Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: a multicenter prospective study

Marco Ulla 0 1 3 Elisa Pizzolato 0 3 Manuela Lucchiari 2 Maria Loiacono 2 Flavia Soardo 0 3 Daniela Forno 0 3 Fulvio Morello 0 3 Enrico Lupia 0 3 Corrado Moiraghi 0 3 Giulio Mengozzi 2 Stefania Battista 0 3 0 Emergency Medicine Department, Citta della Salute e della Scienza University Hospital , Corso Bramante 88, I-10126 Turin , Italy 1 Emergency Medicine Department, Imperial College NHS Trust, St Mary's Hospital , Praed Street, London, W2 1NY , UK 2 Clinical Biochemistry Laboratory, Citta della Salute e della Scienza University Hospital , Corso Bramante 88, I-10126 Turin , Italy 3 Emergency Medicine Department, Citta della Salute e della Scienza University Hospital , Corso Bramante 88, I-10126 Turin , Italy Introduction: Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock. Methods: This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records. Results: Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival. Conclusions: In our experience, presepsin was useful in the early diagnosis of infection in a complex population of patients with SIRS, sepsis, severe sepsis and septic shock who presented to the ED. Presepsin showed a significant prognostic value, and initial values were significantly correlated with in-hospital mortality of patients affected by sepsis, severe sepsis or septic shock. - Introduction Sepsis, severe sepsis and septic shock are some of the most common conditions handled in the Emergency Department (ED) and ICU, and, despite modern antibiotic therapy in conjunction with cardiovascular and respiratory support, mortality rates remain between 30% and 60% [1-3]. According to the most recent guidelines, published in 2013 by the Surviving Sepsis Campaign, early recognition of these conditions and the speed and appropriateness of therapy in the initial hours after presentation are likely to influence the outcomes of septic patients [4]. More recently, the biomarkers used as diagnostic criteria for sepsis, plasma C-reactive protein (CRP) or procalcitonin (PCT) levels more than 2 standard deviations (SD) above the normal value, are now part of the inflammatory variables which, together with infection, whether documented or suspected, constitute a definition of sepsis [4,5]. There is also good evidence that low PCT levels or similar biomarkers can be used to assist the clinician in the critical care areas in the discontinuation of empiric antibiotics in those patients who appear septic, but have no subsequent evidence of infection [6]. Although PCT has an established role as a biomarker in septic patients and has been shown to correlate closely with infection, it has some limitations. It rises transiently in patients with nonseptic conditions and systemic inflammatory response syndromes (SIRS) (for example, trauma, surgery, heatstroke) and is not detectable in certain cases of sepsis. Furthermore, biological predictors of mortality are absent, clinical scores appear to be of limited value and the role of PCT as a poor prognostic factor in patients admitted to the ED because of sepsis remains to be proved [7]. The ideal biomarker should retain high sensitivity and specificity and be cost-effective and promptly available. Cluster of differentiation 14 (CD14) is a glycoprotein expressed on the membrane surface of monocytes and macrophages and serves as a receptor for complexes of lipopolysaccharides (LPSs) and LPS-binding proteins (LPBs). By activating a proinflammatory signaling cascade on contact with infectious agents, CD14 has a role as a pattern recognition molecule in the innate immune response against microorganisms [8]. During inflammation plasma protease activity generates soluble CD14 (sCD14) fragments. One of them, called sCD14 subtype (sCD14-ST), or presepsin, has recently been identified. Presepsin is normally present in very low concentrations in the serum of healthy individuals and has been shown to be increased in response to bacterial infections according to the severity of disease. Moreover, rapid dosage methods, based on chemiluminescence enzyme immunoassay, are available and allow automated measurements in a short time [9,10]. Preliminary studies aAPACHE II: Acute Physiology and Chronic Evaluation II; SIRS: systemic inflammatory response syndrome; SOFA: Sequential Organ Failure Assessment. Values are means and minimum and maximum range. SOFA and APACHE II scores reported were calculated at the very first evaluation in the Emergency Department. suggest that the level of presepsin significantly differs in healthy individuals and in patients with local infection, SIRS, sepsis or severe sepsis [11,12]. Presepsin is currently under investigation in clinical practice as a reliable marker of adult and neonatal sepsis [13,14] and for the postmortem diagnosis of sepsis-related death [15]. On the basis of these premises, we designed a multicenter prospective study to investigate the diagnostic role and efficacy, together with prognostic power, of presepsin, compared to PCT in an adult population presenting to the ED with SIRS (control group) or suspected sepsis or septic shock (study group). Patients and methods Patients and design of the study We conducted a (...truncated)