As acute kidney injury and elevated cumulative fluid balance commonly co-occur in pediatric acute respiratory distress syndrome, we aimed to identify risk factors for their development and evaluate their independent relationships with mortality. We hypothesized that acute kidney injury and elevated cumulative fluid balance would be associated with markers of inflammation and that children with elevated cumulative fluid balance and concomitant acute kidney injury would have worse outcomes than other children.
Prospective observational study using the pediatric Risk, Injury, Failure, Loss, End-Stage acute kidney injury classification.
Five academic PICUs.
Two-hundred sixty patients 1 month to 18 years old meeting the Berlin definition of acute respiratory distress syndrome between 2008 and 2014.
PICU mortality was 13% (34/260). Relative to survivors, nonsurvivors had greater cumulative fluid balance on day 3 of acute respiratory distress syndrome (+90.1 mL/kg; interquartile range 26.6–161.7 vs +44.9 mL/kg; interquartile range 10.0–111.3; p = 0.008) and also had higher prevalence of acute kidney injury on day 3 of acute respiratory distress syndrome (50% vs 23%; p = 0.001). On stratified analysis, greater cumulative fluid balance on day 3 of acute respiratory distress syndrome was associated with mortality among patients with concomitant acute kidney injury (+111.5 mL/kg for nonsurvivors; interquartile range 82.6–236.8 vs +58.5 mL/kg for survivors; interquartile range 0.9–176.2; p = 0.041) but not among patients without acute kidney injury (p = 0.308). The presence of acute kidney injury on acute respiratory distress syndrome day 3 was associated with mortality among patients with positive cumulative fluid balance (29.1% vs 10.4% mortality; p = 0.001) but not among patients with even or negative cumulative fluid balance (p = 0.430). Day 1 plasma interleukin-6 levels were associated with the development of day 3 positive cumulative fluid balance, day 3 acute kidney injury, and PICU mortality and the association between elevated day 1 interleukin-6 and PICU mortality was partially mediated by the interval development of day 3 positive cumulative fluid balance and day 3 acute kidney injury (p < 0.001).
In pediatric acute respiratory distress syndrome, elevated cumulative fluid balance on day 3 of acute respiratory distress syndrome is associated with mortality specifically in patients with concomitant acute kidney injury. Plasma interleukin-6 levels are associated with the development of positive cumulative fluid balance and acute kidney injury, suggesting a potential mechanism by which inflammation might predispose to mortality.
1Division of Critical Care, Department of Pediatrics, Benioff Children’s Hospital, University of California, San Francisco, San Francisco, CA.
2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA.
3Departments of Anesthesia and Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA.
4Division of Critical Care, Department of Pediatrics, Doernbecher Children’s Hospital, Oregon Health & Science University, Portland, OR.
5Department of Pediatrics, Division of Nephrology, University of California, San Francisco Benioff Children’s Hospital, San Francisco, CA.
6Department of Pediatrics, Division of Critical Care, Mattel Children’s Hospital, University of California, Los Angeles, CA.
Drs. Zinter and Spicer have shared first authorship.
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Supported, in part, by grant from National Institute of Child Health and Development (NICHD) K12HD000850 (to Dr. Zinter), NICHD T32HD049303 (to Dr. Spicer), National Institute of Diabetes and Digestive and Kidney Diseases R01DK098233 and R01DK101507 (to Dr. Liu), National Heart, Lung and Blood Institute (NHLBI) R01HL110969 (to Dr. Calfee), NHLBI R37HL051856 and U01HL108713 (to Dr. Matthay), and NHLBI K23 HL085526 and R01HL114484 (to Dr. Sapru).
Dr. Zinter’s institution received funding from the National Institutes of Health (NIH) (K12 training grant). Dr. Spicer’s institution received funding from NIH (T32 training grant), and he received funding from American Academy of Pediatrics (best abstract award). Dr. Liu received funding from Potrero Medical, Quark, Theravance, National Policy Forum on Critical Care and Acute Renal Failure (funding for travel), National Kidney Foundation (Advances in Chronic Kidney Disease Associate Editor), American Society of Nephrology (funding for travel), Abbott (gift of reagents), CMIC, Inc. (gift of reagents), Amgen (stockholder), ZS Pharma (Advisory Board participant), and Durect (consultant). She received other funding from Astute (adjudicated outcomes for clinical trials), Achaogen (consultant), and the NIH/National Heart, Lung and Blood Institute (NHLBI) (Grant Awardee). Dr. Calfee’s institution received funding from GlaxoSmithKline and Bayer, and she received funding from GlaxoSmithKline, Bayer (consulting), and Boehringer Ingelheim (consulting). Dr. Matthay’s institution received funding from the NHLBI, Amgen, GlaxoSmithKline, and Bayer Pharmaceuticals (acute respiratory distress syndrome [ARDS] observational study), and he received other funding from the Department of Defense for supporting a clinical trial of ARDS and Roche-Genentec (Chair of Data Safety and Monitoring Board for asthma trials). Dr. Sapru’s institution received funding from the NIH, National Institute for Child Health and Human Development, and the NHLBI. Drs. Zinter, Spicer, Liu, Calfee, Matthay, and Sapru received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest.
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