Preliminary results from a randomized clinical trial suggest that brief exposure to inhaled anesthesia during surgery does not cause adverse short-term neurodevelopmental effects in infants and young children, according to findings published in Anesthesiology.¹

The study, led by Ji-Hyun Lee, MD, PhD, of Seoul National University Hospital, evaluated 400 children under 2 years of age who underwent surgery lasting less than 90 minutes. Participants were randomly assigned to receive either sevoflurane alone or a “balanced” regimen designed to lower sevoflurane exposure through the addition of intravenous dexmedetomidine and remifentanil.

In a written Q+A with Contemporary Pediatrics, study author Ji-Hyun Lee, MD, PhD, explains findings and implications of the study. For coverage of just the study make-up, outcomes, and results, click here.

Q+A with Ji-Hyun Lee, MD, PhD

Contemporary Pediatrics:

Can you explain the background of your study evaluating neurodevelopmental effects after inhaled anesthesia and surgery in infants and young children?

Lee:

Concerns about anesthetic effects on the developing brain arose from animal studies showing potential long-term neurotoxicity. Yet, clinical evidence in children has been mixed, and randomized data remain limited. Parents frequently ask whether general anesthesia is safe and whether it could affect their child’s intelligence, but there has been little evidence to guide us on which anesthetic regimen might be more favorable when general anesthesia is required.

We therefore conducted a prospective, double-blind, randomized trial including 400 children under 2 years of age, of whom 343 completed neurodevelopmental assessments. Children were randomized to receive sevoflurane alone or sevoflurane with dexmedetomidine and remifentanil.

The primary outcome is full-scale IQ at age 5 years, which is ongoing. This interim report presents secondary outcomes at 28–30 months, and our findings showed no significant differences in cognitive, behavioral, or language outcomes, despite a 30% reduction in sevoflurane exposure in the dexmedetomidine–remifentanil group.

Contemporary Pediatrics:

How important was it to get updated data on this potential association?

Lee:

This question matters greatly because millions of children worldwide require anesthesia each year, and families and clinicians need reliable evidence to guide decisions. Earlier studies such as PANDA², MASK³, and GAS⁴ were reassuring, but each had limitations, either comparing exposed versus unexposed children, or general versus regional anesthesia—approaches that do not reflect everyday pediatric surgical practice.

Our trial was designed to provide more clinically-relevant evidence by testing whether modifying a standard inhalation technique, with adjunct agents thought to be less neurotoxic, could influence outcomes.⁵ The interim results did not show differences at 30 months, which provides cautious reassurance. However, the primary outcome at 5 years will be critical for a more definitive understanding, and updated data like ours are essential to move the field forward.

Contemporary Pediatrics:

What takeaways do you have for colleagues based on these preliminary findings?

Lee:

For colleagues, the main takeaway is that in otherwise healthy infants undergoing a single anesthetic exposure, reducing sevoflurane concentration with adjunct agents did not translate into measurable neurodevelopmental advantages by 30 months. This suggests that standard sevoflurane-based techniques remain appropriate for single procedures in this age group.

The final results, focused on full-scale IQ at 5 years of age with additional follow-up at 7 years, will be essential to confirm or refute any subtle long-term effects. These analyses are ongoing, and we expect to report the primary outcome once the cohort reaches the 5-year mark. Until then, these interim data should be interpreted with caution but can help guide clinical reassurance.

Contemporary Pediatrics:

Would you like to include anything else?

Lee:

Yes. While our current trial focused on single anesthetic exposures, many children with chronic conditions require repeated anesthesia, and the cumulative impact remains uncertain. Our group is conducting a separate study in children with retinoblastoma, who undergo multiple anesthetics for eye examinations and treatments. We hope this will provide valuable data on the effects of repeated exposure, which is a key unanswered question in the field.

References:

1. Fitch J. Study: No short-term neurodevelopmental risk after brief anesthesia in infants. Contemporary Pediatrics. Published September 9, 2025. Accessed September 11, 2025. https://www.contemporarypediatrics.com/view/study-no-short-term-neurodevelopmental-risk-after-brief-anesthesia-in-infants
2. Sun LS, Li G, Miller TLK, Salorio C, Byrne MW, Bellinger DC, Ing C, Park R, Radcliffe J, Hays SR, DiMaggio CJ, Cooper TJ, Rauh V, Maxwell LG, Youn A, McGowan FX: Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood. JAMA 2016; 315: 2312-2320
3. Warner DO, Zaccariello MJ, Katusic SK, Schroeder DR, Hanson AC, Schulte PJ, Buenvenida SL, Gleich SJ, Wilder RT, Sprung J, Hu D, Voigt RG, Paule MG, Chelonis JJ, Flick RP: 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
4. McCann ME, de Graaff JC, Dorris L, Disma N, Withington D, Bell G, Grobler A, Stargatt R, Hunt RW, Sheppard SJ, Marmor J, Giribaldi G, Bellinger DC, Hartmann PL, Hardy P, Frawley G, Izzo F, von Ungern Sternberg BS, Lynn A, Wilton N, Mueller M, Polaner DM, Absalom AR, Szmuk P, Morton N, Berde C, Soriano S, Davidson AJ: Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet 2019; 393: 664-677
5. Ji S-H, Kang P, Cho S-A, Park J-B, Jang Y-E, Kim E-H, Kim J-T, Kim H-S, Jung H-J, Jung H-A, Lee H-C, Lee J-H: Effects of Dexmedetomidine–Remifentanil on Neurodevelopment of Children after Inhalation Anesthesia: A Randomized Clinical Trial. Anesthesiology 2025; 143: 827-834