Abstract
Patients admitted into the intensive care unit (ICU) are the sickest patients in the hospital. Often, these critically ill patients require advanced respiratory support in the form of mechanical ventilation however, there is no robust evidence within the literature with respect to the most optimal approach to supplemental oxygen. An unfortunate complication of oxygen therapy is enhanced oxidative stress which contributes to tissue and organ damage, exacerbating a patient's critical condition. An additional consequence is the oxidization of essential biomolecules such as proteins, resulting in the formation of protein carbonyls. At present, there is an extensive amount of literature which is suggestive of protein carbonyls being a reliable biomarker of oxidative stress. However, there is no consensus on whether these oxidative stress biomarkers vary based on whether critically ill patients receive liberal or conservative oxygen therapy.
This research project is a nested sub study of the Intensive Care Unit Randomised Trail Comparing Two Approaches to Oxygen Therapy (ICU-ROX trial). This trial was a larger, multicentred study which evaluated oxidative stress in critically ill patients randomised to either standard or conservative oxygen therapy. The proposed study utilised plasma samples collected in a subgroup of patients during the ICU-ROX trial, to assess the effects of oxygen therapy on protein carbonyl levels.
This current project aimed to assess the effects of critically ill patients receiving either conservative or standard oxygen therapy on protein carbonyls, as a biomarker of oxidative stress in ICU adults receiving mechanical ventilation. Secondly, this project aimed to assess correlations between protein carbonyl concentrations and clinical outcomes.
Blood samples were collected at admission and then daily for three days, from 60 patients receiving mechanical ventilation, from Wellington hospital ICU. An enzyme-linked immunosorbent assay (ELISA) was utilised for the detection and measurement of protein carbonyls in plasma samples. Protein carbonyls were compared between the two approaches to oxygen therapy and clinical outcomes. Statistical analyses were performed on all findings to identify the presence of any significant correlations between the data.
This study found no significant changes in protein carbonyl concentrations in mechanically ventilated ICU adults, over three days. Additionally, no significant differences were found in protein carbonyl levels between patients receiving standard or conservative oxygen therapy. A slight statistical difference was observed in clinical measurements of FiO2 (p?0.0005) and PaO2 (p?0.001), however, these findings were lost after day one between the two treatment groups. There were no significant correlations between demographic factors such as participant age or gender and protein carbonyl levels. Although cardiovascular conditions represented 43% of conditions within the total cohort, there appeared to be no direct association with protein carbonyl levels. Similarly, there were no correlations with mortality at day 180. However, the subgroup of participants diagnosed with sepsis exhibited significantly higher protein carbonyl concentrations (p?0.05), relative to other conditions within the cohort. These findings suggest that endogenous oxidative pathways such as the activation of phagocytes are likely contributing to oxidative damage instead of the administration of supplemental oxygen specifically.
When contextualised with wider literature, the current study demonstrates that enhanced oxidative stress is present in septic patients, evident through higher concentrations of protein carbonyls being observed in this sub-group. Thus, findings from this study support the use of protein carbonyls as a measure of oxidative stress in critically ill patients, particularly septic patients. The clinical detection and measurement of protein carbonyls in these patients may give rise to future guidelines and therapies that may benefit from treatment of such conditions.
Findings from this study also provide a rationale for upcoming research and has several implications to the future of nursing practice, including the development of nursing skills and interventions, which collectively contribute towards improved patient outcomes.