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

Abstract

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 (mitoPO 2 ), consumption (mitoVO 2 ) and delivery (mitoDO 2 ) 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 mitoPO 2 , mitoVO 2 , and mitoDO 2 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 (mitoPO 2 ) 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