Mechanical Ventilation, Directed by Esophageal Pressure Measurements, in Patients With Acute Lung Injury

Study Overview
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Brief Summary
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The purpose of this study is to see whether esophageal pressure (PES) measurements will allow the investigators to choose the best method of mechanical ventilation in patients with acute lung injury (ALI).

Detailed Description
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The current standard of practice for ventilating patients with acute respiratory distress syndrome (ARDS) is the ARDSnet protocol (N Engl J Med 2000; 342:1301-1308) which has been shown to improve survival by limiting tidal volumes and thus preventing over distention of the lungs. However, the lungs can also be damaged by under-inflation during mechanical ventilation, and current practice ignores the effects of chest wall compression of the lungs, which can cause under-inflation. The investigators have observed that a fraction of critically ill patients with apparent ARDS have lung function abnormalities caused by extrinsic compression which can be estimated by PES measurements. Changing ventilator settings to apply normal physiological pressure to the lung has been beneficial in many such patients. This protocol will formally test the clinical utility of PES measurements in patients with ARDS. This is a randomized controlled trial of therapy directed by esophageal balloon measurements (PES) versus therapy directed by ARDSnet protocol, the current standard of care.

Official Title
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A RCT of Mechanical Ventilation, Directed by Esophageal Pressure Measurements, in Patients With Acute Lung Injury

Conditions
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Acute Lung Injury, Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Procedure: Placement of an esophageal balloon measurements
* Other: Low tidal volume ventilation
* Other: Transpulmonary pressure-directed ventilation (EPVent)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with ALI/ARDS according to the International Consensus Conference criteria: PaO2/FiO2 ratio < 300 Acute onset Bilateral infiltrates on chest radiography PAOP < 18 or, in patients without a pulmonary artery catheter, no other evidence of abnormal cardiac function Exclusion Criteria: Patients with esophageal varices Patients with esophageal trauma Patients with recent esophageal surgery Patients with coagulopathy (platelets < 80k or International Normalized Ratio [INR]> 2 ) Post transplant patients Patients with significant broncho-pleural fistula

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 |
| --- | --- |
| Experimental: EPVent<br>All patients will have an esophageal balloon placed for the purpose of obtaining transpulmonary pressure measurements. The intervention group will undergo transpulmonary pressure-directed controlled mechanical ventilation using parameters directed by the initial balloon measurements. Driving pressures will be adjusted to maintain a transpulmonary plateau pressure of less then 30. The PEEP setting will be set to achieve a transpulmonary end expiratory pressure of 0. Repeat PES measurements will be done at 24, 48 and 72 hours following the initial measurements. Additional measurements will be taken as clinically indicated. Ventilator management by PES measurements will continue for a period of 72 hours. | Procedure: Placement of an esophageal balloon measurements<br>* In both groups an esophageal balloon will be placed and baseline measurements recorded. In the EP group the mechanical ventilation settings will be determined based on these measurements. In the control group measurements will be recorded but ventilation will be based in the existing standard of care wich is the ARDSnet low tidal volume ventilation study. measurements will be repeated at 24, 48 and 72 hours or as needed.<br>Other: Transpulmonary pressure-directed ventilation (EPVent)<br>* Transpulmonary pressure-directed ventilation using measurements from the esophageal balloon.<br>|
| Active Comparator: Control<br>All patients will have an esophageal balloon placed for the purpose of obtaining transpulmonary pressure measurements. The control group will be managed using the low tidal volume strategy laid out by the NIHBLI ARDSnet study. These recommendations include a set tidal volume of 6 ml/ kg. Respiratory rate and PEEP are set to maintain adequate ventilation and oxygenation. These settings will be continued for a period of 72 hours. | Procedure: Placement of an esophageal balloon measurements<br>* In both groups an esophageal balloon will be placed and baseline measurements recorded. In the EP group the mechanical ventilation settings will be determined based on these measurements. In the control group measurements will be recorded but ventilation will be based in the existing standard of care wich is the ARDSnet low tidal volume ventilation study. measurements will be repeated at 24, 48 and 72 hours or as needed.<br>Other: Low tidal volume ventilation<br>* Low tidal volume ventilation strategy (ARDSnet)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygenation as measured by the PO2/FiO2 (P/F) ratio |  | 72 hours from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator free days |  | At 28 days | 
| Markers of inflammation |  | In first 72 hours | 
| Mortality |  | At 28, 90 and 180 days | 
| Length of stay |  | Hospital and ICU | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Lung Injury, Acute Respiratory Distress Syndrome, Mechanical Ventilation, Esophageal Pressures, Randomized Controlled Trial