Mitochondrial Function in Septic Patients

Abstract

Sepsis is the fourth leading cause of death globally, with mortality rate now reaching 70%. There is an increasing amount of evidence to demonstrate that even after resuscitation using the standard sepsis care bundle, there is still the potential for patients to die. It has been shown that mitochondrial oxidative stress and mitochondrial dysfunction are severe consequences of sepsis. Currently, none of the physiological parameters used in sepsis care can predict the levels of oxidative stress and mitochondrial dysfunction. This study aims to test the hypothesis that impaired mitochondrial function is associated with increased serum lactate, central venous oxygen saturation (ScvO2), and venous-to-arterial carbon dioxide tension difference (delta PCO2). A prospective cohort study was conducted in a single tertiary emergency department from April 2017 to March 2019. Patients who visited the emergency department with suspected sepsis were included in the study. Serum lactate, ScvO2 and delta PCO2 were evaluated. Mitochondrial function was determined in the peripheral blood mononuclear cells.Forty-six patients with suspected sepsis and eight healthy controls were recruited onto the study. Of the 46, 38 patients were diagnosed with sepsis. In the sepsis group, thev28-day mortality rate was higher than in the controls (23.3% vs. 0%, p < 0.05). Of these,twenty patients were diagnosed with septic shock, and ScvO2 was recorded.Mitochondrial oxidative stress levels were greater in the high ScvO2 group (ScvO2 > 80%,n = 6), in comparison with the normal ScvO2 (70 - 80%, n = 9) and low ScvO2 (< 70%, n =5) groups. A strong linear relationship was observed between mitochondrial oxidative stress and ScvO2 (r = 0.75; p = 0.01), and the stress began increasing at a ScvO2 level of 70%. However, mitochondrial respiration and ATP-linked respiration were higher in the low ScvO2 group, when compared with the other groups. Also, mitochondrial complex II protein levels were significantly decreased in the high ScvO2 group (p < 0.05). This study is the first which shows that ScvO2 may be used as a marker for mitochondrial dysfunction in cases of sepsis.The findings indicate that ScvO2 may bepotentially useful in the development of novel therapeutic strategies to attenuate mitochondrial dysfunction in sepsis patients