Life After Pediatric Sepsis Evaluation, LAPSE

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DESCRIPTION (provided by applicant): LAPSE: Life After Pediatric Sepsis Evaluation It is well known that sepsis represents the leading cause of childhood mortality worldwide. However, as distinct from adult medicine, there exists a large knowledge gap regarding long-term health-related quality of life (HRQL) and functional status (FS) following pediatric sepsis. This lack of sepsis outcomes data is critical because failure to identify children at risk for sepsis-associated HRQL/FS deterioration may delay delivery of crucial rehabilitation medicine efforts to facilitate recovery. Moreover, failure to identify mechanisms of sepsis- associated HRQL/FS deterioration may impede development of novel, effective interventions for these children. For the first time this investigation will measure the incidence, intensity and duration of HRQL/FS alterations among children surviving septic shock, and examine potential clinical risk factors for such adverse outcomes. Mechanisms underlying adverse sepsis-associated outcomes among children are poorly understood at this time. Clinically however, two circular reciprocating sepsis insults, namely inflammation and ischemia/dysoxia, appear to be key antecedents for multiple organ dysfunction syndrome (MODS) that has been linked to sepsis mortality and perhaps long term morbidity. Organ failure burden, particularly cardiovascular and pulmonary dysfunction, has been shown to be strongly associated with long term morbidity and mortality following adult critical illness. The LAPSE investigation hypothesizes that validated measures of sepsis-mediated organ dysfunction will predict magnitude of sepsis-associated deterioration in HRQL/FS, and that recovery towards baseline HRQL/FS will be strongly influenced by complexity of children's chronic comorbid conditions and parent, family and home characteristics. As improving HRQL may be the most important goal of medicine, the long-term goal of this research program is to timely identify children at high risk of sepsis-mediated HRQL/FS deterioration and to ultimately design effective interventions to minimize such risk. The primary objectives of this application are to comprehensively characterize HRQL/FS outcomes and to critically examine the potential clinical risk factors for sepsis-associated HRQL/FS deterioration. The central hypothesis is that magnitude of HRQL/FS deterioration will be predicated on validated clinical markers of organ dysfunction, and that parent, family and home characteristics as well as premorbid conditions will influence trajectory back to baseline HRQL/FS. Knowledge of the contemporary natural history of pediatric septic shock will facilitate development of targeted interventions to maximize HRQL/FS among children surviving sepsis.