This is a trial of a new way of treating patients with respiratory failure. The investigators propose to deliver a multi-centre clinical trial to determine whether veno-venous extracorporeal carbon dioxide removal (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

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). 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.

The few interventions that have been shown to reduce the high mortality in these patients have targeted ventilator-induced lung injury (VILI). A landmark trial by the ARDSNet trials group found that ventilating patients with acute hypoxaemic respiratory failure secondary to ARDS with a lung protective strategy aiming for a reduced tidal volume of 6ml/kg predicted body weight (PBW) and a maximum end-inspiratory plateau pressure (Pplat) ≤ 30cmH2O decreased mortality from 40% (in the conventional arm treated with tidal volume less than 12ml/kg PBW) to 31%.

Extracorporeal carbon dioxide removal (ECCO2R) in association with mechanical ventilation offers a potentially attractive solution to permit tidal volume reduction to less than 6ml/kg PBW and to achieve low plateau pressures (< 25cmH2O). Using these extracorporeal circuits, carbon dioxide can be 'dialysed' out of the blood while the lungs are ventilated in a more protective manner. In recent years, more efficient veno-venous devices have become available. These have replaced arterio-venous devices and have the advantage of not requiring arterial puncture. These can achieve carbon dioxide removal with relatively low extracorporeal blood flows (0.4-1 l/min) requiring only a smaller dual lumen venous catheter. In addition these ECCO2R devices use more biocompatible materials making the device more resistant to clot formation and cause less platelet and clotting factor consumption. Therefore only minimal systemic anticoagulation is required which reduces the likelihood of bleeding complications. These devices are now comparable to renal dialysis equipment, which is routinely used safely as standard care in ICUs in the United Kingdom.

Together this highlights the need for a large randomised controlled trial to establish whether VV-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective ventilatory strategy and is associated with improved patient outcomes. Importantly, if there was no benefit, the trial would provide evidence to stop the widespread adoption of an expensive and ineffective or potentially harmful treatment in this setting.

Inclusion Criteria:

• Invasive mechanical ventilation using positive end expiratory pressure (PEEP) ≥ 5cmH2O
• Acute and potentially reversible cause of acute respiratory failure as determined by the treating physician
• Within 48 hours of the onset of hypoxemia as defined by Pa02/Fi02 less than or equal to 20kPA

Exclusion Criteria:

• Age < 16 years old
• Intubated and mechanically ventilated via an endotracheal or tracheostomy tube ≥ 7 days (168 hours) up to the time of randomisation
• Ability to maintain Vt to ≤ 3ml/kg PBW while maintaining pH ≥ 7.2 as determined by the treating physician
• Receiving, or decision to commence, ECMO in the next 24 hours
• Mechanical ventilation using high frequency oscillation ventilation or airway pressure release ventilation
• Untreated pulmonary embolism, pleural effusion or pneumothorax as the primary cause of acute respiratory failure
• Acute respiratory failure fully explained by left ventricular failure or fluid overload (May be determined by clinical assessment or echocardiography/cardiac output monitoring)
• Left ventricular failure requiring mechanical support
• Contra-indication to limited systemic anticoagulation with heparin
• Unable to obtain vascular access to a central vein (internal jugular or femoral vein)
• Consent declined
• Treatment withdrawal imminent within 24 hours
• Patients not expected to survive 90 days on basis of premorbid health status
• DNAR (Do Not Attempt Resuscitation) order (excluding advance directives) in place
• Severe chronic respiratory disease requiring domiciliary ventilation (except for sleep disordered breathing)
• Severe chronic liver disease (Child Pugh >11)
• Platelet count < 40,000 mm3 (Prior to catheter insertion)
• Previously enrolled in the REST trial
• Prisoners