Diagnostic value of a combination of biomarkers in patients with sepsis and severe sepsis in emergency department

Abstract

To determine a combination of biomarkers that assure the diagnosis of sepsis and severe sepsis in patients in emergency department (ED). A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462 cases) according to the diagnosis of severe sepsis. Logistic regression was performed to identify the independent factors for the diagnosis of sepsis and severe sepsis, and the optimal combination of biomarkers was established. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the combination and the biomarkers.A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462 cases) according to the diagnosis of severe sepsis. Logistic regression was performed to identify the independent factors for the diagnosis of sepsis and severe sepsis, and the optimal combination of biomarkers was established. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the combination and the biomarkers. PCT, IL-6 and D-dimer were independent factors for diagnosis of sepsis and severe sepsis. The area under the ROC curve (AUC) of the combination of three biomarkers was 0.866 for diagnosis of sepsis, and it was higher than the AUC of PCT (0.803), IL-6 (0.770) and D-dimer (0.737) alone, and this new combination showed better sensitivity, specificity, positive predictive (PPV), and negative predictive (NPV) values than that when the three biomarkers was used individually (the results of combination were 81.2%, 81.0%, 90.6%, 56.5%; that of PCT were 75.2%, 80.0%, 89.5%, 58.8%; that of IL-6 were 81.0%, 61.0%, 82.4%, 58.7%; and that of D-dimer were 79.9%, 59.0%, 81.5%, 56.5%, respectively). The AUC of the combination was 0.815 for the diagnosis of severe sepsis and was better than the three biomarkers used alone, which was 0.758 for PCT, 0.740 for IL-6, and 0.704 for D-dimer respectively. Moreover, the sensitivity, specificity, PPV and NPV of the combination were higher than that of the three biomarkers used singularly (the results of combination were 81.6%, 73.6%, 56.0%, 90.6%; that of PCT were 79.5%, 65.0%, 48.2%, 88.5%; that of IL-6 were 65.8%, 70.6%, 47.9%, 83.4%; and that of D-dimer were 60.5%, 73.2%, 48.1%, 81.8%, respectively). The combination of PCT, IL-6 and D-dimer enhances the diagnostic ability for sepsis and severe sepsis.