PEEP and Spontaneous Breathing During ARDS

Study Overview
=================
Brief Summary
-----------------
Prospective, physiological study to systematically assess the effects of high positive end-expiratory pressure (PEEP) with and without inspiratory synchronization in patients with moderate to severe acute respiratory distress syndrome (ARDS) exhibiting intense inspiratory effort while on assisted ventilation.

Detailed Description
-----------------
This prospective, physiological, randomized, cross-over study will be conducted in the 20-bed general ICU of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. Patients with ARDS will be screened for eligibility. ARDS will be defined according to the Berlin Definition. Intubated patients fulfilling ARDS criteria, undergoing assisted ventilation as per clinical decision and exhibiting intense inspiratory effort (occlusion pressure equal or greater than 13 cmH2O) will be enrolled. Patients will be placed in a 30°-45° head up position during all study phases. According to our institution protocol, pressure support setting will be selected by the attending physician to target a predefined tidal volume range of 6-8 mL/kg of predicted body weight (PBW) (female PBW [kg] = 45.5 + 0.91 [cm of height - 152.4]; male PBW [kg] = 50 + 0.91 [cm of height - 152.4]).The lowest pressure support level allowed will be 7 cmH2O, even if Vt <8 ml/Kg PBW is not achieved. In each patient, four different ventilator settings will be applied in a random order. Each step will last 45 minutes.

Official Title
-----------------
Effects of Positive End-expiratory Pressure With and Without Inspiratory Synchronization During Moderate to Severe ARDS

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

Intervention / Treatment
-----------------
* Other: Mechanical Ventilation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: (a) ARDS according to the Berlin definition (ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ≤ 300 mmHg); (b) assisted ventilation, as prescribed by the attending physician (c) intense inspiratory effort, defined as a negative deflection in the airway pressure equal or greater than 13 cmH2O in the first breath recorded during an end-expiratory occlusion Exclusion Criteria: Pregnancy, clinically documented barotrauma, contraindication to electrical impedance tomography (EIT) use (e.g., presence of pacemaker or automatic implantable cardioverter defibrillator), impossibility to place the EIT belt in the right position (e.g., presence of surgical wounds dressing), and any contraindication to the insertion of a nasogastric tube (eg, recent upper-gastrointestinal surgery, esophageal varices), chest tubes with active air leaks, fever.

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

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low PEEP and full inspiratory synchronization<br>PEEP = 5 cmH2O + clinically selected pressure support (PSVclin) | Other: Mechanical Ventilation<br>* Respiratory support through mechanical ventilator<br>|
| Experimental: High PEEP and full inspiratory synchronization<br>PEEP = 15 cmH2O + clinically selected pressure support (PSVclin) | Other: Mechanical Ventilation<br>* Respiratory support through mechanical ventilator<br>|
| Experimental: Low PEEP and inspiratory desynchronization<br>PEEP = 5 cmH2O + bilevel positive airway pressure (Respiratory rate 15 breaths/minute, inspiratory time=1 sec, Inspiratory pressure=PSVclin+PEEP, PS=0 cmH2O) | Other: Mechanical Ventilation<br>* Respiratory support through mechanical ventilator<br>|
| Experimental: High PEEP and inspiratory desynchronization<br>PEEP = 15 cmH2O + bilevel positive airway pressure (Respiratory rate 15 breaths/minute, inspiratory time=1 sec, Inspiratory pressure=PSVclin+PEEP, PS=0 cmH2O) | Other: Mechanical Ventilation<br>* Respiratory support through mechanical ventilator<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inspiratory effort | The negative deflection in esophageal pressure during inspiration | 45 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygenation | Ratio of PaO2 to FiO2 | 45 minutes | 
| Respiratory mechanics | Respiratory mechanics assessed by end-inspiratory occlusion | 45 minutes | 
| Lung mechanics | Respiratory mechanics assessed by esophageal pressure monitoring during an end-inspiratory occlusion | 45 minutes | 
| Work of breathing | Esopghageal pressure pressure-time product per minute | 45 minutes | 
| Respiratory rate | Respiratory rate per minute | 45 minutes | 
| Regional Tidal volume distribution | Distribution of tidal volume in the different lung zones, assessed by electrical impedance tomography | 45 minutes | 
| Alveolar recruitment | Change in end-expiratory lung impedance, assessed by electrical impedance tomography | 45 minutes | 
| Pendelluft | Occurrence of intra-tidal shift of gas within different lung regions at beginning of inspiration | 45 minutes | 
| Carbon dioxide | Blood carbon dioxide, as assessed by arterial blood gas analysis | 45 minutes | 
| Tidal volume | Average Tidal volume received by the patient | 45 minutes | 
| Dynamic transpulmonary driving pressure | The average positive swing in transpulmonary driving pressure during tidal breathing | 45 minutes |