Comparison of 2 Strategies of Adjustment of Mechanical Ventilation in Patients With Acute Respiratory Distress Syndrome

Comparison of Two Strategies for Setting Positive End-Expiratory Pressure in Acute Lung Injury/ Acute Respiratory Distress Syndrome (ExPress Study).

The aim of this multicenter randomized controlled trial is to compare the impact on mortality of patients mechanically ventilated for acute lung injury or acute respiratory distress syndrome of two strategies for setting end-expiratory pressure.

Most patients suffering from acute lung injury or acute respiratory distress syndrome require mechanical ventilation. In this setting, positive end-expiratory pressure is used to improve arterial oxygenation. While the beneficial effect on clinical outcome of using low tidal volume is clearly proven, the best way to titrate PEEP is not known. Higher PEEP levels may better improve oxygenation and reduce ventilator-induced lung injury by reducing end-expiratory alveolar collapse but may also cause circulatory depression and aggravate lung injury from end-inspiratory overdistension. This trial compares the impact on outcome of two strategies for setting PEEP. In the "minimal alveolar distension" arm, PEEP is set for a total PEEP (PEEP + intrinsic PEEP) between 5 and 9 cm H20). In the "maximal alveolar recruitment" arm, PEEP is set for a plateau pressure between 28 and 30 cm H20. A tidal volume of 6 ml/kg predicted body weight is used in the two arms. The goals for arterial oxygenation and PaCO2 are the same in the two arms.

Inclusion Criteria:

• Mechanical ventilation through an endotracheal tube
• Bilateral infiltrates consistent with pulmonary edema
• PaO2/FiO2 < 300 mmHg
• No clinical evidence of left atrial hypertension. If measured, pulmonary artery occlusion pressure < 18 mmHg
• Criteria 1, 2 et 3 jointly present for less than 48 hours
• Written informed consent obtained from the patient or surrogate

Exclusion Criteria:

• Age < 18 years
• Pregnancy
• Expected duration of mechanical ventilation through an endotracheal tube < 48 hours
• Participation in other trials within the previous 30 days
• Increased intracranial pressure
• Severe chronic respiratory disease
• Morbid obesity (weight > 1kg/cm)
• Sickle cell disease
• Bone marrow transplant or chemotherapy-induced neutropenia
• Extended burns (> 30 % total body surface area)
• Severe chronic liver disease (Child-Pugh score C)
• Pneumothorax