Efficacity and Safety of Mechanical Insufflation-exsufflation on ICU

Study Overview
=================
Brief Summary
-----------------
Critically ill and intubated patients on mechanical ventilation (IMV) often present retention of respiratory secretions, increasing the risk of respiratory infections and associated morbidity. Endotracheal suctioning (ETS) is the main strategy to prevent mucus retention, but its effects are limited to the first bronchial bifurcation. Mechanical in-exsufflation devices (MI-E) are a non-invasive chest physiotherapy (CPT) technique that aims to improve mucus clearance in proximal airways by generating high expiratory flows and simulating cough. Currently there are no studies that have specifically assessed the effects of MI-E in critically ill and intubated patients. Thus, the aims of this study are to evaluate efficacy and safety of MI-E to improve mucus clearance in critically ill and intubated patients.

Detailed Description
-----------------
Controlled randomized, cross-over, single blind trial conducted at University Hospital of Bordeaux (France). Inclusion criteria: Patients (>18 yo) intubated [internal diameter (ID) 7 to 8], sedated [Richmond Agitation Sedation Scale (RASS) -3 to -5], connected to IMV at least 48 h and expected IMV of at least 24h. Exclusion criteria: Lung disease or pulmonary parenchyma damage, respiratory inspired fraction of oxygen (FiO2) >60% and/or positive end-expiratory pressure (PEEP) > 10 centimetres of water (cmH2O) and/or hemodynamic instability (mean arterial pressure (MAP) < 65 millimetres of mercury (mmHg) although use of vasopressors] , hemofiltered patients through a central jugular catheter, patients on strict dorsal decubitus by medical prescription, and high respiratory infectious risk. Design: All patients will receive CPT followed by ETS twice daily. However, patients will randomly receive in one of the sessions an additional treatment of MI-E before ETS. MI-E treatment consists in 4 series of 5 in-expiratory cycles at +/- 40 cmH2O, 3 and 2 sec of inspiratory-expiratory time and 1 sec pause between cycles. Variables: Mucus clearance will be assessed through wet volume of suctioned sputum through a suction catheter connected to a sterile collector container. Pulmonary mechanics will be measured before, after and 1 h post-intervention through a pneumotachograph (PNT). Peak expiratory flow (PEF) generated by MI-E will be continuously measured through a PNT. Hemodynamic measurements will be recorded before, after and 1 h post-intervention.

Official Title
-----------------
Efficacity and Safety of Mechanical Insufflation-exsufflation on Intubated and Mechanically Ventilated Patients

Conditions
-----------------
Mucus Retention, Mechanical Ventilation Complication, Mucus; Plug, Tracheobronchial

