Kurt Drury, MD
Oregon Health and Sciences University
Portland, Oregon
Disclosure information not submitted.
Trevor Hall, PsyD, ABPdN
Associate Professor of Pediatrics; Pediatric Neuropsychologist
Oregon Health and Science University, United States
Disclosure information not submitted.
Skyler Leonard, PhD
Post Doctoral Scholar
Oregon Health and Science University, Oregon, United States
Disclosure information not submitted.
Benjamin Orwoll, BA, MD, MS
Assistant Professor of Pediatrics, Division of Pediatric Critical Care
Oregon Health and Science University, United States
Disclosure information not submitted.
Cydni Williams, MD
Associate Professor of Pediatrics, Division of Pediatric Critical Care
Oregon Health and Sciences University, United States
Disclosure information not submitted.
Title: Sedative Exposure and Cognitive Outcomes Following Pediatric Critical Care
Introduction: Pediatric critical care survivors with acquired brain injury (ABI) often develop chronic cognitive morbidities. Sedative and analgesic medications are linked to cognitive morbidity in children as these medications alter neurotransmitter pathways and lead to long-term receptor adaptation, interfering with neurodevelopment and healing after injury. We hypothesized increased medication exposure during critical care would be associated with poorer cognitive outcomes in a sample of children with ABI.
Methods: We performed a retrospective cohort analysis of 92 children with ABI aged 8-18 years following critical care. Participants were grouped based on exposure to opioids, benzodiazepines, and propofol. High dose was defined as greater than cohort median total equivalent class doses in mg/kg. The primary outcome was a standardized neurocognitive index (NCI) derived through Principal Component Analysis from an assessment battery of cognitive function 1-3 months after discharge. Pre-admission ability was estimated from the Wide Range Achievement Test (WRAT-4) word reading score. Pearson’s correlation (rᵖ), ANOVA, and multiple linear regression were used to assess relationships between medication exposures and NCI. Covariates selected and significance defined at p< .05.
Results: 81 (88%) children received medication: 79% opioids, 61% benzodiazepines, 50% propofol. Worse NCI significantly correlated with higher opioid total dose/kg (rᵖ =-.23), higher benzodiazepine total dose/kg (rp=-.24), worse WRAT-4 (rᵖ =.65), and worsened Functional Status Scale (FSS; rᵖ =-.22). High dose benzodiazepine (mean difference =-.45; p=.03), Medicaid (mean difference=-.87; p< .01), and chronic comorbidity (mean difference=-.51; p=.02) were associated with significantly worse NCI. When controlling for WRAT-4, worsened FSS from baseline, Medicaid, and chronic comorbidity, high dose benzodiazepine use was independently associated with worse NCI (ß=-.38, 95% confidence interval=-.68,-.08).
Conclusion: High dose benzodiazepines in critically ill children with ABI were associated with worse cognitive outcomes. Inter-provider variability in choice of sedation and analgesia provides an opportunity to optimize cognitive outcomes. Further research is needed to determine ideal medication regimens and impact on long-term cognitive morbidity.