Mechanically ventilated patients from hypoxic respiratory failure. Surgery
Conditions
Interventions
Participants from UK-ROX will be enrolled. They will receive methyl-D9 choline infusion followed by endotracheal aspirate, and blood sampling will be done 0, 48 and 72 hours after the study initiation
Sponsors
University Hospital Southampton NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Enrolled in UK-ROX study 2. Aged greater or equal to 18 years 3. Receiving invasive mechanical ventilation in the ICU for hypoxaemic respiratory failure 4. Receiving supplemental oxygen (fractional inspired concentration of oxygen (FiO2>0.21 at the time of enrolment) 5. Anticipated to be mechanically ventilated for a minimum of 72 hours
Exclusion criteria
Exclusion criteria: 1. Currently receiving extra corporeal membrane oxygenation (ECMO) 2. The treating clinician considers that one UK-ROX trial intervention arm is either indicated or contraindicated
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The difference of percentage of DPPC (PC32:0) in relation to total phosphatidylcholine composition (% of total PC in surfactant) at 48 hours between conservative and usual oxygen target groups. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Surfactant index: This is a composite PC surfactant molecular index calculated from surfactant specific PC molecules (PC32:0, PC32:1 and PC30:0) and unsaturated surfactant PC34:1. This index will give a composite measure of surfactant PC alterations, which will provide a measure of surfactant PC status for the two different targets after 48 hours of oxygen therapy. This outcome is a measure of surfactant specific PC composition. Surfactant index = {????32:0+????32:1+????30:0} ????34:1 2. Surfactant phosphatidylcholine concentration (urea corrected) at 48 hours. This outcome is a measure of endogenous surfactant level. 3. Systemic oxidative stress: Total free thiols, lipid peroxides and total surfactant oxidation products. This outcome will measure whole-body oxidative stress. Secondary explanatory outcomes 1. Surfactant total phosphatidylcholine and PC32:0 methyl-D9choline enrichment at 48 hours. Measure of endogenous surfactant synthesis. This will measure the surfactant PC synthesis via the CDP-Choline pathway. 2. Surfactant total lysoPC and lysoPC16:0 concentrations, composition and methyl-D9 choline enrichment at 48 hours. This outcome is a measure of endogenous surfactant breakdown. This will help to assess dynamic surfactant PC breakdown through hydrolysis. 3. Surfactant oxidised PC composition and concentrations at 48 hours. Measure of endogenous surfactant breakdown. This will help to assess dynamic surfactant breakdown by oxidation. 4. Whole- body redox balance by quantifying stable products of ROS (e.g., isoprostanes), RNS (e.g., nitrite, nitrate, nitrosation products) and RSS (e.g., total free thiols, thiosulfate, low molecular weight thiols including sulfide) at 48 hours from tracheal aspirates and plasma. Measure of lung and systemic redox status. 5. Comparison of clinical outcomes (ICU mortality, hospital mortality, 90-day mortality, ICU, and hospital length of stay) in relation to surfactant abnormalities. 6. Comparison of clinical o | — |
Countries
England, United Kingdom
Outcome results
None listed