Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department

Liu et al. Critical Care Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department Bo Liu 1 Yun-Xia Chen 1 Qin Yin 1 Yun-Zhou Zhao 1 Chun-Sheng Li 1 0 Worker's Stadium South Road, Beijing , Chao-yang District 100020 , China 1 Emergency Department, Beijing Chao-yang Hospital, Capital Medical University , 8 Introduction: Presepsin levels are known to be increased in sepsis. The aim of this study was to evaluate the early diagnostic and prognostic value of Presepsin compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score in septic patients in an emergency department (ED) and to investigate Presepsin as a new biomarker of sepsis. Methods: This study enrolled 859 consecutive patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang Hospital ED from December 2011 to October 2012, and 100 age-matched healthy controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score and APACHE II score were calculated at enrollment. Comparisons were analyzed using the Kruskal-Wallis and Mann-Whitney U tests. Results: On admission, the median levels of plasma Presepsin increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of Presepsin were greater than those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock. The AUC of Presepsin for predicting 28-day mortality in septic patients was slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a combination of Presepsin and MEDS score or APACHE II score was significantly higher than that of MEDS score or APACHE II score alone in predicting severe sepsis, and was markedly higher than that of Presepsin alone in predicting septic shock and 28-day mortality in septic patients, respectively. Plasma Presepsin levels in septic patients were significantly higher in non-survivors than in survivors at 28 days' follow-up. Presepsin, MEDS score and APACHE II score were found to be independent predictors of severe sepsis, septic shock and 28-day mortality in septic patients. The levels of plasma Presepsin were positively correlated with PCT, MEDS score and APACHE II score in every septic group. Conclusion: Presepsin is a valuable biomarker for early diagnosis of sepsis, risk stratification, and evaluation of prognosis in septic patients in the ED. - Introduction Sepsis still represents a major cause of morbidity and mortality in critically ill patients despite the use of modern antibiotics and resuscitation therapies [1]. There is a lack of early diagnosis and timely intervention for sepsis in the emergency department (ED), and recent interest has focused on biomarkers for early diagnosis, risk stratification, and evaluation of prognosis of sepsis. CD14, the high-affinity receptor for lipopolysaccharide/ lipopolysaccharide binding protein complexes, is a glycoprotein expressed in macrophage, monocyte, and granulocyte cells and their cell membranes [2]. The lipopolysaccharidelipopolysaccharide binding proteinCD14 complex is released into circulation by shedding of CD14 from the cell membrane, yielding soluble CD14. Presepsin (soluble CD14-ST), a novel biomarker for diagnosing sepsis, is a subtype of soluble CD14, and is a 13 kDa protein that is a truncated N-terminal fragment of CD14 [3]. Although some clinical studies confirmed that plasma presepsin levels were significantly increased in septic patients, and were positively correlated with the severity of sepsis, the sample sizes were relatively small [4-9], and these findings have not yet been corroborated in a large number of septic patients in the ED. The aim of this study was to investigate the clinical value of presepsin in early diagnosis, risk stratification and prognostic evaluation of sepsis in a large sample of septic patients in a hospital ED, and to compare it with the prognostic value of procalcitonin (PCT), the Mortality in Emergency Department Sepsis (MEDS) score and the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Methods Patient inclusion and exclusion criteria This prospective study was conducted in the ED of Beijing Chao-yang Hospital, a university teaching hospital with approximately 240,000 to 260,000 ED admissions per year. From December 2011 to October 2012, consecutive patients who fulfilled the criteria for sepsis as defined by the American College of Chest Physicians/ Society of Critical Care Medicine (ACCP/SCCM) were enrolled [10]. Patients were classified at the time of enrollment as having sterile systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis and septic shock, according to ACCP/SCCM criteria [10]. Exclusion criteria were as follows: <18 years old, terminal stage of disease (malignant cancer of any type, acquired immunodeficiency syndrome, end-stage liver or renal disease), and the patient or relatives did not consent to inclusion. Finally, after excluding 92 patients who did not meet the inclusion criteria and 49 patients who were lost to follow-up, 859 patients were enrolled and were followed for 28 days or until death. At the same time, 100 age-matched healthy individuals were enrolled as controls. This study was approved by the Beijing Chao-yang Hospital Ethics Committee. Written informed consent was obtained from every subject. Establishment of infection The infections of different diseases in our study were clinically established on the basis of clinical features, laboratory findings, and imaging tests according to criteria of the International Sepsis Forum Consensus Conference on Definitions of Infection [11]. For example, the diagnosis of community-acquired pneumonia was mainly based on a new infiltrate plus at least one recently acquired respiratory symptom (cough, sputum production, dyspnea, tachypnea, pleuritic pain) or sign (auscultatory findings of abnormal breath sounds and rales). Intraabdominal infections comprised the following diseases in our study: the diagnosis of peritonitis was based on clinical findings including abdominal pain, tenderness to palpation, and peritoneal signs such as rigidity or rebound tenderness, which were supported by radiographic findings, such as free air under the diaphragm or localized fluid collection visualized by computed tomography with a compatible clinical illness; the diagnosis of biliary tract infection was on the basis of clinical evidence of biliary tract infection with surgical or radiographic evidence of supportive complications; typhlitis was diagnosed according to a compatible clinical presentation with radiographic evidence of bowel wall edema and/or gas and/or hemorrhagic necrosis within the bowel wall of the cecum; and the diagnosis of pyelonephritis was based on c (...truncated)