Can plasma-free DNA concentration be a diagnostic tool in critically ill septic patients?

Abstract

Recent evidence suggests that the plasma-free DNA concentration has potential use as a prognostic marker in many clinical situations including sepsis, trauma, and acute stroke [1]. However, its predictive value is arguable. We hypothesized that plasma DNA is increased in septic patients admitted to the ICU compared with nonseptic ICU patients, and it is correlated with disease severity and clinical outcome. Forty-two consecutive patients (11 septic, 31 nonseptic) admitted to a mixed ICU and mechanically ventilated were recruited. Plasma-free DNA concentration was measured by real-time PCR assay for the β-globin gene, and the APACHE II score, SOFA score, serum C-reactive protein (CRP) concentrations, procalcitonin (PCT) concentrations, serum lipid concentrations, and clinical outcome (ICU/hospital days and mortality) were assessed on admission to the ICU. Assessments and samplings were repeated as the diagnosis of the patients changed (sepsis, severe sepsis and septic shock). Finally, 86 plasma samples were collected. Descriptive statistics, Mann–Whitney U, Kruskall–Wallis and Spearman's tests, and receiver operating characteristic analysis were used when appropriate. Demographic data were similar. ICU and hospital mortalities were 26.2% and 33.3%, respectively. The mean DNA concentrations on admission were significantly higher in ICU patients compared with healthy subjects (n = 11) (13,405 GE/ml versus 390 GE/ml, P < 0.05) and septic patients compared with nonseptic patients (33,170 GE/ml versus 1,171 GE/ml, P < 0.001). Furthermore, during the overall ICU stay, increased DNA concentration associated with the increase of severity of illness was noted; however, this increase was statistically significant only between septic and septic shock samples (26,624 GE/ml versus 42,861 GE/ml, P < 0.05). The area under the curve obtained for the plasma-free DNA concentration in distinguishing between septic and nonseptic patients on admission was 0.9 (sensitivity 84%, specificity, 95%; cutoff 4,083 GE/ml). Also, the plasma-free DNA concentration was found to be higher in patients who died in the ICU compared with patients who survived, although not statistically significant. The DNA concentration demonstrated a significant correlation with CRP (P = 0.037, r = 0.365), PCT (P = 0.007, r = 0.457) and high-density lipoprotein (P = 0.015, r = -0.415) concentrations. In conclusion, plasma DNA may be a potentially valuable tool to confirm the diagnosis of sepsis on admission to the ICU and to monitor disease severity.