-term Effects of Single of Multiple Neonatal Sevoflurane Exposures on Rat Hippocampal Ultrastructure. Anesthesiology. 2015;122(1):87-95
[29] Ramsay JG, Roizen M. SmartTots: a public-private partneship between the United States Food and Drug Administration (FDA) and the International Anesthesia Research Society (IARS). Pediatric Anesthesia 2012;22:969-72
How to Cite
FARIAS REBOUÇAS, Jéssica et al. General anesthetics in children: neurotoxic or neuroprotective?. International Archives of Medicine, [S.l.], v. 10, feb. 2017. ISSN 1755-7682. Available at: <>. Date accessed: 29 june 2017. doi:
Anesthesiology & Emergency Medicine