Revisiting Post-ICU Admission Fluid Balance Across Pediatric Sepsis Mortality Risk Strata: A Secondary Analysis of a Prospective Observational Cohort Study

Mihir R. Atreya, MD, MPH; Natalie Z. Cvijanovich, MD; Julie C. Fitzgerald, MD, PhD; Scott L. Weiss, MD, MSCE; Michael T. Bigham, MD; Parag N. Jain, MD; Kamal Abulebda, MD; Riad Lutfi, MD; Jeffrey Nowak, MD; Neal J. Thomas, MD, MSc; Torrey Baines, MD; Michael Quasney, MD, PhD; Bereketeab Haileselassie, MD; Rashmi Sahay, MS; Bin Zhang, PhD; Matthew N. Alder, MD, PhD; Natalja L. Stanski, MD; Stuart L. Goldstein, MD

doi:10.1097/CCE.0000000000001027

Critical Care Explorations (Jan 2024)

Revisiting Post-ICU Admission Fluid Balance Across Pediatric Sepsis Mortality Risk Strata: A Secondary Analysis of a Prospective Observational Cohort Study

Mihir R. Atreya, MD, MPH,
Natalie Z. Cvijanovich, MD,
Julie C. Fitzgerald, MD, PhD,
Scott L. Weiss, MD, MSCE,
Michael T. Bigham, MD,
Parag N. Jain, MD,
Kamal Abulebda, MD,
Riad Lutfi, MD,
Jeffrey Nowak, MD,
Neal J. Thomas, MD, MSc,
Torrey Baines, MD,
Michael Quasney, MD, PhD,
Bereketeab Haileselassie, MD,
Rashmi Sahay, MS,
Bin Zhang, PhD,
Matthew N. Alder, MD, PhD,
Natalja L. Stanski, MD,
Stuart L. Goldstein, MD

Affiliations

Mihir R. Atreya, MD, MPH: 1 Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center Cincinnati, Cincinnati, OH.
Natalie Z. Cvijanovich, MD: 3 Department of Pediatrics, UCSF Benioff Children’s Hospital Oakland, Oakland, CA.
Julie C. Fitzgerald, MD, PhD: 4 Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA.
Scott L. Weiss, MD, MSCE: 5 Department of Pediatrics, Nemours Children’s Hospital, Wilmington, DE.
Michael T. Bigham, MD: 6 Department of Pediatrics, Akron Children’s Hospital, Akron, OH.
Parag N. Jain, MD: 7 Department of Pediatrics, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX.
Kamal Abulebda, MD: 8 Department of Pediatrics, Riley Hospital for Children, Indianapolis, IN.
Riad Lutfi, MD: 8 Department of Pediatrics, Riley Hospital for Children, Indianapolis, IN.
Jeffrey Nowak, MD: 9 Department of Pediatrics, Children’s Hospital and Clinics of Minnesota, Minneapolis, MN.
Neal J. Thomas, MD, MSc: 10 Department of Pediatrics, Penn State Hershey Children’s Hospital, Hershey, PA.
Torrey Baines, MD: 11 Department of Pediatrics, University of Florida Health Shands Children’s Hospital, Gainesville, FL.
Michael Quasney, MD, PhD: 12 Department of Pediatrics, CS Mott Children’s Hospital at the University of Michigan, Ann Arbor, MI.
Bereketeab Haileselassie, MD: 13 Department of Pediatrics, Lucile Packard Children’s Hospital Stanford, Palo Alto, CA.
Rashmi Sahay, MS: 14 Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center Cincinnati, Cincinnati, OH.
Bin Zhang, PhD: 14 Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center Cincinnati, Cincinnati, OH.
Matthew N. Alder, MD, PhD: 1 Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center Cincinnati, Cincinnati, OH.
Natalja L. Stanski, MD: 1 Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center Cincinnati, Cincinnati, OH.
Stuart L. Goldstein, MD: 2 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.

DOI: https://doi.org/10.1097/CCE.0000000000001027
Journal volume & issue: Vol. 6, no. 1
p. e1027

Abstract

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OBJECTIVES:. Post-ICU admission cumulative positive fluid balance (PFB) is associated with increased mortality among critically ill patients. We sought to test whether this risk varied across biomarker-based risk strata upon adjusting for illness severity, presence of severe acute kidney injury (acute kidney injury), and use of continuous renal replacement therapy (CRRT) in pediatric septic shock. DESIGN:. Ongoing multicenter prospective observational cohort. SETTING:. Thirteen PICUs in the United States (2003–2023). PATIENTS:. Six hundred and eighty-one children with septic shock. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Cumulative percent PFB between days 1 and 7 (days 1–7 %PFB) was determined. Primary outcome of interest was complicated course defined as death or persistence of greater than or equal to two organ dysfunctions by day 7. Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-II biomarkers were used to assign mortality probability and categorize patients into high mortality (n = 91), intermediate mortality (n = 134), and low mortality (n = 456) risk strata. Cox proportional hazard regression models with adjustment for PERSEVERE-II mortality probability, presence of sepsis-associated acute kidney injury on day 3, and use of CRRT, demonstrated that time-dependent variable days 1–7%PFB was independently associated with an increased hazard of complicated course. Risk-stratified analyses revealed that each 10% increase in days 1–7 %PFB was associated with increased hazard of complicated course only among patients with high mortality risk strata (adjusted hazard ratio 1.24 (95% CI, 1.08–1.43), p = 0.003). However, this association was not causally mediated by PERSEVERE-II biomarkers. CONCLUSIONS:. Our data demonstrate the influence of cumulative %PFB on the risk of complicated course in pediatric septic shock. Contrary to our previous report, this risk was largely driven by patients categorized as having a high mortality risk based on PERSEVERE-II biomarkers. Incorporation of such prognostic enrichment tools in randomized trials of restrictive fluid management or early initiation of de-escalation strategies may inform targeted application of such interventions among at-risk patients.

Published in Critical Care Explorations

ISSN: 2639-8028 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://journals.lww.com/ccejournal/pages/default.aspx

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