Significance: A large proportion of children who die in the pediatric ICU have Acute Respiratory Distress Syndrome (ARDS), but all pediatric therapeutic randomized controlled trials have been negative. Recent recommendations for PARDS management are based on consensus opinion, but it is unclear whether following these recommendations improves outcomes. Objectives: Through secondary analysis of the largest international observational PARDS study (which we are leading), we seek to develop, validate, and apply a robust PARDS risk severity model to test whether adherence to consensus recommendations improves outcomes. Hypotheses: (1) Lung protective ventilation recommendations will have low adherence in many subpopulations of children with ARDS. (2)Continuous neuromuscular blockade and prone positioning use will increase as ARDS severity increases, but fewer than 30% of severe patients will receive these therapies, despite high evidence for their use in adults. 1 We can develop and validate accurate severity based predictive models using readily available clinical data in the first 24 hours of PARDS diagnosis. Using these models to adjust for illness severity, we expect that non-adherence to lung protective ventilation recommendations will be
independently associated with fewer ventilator free days (days alive and not on a ventilator) and that for patients with severe PARDS, continuous neuromuscular blockade in the first 48 h and prone positioning will be associated with more ventilator free days. (4) Moreover, variables associated with low adherence to consensus recommendations will not modify the effectiveness of these therapies, after adjusting for severity. Relevance/Future Directions: Our data driven, novel approach will capitalize on the inherent variability in practice patterns amongst ARDS management strategies across the world. We anticipate generating data to enable smarter clinical trial design using patient specific risk factors to target populations most likely to benefit
from interventions, which would be supported through NHLBI RO1/UO1 awards led by CHLA/USC.

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