Abstract
Despite distinct epidemiology and outcomes, pediatric acute respiratory distress syndrome (PARDS) is often managed based on evidence extrapolated from treatment of adults. The impact of non-pulmonary processes on mortality as well as the lower mortality rate compared to adults with acute respiratory distress syndrome (ARDS) renders the utilization of short-term mortality as a primary outcome measure for interventional studies problematic. However, data regarding alternatives to mortality are profoundly understudied, and proposed alternatives, such as ventilator-free days, may be themselves subject to hidden biases. Given the neuropsychiatric and functional impairment in adult survivors of ARDS, characterization of these morbidities in children with PARDS is of paramount importance. The purpose of this review is to frame these challenges in the context of the existing pediatric literature, and using adult ARDS as a guide, suggest potential clinically relevant outcomes that deserve further investigation. The goal is to identify important areas of study in order to better define clinical practice and facilitate future interventional trials in PARDS.
Highlights
Pediatric intensivists were not present for either the 1994 American-European Consensus Conference (AECC) [1] or the 2012 Berlin re-definition [2] of acute respiratory distress syndrome (ARDS), and so pediatric considerations were not addressed
AECC and Berlin definitions were historically applied to children without modification, despite the different epidemiology and outcomes of pediatric ARDS
The purpose of this review is to identify the challenges in identifying appropriate outcomes for current and future studies in pediatric acute respiratory distress syndrome (PARDS), framed in the context of the existing literature
Summary
Pediatric intensivists were not present for either the 1994 American-European Consensus Conference (AECC) [1] or the 2012 Berlin re-definition [2] of acute respiratory distress syndrome (ARDS), and so pediatric considerations were not addressed. Prone position in severe ARDS (PROSEVA) required even more stringent enrollment criteria, as it requires PaO2/FiO2 ≤150 after 12–24 h of initial stabilization, thereby excluding patients who rapidly improved with standard ventilator management In both cases, the goal was enrichment of a higher risk population in which the tested intervention could plausibly impact mortality with a reasonable sample size. The 2012 Berlin definition [2] demonstrated an increase in duration of mechanical ventilation in survivors across increasing severity classes of ARDS, which was confirmed in LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) [35] This observation has been corroborated in PARDS when using oxygenation at 24 h, rather than at PARDS onset [5]. Given the increased utilization of non-invasive ventilation both prior to [37,38,39] and after endotracheal intubation, duration of mechanical ventilation requires clear definition
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