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Abstract

Introduction: Critically ill children suffer from post-traumatic stress disorder and deficits in attention, and spatial and verbal memory, following discharge. The impact of critical illness on executive function, which is necessary for purposeful, goal-directed, and problem-solving behavior in addition to higher learning, has not been studied in children. Methods: In this prospective cohort study, we enrolled patients aged 5-17 years admitted to the pediatric intensive care unit (PICU) with 1 of the following: mechanical ventilation (MV), vasopressor therapy, a Pediatric Risk of Mortality (PRISM III) score over 15, or a neurologic admission diagnosis. We collected demographic data upon enrollment and in-hospital data until PICU discharge. Our primary outcome was executive function, which is measured by the Behavior Rating Inventory of Executive Function (BRIEF). The BRIEF was completed upon enrollment and then at 3 and 6 months following discharge. The BRIEF assesses 8 domains of executive function and is reported as a Global Executive Composite (GEC) T-score. For the GEC, a T-score of 50 reflects the age/gender adjusted norm for that population, and a 10 point increase indicates a 1-standard deviation (SD) worsening in outcome. The Child PTSD Symptom Scale was completed in children at least 8 years of age. Linear regression assessed the relationship between duration of mechanical ventilation with GEC outcomes at 3 months and 6 months separately, adjusting for a priori determined covariates (PRISM and baseline GEC scores). Results: The median PRISM score for the 99 patients enrolled was 6 (2.5, 11) reflecting moderate illness, with 67.7% of patients requiring MV. Median executive function scores (GEC) were 0.5 SD worse than population norms at 3 months [54.6 (p=0.1)] and 6 months [57.1 (p=0.08)] following discharge, though were not significantly different from baseline. In MV patients, however, the GEC was significantly worse at 3 months compared to baseline (p=0.03). For descriptive purposes the 8 subdomains of executive function were analyzed. In our cohort, working memory was significantly worse at 3 months [T-score 55.8 (p=0.02)], and the ability to initiate thought was significantly worse only at 6 months [T score 55.9 (p=0.03)] when compared to baseline. Among patients requiring MV, working memory was significantly worse at 3 months [T-score 55.8 (p=0.01)], and the ability to initiate thought was significantly worse at 3 months [T-score of 52.5 (p=0.03)] and 6 months [53.9 (p=0.05)] following discharge. In patients > 8 years, PTSD occurred in 7% of patients at 3 months, with only 5% having ongoing symptoms at 6 months. In our multivariable regressions, baseline executive function was the strongest predictor of worse GEC scores at 3 and 6 months. Conclusions: Children suffer from cognitive dysfunction and PTSD following critical illness. Larger studies are needed to determine the prevalence of these serious morbidities and to identify potentially modifiable risk factors to target interventional therapies.