Lead Investigator no longer at Institution

This study will compare two ventilator modes in mechanically ventilated patients with acute lung injury.

Acute lung injury (ALI) is a condition in which the lungs are badly injured and are not able to absorb oxygen the way healthy lungs do. About 25% of patients who are ventilated get ALI. ALI causes 75,000 deaths in the US each year.

Ventilators can be set to work in different ways, called modes. One mode, called ARDSNet, pumps a small amount of air into the patient's lungs and then most of the air is released prior to the next breath. Another mode, called Airway pressure release ventilation (APRV), keeps air in the lungs longer between breaths. Both of these modes are currently used at this hospital. The investigators think APRV may help patients with ALI, but we do not know for sure.

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) represent a spectrum of clinical syndromes of rapid respiratory system deterioration that are associated with both pulmonary and systemic illness. These syndromes are associated with 30-40% mortality with our current standard of care and are responsible for approximately 75,000 deaths in the US yearly. The current evidence-based care consists of a strategy of mechanical ventilation utilizing low lung volumes (ARDSNet ventilation) intended to limit further lung injury from overstretch of the lung induced by the ventilator. However, this strategy has been shown to be associated with continued lung injury in some studies and still is associated with about a 30% mortality rate. Airway pressure release ventilation (APRV) is a different, nonexperimental strategy of mechanical ventilation currently in routine clinical use. APRV allows a patient a greater degree of autonomy in controlling his/her breathing while achieving a higher mean airway pressure (at similar plateau pressures) than that typically achieved with ARDSNet. APRV has been associated with less ventilator-associated pneumonia, better oxygenation, and less sedative usage in small studies when compared with other methods of ventilation. However, debate exists over net effects of APRV with regard to ventilator-associated lung injury. Additionally, we recently completed a study showing that APRV was associated with lower ventilator associated pneumonia (VAP) rates, but this benefit did not appear to be mediated by sedation differences. We hypothesized that the VAP benefits might be mediated by greater lung recruitment and possibly less ventilator-induced lung injury with APRV. We propose a randomized, crossover study looking at biomarkers of lung injury in patients with acute lung injury ventilated with APRV and ARDSNet. Our hypothesis is that airway pressure release ventilation is associated with lower levels of lung injury biomarkers than ARDSNet ventilation.

Inclusion Criteria:

• Age greater than or equal to 18
• Admitted to intensive care unit
• Has legally authorized representative (LAR) available to provide informed consent in languages allowed by IRB
• Has required mechanical ventilator for less than 14 days
• Meets all of the following American-European Consensus Criteria for Acute Lung Injury or Acute Respiratory Distress Syndrome: a. Acute onset of respiratory compromise, AND b. Bilateral chest radiographic infiltrates, AND c. PaO2/FiO2 ratio less than 300, OR if no arterial blood gas has been drawn by the clinical care team, a saturation O2/FiO2 ratio less than 315 with an O2 saturation less than 97%), AND d. Known pulmonary wedge pressure less than 18 mmHg, OR if pulmonary wedge pressure is not known, left-sided heart failure is not the most likely explanation for the patient's clinical findings of bilateral infiltrates and/or low PaO2/FiO2 ratio
• Has met ALI criteria for less than 7 days prior to enrollment
• Approval of intensive care unit attending physician
• Has arterial catheter in place
• Meets Clinical Stability Criteria for at least one hour prior to the start of study procedures. Note: Clinical Stability Criteria must be maintained throughout the duration of the intervention period.

Exclusion Criteria:

• Patient has a Do Not Resuscitate Order
• Evidence of increased intracranial pressure (e.g. presence of intraventricular catheter, brain herniation)
• Patient is pregnant (if pregnancy test was not performed as part of routine clinical care, a urine pregnancy test must be performed for women of childbearing potential after informed consent obtained)
• Planned transport out of ICU during study protocol
• Coagulopathy within the past 48 hours (INR greater than 2.0 or PTT greater than 50 seconds)
• Severe thrombocytopenia within the past 48 hours (platelets less than 20,000 per μL)
• History of obstructive lung disease (asthma and/or COPD)
• Patients who are currently prisoners