A new randomized clinical trial provides reassuring evidence that brief exposure to inhaled anesthesia during surgery does not lead to adverse short-term neurodevelopmental outcomes in infants and young children. The findings, published in Anesthesiology, offer important guidance for families and clinicians concerned about anesthesia safety in pediatric populations.
Study Design and Methodology
The trial, led by Ji-Hyun Lee, MD, PhD, of Seoul National University Hospital, compared two approaches to general anesthesia in 400 children under the age of 2 years undergoing surgery lasting less than 90 minutes. One group received sevoflurane alone, while the other received a "balanced" regimen designed to lower sevoflurane exposure through the addition of intravenous dexmedetomidine and the opioid remifentanil.
At approximately 30 months of age, participants underwent comprehensive assessments of nonverbal intelligence and parent-reported behavioral outcomes. Investigators analyzed complete data from 343 children to evaluate potential differences between the two anesthetic approaches.
Key Findings
The study found no meaningful differences in IQ, behavior, or language development between the groups. While the balanced approach "effectively reduced sevoflurane requirements during surgery, it did not provide measurable developmental advantages," according to Lee and coauthors.
These preliminary results suggest that concerns about brief anesthetic exposure may be unfounded, at least in the short term. However, the authors emphasized that these findings are preliminary, and full, final results will feature long-term follow-ups at age 5 years, which will include full-scale IQ assessment.
Supporting Evidence from Previous Research
The current findings add to existing evidence, including the earlier GAS trial, that single, brief anesthetic exposures are unlikely to cause clinically significant neurodevelopmental impairment. The GAS trial was an international, assessor-masked, equivalence, randomized, controlled trial conducted at 28 hospitals across multiple countries including Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand.
In the GAS study, patients were randomly assigned to receive either awake-regional anesthetic or sevoflurane-based general anesthetic. The median duration of general anesthesia was 54 minutes. The mean full-scale intelligence quotient (FSIQ) score was 99.08 in the awake-regional anesthesia group and 98.97 in the general anesthesia group, with a difference in means of 0.23, providing strong evidence of equivalence.
Clinical Context and FDA Warnings
Previous concerns about potential risks stemmed from animal studies showing possible neurotoxicity of anesthetics in developing brains, which led the FDA in 2017 to issue warnings about repeated or prolonged use in children younger than 3 years. The current study's findings appear to address these concerns for brief, single exposures.
"These results provide reassurance for families and clinicians that brief surgical anesthesia is not associated with short-term developmental harm," wrote Lee and colleagues. "These findings support existing evidence suggesting that brief anesthetic exposure is unlikely to result in clinically significant neurodevelopmental impairment."
Expert Commentary
In an accompanying editorial, Andrew Davidson, MBBS, MD, and Caleb Ing, MD, MS, noted the challenges of studying anesthesia safety in young children, particularly given the role of underlying health conditions in neurodevelopment. However, they emphasized the value of these preliminary results.
"The lack of an effect of differing sevoflurane dose on neurodevelopment may argue against sevoflurane being a cause of neurotoxicity," they concluded.
Implications for Clinical Practice
The study results provide important reassurance to parents and healthcare providers who must weigh the risks and benefits of necessary surgical procedures in young children. While researchers emphasize that long-term follow-up is still underway, the findings contribute to a growing body of evidence that short, one-time anesthesia use is safe in pediatric populations.
The research specifically addresses concerns about sevoflurane, a commonly used inhaled anesthetic, and suggests that efforts to minimize exposure through balanced anesthesia techniques may not be necessary from a neurodevelopmental safety perspective, though such approaches may still offer other clinical benefits.
