Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients

Abstract

Introduction: Risk stratification of severely ill patients remains problematic, resulting in increased interest in potential circulating markers, such as cytokines, procalcitonin and brain natriuretic peptide. Recent reports have indicated the usefulness of plasma DNA as a prognostic marker in various disease states such as trauma, myocardial infarction and stroke. The present study assesses the significance of raised levels of plasma DNA on admission to the intensive care unit (ICU) in terms of its ability to predict disease severity or prognosis.

Methods: Fifty-two consecutive patients were studied in a general ICU. Blood samples were taken on admission and were stored for further analysis. Plasma DNA levels were estimated by a PCR method using primers for the human beta-haemoglobin gene.

Results: Sixteen of the 52 patients investigated died within 3 months of sampling. Nineteen of the 52 patients developed either severe sepsis or septic shock. Plasma DNA was higher in ICU patients than in healthy controls and was also higher in patients who developed sepsis (192 (65-362) ng/ml versus 74 (46-156) ng/ml, P = 0.03) or who subsequently died either in the ICU (321 (185-430) ng/ml versus 71 (46-113) ng/ml, P < 0.001) or in hospital (260 (151-380) ng/ml versus 68 (47-103) ng/ml, P < 0.001). Plasma DNA concentrations were found to be significantly higher in patients who died in the ICU. Multiple logistic regression analysis determined plasma DNA to be an independent predictor of mortality (odds ratio, 1.002 (95% confidence interval, 1.0-1.004), P = 0.05). Plasma DNA had a sensitivity of 92% and a specificity of 80% when a concentration higher than 127 ng/ml was taken as a predictor for death on the ICU.

Conclusion: Plasma DNA may be a useful prognostic marker of mortality and sepsis in intensive care patients.

Figure 1

Box and whisker plot for plasma DNA levels between controls and patients who survived or died in the intensive care unit. The box represents a median and interquartile range, whereas the whiskers represent the range.

Figure 2

Receiver operating characteristic curves for plasma DNA and the Sepsis-related Organ Failure Assessment (SOFA) score to predict intensive care outcome. The area under the curve for plasma DNA is 0.84 (95% confidence interval, 0.71–0.97) and that for the SOFA score is 0.76 (95% confidence interval, 0.61–0.92).