Intervention / Treatment
-----------------
* Other: Chest physiotherapy techniques
* Device: Mechanical insufflation-exsufflation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : Patients over 18 years old. Patents endotracheally intubated (tubes between 7mm and 8mm of internal diameter). Invasive mechanical ventilation > 48h Invasive mechanical ventilation expected > 24h RASS between -3 and -5 Exclusion criteria : Lung disease with pulmonary parenchyma injury or diseases where mechanical insufflation-exsufflation use is not recommended (eg: emphysema, pneumothorax, pneumomediastinum, hemoptyses, airway instability, acute barotrauma). Hemofiltered patients through a central jugular catheter. Respiratory instability (FiO2) >60% and/or (PEEP) > 10cmH2O, and/or hemodynamic instability (MAP) < 65mmHg although use of vasopressors)] instability Patients on strict dorsal decubitus by medical prescription. High risk infection patients (eg: tuberculosis, H1N1) that cannot be disconnected from IMV.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chest physiotherapy techniques<br>Manual chest physiotherapy techniques applied | Other: Chest physiotherapy techniques<br>* Respiratory manual CPT<br>|
| Experimental: Chest physiotherapy techniques + Mechanical in-exsufflation<br>Mechanical insufflation-exsufflation in addition to manual chest physiotherapy techniques | Device: Mechanical insufflation-exsufflation<br>* CPT + MI-E (4 series of 5 inspiratory-expiratory cycles at +/- 40 cmH2O, 3 seconds of inspiratory time, 2 seconds of expiratory time and 1 second pause between cycles).<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucus volume retrieved | respiratory secretions (ml) will be suctioned by a suctioning catheter connected to a sterile collector container | Immediately after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary mechanics | Pulmonary mechanics will be measured with a pulmonary mechanics monitor connected to endotracheal tube. We will obtain positive inspiratory pressure (PIP; cmH20), plateau pressure (Ppl; cmH20), tidal volume (Vt; ml). We will combine PIP, Ppl and Vt to obtain static compliance (Cst) (ml/cmH2O). | Immediately before treatment | 
| Pulmonary mechanics | Pulmonary mechanics will be measured with a pulmonary mechanics monitor connected to endotracheal tube. We will obtain airway resistance (Raw) (cmH2O/l/s). | Immediately before treatment | 
| Pulmonary mechanics | Pulmonary mechanics will be measured with a pulmonary mechanics monitor connected to endotracheal tube. We will obtain positive inspiratory pressure (PIP; cmH20), positive expiratory pressure (PEEP; cmH20), and peak inspiratory flow (PIF; l/s). We will combine PIP, PEEP and PIF to obtain respiratory system resistance (Rsr) (cmH2O/l/s). | Immediately before treatment | 
| Pulmonary mechanics | Pulmonary mechanics will be measured with a pulmonary mechanics monitor connected to endotracheal tube. We will obtain airway resistance (Raw) (cmH2O/l/s). | Immediately after treatment | 
| Pulmonary mechanics | Pulmonary mechanics will be measured with a pulmonary mechanics monitor connected to endotracheal tube. We will obtain positive inspiratory pressure (PIP; cmH20), plateau pressure (Ppl; cmH20), tidal volume (Vt; ml). We will combine PIP, Ppl and Vt to obtain static compliance (Cst) (ml/cmH2O). | Immediately after treatment | 
| Pulmonary mechanics | Pulmonary mechanics will be measured with a pulmonary mechanics monitor connected to endotracheal tube. We will obtain positive inspiratory pressure (PIP; cmH20), positive expiratory pressure (PEEP; cmH20), and peak inspiratory flow (PIF; l/s). We will combine PIP, PEEP and PIF to obtain respiratory system resistance (Rsr) (cmH2O/l/s). | Immediately after treatment | 
| Pulmonary mechanics | Pulmonary mechanics will be measured with a pulmonary mechanics monitor connected to endotracheal tube. We will obtain airway resistance (Raw) (cmH2O/l/s). | 1 hour after treatment | 
| Pulmonary mechanics | Pulmonary mechanics will be measured with a pulmonary mechanics monitor connected to endotracheal tube. We will obtain positive inspiratory pressure (PIP; cmH20), plateau pressure (Ppl; cmH20), tidal volume (Vt; ml). We will combine PIP, Ppl and Vt to obtain static compliance (Cst) (ml/cmH2O). | 1 hour after treatment | 
| Pulmonary mechanics | Pulmonary mechanics will be measured with a pulmonary mechanics monitor connected to endotracheal tube. We will obtain positive inspiratory pressure (PIP; cmH20), positive expiratory pressure (PEEP; cmH20), and peak inspiratory flow (PIF; l/s). We will combine PIP, PEEP and PIF to obtain respiratory system resistance (Rsr) (cmH2O/l/s). | 1 hour after treatment | 
| Hemodynamic measurements | Heart Beat per minute (HB) with continous monitoring | Immediately before treatment | 
| Hemodynamic measurements | Heart Beat per minute (HB) with continous monitoring | Immediately after treatment | 
| Hemodynamic measurements | Heart Beat per minute (HB) with continous monitoring | 1 hour after treatment | 
| Hemodynamic measurements | Blood Pressure in mmHg will be measured with continous monitoring | Immediately before treatment | 
| Hemodynamic measurements | Blood Pressure in mmHg will be measured with continous monitoring | Immediately after treatment | 
| Hemodynamic measurements | Blood Pressure in mmHg will be measured with continous monitoring | 1 hour after treatment | 
| Arterial blood gases | pH (in units) will be obtained from radial artery and blood gases analyzed. | Immediately before treatment | 
| Arterial blood gases | pH (in units) will be obtained from radial artery and blood gases analyzed. | Immediately after treatment | 
| Arterial blood gases | pH (in units) will be obtained from radial artery and blood gases analyzed. | 1 hour after treatment | 
| Arterial blood gases | Partial pressure of oxygen (PO2; mmHg) will be obtained from radial artery and blood gases analyzed. | Immediately before treatment | 
| Arterial blood gases | Partial pressure of oxygen (PO2; mmHg) will be obtained from radial artery and blood gases analyzed. | Immediately after treatment | 
| Arterial blood gases | Partial pressure of oxygen (PO2; mmHg) will be obtained from radial artery and blood gases analyzed. | 1 hour after treatment | 
| Arterial blood gases | Partial pressure of carbon dioxide (PCO2; mmHg) will be obtained from radial artery and blood gases analyzed. | Immediately before treatment | 
| Arterial blood gases | Partial pressure of carbon dioxide (PCO2; mmHg) will be obtained from radial artery and blood gases analyzed. | Immediately after treatment | 
| Arterial blood gases | Partial pressure of carbon dioxide (PCO2; mmHg) will be obtained from radial artery and blood gases analyzed. | 1 hour after treatment | 
| Arterial blood gases | Peripheral oxygen saturation (SPO2; %) will be obtained from radial artery and blood gases analyzed. | Immediately before treatment | 
| Arterial blood gases | Peripheral oxygen saturation (SPO2; %) will be obtained from radial artery and blood gases analyzed. | Immediately after treatment | 
| Arterial blood gases | Peripheral oxygen saturation (SPO2; %) will be obtained from radial artery and blood gases analyzed. | 1 hour after treatment | 
| Complications | We will asess the following adverse events that could happen while we will applying protocol: Mean arterial pressure lower than 15% from baseline Systolic blood pressure higher or lower than 15% from baseline Diastolic blood pressure higher or lower than 15% from baseline Heart rate higher or lower than 20% from baseline Oxygen saturation < 85% | Through study completion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
intensive care, invasive mechanical ventilation, mechanical insufflation-exsufflation, airway mucus clearance, chest physiotherapy, peak expiratory flow, pulmonary mechanics