Circulating myeloperoxidase is elevated in septic shock and is associated with systemic organ failure and mortality in critically ill patients

Background: Neutrophils are elevated in critically ill patients during the systemic inflammatory response to trauma and sepsis. The neutrophil-derived enzyme myeloperoxidase generates reactive oxygen species which can react with host tissue resulting in cell damage and dysfunction. Thus, elevated myeloperoxidase in the circulation may be associated with adverse patient outcomes. Methods: Circulating myeloperoxidase concentrations were measured in a cohort of 44 critically ill patients, 55% of whom were diagnosed with septic shock, and 44 healthy controls. Intensive care mortality prediction scores (SOFA, SAPS, APACHE) and ICU and hospital mortality were obtained from the patients' clinical notes. Hematological and biochemical assessments included blood cell counts, lactate, alanine transaminase, creatinine, bilirubin, C-reactive protein, and PaO2. Myeloperoxidase was measured using a commercial ELISA kit and cell free DNA was detected using SytoxGreen (TM) fluorescence staining. Results: Myeloperoxidase concentrations were significantly higher in critically ill patients than control samples (234 +/- 30 ng/ml versus 15 +/- 4 ng/ml, p < 0.001), and were elevated in septic shock relative to non-septic patients (302 +/- 42 ng/ml versus 156 +/- 38 ng/ml, p = 0.02), despite neutrophil counts being comparable between the two subgroups (p = 0.6). Myeloperoxidase correlated with SOFA scores in the critically ill patients (r = 0.395, p = 0.02), and with markers of tissue dysfunction and injury such as lactate (r = 0.572, p < 0.001), log(10) alanine transferase (r = 0.392, p = 0.016) and log(10) cell free DNA (r = 0.371, p = 0.03). The subgroup of patients with higher than mean APACHE III scores (i.e.> 78, n = 16) exhibited significantly elevated myeloperoxidase concentrations in the non-survivors compared with survivors (416 +/- 59 ng/ml versus 140 +/- 33 ng/mL, p = 0.001). Hospital mortality for the whole cohort was 27%; mortality in the high APACHE III subgroup was 38%, and when combined with higher than mean myeloperoxidase (i.e.> 234 ng/mL), mortality increased to 71%. Conclusions: Myeloperoxidase is associated with markers of tissue injury and systemic organ failure, particularly in septic patients. The enzyme is also associated with mortality in patients with higher APACHE III scores, and thus has potential as an additional diagnostic marker to improve mortality prediction.