Association of inflammatory biomarkers with new functional morbidity at hospital discharge in children who survive severe sepsis

Mallory A Perry-Eaddy ^1,2,3* Walter Faig ^4* Martha AQ Curley ^4,5* Scott L Weiss ^6,7*

• ¹ University of Connecticut, Storrs, United States
• ² Department of Pediatrics, School of Medicine, University of Connecticut, Farmington, Connecticut, United States
• ³ Connecticut Children's Medical Center, Hartford, Connecticut, United States
• ⁴ Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
• ⁵ University of Pennsylvania, Philadelphia, Pennsylvania, United States
• ⁶ Thomas Jefferson University Hospital, Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
• ⁷ Alfred I. duPont Hospital for Children, Wilmington, Delaware, United States

Objective: New functional morbidity in critically ill children who survive sepsis is common; yet, the underlying biological mechanism, particularly the impact of inflammation is unknown. We sought to test the hypothesis that increased levels of inflammatory biomarkers during the acute phase of pediatric sepsis are associated with new functional morbidity at hospital discharge. Methods: Post-hoc secondary analysis of the MitoPSe clinical study, including one hundred and nineteen (N=119) critically ill children who survived sepsis. Data included demographic, clinical variables and thirty-one inflammatory biomarkers collected at three distinct timepoints (within 1-2 days of PICU admission, days 3-5, and days 8-14). The primary outcome is new functional morbidity, defined as at least one point increase in the Pediatric Overall Performance Category from baseline to hospital discharge. Results: New functional morbidity occurred in 38 children (32%) and was associated with increased plasma levels of IL-6, IL-18, sIL-2Ra, MCP1, IL-8 [CXCL8], sIL-1RII, IL-10, MIP1a, and IL-2r and decreased RANTES [CCL5] (p <.001) at all three timepoints. However, after adjusting for differences in chronic comorbid conditions, hospital length of stay, number of organ dysfunctions, and severity of illness, absolute biomarker levels and trajectories were not significantly different between patients with or without new functional morbidity at hospital discharge. Conclusions: In this sample of critically ill children treated for sepsis, increased inflammatory biomarkers levels and the trajectory of change of during the acute phase of pediatric sepsis were not independently associated with new functional morbidity at hospital discharge. Inflammatory biomarker levels likely reflect illness severity and other clinical variables associated with illness. However, these biomarkers may still be useful in identifying patients at risk of developing functional morbidity, despite lack of causation within this study.