Full title: pRotective vEntilation with veno-venouS lung assisT in respiratory failure

Aim: determine whether VV-ECCO2R and lower tidal volume mechanical ventilation improves outcomes and is cost-effective, in comparison with standard care in patients who are mechanically ventilated for acute hypoxaemic respiratory failure.

Background: Acute hypoxaemic respiratory failure requiring mechanical ventilation is a major cause of morbidity and mortality. A significant proportion of affected patients will have the Acute Respiratory Distress Syndrome (ARDS). ARDS is characterised by non-cardiogenic pulmonary oedema (identified by bilateral infiltrates on chest X-ray) alongside a requirement for supplementary oxygen to maintain normal arterial oxygen tension. Acute hypoxaemic respiratory failure and ARDS occur in response to a variety of insults, such as trauma, pneumonia and severe sepsis; affect all age groups; have a high mortality of up to 30-50% and cause a long-term reduction in quality of life for survivors. Acute hypoxaemic respiratory failure has significant resource implications in terms of ICU and hospital stay. The cost per ICU bed-day exceeds £1800 and delivery of critical care to patients with acute hypoxaemic respiratory failure accounts for a significant proportion of ICU capacity. In addition, survivors often have long-term physical and cognitive impairment requiring support in the community and many survivors are unable to return to work 12 months after hospital discharge. The high incidence, mortality, long-term consequences and high economic costs mean that acute hypoxaemic respiratory failure is an extremely important problem.
In the UK over 100,000 patients each year require mechanical ventilation, of whom over 15,000 patients have acute hypoxaemic respiratory failure as defined in our planned study population (unpublished data UK Intensive Care National Audit & Research Centre). Over the past few decades significant progress has been made in understanding the pathophysiology of acute hypoxaemic respiratory failure and ARDS. Mechanical ventilation is often required to provide adequate gas exchange and although it is life-saving in this setting, it is also now known to contribute to the morbidity and mortality in the condition. Ventilators delivering high pressures and volumes cause regional over distension in the injured lung resulting in further inflammation and non-cardiogenic pulmonary oedema. The release of inflammatory mediators from the damaged lung causes systemic inflammation leading to multi-organ failure and death.