Plasma Levels of Mitochondrial DNA in Patients Presenting to the Emergency Department with Sepsis

Abstract

Introduction Elevated levels of plasma mitochondrial DNA (mtDNA) have been reported in trauma patients, and may contribute to the systemic immune response. We sought to determine the plasma levels of mtDNA in emergency department (ED) patients with and without sepsis and evaluate their association with severity of illness. Methods Prospective observational study of patients presenting to one of three large, urban, tertiary care EDs. Patients were enrolled into one of three cohorts: 1) sepsis defined as suspected infection and two or more SIRS criteria without hypotension; 2) septic shock defined as sepsis plus hypotension despite an adequate fluid challenge; and 3) control defined as non-infected ED patients without SIRS/hypotension. Plasma levels of three mtDNAs were measured using real-time quantitative PCR. Levels of mtDNAs were compared between the three cohorts and linear regression was used to assess the association between mtDNAs, IL-6, IL-10, and sequential organ failure assessment (SOFA) scores in patients with sepsis. Results We enrolled 93 patients: 24 controls, 29 with sepsis, and 40 with septic shock. As expected, co-morbidities and SOFA score increased across categories. We found no difference in mtDNA levels between the three groups (p = 0.14-0.30). Among patients with sepsis, we found a small but significant negative association between mtDNA level and SOFA score, most clearly with cytochrome b (p=0.03). Conclusions We found no difference in mtDNA levels between controls and patients with sepsis. mtDNA levels were negatively associated with organ dysfunction, suggesting that plasma mtDNA does not significantly contribute to the pathophysiology of sepsis.