Parents and clinicians are often faced with an important question: is anesthesia safe for young children? In this episode, medical student Kaavya Gudapati is joined by Dr. Maria Valeria Carrasquero and Dr. Ana Mavarez to review the current evidence on anesthesia exposure and the developing brain, and to provide practical guidance for clinical decision-making and family counseling. Specifically, they will: Review the FDA warning regarding repeated or prolonged anesthesia exposure in children under 3 years of age Compare key findings from animal studies and human clinical trials Summarize major studies including PANDA, MASK, and GAS Discuss strategies for counseling families and addressing parental concerns Identify considerations for timing of elective versus urgent procedures Review approaches to minimize exposure and explore potential neuroprotective strategies Special thanks to Dr. Heather Byrd and Dr. Rebecca Yang for peer reviewing this episode. CME available free with sign up: Link coming soon! References: 1. Vinson AE, Houck CS. Neurotoxicity of Anesthesia in Children: Prevention and Treatment. Curr Treat Options Neurol 2018; 20:1–10. https://doi.org/10.1007/S11940-018-0536-Z/TABLES/1. 2. Hansen TG. Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children. Pediatric Anesthesia 2015; 25:65–72. https://doi.org/10.1111/PAN.12548. 3. O’Leary JD. Human Studies of Anesthesia-Related Neurotoxicity in Children: A Narrative Review of Recent Additions to the Clinical Literature. Clin Perinatol 2019; 46:637–45. https://doi.org/10.1016/j.clp.2019.08.001. 4. FDA Drug Safety Communication: FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women | FDA n.d. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-review-results-new-warnings-about-using-general-anesthetics-and (accessed August 28, 2025). 5. FDA Drug Safety Communication: FDA approves label changes for use of general anesthetic and sedation drugs in young children | FDA n.d. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-approves-label-changes-use-general-anesthetic-and-sedation-drugs (accessed August 28, 2025). 6. SmartTots. SmartTots consensus statement on the use of anesthetic and sedative drugs in infants and toddlers.Published 2015. Updated 2017. Accessed September 17, 2025. https://smarttots.org 7. Sun LS, Li G, Miller TLK, Salorio C, Byrne MW, Bellinger DC, et al. Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA - Journal of the American Medical Association 2016; 315:2312–20. https://doi.org/10.1001/JAMA.2016.6967. 8. Warner DO, Zaccariello MJ, Katusic SK, Schroeder DR, Hanson AC, Schulte PJ, et al. Neuropsychological and behavioral outcomes after exposure of young children to procedures requiring general anesthesia: The mayo anesthesia safety in kids (MASK) study. Anesthesiology 2018; 129:89–105. https://doi.org/10.1097/ALN.0000000000002232. 9. McCann ME, Berde C, Soriano S, Marmor J, Bellinger D, de Graaff JC, et al. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicenter, randomised controlled equivalence trial. Lancet 2019; 393:664. https://doi.org/10.1016/S0140-6736(18)32485-1. 10. Davidson AJ, Disma N, de Graaff JC, Withington DE, Dorris L, Bell G, et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): An international multicentre, randomised controlled trial. The Lancet 2016; 387:239–50. https://doi.org/10.1016/S0140-6736(15)00608-X. 11. Reighard C, Junaid S, Jackson WM, Arif A, Waddington H, Whitehouse AJO, et al. Anesthetic Exposure During Childhood and Neurodevelopmental Outcomes: A Systematic Review and Meta-analysis. JAMA Netw Open 2022;5: e2217427. https://doi.org/10.1001/JAMANETWORKOPEN.2022.17427. 12. Jadhav U, Bhanushali J, Sindhu A, Shiv Kiran Reddy B, Toshniwal A, Rashmika M. A Comprehensive Review of Pediatric Obstructive Sleep Apnea: From Assessment to Intervention 2025. https://doi.org/10.7759/cureus.78051. 13. Andropoulos DB. Neuroprotective strategies in anesthesia-induced neurotoxicity. Best Pract Res Clin Anaesthesiol 2023; 37:52–62. https://doi.org/10.1016/J.BPA.2022.11.005. 14. Ji F, Sun J, Sun L, et al. Effects of Dexmedetomidine and Remifentanil on Neurodevelopmental Outcomes After Sevoflurane Anesthesia in Infants: A Randomized Clinical Trial. Anesthesiology. 2025. 143(4), 827–834. https://doi.org/10.1097/ALN.0000000000005634 15. Saynhalath, R, Disma, N, Taverner, FJ et al. on behalf of the TREX (Trial Remifentanil DEXmedetomidine) Consortium. Short-term Outcomes in Infants after General Anesthesia with Low-dose Sevoflurane/Dexmedetomidine/Remifentanil versus Standard-dose Sevoflurane (the TREX Trial). Anesthesiology 141(6): p 1075-1085, December 2024. | DOI: 10.1097/ALN.0000000000005232 16. Ing C, Warner DO, Sun LS, Flick RP, Davidson AJ, Vutskits L, McCann ME, O'Leary J, Bellinger DC, Rauh V, Orser BA, Suresh S, Andropoulos DB. Anesthesia and Developing Brains: Unanswered Questions and Proposed Paths Forward. Anesthesiology. 2022 Mar 1;136(3):500-512. doi: 10.1097/ALN.0000000000004116. PMID: 35015802.