Avalanche Phenomenon During Airways Opening in Acute Respiratory Distress Syndrome

Study Overview
=================
Brief Summary
-----------------
Acute respiratory distress syndrome accounts for 23% of mechanically ventilated patients and is associated with high mortality rate. Although life-saving, mechanical ventilation may worsen lung injury through two main mechanisms: lung overdistension and atelectrauma. Indeed, the cyclic opening and closure of airways during tidal ventilation may cause lung and bronchial injuries as suggested by animal models and autopsy findings. Complete airways closure has recently been described in 40% of patients with acute respiratory distress syndrome, and setting positive end-expiratory pressure above the airway opening pressure may limit atelectrauma. However, animal and mathematical models suggest that above the airway opening pressure, more distal airways open unevenly according to their own opening pressure, resulting in an avalanche-like phenomenon during lung inflation. This phenomenon has never been described in humans. A better understanding of the opening of airways in acute respiratory distress syndrome may help to limit ventilation-induced lung injury and to improve outcomes.

Official Title
-----------------
Avalanche Phenomenon During Airways Opening in Acute Respiratory Distress Syndrome

Conditions
-----------------
Acute Respiratory Distress Syndrome

Intervention / Treatment
-----------------
* Other: Airway pressure, flow, esophageal pressure, ventilation distribution


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 Moderate-to-severe acute respiratory distress syndrome within the first 72 hours after meeting the Berlin definition criteria: Within 1 week of a known clinical insult or new or worsening respiratory symptoms; Bilateral opacities (not fully explained by effusions, lobar/lung collapse, or nodules); Respiratory failure not fully explained by cardiac failure or fluid overload; PaO2/FiO2 ≤ 200 mmHg with positive end-expiratory pressure ≥ 5 cmH2O. Absence of spontaneous breathing efforts Consent to participate to the study from the patient and/or its surrogate Exclusion Criteria: Pneumothorax Broncho-pleural fistula Tracheostomy Hemodynamic instability Severe hypoxemia Suspected of proven intracranial hypertension Chronic obstructive lung disease Pacemaker or defibrillator Decision to withhold of withdraw life-sustaining measures Under protection

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Airway pressure, flow, esophageal pressure, ventilation distribution|After informed consent, baseline characteristics of patients will be collected. Airway pressure, flow and esophageal pressure will be recorded using high sampling rate and ventilation distribution using electrical impedance tomography will be recorded during the study. The ventilator will be set at a positive end-expiratory pressure of 15 cmH2O during 10 minutes. Then, respiratory rate will be decreased to 8 breaths/min, and positive end-expiratory pressure will be decreased to 5 cmH2O over one breath to measure the recruited volume. Then, three low-flow inflation and deflation pressure-volume curves will be performed before resuming clinical ventilator settings. Patients will be followed until Day 28 after inclusion or ICU discharge. Maneuvers performed are part of the usual care of patients with acute respiratory distress syndrome in our unit.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the prevalence of avalanche phenomenon during low-flow lung inflation. | The distribution of pressure drops on low-flow inflation pressure-volume curves will be described and plotted on a log-log scale graph. Avalanche phenomenon will be defined if this distribution follows power law (i.e. is linear on a log-log scale) with a R2 ≥ 0.80. The prevalence of avalanche phenomenon will be described as frequency and 95% confidence interval. | At inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare characteristics of patients and their outcomes according to the existence of avalanche phenomenon during low-flow lung inflation. | Continuous variables will be summarized as mean ± standard deviation or median [25th-75th percentile] according to their distribution and compared by means of the Mann-Whitney or the Student's t test. Categorical variables will be summarized as frequency (percentage) and 95% confidence interval, and compared by means of Fisher or Chi2 test. | Day 28 | 
| To assess the existence of an inflection point on the low-flow deflation pressure-volume curve. | The slope of the low-flow deflation pressure-volume curve will be computed by means of linear regression and summarized as mean ± standard deviation or median [25th-75th percentile] according to its distribution. The existence of an inflexion point will be summarized as number (percentage) and 95% confidence interval. The airway pressure corresponding to this inflexion point will be summarized as mean ± standard deviation or median [25th-75th percentile] according to its distribution. | At inclusion | 
| To assess the airway pressure value of the inflection point on the low-flow deflation pressure-volume curve in patients with an inflexion point on the low-flow deflation pressure-volume curve | The airway pressure corresponding to the inflexion point on the low-flow deflation pressure-volume curve will be summarized as mean ± standard deviation or median [25th-75th percentile] according to its distribution. | At inclusion |