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Sevoflurane versus propofol and the long-term risk of attention-deficit/hyperactivity disorder in children
Mingyang Sun1,2, Yangyang Wang1, Yuqin Tang1
1Department of Anesthesiology and Perioperative Medicine People's Hospital of Zhengzhou University Henan Provincial People's Hospital Zhengzhou Henan China.
Insights
Sevoflurane anesthesia in children is linked to a higher risk of attention-deficit/hyperactivity disorder (ADHD) compared to propofol. This suggests anesthetic choice may impact long-term neurodevelopmental outcomes.
Area of Science:
- Neuroscience
- Pediatric Anesthesiology
- Developmental Psychology
Background:
- Preclinical studies indicate volatile anesthetics like sevoflurane may harm neurodevelopment.
- Mechanisms include neuronal apoptosis, neuroinflammation, and altered synaptic plasticity.
- Long-term neurobehavioral risks in children exposed to sevoflurane remain unclear.
Purpose of the Study:
- To compare the long-term risk of attention-deficit/hyperactivity disorder (ADHD) after pediatric anesthesia.
- The study specifically contrasted sevoflurane with propofol in a large, multinational cohort.
Main Methods:
- A retrospective multinational cohort study utilized electronic health records from over 150 healthcare organizations.
- Included were children (0-18 years) undergoing a single surgery under general anesthesia (2005-2025), excluding those with prior ADHD or multiple anesthetics.
- Propensity-score matching (1:1) and various analyses ensured robustness of findings.
Main Results:
- The study analyzed 54,102 matched children, with 5.63% developing ADHD after sevoflurane versus 2.95% after propofol.
- Sevoflurane exposure showed a statistically significant association with a higher risk of ADHD (Hazard Ratio 1.21; p < 0.001).
- Results were consistent across subgroups and sensitivity analyses, with similar low mortality rates in both groups.
Conclusions:
- In this large cohort, sevoflurane anesthesia was associated with an increased long-term risk of ADHD compared to propofol.
- Anesthetic choice may have lasting neurobehavioral effects in children.
- Prospective studies are needed to confirm these findings and inform safer pediatric anesthesia practices.
Background:
Preclinical studies have shown that volatile anaesthetics, particularly sevoflurane, can disrupt neurodevelopment by inducing neuronal apoptosis, neuroinflammation and altered synaptic plasticity during critical periods of brain maturation. Whether these mechanisms translate into long-term neurobehavioral risk in children remains uncertain.
Aims:
To compare the long-term risk of attention-deficit/hyperactivity disorder (ADHD) following paediatric anaesthesia with sevoflurane versus propofol in a large, multinational real-world cohort.
Methods:
We conducted a large, multinational, retrospective cohort study using real-world electronic health record data from more than 150 healthcare organisations across North America, Europe and Asia. Children and adolescents (0-18 years) who underwent a single surgical procedure under general anaesthesia between 2005 and 2025 were included. Patients with ADHD or multiple anaesthetic exposures were excluded. The primary exposure was sevoflurane versus propofol as the main anaesthetic. The primary outcome was new-onset ADHD identified by International Classification of Diseases, Ninth or Tenth Revision codes after surgery. Propensity-score matching (1:1), subgroup, sensitivity and positive/negative control analyses were performed to ensure robustness.
Results:
Among 54 102 matched children (27 051 per group), the cumulative incidence of ADHD was 5.63% after sevoflurane and 2.95% after propofol, corresponding to incidence rates of 134.9 and 105.4 per 10 000 person-years. Sevoflurane exposure was associated with a higher risk of ADHD (hazard ratio 1.21; 95% confidence interval 1.11-1.31; p < 0.001). Findings were consistent across subgroups and sensitivity analyses; mortality was rare and similar between groups.
Conclusions:
In this multinational cohort, sevoflurane exposure during paediatric anaesthesia was associated with an increased long-term risk of ADHD compared with propofol. These findings suggest that anaesthetic choice may have enduring neurobehavioral consequences and that prospective validation is warranted to guide safer paediatric anaesthesia practice.
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