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

## TL;DR

This study finds that high propofol exposure in children with a severe epilepsy syndrome is linked to long-term cognitive decline and intellectual disability.

## Contribution

The study introduces a new metric, metabolism-corrected propofol exposure intensity, to assess dose-dependent cognitive outcomes in pediatric FIRES patients.

## Key findings

- Each 100 mg/kg increase in dose residuals was associated with a 0.41-point decrease in Full-Scale Intelligence Quotient.
- Above 2,000 mg/kg exposure, cognitive decline accelerated significantly.
- High propofol exposure was linked to a 79% rate of intellectual disability compared to 44% in the low exposure group.

## Abstract

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.

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.

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) (p = 0.003). The high DR tertile had a mean FSIQ score of 63.7, which is below the intellectual disability threshold (<70). A significant inflection point was observed at MC-PEI = 2,000 mg/kg: above this level, the FSIQ declined by 0.55 points per 100 mg/kg (p < 0.001). High DR was associated with a 79% rate of intellectual disability, compared to 44% in the low DR group (p = 0.009). Additionally, the rate of school re-entry dropped to 21%.

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.