Prognostic value of presepsin (soluble CD14-subtype) in diagnosis of ventilator-associated pneumonia and sepsis in trauma patients

Page 968 VOJNOSANITETSKI PREGLED ORIGINAL ARTICLE Vojnosanit Pregl 2018; 75(10): 968–977. UDC: 615.816.2:616-001-06-037]:[616.24-002+616.94 https://doi.org/10.2298/VSP161104027J Prognostic value of presepsin (soluble CD14-subtype) in diagnosis of ventilator-associated pneumonia and sepsis in trauma patients Prognostička vrednost presepsina (solubilnog CD 14-podtipa) u dijagnozi pneumonija povezanih sa mehaničkom ventilacijom i sepse kod traumatizovanih bolesnika Bojan Jovanović*†, Olivera Djurić*‡, Ljiljana Marković-Denić*‡, Aleksandra Isaković*§, Krstina Doklestić*║, Sanja Stanković¶, Sašenka Vidičević*§, Ivan Palibrk*†, Janko Samardžić**, Vesna Bumbaširević*† University of Belgrade, *Faculty of Medicine, ‡Institute of Epidemiology, §Insitute of Medical and Clinical Biochemistry, Institute of Pharmacology, **Clinical Pharmacology and Toxicology, Belgrade, Serbia; Clinical Center of Serbia, †Center for Anaesthesiology, ║Clinic for Emergency Surgery, ¶Center for Medical Biochemistry, Belgrade, Serbia Abstract Background/Aim. Presepsin (soluble CD14-subtype) is a fragment of CD14 produced in response to bacterial infections and a novel biomarker of pneumonia, sepsis and septic shock. The aim of this study was to compare sensitivity and specificity of persepsin, soluble CD14-subtype (sCD14-ST) with other biomarkers: procalcitonine (PCT), C-reactive protein (CRP) and leukocyte count (Le) in mechanically ventilated injured patients, as a marker of pneumonia, sepsis and septic shock. Methods. The prospective study was undertaken in trauma and surgery intensive care unit of the Emergency Center, the Clinical Center of Serbia from January to April 2013. The study included 39 trauma patients requiring mechanical ventilation, and who developed one of the following inclusion criteria: Systemic Inflammatory Response Syndrome (SIRS), ventilator associated pneumonia (VAP), sepsis and/or septic shock. On admission Acute Physiology and Chronic Health Evaluation II (APACHE II) Score and Injury Severity Score (ISS) were calculated. Seventy-two measurements of four biomarkers (presepsin, PCT, CRP and Le) were performed in 39 patients at the moments of diagnosis of SIRS, VAP, sepsis and/or septic shock (21 when SIRS diagnosis was established, 21 after the di- Apstrakt Uvod/Cilj. Persepsin (solubilni CD14-podtip) je fragment CD14 koji se produkuje kao odgovor na prisustvo bakterijske infekcije i predstavlja novi biomarker u dijagnostici pneumonije, sepse i spetičkog šoka. Cilj ove studije bio je da se uporedi senzitivnost i specifičnost presepsina (solubilnog CD14podtipa) sa ostalim biomarkerima infekcije: prokalcitoninom agnosis of VAP, 18 at the moment of diagnosis of sepsis and the remaining 12 measurements were conducted while diagnosing the septic shock). The Sequential Organ Failure Assessment (SOFA) score was calculated at these points as well. Results. Patients were mainly severely injured (mean ISS = 24.2) and had moderately severe medical condition at admission (mean Apache II score, 14.5). Presepsin concentration significantly differed among all the four groups, except between sepsis and septic shock. The strongest positive correlation of presepsin evinced with PCT (r = 0.741, p < 0.001). The sCD14-ST indicated better performance in diagnosis of both VAP (AUC = 0.909) and sepsis (AUC = 0.899), compared to PCT (AUCs: 0.863, 0.885, respectively), CRP (AUCs: 0.703, 0.677, respectively) and Le (AUCs: 0.668, 0.700, respectively). Conclusion. This study revealed that sCD14-ST is a reliable biomarker for distinguishing sepsis severity. It also showed a good correlation with the infection development as well as worsening in injured patients. Key words: presepsin protein, human; pneumonia, ventilator associated; sepsis; shock septic; biomarkers; sensitivity and specificity; diagnosis. (PCT), C-reaktivnim proteinom (CRP) i brojem leukocita (Le) kod povređenih bolesnika na mehaničkoj ventilaciji, kao markera pneumonije, sepse i septičkog šoka. Metode. Prospektivna studija sprovedena je u dve jedinice intenzivnog lečenja (JIL) (traumatološka i hirurška) Kliničkog centra Srbije u periodu od januara do aprila 2013. godine. U studiju je bilo uključeno 39 traumatizovanih bolesnika na mehaničkoj ventilaciji kod kojih se razvio neki od sledećih ishoda koji su bili i kriterijumi za Correspondence to: Bojan Jovanović, Clinical Center of Serbia, Center for Anaesthesiology, Grčića Milenka 4B/94, 11 000 Belgrade, Serbia. Email: Vol. 75, No 10 VOJNOSANITETSKI PREGLED uključivanje: sisemski inflamatorni odgovor (SIRS), pneumonija povezana sa mehaničkom ventilacijom (VAP), sepsa i/ili septički šok. Na prijemu u JIL Acute Physiology and Chronic Health Evaluation II (APACHE II) skor i Injury Severity Score (ISS) su računati za svakog bolesnika. Sedamdeset i dva merenja koncentracije četiri biomarkera (presepsin, PCT, CRP i Le) urađena su kod 39 bolesnika u trenutku postavljanja dijagnoze SIRS, VAP, sepse i/ili septičkog šoka. Sequential Organ Failure Assessment (SOFA) skor takođe je meren istovremeno. Rezultati. Većina bolesnika na prijemu bila je teško povređena (srednja vrednost ISS skora = 24.2) i bila je u srednje teškom stanju (srednja vrednost APACHE II skora = 14.5). Koncentracije presepsina značajno su se razlikovale između sve četiri grupe bolesnika, osim između grupa sa sepsom i septičkim šokom. Introduction Ventilator associated pneumonia (VAP) is one of the most common nosocomial infections appearing in the intensive care unit 1. Up to 10% of patients receiving mechanical ventilation will eventually develop VAP, with an attributable mortality rate estimated between 1% to 1.5% 2. In critically injured patients, incidence, morbidity and mortality of VAP are even higher 3. Sepsis is infrequent but significant cause of death in patients with blunt injury. In modern era of intensive care medicine, delays in the initiation of antimicrobial treatment is not rare and while the mortality of patients with sepsis is gradually decreasing, it is still quite high 4. A cause of this could be found in non-specific symptoms of the infection leading to an inappropriate empirical treatment and increased resistance profile of pathogens. In septic complication, however, it is important to bear in mind not only the fact that the sensitivity of blood cultures for the diagnosis of pneumonia sepsis is less than 25% but also that, when present, the organisms may originate from an extrapulmonary site of infection, in as many as 64% of cases, even if VAP is present 5. Since clinical criteria have low sensitivity and specificity, there is no “gold standard” for diagnosing either VAP or sepsis 6. Currently, procalcitonin (PCT) together with C-reactive protein (CRP) and different haematological parameters [white blood cell (WBC) count] are used as markers to diagnose sepsis or severe sepsis 7. On the other hand, several invasive or semi-invasive methods can be used to diagnose VAP, with certain disadvantages (...truncated)