Received on November 26, 2007
Accepted on March 5, 2008

Molecular Diagnostics and Genetics

Cell-Free Plasma DNA as a Predictor of Outcome in Severe Sepsis and Septic Shock

¹ Department of Medicine and Emergency Care, Helsinki University Central Hospital, Helsinki, Finland
² Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland, and Minerva Research Institute, Helsinki, Finland
³ Department of Surgery, Intensive Care Unit, Helsinki University Central Hospital, Helsinki, Finland
⁴ Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland
⁵ Department of Anesthesiology and Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland
⁶ Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland
⁷ Departments of Medicine and Emergency Care, Helsinki University Central Hospital, Helsinki, Finland, and Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland, and Department of Surgery, Intensive Care Unit, Helsinki University Central Hospital, Helsinki, Finland, and Minerva Research Institute, Helsinki, Finland, and Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland, and Department of Anesthesiology and Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland

^* To whom correspondence should be addressed. E-mail: katri.saukkonen{at}helsinki.fi.

BACKGROUND: Increased concentrations of cell-free DNA have been found in plasma of septic and critically ill patients. We evaluated the value of plasma DNA for the prediction of intensive care unit (ICU) and hospital mortality and its association with the degree of organ dysfunction and disease severity in patients with severe sepsis.

METHODS: We studied 255 patients with severe sepsis or septic shock. We obtained blood samples on the day of study inclusion and 72 h later and measured cell-free plasma DNA by real-time quantitative PCR assay for the -globin gene.

RESULTS: Cell-free plasma DNA concentrations were higher at admission in ICU nonsurvivors than in survivors (median 15 904 vs 7522 genome equivalents [GE]/mL, P < 0.001) and 72 h later (median 15 176 GE/mL vs 6758 GE/mL, P = 0.004). Plasma DNA values were also higher in hospital nonsurvivors than in survivors (P = 0.008 to 0.009). By ROC analysis, plasma DNA concentrations had moderate discriminative power for ICU mortality (AUC 0.70–0.71). In multiple regression analysis, first-day plasma DNA was an independent predictor for ICU mortality (P = 0.005) but not for hospital mortality. Maximum lactate value and Sequential Organ Failure Assessment score correlated independently with the first-day plasma DNA in linear regression analysis.

CONCLUSIONS: Cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA concentration was an independent predictor for ICU mortality, but not for hospital mortality, a finding that decreases its clinical value in severe sepsis and septic shock.