Are IL-6, IL-10 and PCT plasma concentrations more reliable than APACHE-III or SAPS-II for the individual mortality risk prediction in severe sepsis?

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Introduction

Scoring systems such as APACHE-III and SAPS-II often fail to reliably predict the individual mortality risk particularly in patients with severe sepsis. Cytokines and procalcitonin (PCT) have been shown to play a crucial role both in the pathogenesis of sepsis and as diagnostic tools for the inflammatory process. The objective of this study was to investigate the relationship between plasma cytokine and PCT concentrations and the actual and predicted mortality using APACHE-III and SAPS-II in patients with severe sepsis.

Material and methods

The SCCM/ACCP selection criteria were used to identify the patients with severe sepsis. After severe sepsis was diagnosed SAPS-II and APACHE-III scores were calculated. In addition, blood samples were taken daily for the analysis of IL-6, IL-10 and PCT plasma concentrations for three consecutive days. IL-6 and IL-10 were analysed using a sandwich type of a immunoenzymatic assay (Immunotech, Marseille, France) PCT plasma concentrations were measured using a specific, ultra sensitive immunoluminometric assay (LUMItest PCT assay, BRAHMS Diagnostica, Berlin, Germany).

Results

Out of the 29 patients of this study, 13 patients died leading to a mortality rate of 44.8%. The APACHE-III and SAPS-II scoring systems produced almost identical results for the predicted mortality risks, but the areas under the ROC-curves (AUC) formed by the plot of possible pairs of false-positive and true-positive rates exhibited a poor prognostic validity for both scores (day 1: 0.5612; day 2: 0.5593; day 3: 0.5732). The plasma PCT concentrations were significantly higher in non-survivors compared to survivors (day 1: P<0.01; day 2: P<0.07; day 3: P<0.015). However, a discrimination value, to simply distinguish between survivors and non-survivors, was not found. The determination of plasma IL-6 concentrations on the first three days after inclusion into the study showed no significant difference between survivors and non-survivors. The IL-10 plasma concentrations of the patients who died were significantly higher compared with those of the survivors measured on the first two days (day 1: P<0.001; day 2: P<0.005). The degree of correlation between PCT-values and the APACHE-III scores on all days of study was high (day 1: P<0.0004; day 2: P<0.001; day 3: P<0.03). For the PCT plasma concentrations and the SAPS-II score, a good correlation was only found on the first day (day 1: P<0.005). The IL-6 concentrations showed a good correlation with the APACHE-III scores only on the first day (day 1: P<0.04) and the IL-10concentrations correlated well with the APACHE-III score at day 1 and day 3 (day 1: P<0.006; day 3: P<0.026). No correlation was found between the interleukin concentrations and the SAPS-II scoring system.

Conclusion

Our results demonstrate that the APACHE-III and the SAPS-II scoring systems evaluate a similar mortality rate in severe sepsis. However, in terms of individual mortality risk prediction, the reliability and precision of both scores is limited and does not allow a precise statement about the mortality risk. In contrast, the plasma concentrations of PCT and IL-10 were significantly higher in the non-survivors and showed a good correlation with the actual mortality. IL-6 was not useful in this context. Thus, daily analyses of plasma PCT and IL-10 concentrations might be a helpful tool to improve the individual mortality risk prediction in patients with severe sepsis, possibly in combination with scores assessing the severity of illness.