Neutropenic sepsis is associated with distinct clinical and biological characteristics: a cohort study of severe sepsis.

John P Reilly,Altaf Kazi,Mark E Mikkelsen,Michael G S Shashaty,Kristin M Hudock,Dudley Charles,Anna Tommasini,Thomas G Dunn,Brian J Anderson,Jason D Christie,Nuala J Meyer

doi:10.1186/s13054-016-1398-y

Abstract

BackgroundImmunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; however, it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics.MethodsWe conducted a prospective cohort study of patients admitted to the medical intensive care unit of an academic medical center with severe sepsis. Patients were followed for the development of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality. Plasma proteins, representing the host inflammatory response, anti-inflammatory response, and endothelial leak were measured in 30 % of subjects. Clinical characteristics and plasma protein concentrations of patients with neutropenia at enrollment were compared to patients without neutropenia.ResultsOf 797 subjects enrolled, 103 (13 %) were neutropenic at ICU admission. The neutropenic subjects were more often in shock, admitted from the hospital ward, had higher APACHE III scores, and more likely bacteremic. Neutropenia was an independent risk factor for AKI (RR 1.28; 95 % CI 1.04, 1.57; p = 0.03), but not ARDS (RR 0.90; 95 % CI 0.70, 1.17; p = 0.42) or 30-day mortality (RR 1.05; 95 % CI 0.85, 1.31; p = 0.65). Neutropenic subjects had higher plasma interleukin (IL)-6 (457 vs. 249 pg/ml; p = 0.03), IL-8 (581 vs. 94 pg/ml; p <0.001), and granulocyte colony-stimulating factor (G-CSF) (3624 vs. 99 pg/ml; p <0.001). Angiopoietin-2 and IL-1 receptor antagonist concentrations did not differ between groups.ConclusionsNeutropenic sepsis is associated with a higher AKI risk and concentrations of inflammatory mediators IL-6, IL-8, and G-CSF relative to non-neutropenic patients. These differences may have implications for future therapies targeting neutropenic sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1398-y) contains supplementary material, which is available to authorized users.

Highlights

Immunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics
Immunocompromise caused by cancer, immunodeficiency, or immunosuppressing therapy is increasingly common in intensive care unit (ICU) and is a strong contributor to sepsis risk [6]
Patients who met the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria for severe sepsis or septic shock [23] were eligible for participation in the Molecular Epidemiology of Severe Sepsis in the ICU (MESSI) cohort study if infectionrelated organ dysfunction was deemed the primary cause for ICU admission [24]

Summary

Introduction

Immunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics. Immunocompromise caused by cancer, immunodeficiency, or immunosuppressing therapy is increasingly common in ICUs and is a strong contributor to sepsis risk [6]. Immunocompromised states are associated with lower sepsis survival [7], with neutropenia being a high-risk condition for critically ill patients with sepsis [8]. As the neutrophil is believed to have a central role in the pathogenesis of sepsis and related organ dysfunction [9, 10], understanding whether neutropenic patients with sepsis demonstrate distinct clinical or molecular characteristics is an important yet unanswered question

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