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Open Access 01-10-2010 | Research

The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis

Authors: Nathan I Shapiro, Philipp Schuetz, Kiichiro Yano, Midori Sorasaki, Samir M Parikh, Alan E Jones, Stephen Trzeciak, Long Ngo, William C Aird

Published in: Critical Care | Issue 5/2010

Abstract

Introduction

Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death.

Methods

This is a prospective, observational study including adult patients (age 18 years or older) presenting with clinical suspicion of infection to the emergency department (ED) of an urban, academic medical center between February 2005 and November 2008. Blood was sampled during the ED visit and biomarkers of endothelial cell activation, namely soluble fms-like tyrosine kinase-1 (sFlt-1), plasminogen activator inhibitors -1 (PAI-1), sE-selectin, soluble intercellular adhesion molecule (sICAM-1), and soluble vascular cell adhesion molecule (sVCAM-1), were assayed. The association between biomarkers and the outcomes of sepsis severity, organ dysfunction, and in-hospital mortality were analyzed.

Results

A total of 221 patients were included: sepsis without organ dysfunction was present in 32%, severe sepsis without shock in 30%, septic shock in 32%, and 6% were non-infected control ED patients. There was a relationship between all target biomarkers (sFlt-1, PAI-1, sE-selectin, sICAM-1, and sVCAM-1) and sepsis severity, P < 0.05. We found a significant inter-correlation between all biomarkers, including the strongest correlations between sFlt-1 and sE-selectin (r = 0.55, P < 0.001), and between sFlt-1 and PAI-1 (0.56, P < 0.001). Among the endothelial cell activation biomarkers, sFlt-1 had the strongest association with SOFA score (r = 0.66, P < 0.001), the highest area under the receiver operator characteristic curve for severe sepsis of 0.82, and for mortality of 0.91.

Conclusions

Markers of endothelial cell activation are associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.

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Title: The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis
Authors: Nathan I Shapiro
Philipp Schuetz
Kiichiro Yano
Midori Sorasaki
Samir M Parikh
Alan E Jones
Stephen Trzeciak
Long Ngo
William C Aird
Publication date: 01-10-2010
Publisher: BioMed Central
Published in: Critical Care / Issue 5/2010
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/cc9290

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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