Objectives: In the Fluid and Catheter Treatment Trial (NCT00281268), adults with acute lung injury randomized to a conservative vs. liberal fluid management protocol had increased days alive and free of mechanical ventilator support (ventilator-free days). Recruiting sufficient children with acute lung injury into a pediatric trial is challenging. A Bayesian statistical approach relies on the adult trial for the a priori effect estimate, requiring fewer patients. Preparing for a Bayesian pediatric trial mirroring the Fluid and Catheter Treatment Trial, we aimed to: 1) identify an inverse association between fluid balance and ventilator-free days; and 2) determine if fluid balance over time is more similar to adults in the Fluid and Catheter Treatment Trial liberal or conservative arms.
Design: Multicentered retrospective cohort study.
Setting: Five pediatric intensive care units.
Patients: Mechanically ventilated children (age ≥1 month to <18 yrs) with acute lung injury admitted in 2007–2010.
Measurements and Main Results: Fluid intake, output, and net fluid balance were collected on days 1–7 in 168 children with acute lung injury (median age 3 yrs, median PaO2/FIO2 138) and weight-adjusted (mL/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FIO2, and vasopressor use, increasing cumulative fluid balance (mL/kg) on day 3 was associated with fewer ventilator-free days (p = .02). Adjusted for weight, daily fluid balance on days 1–3 and cumulative fluid balance on days 1–7 were higher in these children compared to adults in the Fluid and Catheter Treatment Trial conservative arm (p < .001, each day) and was similar to adults in the liberal arm.
Conclusions: Increasing fluid balance on day 3 in children with acute lung injury at these centers is independently associated with fewer ventilator-free days. Our findings and the similarity of fluid balance patterns in our cohort to adults in the Fluid and Catheter Treatment Trial liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with acute lung injury and support a Bayesian trial mirroring the Fluid and Catheter Treatment Trial.
From the Critical Care Division (SLV, DAG, MB, AGR), Department of Anesthesia, Perioperative and Pain Medicine, Children’s Hospital Boston, Boston, MA; Department of Anesthesia (SLV, AGR), Harvard Medical School, Boston, MA; Critical Care Division (AS, MC), Department of Pediatrics, University of California San Francisco, San Francisco, CA; Dell Children’s Medical Center of Central Texas (RAH, LMC), Austin, TX, Critical Care Division (PCS), Department of Pediatrics, Washington University in St Louis, St Louis, MO; Pediatric Critical Care (HRF), Children’s Hospital and Research Center Oakland, Oakland, CA; and Department of Pediatrics (LK), Connecticut Children’s Medical Center, Hartford, CT.
*See also p. 2918.
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Dr. Valentine received research support from the National Research Service Award Ruth T. Kirschstein Award, Agency for Healthcare Research and Quality T32 HS000063, as a fellow in the Harvard Pediatric Health Services Research Fellowship Program. AS received research support from National Institute of Child Health and Human Development HD047349 and National Heart, Lung, and Blood Institute K23 HL085526. This work was conducted with support from the Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Institutes of Health Award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic healthcare centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, The National Center for Research Resources, or The National Institutes of Health.
The authors have not disclosed any potential conflicts of interest.
Address requests for reprints to: Stacey L. Valentine, MD, MPH, Department of Anesthesia, Perioperative and Pain Medicine, Division of Critical Care Medicine, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115. E-mail: firstname.lastname@example.org