Progression of peripheral blood mononuclear cell mitochondrial function during the early phase of sepsis in intensive care unit patients

Sepsis is associated with high rates of multiorgan failure and mortality. Altered mitochondrial function is an essential component of the early sepsis syndrome. However, its progression over time in peripheral blood mononuclear cells (PBMCs) is thus far unclear. Our purpose was to investigate this in the early phase of sepsis in ICU patients. A single-centre prospective observational cohort study was conducted in sepsis patients and compared with age- and sex-matched controls. Mitochondrial function was measured in PBMCs thrice during the first ICU week. RT-qPCR was used for semi-quantitative analysis of expression of genes involved in oxidative phosphorylation. Secondary endpoints included associations between mitochondrial function and (I) sepsis severity and (II) clinical outcomes, including 3-month mortality. Basal, ATP-linked, maximal and proton leak associated respiration were increased in sepsis patients (n = 25) compared to matched controls (n = 24) at all time points. This was associated with increased expression of SDBH (complex II) and ATP5F1A (complex V). Increased basal respiration was associated with 3-month mortality (HR 3.794, 95% CI 1.018-14.149, p = 0.047). No differences were observed in other secondary outcomes. PBMC mitochondria were shown to have an increased respiratory rate during the first week of sepsis. Moreover, a progressive increase was negatively associated with 3-month survival.