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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Acute Respiratory Distress Syndrome, Acute Lung Injury

Intervention / Treatment
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* Device: Setting of positive end-expiratory pressure


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Minimal alveolar distension<br>PEEP is set for a total PEEP (PEEP + intrinsic PEEP) between 5 and 9 cm H2O | Device: Setting of positive end-expiratory pressure<br> <br> |
| Experimental: Maximal alveolar distension<br>PEEP is set for a plateau pressure between 28 and 30 cm H20 | Device: Setting of positive end-expiratory pressure<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at 28 days |  | day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at 60 days |  | day 60 | 
| In hospital mortality |  | day 60 | 
| Ventilator free Days through day 28 |  | day 28 | 
| Number of new organ failure before day 28 |  | day 28 | 
| Proportion of patients alive and unassisted breathing at 28 days |  | day 28 | 
| Number of patients with pneumothorax |  | day 28 | 
| Number of days alive between the first positive potential weanability test and day 28 |  | day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute respiratory distress syndrome, Positive end-expiratory pressure, Acute lung injury, Mechanical ventilation, Randomized controlled trial