The Relationship of Fluid Administration to Outcome in the Pediatric Calfactant in Acute Respiratory Distress Syndrome Trial*

Abstract

Adult studies have demonstrated the relationship between fluid overload and poor outcomes in acute lung injury/acute respiratory distress syndrome. The approach of pediatric intensivists to fluid management in acute lung injury/acute respiratory distress syndrome and its effect on outcomes is less clear. In a post hoc analysis of our Calfactant in Acute Respiratory Distress Syndrome trial, we examined the relationship of fluid balance to in-hospital outcomes in subjects with acute lung injury/acute respiratory distress syndrome. Calfactant in Acute Respiratory Distress Syndrome was a masked randomized controlled trial of calfactant surfactant versus placebo in pediatric patients with acute lung injury/acute respiratory distress syndrome due to direct lung injury. Caregivers were encouraged to follow a conservative fluid management guideline based on the adult Fluid and Catheter Treatment Trial. Daily fluid balance was collected for the first 7 days after trial enrollment and correlated with clinical outcomes. Children admitted to PICUs with acute lung injury/acute respiratory distress syndrome from 24 children's hospitals in six different countries. Post hoc analysis of daily fluid balance in subjects from the Pediatric Calfactant in Acute Respiratory Distress Syndrome trial. Despite the conservative fluid guideline, fluid management was more consistent with a "liberal" approach. On average, study subjects accumulated 1.96 ± 4.2 L/m over the first 7 days of the trial. Subjects who died accumulated on average 8.7 ± 9.5 L/m versus 1.2 ± 2.4 L/m in survivors. Increasing fluid accumulation was associated with fewer ventilator-free days and worsening oxygenation. Multivariable regression models that included age, gender, Pediatric Risk of Mortality score, initial oxygen saturation index and PaO2/FIO2 ratio, injury category, and treatment arm failed to account for the differences in fluid management. Pediatric intensivists generally follow a "liberal" approach to fluid management in children with acute lung injury/acute respiratory distress syndrome. Illness severity or oxygenation disturbance did not explain differences in fluid accumulation but such accumulation was associated with worsening oxygenation, a longer ventilator course, and increased mortality. A more conservative approach to fluid management may improve outcomes in children with acute lung injury/acute respiratory distress syndrome.