Abstract
Kallistatin, an endogenous serine proteinase inhibitor, is protective against sepsis in animal models. The aim of this study was to determine the plasma concentration of kallistatin in intensive care unit (ICU) patients with severe sepsis and septic shock and to determine their potential correlation with disease severity and outcomes. We enrolled 86 ICU patients with severe sepsis and septic shock. Their plasma concentrations of kallistatin, kallikrein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 were measured by enzyme-linked immunosorbent assay. The association of kallistatin levels with disease severity and patient outcomes was evaluated. The relationship between kallistatin and other biomarkers was also analyzed. Plasma kallistatin levels on day 1 of ICU admission were lower in patients with septic shock compared with patients with severe sepsis (p = 0.004). Twenty-nine patients who died in the hospital had significantly lower day 1 kallistatin levels than patients who survived (p = 0.031). Using the optimal cutoff value (4 μg/ml) of day 1 plasma kallistatin determined by receiver operating characteristic curves for 60-day mortality, we found that high kallistatin levels were associated with a preferable 60-day survival (p = 0.012) by Kaplan-Meier analysis and lower Sequential Organ Failure Assessment (SOFA) scores over the first 5 days in the ICU (p = 0.001). High kallistatin levels were also independently associated with a decreased risk of septic shock, the development of acute respiratory distress syndrome, and positive blood cultures. In addition, there were inverse correlations between day 1 kallistatin levels and the levels of TNF-α, IL-1β, IL-6, and C-reactive protein, and SOFA scores on day 1. Our results indicate that during severe sepsis and septic shock, a decrease in plasma concentrations of kallistatin reflects increased severity and poorer outcome of disease.
Highlights
Sepsis is a major cause of death in the intensive care unit (ICU)
Of 249 patients admitted to ICUs with suspected sepsis, 28 patients were screened but refused to provide informed consent, 39 had prior hospitalization within 14 days before admission, 53 had an underlying terminal illness receiving palliative treatment, 13 had prior episodes during hospitalization, 21 had delayed enrollment for more than 48 hours, and 9 had their diagnosis of sepsis excluded later; 86 patients were included in this study
Survivors and nonsurvivors were similar in terms of age, sex, primary infection site, comorbidities, frequency of acute respiratory distress syndrome (ARDS), white blood cell count at ICU admission, need for invasive mechanical ventilation, positive blood cultures, Fig 1
Summary
Sepsis is a major cause of death in the intensive care unit (ICU). Between 11% and 15% of patients admitted to ICUs have or will develop severe sepsis, and the mortality rate for these. Plasma kallistatin and sepsis in the ICU patients varies between 30% and 60% [1,2,3]. Sepsis is characterized by a generalized overwhelming inflammatory process and subsequent development of multiple organ dysfunction, potentially leading to death. Despite recent advances in its early diagnosis, the early administration of antibiotics and fluids, hemodynamic optimization, and better technological support of organ function, treatment of sepsis remains exclusively expectant and supportive [4]. Pharmacological agents that interfere with the effects of inflammation during sepsis are still of intense clinical interest
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