Sevoflurane versus propofol and the long‐term risk of attention‐deficit/ hyperactivity disorder in children

Preclinical studies have long indicated that volatile anaesthetics, such as sevoflurane, may disrupt brain development by inducing neuronal apoptosis, neuroinflammation, and altered synaptic plasticity during critical periods of maturation. However, whether these biological effects translate into clinically meaningful outcomes in children remained unclear. A new study published in General Psychiatry tried to address this gap using a large, population-based cohort spanning two decades. This large multinational study provides new real-world evidence that the type of anaesthetic used during pediatric surgery may influence long-term neurobehavioral outcomes.

On the foundation of electronic health records from more than 150 healthcare organizations across North America, Europe and Asia, researchers suggest that exposure to sevoflurane is associated with a higher subsequent risk of attention-deficit/hyperactivity disorder (ADHD) compared with propofol. Analysis included children and adolescents aged 0–18 years who underwent a single surgical procedure under general anaesthesia between 2005 and 2025. Besides, patients with pre-existing ADHD or multiple anaesthetic exposures were excluded to minimize confounding effects. Employing propensity score matching, 54,102 children were balanced between the sevoflurane and propofol groups.

Results showed that ADHD developed in 5.63% of children exposed to sevoflurane compared with 2.95% of those who received propofol, which corresponded to a statistically significant increase in risk. Importantly, the association remained consistent across multiple subgroups and sensitivity analyses, reinforcing the robustness of the findings. To further strengthen inference, the study incorporated positive and negative control analyses to assess potential residual bias. Mortality was rare and comparable between the two groups, indicating that the observed differences were specific to neurobehavioral outcomes rather than overall health status.

“Our findings extend a substantial body of preclinical and clinical evidence suggesting that volatile anaesthetics, particularly sevoflurane, may exert long‐term neurodevelopmental effects,” the authors note. “Such work will be essential to refine perioperative counselling, inform anaesthesia stewardship policies and ultimately optimise neurodevelopmental safety in children undergoing surgery.” Researchers emphasise that, despite observational design limitations, causal interpretation is limited, and unmeasured confounding cannot be fully excluded, the consistency of results across analyses and alignment with mechanistic evidence from animal studies strengthen confidence in the observed association.

By integrating large-scale real-world data with experimental insights, the study highlights a potentially modifiable factor in childhood neurodevelopment. However, further prospective studies and clinical trials are needed to validate these findings and to inform evidence-based guidance on safer anaesthetic strategies in paediatric care. Overall, the research underscores the importance of considering long-term neurodevelopmental outcomes when selecting anaesthetic agents and provides a foundation for future efforts to optimise surgical care in children while minimising unintended neurological risks.