Targeted OXYgen Therapy in Critical Illness

The investigators aim is to determine whether revising standard targets for blood oxygen levels in patients requiring artificial ventilation on a critical care unit is feasible and whether this affects specific blood biomarker levels.

Investigators in this area of expertise currently lack the information necessary to determine how much oxygen should be given to adult critically ill patients on a mechanical ventilator to assist their breathing in order to achieve the best clinical outcomes i.e. minimal morbidity and mortality. Excessive oxygen administration (both its concentration and duration) and hyperoxaemia (an excessively high blood oxygen level) are known to be harmful to critically ill patients. The reason for this is that oxygen in high concentration is toxic, because it results in the release of molecules called reactive oxygen species (ROS). ROS lead to a state known as 'oxidative stress', in which cells and tissues are rapidly destroyed by these destructive molecules.

The difficulty with treating critically ill patients is that they are usually extremely unwell, requiring artificial ventilation to support their breathing. Unfortunately, these patients appear to be exceptionally prone to the harms of oxidative stress, leading to permanent damage of their lungs. Yet it is precisely this group of patients who require high concentration oxygen to keep their blood oxygen levels within the normal. It has therefore been hypothesised that using lower blood oxygen targets than usual may be beneficial to these patients through the avoidance of excessively high concentrations of oxygen. The investigator proposes that in mechanically ventilated critically ill patients harm (morbidity and mortality) will be reduced by using 'targeted oxygen therapy' (TO2T) to achieve lower blood oxygen levels than normal when compared to standard practice (normal blood oxygen levels). The levels are only moderately lower than normal and well within what most clinicians would consider to be safe in these patients.

Prior to any large-scale study, it is important to understand if this approach to managing critically ill patients is feasible. This prospective, dual site randomised controlled trial will therefore establish whether it is possible to conduct a trial in which blood oxygen levels are carefully titrated by the critical care team, to achieve specific targets. Participants will be allocated into one of two groups: i) normal blood oxygen levels, and ii) low blood oxygen levels. For the time that participants are artificially ventilated by a breathing (endotracheal) tube, they will remain in their allocated treatment group. Information will be collected from the patient's charts and records during their stay on the CCU to assess the impact of the treatment. A series of blood samples will also be collected from participants to quantify the degree of oxidative stress through the measurement of several specific biomarkers. A total of 60 patients will be enrolled at two sites.

As oxygen is a drug that is administered to almost every patient admitted to a critical care unit (CCU), it is imperative that decisions regarding oxygenation are based upon evidence rather than conjecture. Limited work has been undertaken to date to understand whether lowering blood oxygen levels is achievable in this complex patient group. The information from this study will be used to design a subsequent much larger study to fully evaluate whether TO2T to achieve lower blood oxygen levels saves lives in critically ill patients. If lower blood oxygen levels improve survival in critically ill patients implementation of this intervention could have an immediate and cost-effective impact across the entire National Health Service.