Predictive value of circulating plasma mitochondrial DNA for Sepsis in the emergency department: observational study based on the Sepsis-3 definition

Abstract

BackgroundThe definition of sepsis is regularly updated; however, there is no standard diagnostic test. To improve diagnosis and prognostic prediction, the aim of this study was to determine the predictive value of circulating plasma mitochondrial DNA (mtDNA) levels in patients admitted to the emergency department (ED) with sepsis.MethodsA total of 107 patients hospitalized from June 2018 to January 2019 were divided into the sepsis (n = 72) and septic shock (n = 35) groups based on the sepsis-3 definition. Clinical and laboratory data were measured within 24 h of admission. The mtDNA concentrations in clarified plasma were estimated by quantitative polymerase chain reaction. Binary logistic regression analysis and the receiver operating characteristic (ROC) curve were used to determine predictive value of mtDNA and other markers for sepsis outcome (28-day mortality).ResultsThe median plasma mtDNA levels on admission were significantly higher in the septic shock patients than in the sepsis patients (134,252(IQR 70215–203,184) vs. 59,945(IQR 13274–95,319) copies/μL, P < 0.01), and were also higher in non-survivors than in survivors within 28 days (165,291(IQR 89919–272,228)vs. 63,025(IQR 17031–98,401)copies/μL, P < 0.01). Binary logistic regression showed that plasma lactate and mtDNA levels were independent risk factors for 28-day mortality [odds ratio (OR) 1.341, 95% confidence interval (CI) 1.035–1.736, P = 0.026 and OR 13.299, 95%CI 2.765–63.956, P = 0.001, respectively). The area under the ROC curve values for plasma mtDNA levels, lactate concentration, and their combined were 0.781 (p < 0.001, 95%CI 0.671–0.891), 0.733 (p < 0.001, 95%CI 0.635–0.832), and 0.799 (p < 0.001, 95%CI 0.698–0.901), respectively. The calibration test for the combined variable showed X2 of 2.559 and P = 0.923.ConclusionA higher plasma mtDNA level was associated with a poor prognosis of sepsis in the emergency room, and could serve as a predictor of sepsis for 28-day mortality.