Diagnostic and prognostic utility of soluble CD 14 subtype (presepsin) for severe sepsis and septic shock during the first week of intensive care treatment

Michael Behnes, Thomas Bertsch, Dominic Lepiorz, Siegfried Lang, Frederik Trinkmann, Martina Brueckmann, Martin Borggrefe, Ursula Hoffmann, Michael Behnes, Thomas Bertsch, Dominic Lepiorz, Siegfried Lang, Frederik Trinkmann, Martina Brueckmann, Martin Borggrefe, Ursula Hoffmann

Abstract

Introduction: The aim of this study was to evaluate the diagnostic and prognostic value of presepsin in patients with severe sepsis and septic shock during the first week of ICU treatment.

Methods: In total, 116 patients with suspected severe sepsis or septic shock were included during the first 24 hours of ICU treatment. Blood samples for biomarker measurements of presepsin, procalcitonin (PCT), interleukin 6 (IL-6), C reactive protein (CRP) and white blood cells (WBC) were drawn at days 1, 3 and 8. All patients were followed up for six months. Biomarkers were tested for diagnosis of sepsis, severe sepsis, septic shock and for prognosis of 30-days and 6-months all-cause mortality at days 1, 3 and 8. Diagnostic and prognostic utilities were tested by determining diagnostic cutoff levels, goodness criteria, C-statistics and multivariable Cox regression models.

Results: Presepsin increased significantly from the lowest to most severe sepsis groups at days 1, 3 and 8 (test for linear trend P <0.03). Presepsin levels revealed valuable diagnostic capacity to diagnose severe sepsis and septic shock at days 1, 3 and 8 (range of diagnostic area under the curves (AUC) 0.72 to 0.84, P = 0.0001) compared to IL-6, PCT, CRP and WBC. Goodness criteria for diagnosis of sepsis severity were analyzed (≥sepsis, cutoff = 530 pg/ml; ≥severe sepsis, cutoff = 600 pg/ml; ≥septic shock, cutoff = 700 pg/ml; P <0.03). Presepsin levels revealed significant prognostic value for 30 days and 6 months all-cause mortality (presepsin: range of AUC 0.64 to 0.71, P <0.02). Patients with presepsin levels of the 4th quartile were 5 to 7 times more likely to die after six months than patients with lower levels. The prognostic value for all-cause mortality of presepsin was comparable to that of IL-6 and better than that of PCT, CRP or WBC.

Conclusions: In patients with suspected severe sepsis and septic shock, presepsin reveals valuable diagnostic capacity to differentiate sepsis severity compared to PCT, IL-6, CRP, WBC. Additionally, presepsin and IL-6 reveal prognostic value with respect to 30 days and 6 months all-cause mortality throughout the first week of ICU treatment.

Trial registration: ClinicalTrials.gov http://NCT01535534. Registered 14 February 2012.

Figures

Figure 1
Figure 1
Presepsin (top), procalcitonin (PCT, middle) and IL-6 plasma levels (bottom) in patients admitted to the internal ICU with proven criteria of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis and septic shock. Left diagrams show results of biomarker measurements at day 1, middle diagrams show results at day 3 and right diagrams show results at day 8. Sixty individuals served as a control group at day 1. Data are presented as medians with 25th and 75th percentiles (boxes) and 5th and 95th percentiles (whiskers).
Figure 2
Figure 2
Presepsin (left column) and IL-6 levels (right column) were significantly increased (P<0.001) in non-survivors compared to survivors after 30 days (top) and 6 months (bottom) consistently at days 1, 3 and 8 of ICU treatment. IL-6 levels decreased both in survivors and non-survivors during the first week of ICU treatment (survivors: after 30 days, n = 58; 6 months, n = 44; non-survivors: after 30 days, n = 58; 6 months, n = 72; P = 0.001). A significant decrease of presepsin levels over days 1, 3 and 8 of ICU treatment was not detected (P = 0.59 and P = 0.39). Log-transformed biomarker concentrations were analyzed by two-way analysis of variance (ANOVA) to estimate the effects of the two factors, time and survival on biomarker levels. An interaction of survival with time was not detected. Data are presented as medians with 25th and 75th percentiles (boxes), smallest and largest values without extreme values (whiskers) and extreme values (points).
Figure 3
Figure 3
Kaplan-Meier survival curves evaluated by quartiles of presepsin after 30 days (left column) and 6 months (right column) of follow up in the total study cohort (n = 116). Hazard ratios (HR) were calculated for each risk group according to presepsin quartiles measured at day 1 (top) and day 8 (bottom).

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