Revisiting post-ICU admission fluid balance across pediatric sepsis mortality risk strata: A secondary analyses from a prospective observational cohort study

INTRODUCTION: 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 (AKI), and use of renal replacement therapy (CRRT) in pediatric septic shock. DESIGN: Ongoing multi-center prospective observational cohort. SETTING: Thirteen pediatric ICUs in the United States (2003–2023). PATIENTS: Six hundred and eighty-one children with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cumulative percent positive fluid balance between day 1–7 (Day 1–7%PFB) was determined. Primary outcome of interest was complicated course defined as death or persistence of ≥ 2 organ dysfunctions by day 7. PERSEVERE-II biomarkers were used to assign mortality probability and categorize patients into high (n = 91), intermediate (n = 134), and low (n = 456) mortality risk strata. Cox proportional hazard regression models with adjustment for PERSEVERE-II mortality probability, presence of sepsis associated acute kidney injury (SA-AKI) on Day 3, and any use of CRRT, demonstrated that time-dependent variable Day 1–7%PFB was independently associated with increased hazard of complicated course in the cohort. Risk stratified analyses revealed that each 10% increase in Day 1–7%PFB was independently associated with increased hazard of complicated course among patients with high mortality risk strata (adj HR of 1.24 (95%CI: 1.08–1.42), p = 0.002), but not among those categorized as intermediate- or low- mortality risk. CONCLUSIONS: Our data demonstrate the independent influence of cumulative %PFB on the risk of complicated course. Contrary to our previous report, this risk was largely driven by patients categorized as having a high-mortality risk based on PERSEVERE-II biomarkers. Further research is necessary to determine whether this subset of patients may benefit from targeted deployment of restrictive fluid management or early initiation of de-escalation therapies upon resolution of shock.