Plasma DNA Concentration as an Early Predictor of Outcome in Critically-Ill Septic Patients
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- Category: Vol. 78, June 2010
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Plasma DNA Concentration as an Early Predictor of Outcome in Critically-Ill Septic Patients,HAZEM EL-AKABAWY, SHEREN ELGENGEHY, WAHED RADWAN, AMAL REZK and ADEL ALSISI
Abstract
Background: Sepsis, defined as the systemic inflammatory response syndrome that occurs during infection, is a major cause of morbidity and mortality in patients in the ICU. Sepsis is associated with cell necrosis and apoptosis. Indeed, plasma DNA levels have been shown to be increased in patients with sepsis [1,2].
Purpose: To investigate the prognostic value of circulating levels of cell-free DNA in patients with sepsis in the intensive care setting regarding the clinical course and final outcome. Moreover, to compare this prognostic value of circulating cell-free DNA levels with other commonly used biochemical markers for prognosis of sepsis (CRP and Procalcitonin) and with the APACHE II and SOFA scoring systems.
Methods: A total of 80 critically ill patients with sepsis admitted to the Critical Care Department, Cairo University, were included in a prospective, randomized, single center study. All included septic patients were subjected to the measurement of cell-free plasma DNA concentrations (meas-ured by real-time polymerase chain reaction assay for the P-globin gene), CRP levels and Procalcitonin concentrations, all measured on admission to the ICU. APACHE II score was calculated once (24h after ICU admission) and SOFA score was calculated at baseline and subsequently thereafter every day until ICU discharge or death. Clinical outcome (duration of stay in the ICU, need for mechanical ventilation, need for inotropic/ vasopressor support, need for haemodialysis, and final outcome of survival/mortality rates) were recorded for all patients.
Results: The median plasma DNA concentration in criti-cally ill septic patients was 195.7ng/ml and this was signifi-cantly (approximately 7-fold) higher than the DNA concen-tration in healthy subjects 27ng/ml, (p<0.001). The patients who required mechanical ventilation had significantly higher median DNA concentration compared to those who did not require it (205.6ng/ml versus 123.7ng/ml; p=0.006). The patients who were on inotropic/vasopressor support had significantly higher DNA concentrations compared to non-supported patients (234.6ng/ml versus 114.7ng/ml; p<0.001). The median plasma DNA level was significantly higher in patients who required renal supportive therapy (haemodialysis) (244.2ng/ml versus 181.1ng/ml; p=0.001). DNA concentration demonstrated a highly significant correlation with C-reactine protein (CRP) concentration (r=0.661, p<0.001), procalcitonin concentration (PCT) (r=0.820, p<0.001), Sepsis-related Organ Failure Assessment (SOFA) score (r=0.710, p<0.001), and with Acute Physiology and Chronic Health Evaluation (APACHE II) score (r=0.559, p<0.001). The median plasma DNA concentration in nonsurvivors (38 of 80 patients "47.5%") was 234.8ng/ml, and this was significantly (approximately 2-fold) higher than that in survivors 115.5ng/ml, (p<0.001). Receiver operator characteristic (ROC) analysis of the data indicated a sensitivity of 95% and a specificity of 81% when DNA concentration of 186.5ng/ml was taken as a predictor of ICU mortality.
Conclusion: This study indicates that the plasma cell-free DNA (measured by real-time quantitative polymerase chain reaction (PCR) assay which is a relatively simple, rapid, easy assay) may be a potentially useful marker for the evaluation of septic patients when admitted to the ICU and for the prediction of their adverse outcomes. The ability for rapid risk stratification may allow clinicians to make more rational therapeutic decisions to ensure that the hospital resources are used efficiently and appropriately.