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Systemic Endothelial Activation Is Associated With Early Acute Respiratory Distress Syndrome in Children With Extrapulmonary Sepsis
Journal article   Open access   Peer reviewed

Systemic Endothelial Activation Is Associated With Early Acute Respiratory Distress Syndrome in Children With Extrapulmonary Sepsis

Jane E Whitney, Binqing Zhang, Natalka Koterba, Fang Chen, Jenny Bush, Kathryn Graham, Simon F Lacey, Jan Joseph Melenhorst, David T Teachey, Janell L Mensinger, …
Critical care medicine, v 48(3), pp 344-352
Mar 2020
DOI: https://doi.org/10.1097/CCM.0000000000004091
PMID: 32058372
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749338View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Adolescent Biomarkers Blood Proteins - metabolism Cell Adhesion Molecules - metabolism Child Child, Preschool Endothelium - physiopathology Female Hospital Mortality Humans Infant Inflammation Mediators Intensive Care Units, Pediatric - statistics & numerical data Longitudinal Studies Male Organ Dysfunction Scores Prognosis Respiratory Distress Syndrome - blood Respiratory Distress Syndrome - epidemiology Sepsis - blood Sepsis - epidemiology Sepsis - physiopathology Time Factors
Systemic endothelial activation may contribute to sepsis-associated organ injury, including acute respiratory distress syndrome. We hypothesized that children with extrapulmonary sepsis with versus without acute respiratory distress syndrome would have plasma biomarkers indicative of increased endothelial activation and that persistent biomarker changes would be associated with poor outcome. Observational cohort. Academic PICU. Patients less than 18 years old with sepsis from extrapulmonary infection with (n = 46) or without (n = 54) acute respiratory distress syndrome and noninfected controls (n = 19). None. Endothelial (angiopoietin-1, angiopoietin-2, tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2, vascular endothelial growth factor, soluble fms-like tyrosine kinase, von Willebrand factor, E-selectin, intercellular adhesion molecule, vascular cell adhesion molecule, thrombomodulin) and inflammatory biomarkers (C-reactive protein, interleukin-6, and interleukin-8) were measured from peripheral plasma collected within 3 days (time 1) of sepsis recognition and at 3-6 days (time 2) and 7-14 days (time 3). Time 1 biomarkers and longitudinal measurements were compared for sepsis patients with versus without acute respiratory distress syndrome and in relation to complicated course, defined as greater than or equal to two organ dysfunctions at day 7 or death by day 28. Angiopoietin-2, angiopoietin-2/angiopoietin-1 ratio, tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2, vascular endothelial growth factor, von Willebrand factor, E-selectin, intercellular adhesion molecule, vascular cell adhesion molecule, thrombomodulin, endocan, C-reactive protein, interleukin-6, and interleukin-8 were different between sepsis and noninfected control patients at time 1. Among patients with sepsis, those with acute respiratory distress syndrome had higher angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor, vascular cell adhesion molecule, thrombomodulin, endocan, interleukin-6, and interleukin-8 than those without acute respiratory distress syndrome (all p < 0.003). Angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratio remained higher in sepsis with versus without acute respiratory distress syndrome after multivariable analyses. Time 1 measures of angiopoietin-2, angiopoietin-2/-1 ratio, von Willebrand factor, and endocan were indicative of complicated course in all sepsis patients (all area under the receiver operating curve ≥ 0.80). In sepsis without acute respiratory distress syndrome, soluble fms-like tyrosine kinase decreased more quickly and von Willebrand factor and thrombomodulin decreased more slowly in those with complicated course. Children with extrapulmonary sepsis with acute respiratory distress syndrome had plasma biomarkers indicative of greater systemic endothelial activation than those without acute respiratory distress syndrome. Several endothelial biomarkers measured near sepsis recognition were associated with complicated course, whereas longitudinal biomarker changes yielded prognostic information only in those without sepsis-associated acute respiratory distress syndrome.

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Critical Care Medicine
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