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Am J Respir Crit Care Med. 2017 Oct 15;196(8):1004-1011. doi: 10.1164/rccm.201611-2307OC.

A Two-Biomarker Model Predicts Mortality in the Critically Ill with Sepsis.

Author information

1
1 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
2
2 Department of Biostatistics.
3
3 Department of Pulmonary and Critical Care Medicine, Swedish Medical Center, Seattle, Washington.
4
4 Kidney Research Institute, and.
5
5 Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington.
6
6 Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and.
7
7 Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.

Abstract

RATIONALE:

Improving the prospective identification of patients with systemic inflammatory response syndrome (SIRS) and sepsis at low risk for organ dysfunction and death is a major clinical challenge.

OBJECTIVES:

To develop and validate a multibiomarker-based prediction model for 28-day mortality in critically ill patients with SIRS and sepsis.

METHODS:

A derivation cohort (n = 888) and internal test cohort (n = 278) were taken from a prospective study of critically ill intensive care unit (ICU) patients meeting two of four SIRS criteria at an academic medical center for whom plasma was obtained within 24 hours. The validation cohort (n = 759) was taken from a prospective cohort enrolled at another academic medical center ICU for whom plasma was obtained within 48 hours. We measured concentrations of angiopoietin-1, angiopoietin-2, IL-6, IL-8, soluble tumor necrosis factor receptor-1, soluble vascular cell adhesion molecule-1, granulocyte colony-stimulating factor, and soluble Fas.

MEASUREMENTS AND MAIN RESULTS:

We identified a two-biomarker model in the derivation cohort that predicted mortality (area under the receiver operator characteristic curve [AUC], 0.79; 95% confidence interval [CI], 0.74-0.83). It performed well in the internal test cohort (AUC, 0.75; 95% CI, 0.65-0.85) and the external validation cohort (AUC, 0.77; 95% CI, 0.72-0.83). We determined a model score threshold demonstrating high negative predictive value (0.95) for death. In addition to a low risk of death, patients below this threshold had shorter ICU length of stay, lower incidence of acute kidney injury, acute respiratory distress syndrome, and need for vasopressors.

CONCLUSIONS:

We have developed a simple, robust biomarker-based model that identifies patients with SIRS/sepsis at low risk for death and organ dysfunction.

KEYWORDS:

IL-8; biomarkers; sepsis; systemic inflammatory response syndrome; tumor necrosis factor receptor

PMID:
28418697
PMCID:
PMC5649981
DOI:
10.1164/rccm.201611-2307OC
[Indexed for MEDLINE]
Free PMC Article

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