Background: This study investigated the clinical value of interleukin-6 (IL-6), pentraxin 3 (PTX3), and procalcitonin (PCT) in patients with sepsis and septic shock diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Methods: Serum levels of IL-6, PTX3, and PCT were measured in 142 enrolled subjects (51 with sepsis, 46 with septic shock, and 45 as controls). Follow-up IL-6 and PTX3 levels were measured in patients with initial septic shock within 24 h of hospital discharge. Optimal cut-off values were determined for sepsis and septic shock, and prognostic values were evaluated. Results: Serum IL-6 levels could discriminate sepsis (area under the curve [AUC], 0.83–0.94, P < 0.001; cut-off value, 52.60 pg/mL, 80.4% sensitivity, 88.9% specificity) from controls and could distinguish septic shock (AUC, 0.71–0.89; cut-off value, 348.92 pg/mL, 76.1% sensitivity, 78.4% specificity) from sepsis. Twenty-eight-day mortality was significantly higher in the group with high IL-6 (≥ 348.92 pg/mL) than in the group with low IL-6 (< 348.92 pg/mL) (P = 0.008). IL-6 was an independent risk factor for 28-day mortality among overall patients (hazard ratio, 1.0004; 95% confidence interval, 1.0003–1.0005; p = 0.024). In septic shock patients, both the initial and follow-up PTX3 levels were consistently significantly higher in patients who died than in those who recovered (initial p = 0.004; follow-up P < 0.001). Conclusions: The diagnostic and prognostic value of IL-6 was superior to those of PTX3 and PCT for sepsis and septic shock.

Background: We investigated the diagnostic and prognostic value of presepsin among patients with organ failure, including sepsis, in accordance with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Methods: This prospective observational study included 420 patients divided into three groups: non-infectious organ failure (n = 142), sepsis (n = 141), and septic shock (n = 137). Optimal cut-off values of presepsin to discriminate between the three groups were evaluated using receiver operating characteristic curve analysis. We determined the optimal cut-off value of presepsin levels to predict mortality associated with sepsis and performed Kaplan–Meier survival curve analysis according to the cut-off value. Cox proportional hazards model was performed to determine the risk factors for 30-day mortality. Results: Presepsin levels were significantly higher in sepsis than in non-infectious organ failure cases (p < 0.001) and significantly higher in patients with septic shock than in those with sepsis (p = 0.002). The optimal cut-off value of the presepsin level to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (p < 0.001) and between sepsis and septic shock was 1285 pg/mL (p < 0.001). The optimal cut-off value of the presepsin level for predicting the 30-day mortality was 821 pg/mL (p = 0.005) for patients with sepsis. Patients with higher presepsin levels (≥ 821 pg/mL) had significantly higher mortality rates than those with lower presepsin levels (< 821 pg/mL) (log-rank test; p = 0.004). In the multivariate Cox proportional hazards model, presepsin could predict the 30-day mortality in sepsis cases (hazard ratio, 1.003; 95% confidence interval 1.001–1.005; p = 0.042). Conclusions: Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and could help clinicians identify patients with sepsis with poor prognosis. Presepsin was an independent risk factor for 30-day mortality among patients with sepsis and septic shock.

The 2016 Surviving Sepsis Campaign guidelines suggest guiding resuscitation to normalize lactate levels in patients with sepsis-associated hyperlactatemia as a marker of tissue hypoperfusion. This study evaluated the prognostic value of lactate levels and lactate clearance for 30-day mortality in patients with sepsis and septic shock diagnosed in the emergency department. We performed a retrospective cohort study of sepsis patients with initial lactate levels of ≥2 mmol/L. All patients met the Sepsis-3 definitions. The prognostic value of 6-hour lactate levels, 6-hour lactate clearance, 6-hour lactate metrics (≥2 mmol/L), and lactate clearance metrics (<10%, <20%, and <30%) was evaluated. We compared the sensitivity and specificity between metrics. Of the 363 sepsis and septic shock patients, 148 died (30-day mortality: 40.8%). Nonsurvivors had significantly higher 6-hour lactate levels and lower 6-hour lactate clearance than those of survivors. Six-hour lactate levels and 6-hour lactate clearance were associated with 30-day mortality after adjusting for potential confounders (odds ratio, 1.191 [95% confidence interval (CI), 1.097–1.294] and 0.989 [0.983–0.995], respectively). Six-hour lactate levels had better prognostic value than 6-hour lactate clearance (area under the curve, 0.720 [95% CI, 0.670–0.765] vs 0.656 [0.605–0.705]; P = .02). Six-hour lactate levels of ≥3.5 mmol/L and 6-hour lactate clearance of <24.4% were the optimal cut-off value in predicting the 30-day mortality. The prognostic value of 6-hour lactate metrics and 6-hour lactate clearance metrics did not differ. Six-hour lactate levels (≥2 mmol/L) had the highest sensitivity (89.2%). Six-hour lactate levels proved to be more accurate in predicting 30-day mortality than 6-hour lactate clearance and initial lactate levels.

Biomarkers are valuable tools for the prediction of mortality in patients with sepsis. However, the use of a single biomarker to predict patient outcomes is challenging owing to the complexity and redundancy of the immune response to infections. We aimed to conduct a prospective observational analysis to investigate the prognostic value of pentraxin 3, interleukin 6, procalcitonin, and lactate combined in predicting the 28-day mortality rate in patients with sepsis or septic shock (n = 160; sepsis, 78; sepsis shock, 82). Two methods (the frequency sum of values above the cutoff, and the multivariate logistic regression model) were used to assess the prognostic value of the biomarker combination. In the receiver operating characteristic curve analyses, the combination of the 4 biomarkers was better than the Sequential Organ Failure Assessment (SOFA) score in predicting the 28-day mortality rate, regardless of whether the frequency sum of values above the cutoff or the multivariate logistic model was used for the analysis. The addition of the SOFA score to the biomarker combination did not result in a better performance for the prediction of mortality. The combined biomarker approach showed good performance in predicting 28-day all-cause mortality among patients diagnosed with either sepsis or septic shock according to the Sepsis-3 definitions. Furthermore, it was superior to the SOFA score in predicting mortality.

Vasoactive and inotropic medications are essential for sepsis management; however, the association between the maximum Vasoactive-Inotropic score (VISmax) and clinical outcomes is unknown in adult patients with sepsis. We investigated the VISmax as a predictor for mortality among such patients in the emergency department (ED) and compared its prognostic value with that of the sequential organ failure assessment (SOFA) score. This single-center retrospective study included 910 patients diagnosed with sepsis between January 2016 and March 2020. We calculated the VISmax using the highest doses of vasopressors and inotropes administered during the first 6 h on ED admission and categorized it as 0–5, 6–15, 16–30, 31–45, and >45 points. The primary outcome was 30-day mortality. VISmax for 30-day mortality was significantly higher in non-survivors than in survivors. The mortality rates in the five VISmax groups were 17.2%, 20.8%, 33.3%, 54.6%, and 70.0%, respectively. The optimal cut-off value of VISmax to predict 30-day mortality was 31. VISmax had better prognostic value than the cardiovascular component of the SOFA score and initial lactate levels. VISmax was comparable to the APACHE II score in predicting 30-day mortality. Multivariable analysis showed that VISmax 16–30, 31–45, and >45 were independent risk factors for 30-day mortality. VISmax in ED could help clinicians to identify sepsis patients with poor prognosis.