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

Willson, Douglas F. MD1; Thomas, Neal J. MD, MSc2; Tamburro, Robert MD2; Truemper, Edward MD3; Truwit, Jonathon MD, MBA4; Conaway, Mark PhD5; Traul, Christine MD1,6; Egan, Edmund E. MD7,8

Pediatric Critical Care Medicine: September 2013 - Volume 14 - Issue 7 - p 666–672
doi: 10.1097/PCC.0b013e3182917cb5
Feature Articles

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.

1Department of Pediatrics, University of Virginia Health Sciences System, Charlottesville, VA.

2Department of Pediatrics, Penn State M.S. Hershey Medical Center, Hershey, PA.

3Department of Pediatrics, Children’s Hospital and Medical Center of the University of Nebraska, Omaha, NE.

4Department of Internal Medicine, University of Virginia Health Sciences System, Charlottesville, VA.

5Public Health Sciences, University of Virginia Health Sciences System, Charlottesville, VA.

6Department of Pediatrics, Children’s Hospital Cleveland Clinic, Cleveland, OH.

7Pneuma Pharmaceuticals, Buffalo, NY.

8Department of Pediatrics, State University of New York at Buffalo, Buffalo, NY.

* See also p. 716.

Supported, in part, by Pneuma Pharmaceuticals, Amherst, New York.

The University of Virginia received compensation from Pneuma Pharmaceuticals to support, in part, the salaries of Drs. Willson, Truwit, Conaway, and Traul. Collaborating investigators were paid compensation for patients successfully enrolled in the study as well as support for the work of their research assistants. Dr. Willson received grant support and support for travel from Pneuma Pharmaceuticals. Dr. Thomas received grant support from Pneuma Pharmaceuticals and consulted for Discovery Laboratories. Dr. Tamburro received grant support from ONY. Dr. Tamburro’s institution received funding on a per patient basis (as a participating site in the trial). Dr. Truemper received grant support and support for travel from the University of Nebraska College of Medicine, provisions of the study drug (Cattactant - supplied to Children's Hospital and Medical Center for the duration of the trial), and lectured for the Nebraska Society of Respiratory Care. Dr. Truwit received grant support from Pneuma Pharmaceuticals, NIH, and ARDSNet and support for travel from Pneuma Pharmaceuticals. Dr. Conaway received support for participation in review activities from Pneuma Pharmaceuticals. Dr. Traul received grant support and support for travel from Pneuma Pharmaceuticals. Dr. Egan served as a board member, is employed by, and is the officer and substantial owner of Pneuma Pharmaceuticals.

For information regarding this article, E-mail: dfw4m@virginia.edu

©2013The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies