The Variable Ventilation Trial (Part A)

Inclusion criteria

• Patients ≥21 years old admitted to the Surgical, Trauma, Burn, Coronary or Medical ICUs with ARDS according to the Berlin criteria [50] and requiring mechanical ventilation will be eligible for inclusion.
• Not more than 96 hours of mechanical ventilation before randomization
• Anticipated need for at least 48 more hours of controlled mechanical ventilation
• Intubated and mechanically ventilated for ARDS according to the Berlin criteria

• Hypoxemia of acute onset, within the past 7 days
• Mild or moderate hypoxemia, PaO2/FiO2 ratio 100 - 300 mm Hg
• Presence of a risk factor for ARDS
• Respiratory failure not fully explained by cardiac failure or fluid overload
• Bilateral opacities not explained by effusions, lobar collapse, or nodules

Exclusion criteria

Demographic

• Age less than 21 years
• Pregnant or breastfeeding
• Prisoner
• Concurrent participation in another investigational drug study
• Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if they would receive all supportive care except for attempts at resuscitation from cardiac arrest)
• No consent or inability to obtain consent or appropriate legal representative not available
• Physician refusal to allow enrollment in the trial
• Moribund patient not expected to survive 24 hours
• Treating team unwilling to use ARDS network low tidal volume strategy or variable ventilation mode
• Use, or planned use of ECMO
• Stroke (ischemic or hemorrhagic) or traumatic brain injury (TBI) within the prior 3 months
• Burns > 40% total body surface area (TBSA)
• Severe airway inhalational injury
• Diffuse alveolar hemorrhage
• Any of the following hallmarks of Severe COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 3 or 4

• FEV1 < 50% predicted
• Resting arterial blood gas values PaO2<55, SaO2<88%, or PaCO2>55
• Home invasive or non-invasive ventilation other than for sleep apnea
• Cor Pulmonale
• Candidate for, or has received, lung volume reduction surgery, bronchoscopic intervention to reduce end-expiratory lung volume, or lung transplantation
• Any of the following cardiac problems:

• Acute myocardial infarction (MI) or acute coronary syndrome within the last 90 days
• Coronary artery bypass graft (CABG) surgery within 30 days
• Angina pectoris, or use of nitrates, with activities of daily living
• Cardiopulmonary disease classified as NYHA class IV

Physiological Exclusions

• Evidence of current barotrauma (e.g., pneumothorax, pneumomediastinum, or subcutaneous emphysema)
• Hemodynamic instability defined by inability to maintain a mean arterial pressure > 60 mm Hg.
• Other respiratory instability PEEP ≥18 cmH2O, suctioning more than hourly, Pplateau > 35 cm H2O, severe respiratory acidosis pH<7.25.
• Increased ICP > 20 cmH2O or mechanism of injury leading to concern for increased ICP
• Active bleeding with hemodynamic instability.