This study is designed to test a proposed strategy for lung- and diaphragm-protective ventilation (LDPV) in patients with acute hypoxemic respiratory failure. Ventilation and sedation will be titrated to evaluate whether it is feasible and safe within this patient population.

Lung injury and diaphragm injury incurred by mechanical ventilation have very serious adverse effects on patients with acute respiratory failure. Lung injury results from excessive mechanical stress and strain applied to the lung by the ventilator and/or respiratory muscles, while diaphragm injury results from either insufficient or excessive inspiratory effort.

The objective of this study is to investigate a new LDPV strategy designed to prevent both disuse-mediated and load-induced diaphragm injury, while also preventing excess global and regional mechanical stress and strain in the injured lung. To achieve these goals, the following specific targets to be met are: (1) respiratory muscle effort similar to that of healthy subjects breathing at rest, (2) lung stress within safe limits, and (3) clinically acceptable gas exchange.

Targets are assessed through measurements of global lung stress, tidal recruitment, inspiratory effort, diaphragm contractile effort and adequacy of respiratory muscle and systemic tissue perfusion. Measurements commence at enrollment and continue for 24 hours consecutively.

Inclusion Criteria:

• Diagnosed with acute hypoxemic respiratory failure
• PaO2:FiO2 ratio less than or equal to 300 mm Hg at time of screening
• Oral endotracheal intubation and mechanical ventilation
• Bilateral airspace opacities on chest radiograph or chest CT scan

Exclusion Criteria:

• Liberation from mechanical ventilation is anticipated within 24 hours
• Intubated for traumatic brain injury or stroke
• Contraindication to esophageal catheterization
• Intracranial hypertension