Lung and Diaphragm-Protective Ventilation by Means of Assessing Respiratory Work

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Lung and Diaphragm-Protective Ventilation by Means of Assessing Respiratory Work

Conditions
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Diaphragm Injury, Lung Injury, Respiratory Insufficiency, Mechanical Ventilation Complication

Intervention / Treatment
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* Procedure: Lung- and Diaphragm-Protective Ventilation


Participation Criteria
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Eligibility Criteria
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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

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lower PEEP<br>Lung- and Diaphragm-Protective Ventilation - PEEP will be set at 8 cm H2O | Procedure: Lung- and Diaphragm-Protective Ventilation<br>* Ventilation and sedation will be progressively modified according to the LDPV algorithm to achieve targets. Patients will be crossed-over to the opposite PEEP strategy. LDPV titration will then be repeated to achieve LDPV targets. After establishing a combination of ventilation and sedation settings at which LDPV targets are achieved, the targets will be maintained over a 24-hour period.<br>* Other names: LDPV;|
| Experimental: Higher PEEP<br>Lung- and Diaphragm-Protective Ventilation - PEEP will be titrated to achieve end-expiratory PL = 2-3 cm H20 and at least 5 cm H2O greater than the level applied in the lower PEEP arm | Procedure: Lung- and Diaphragm-Protective Ventilation<br>* Ventilation and sedation will be progressively modified according to the LDPV algorithm to achieve targets. Patients will be crossed-over to the opposite PEEP strategy. LDPV titration will then be repeated to achieve LDPV targets. After establishing a combination of ventilation and sedation settings at which LDPV targets are achieved, the targets will be maintained over a 24-hour period.<br>* Other names: LDPV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients achieving and maintaining LDPV targets |  | Assessed after achievement of LDPV targets for 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inspiratory effort at lower and higher PEEP levels |  | Assessed 10 minutes after PEEP and sedation are adjusted | 
| Expiratory diaphragmatic effort at lower and higher PEEP levels |  | Assessed 10 minutes after PEEP and sedation are adjusted | 
| Lung stress and strain at low and high sweep gas flow rates |  | Assessed 10 minutes after PEEP and sedation are adjusted | 
| Inspiratory effort at low and high sweep gas flow rates |  | Assessed 10 minutes after PEEP and sedation are adjusted | 
| Sedative infusion rate at low and high sweep gas flow rates |  | Assessed 10 minutes after PEEP and sedation are adjusted | 
| Accuracy of artificial intelligence model in predicting patient outcomes | We will compare the model's prediction of patient's esophageal pressure, pH and transpulmonary pressure to the actual observed values | Assessed after completing the 24-hour maintenance period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diaphragm Dysfunction, Acute Respiratory Failure, Sedation, Mechanical Ventilation, Lung Stress