Metabolism-corrected propofol exposure intensity and long-term intelligence quotient in pediatric febrile infection-related epilepsy syndrome: a retrospective cohort study.

Background: Febrile infection-related epilepsy syndrome (FIRES) often requires prolonged gamma-aminobutyric acid (GABA)-ergic anesthesia for super-refractory status epilepticus; however, the neurocognitive impact of propofol, independent of disease severity, remains unclear. This study aimed to distinguish practice-driven propofol administration from illness severity-driven necessity and to evaluate the dose-dependent association of propofol with long-term cognitive outcomes in children. Methods: This retrospective cohort study included 74 FIRES survivors (median age: 7.2 years) who were admitted from 2014 to 2022. We developed the metabolism-corrected propofol exposure intensity (MC-PEI) metric, which standardizes cumulative propofol dose (mg/kg) to ideal body weight and adjusts for organ dysfunction. A generalized additive model linked MC-PEI to illness severity markers to derive dose residuals (DR), reflecting variation in clinical practice. Results: The median MC-PEI was 2,180 mg/kg. After applying inverse probability of treatment weighting (IPTW), each 100 mg/kg increase in DR was independently associated with a decrease of 0.41 points in the Full-Scale Intelligence Quotient (FSIQ) ( Conclusion: Practice-driven propofol exposure significantly impairs long-term cognition in a dose-dependent manner in FIRES, with accelerated neurotoxicity beyond 2,000 mg/kg. This threshold should prompt a mandatory multidisciplinary review and consideration of alternative treatment options.