The Oscillation for Acute Respiratory Distress Syndrome (ARDS) Treated Early (OSCILLATE) Trial

Inclusion Criteria: * Acute onset of respiratory failure, with fewer than 2 weeks of new pulmonary symptoms; * Endotracheal intubation or tracheostomy; * Hypoxaemia - defined as a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) less than or equal to 200mmHg on FiO2 greater than or equal to 0.5, regardless of positive end expiratory pressure (PEEP) * Bilateral alveolar consolidation (airspace disease) seen on frontal chest radiograph In addition, to qualify for randomization, patients are assessed on the following ventilator settings: * Mode: pressure control or volume control or pressure support * FiO2 greater than 0.6 (or higher if necessary to keep pulse oximetric saturation \[SpO2\] greater than 90%) * PEEP greater than 10 cm H2O (or greater if necessary to keep SpO2 greater than 90%) * Tidal volume 6 ml/kg predicted body weight (PBW) After at least 30 minutes on these settings, we sample arterial blood to assess oxygenation. If PaO2 is less than or equal to 200 mmHg, the patient qualifies for randomization; if PaO2/FiO2 greater than 200 mmHg, standardized hypoxaemia assessments are repeated at least once daily for the following 72 hours (providing eligibility criteria are still met). Exclusion Criteria: * Remaining duration of mechanical ventilation less than 48 hours, as judged by the attending physician * Primary cause of acute respiratory failure judged by attending physician to be circulatory overload due to, for example, congestive heart failure, hyper-resuscitation, or need for dialysis * Suspected pulmonary haemorrhage syndrome * Lack of commitment to ongoing life support (note that this does not include the presence of a "Do Not Resuscitate" order alone, if there is a commitment to ongoing life support * Aged less than 16 years or greater than 85 years * Weight less than 35 kg * Severe chronic respiratory disease, as indicated by any of: * Baseline forced expiratory volume in one second (FEV1) less than 20 ml/kg predicted body weight * Pre-existing chronic interstitial lung disease with chronic interstitial infiltration on chest x-ray * Documented chronic carbon dioxide (CO2) retention (partial pressure of carbon dioxide in arterial blood \[PaCO2\] less than 50 mmHg) and/or chronic hypoxaemia(PaO2 less than 55 mmHg on FiO2=0.21) * Chronic restrictive, obstructive, neuromuscular, chest wall or pulmonary vascular disease resulting in severe exercise restriction (e.g., unable to climb stairs or perform household duties), secondary polycythaemia, severe pulmonary hypertension (mean pulmonary arterial pressure \[PAP\] greater than 40 mmHg), or ventilator dependency * Morbid obesity - defined as greater than 1 kg/cm body height * Underlying pre-existing condition with expected 6-month mortality greater than 50% * Neurological conditions with risk of intracranial hypertension (where hypercapnia should be avoided) * Neuromuscular disease that will result in prolonged need for mechanical ventilation, including (but not limited to): * Guillain Barre syndrome * Cervical spinal cord injury * Previous randomization in this trial * All inclusion criteria present for greater than 73 hours in study intensive care unit (ICU) * On HFO at the time of screening