Reversible impairment of non-invasively assessed mitochondrial oxygen metabolism in the long-term course of patients with sepsis: a prospective monocentric cohort study.

BACKGROUND: Sepsis is characterized by organ dysfunction due to infection, with increasing evidence of mitochondrial dysfunction assessed preclinically and invasively. Protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) permits non-invasive determination of cellular oxygen metabolism and may provide deeper pathophysiological insights. METHODS: This analysis is part of a prospective monocentric cohort study. ICU patients with sepsis and septic shock and healthy controls were enrolled between May 2018 and June 2022. Mitochondrial oxygen tension (mitoPO2), consumption (mitoVO2) and delivery (mitoDO2) were assessed in the skin of healthy controls and patients with sepsis in the acute phase (3 ± 1 days after onset) and long-term course of disease (6 ± 2 months after onset) using PpIX-TSLT (CE-certified Cellular Oxygen METabolism system). Primary endpoints were differences in mitoPO2, mitoVO2, and mitoDO2 between patients in the acute phase of sepsis and controls. We tested group differences with t-tests and report Cohen's d (d) as effect size. RESULTS: In the acute phase, mitochondrial oxygen tension (mitoPO2) was significantly reduced (n = 133, mean ± standard deviation: 58.4 ± 19.2 mmHg) compared to controls (n = 79, 67.3 ± 17.7 mmHg, p = 0.002, d = - 0.48). We found no significant differences in oxygen tension in the long-term course (n = 43) or in oxygen consumption and delivery between acute and long-term course of sepsis and controls. In the acute phase, lower mitochondrial oxygen delivery was associated with higher Sequential Organ Failure Assessment score (Spearman's ρ = - 0.23, p = 0.009) and higher lactate concentrations (ρ = - 0.21, p = 0.021) and, thus, correlated with disease severity. CONCLUSIONS: Our results suggest that cellular oxygen metabolism in sepsis is characterized by a reversible restriction of oxygen tension without an impairment of mitochondrial oxygen consumption. Additionally, oxygen delivery is dependent on disease severity. These findings should be re-validated in a larger cohort. TRIAL REGISTRATION: NCT03620409 (Ethics vote: 5276-09/17; German Register of Clinical Studies: DRKS00013347), Principal investigator: Sina M. Coldewey, Date of Registration: 11-30-2017 NCT03620409.