The relationship of fluid administration to outcome in the pediatric calfactant in acute respiratory distress syndrome trial

Objectives: 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. Design: 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. Patients and Setting: Children admitted to PICUs with acute lung injury/acute respiratory distress syndrome from 24 children's hospitals in six different countries. Intervention: Post hoc analysis of daily fluid balance in subjects from the Pediatric Calfactant in Acute Respiratory Distress Syndrome trial. Measurements and Main Results: Despite the conservative fluid guideline, fluid management was more consistent with a "liberal" approach. On average, study subjects accumulated 1.96 ± 4.2 L/m2 over the first 7 days of the trial. Subjects who died accumulated on average 8.7 ± 9.5 L/m2 versus 1.2 ± 2.4 L/m2 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. Conclusions: 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.