Clinical and biological markers for predicting ARDS and outcome in septic patients

Abstract

Sepsis is a common cause of acute respiratory distress syndrome (ARDS) associated with a high mortality. A panel of biomarkers (BMs) to identify septic patients at risk for developing ARDS, or at high risk of death, would be of interest for selecting patients for therapeutic trials, which could improve ARDS diagnosis and treatment, and survival chances in sepsis and ARDS. We measured nine protein BMs by ELISA in serum from 232 adult septic patients at diagnosis (152 required invasive mechanical ventilation and 72 had ARDS). A panel including the BMs RAGE, CXCL16 and Ang-2, plus PaO₂/FiO₂, was good in predicting ARDS (area under the curve = 0.88 in total septic patients). Best performing panels for ICU death are related to the presence of ARDS, need for invasive mechanical ventilation, and pulmonary/extrapulmonary origin of sepsis. In all cases, the use of BMs improved the prediction by clinical markers. Our study confirms the relevance of RAGE, Ang-2, IL-1RA and SP-D, and is novel supporting the inclusion of CXCL16, in BMs panels for predicting ARDS diagnosis and ARDS and sepsis outcome.

Figure 1

Predictive value of biomarkers and clinical variables in ARDS diagnosis in septic patients. Panels represent ROC curve analysis comparing predictive value of the best performing BM, clinical variable, BMs panel and final panel combining BMs and clinical variable in patients with (a) sepsis, (b) sepsis requiring IMV, and (c) extrapulmonary sepsis. ARDS acute respiratory distress syndrome, BM biomarker, IMV invasive mechanical ventilation.

Figure 2

Predictive value of biomarkers and clinical variables on ICU mortality of septic patients. Panels represent ROC curve analysis comparing predictive value of the best performing BM, clinical variable, BMs panel and final panel combining BMs and clinical variable in patients with (a) sepsis, (b) sepsis requiring IMV, and (c) sepsis with ARDS. ICU intensive care unit, BM biomarker, IMV invasive mechanical ventilation, ARDS acute respiratory distress syndrome.

Figure 3

Predictive value of biomarkers and clinical variables on cumulative ICU survival in septic patients. Panels represent Kaplan–Meier survival curves for low and high scores of the best performing panels in patients with (a) sepsis, (b) sepsis requiring IMV, and (c) sepsis with ARDS. The BMs and clinical variable that integrate the best performing panels are presented under the plots, including the cut-off values used for the scoring. Dotted lines represent the groups of patients with low total scores, and solid lines those with high total scores. ICU intensive care unit, BM biomarker, IMV invasive mechanical ventilation, ARDS acute respiratory distress syndrome.