Revisiting Post-ICU Admission Fluid Balance Across Pediatric Sepsis Mortality Risk Strata: A Secondary Analysis of a
Mihir R Atreya1,2, Natalie Z Cvijanovich3, Julie C Fitzgerald4
1Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center Cincinnati, Cincinnati, OH.
Insights
Positive fluid balance in pediatric septic shock increases mortality risk, particularly in high-risk patients identified by PERSEVERE-II biomarkers. This highlights the need for targeted fluid management strategies in critically ill children.
Area of Science:
- Pediatric critical care medicine
- Septic shock research
- Fluid management in intensive care
Background:
- Positive fluid balance (PFB) post-intensive care unit (ICU) admission is linked to higher mortality in critically ill patients.
- Understanding how PFB risk varies across different patient subgroups is crucial for optimizing treatment.
Purpose of the Study:
- To investigate if the association between PFB and adverse outcomes in pediatric septic shock differs among biomarker-defined risk strata.
- To adjust for illness severity, acute kidney injury, and continuous renal replacement therapy (CRRT) when assessing PFB risk.
Main Methods:
- A multicenter prospective observational cohort study involving 681 children with septic shock across 13 US PICUs (2003-2023).
- Cumulative percent PFB (days 1-7 %PFB) was assessed.
- Patients were stratified into high, intermediate, and low mortality risk groups using Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-II biomarkers.
- Cox proportional hazard regression models were used for analysis.
Main Results:
- Cumulative PFB between days 1 and 7 was independently associated with an increased hazard of a complicated course (death or persistent organ dysfunction by day 7).
- This association was significant only in the high mortality risk strata (adjusted hazard ratio 1.24; p = 0.003) per 10% increase in days 1-7 %PFB.
- The association was not causally mediated by PERSEVERE-II biomarkers.
Conclusions:
- Cumulative PFB significantly influences the risk of a complicated course in pediatric septic shock.
- The heightened risk associated with PFB is primarily driven by patients identified as high mortality risk by PERSEVERE-II biomarkers.
- Prognostic tools like PERSEVERE-II can help target interventions, such as restrictive fluid management, to high-risk pediatric septic shock patients.
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.
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