Abstract
Background: Supplemental oxygen is delivered to critically ill patients who require mechanical ventilation. Oxidative stress is a potential complication of oxygen therapy, resulting in damage to essential biomolecules such as proteins, lipids, and nucleic acids. Whether plasma levels of oxidative stress biomarkers vary based on how liberally oxygen therapy is applied during mechanical ventilation is unknown.
Methods: We carried out an oxidative stress substudy nested within a large multi-centre randomized controlled trial in which critically ill adults were randomized to receive either conservative oxygen therapy or standard oxygen therapy. Blood samples were collected at enrolment, and daily thereafter for up to three days. The antioxidant ascorbate (vitamin C) was assessed using HPLC with electrochemical detection and protein oxidation using a sensitive protein carbonyl ELISA. We also assessed whether critically ill patients with different disease states exhibited varying levels of oxidative stress biomarkers.
Results: A total of 125 patients were included. Mean ascorbate concentrations decreased over time (from 25 +/- 9 mu mol/L to 14 +/- 2 mu mol/L, p < 0.001), however, there was no significant difference between the conservative oxygen group and standard care (p = 0.2), despite a significantly lower partial pressure of oxygen (PaO2) in the conservative oxygen group (p = 0.03). Protein carbonyl concentrations increased over time (from 208 +/- 30 mu mol/L to 249 +/- 29 mu mol/L; p = 0.016), however, there was no significant difference between the conservative and standard oxygen groups (p = 0.3). Patients with sepsis had significantly higher protein carbonyl concentrations than the other critically ill patients (293 +/- 92 mu mol/L vs 184 +/- 24 mu mol/L, p = 0.03). Within the septic subgroup, there were no significant differences in protein carbonyl concentrations between the two interventions (p = 0.4).
Conclusions: Conservative oxygen therapy does not alter systemic markers of oxidative stress in critically ill ventilated patients compared with standard oxygen therapy. Patients with sepsis exhibited elevated protein carbonyls compared with the other critically ill patients implying increased oxidative stress in this patient subgroup.