Visualization of Inspiratory Effort and Respiratory Mechanics to Promote Lung- and Diaphragm Protective Ventilation

Study Overview
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Brief Summary
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This is a multicentre prospective cohort trial in adult and pediatric ICU patients. The investigators will measure the effect of a patient's inspiratory effort during mechanical ventilation on the lungs and diaphragm. The investigators will daily (for a maximum of 8 days) measure esophageal pressures with a balloon catheter to quantify inspiratory effort and respiratory muscle function, and perform daily ultrasound measurements of the diaphragm and the lungs. The investigators hypothesize that a small inspiratory effort will result in the preservation of diaphragm function and have no adverse effect on lung function.

Official Title
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Visualization of Inspiratory Effort and Respiratory Mechanics to Promote Lung- and Diaphragm Protective Ventilation

Conditions
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Respiratory Muscles, Respiration, Artificial, Respiratory Function Tests

Intervention / Treatment
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* Device: Placement of nasogastric balloon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 28 days weight > 3kg requiring invasive mechanical ventilation anticipated length of ventilation > 48h Exclusion Criteria: refusal of consent mechanical ventilation ≤ 2 weeks before inclusion known anatomical malformation of the diaphragm (including congenital diaphragmatic hernia) contra-indication to the placement of a naso-gastric esophageal balloon catheter

Ages Eligible for Study
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Minimum Age: 29 Days

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Overall group<br>Placement of a nasogastric balloon | Device: Placement of nasogastric balloon<br>* A nasogastric balloon catheter will be inserted after inclusion. This will be a NutriVent (Sidam S.R.L., Mirandola, Italy) for patients >40kg, and a SmartCath Esophageal pressure catheter (Vyaire/Carefusion) for patients <40kg. This placement is similar to a standard nasogastric tube placement, which is a common procedure in an ICU. Potential minor side effects include a nosebleed, sore throat and erosion of the nose where the tube is anchored. All patients will receive this intervention. When the esophageal catheter becomes displaced or is accidentally removed during the study period, it will be replaced.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tidal esophageal pressure swing (∆Pes) - D1 | Our primary endpoint is the amount of total inspiratory muscle activity as represented by ∆Pes, measured at least once daily during the first 8 days of mechanical ventilation. | ∆Pes (average over 1 minute recording) at day 1 of mechanical ventilation | 
| Tidal esophageal pressure swing (∆Pes) - D2 | Our primary endpoint is the amount of total inspiratory muscle activity as represented by ∆Pes, measured at least once daily during the first 8 days of mechanical ventilation. | ∆Pes (average over 1 minute recording) at day 2 of mechanical ventilation | 
| Tidal esophageal pressure swing (∆Pes) - D3 | Our primary endpoint is the amount of total inspiratory muscle activity as represented by ∆Pes, measured at least once daily during the first 8 days of mechanical ventilation. | ∆Pes (average over 1 minute recording) at day 3 of mechanical ventilation | 
| Tidal esophageal pressure swing (∆Pes) - D4 | Our primary endpoint is the amount of total inspiratory muscle activity as represented by ∆Pes, measured at least once daily during the first 8 days of mechanical ventilation. | ∆Pes (average over 1 minute recording) at day 4 of mechanical ventilation | 
| Tidal esophageal pressure swing (∆Pes) - D5 | Our primary endpoint is the amount of total inspiratory muscle activity as represented by ∆Pes, measured at least once daily during the first 8 days of mechanical ventilation. | ∆Pes (average over 1 minute recording) at day 5 of mechanical ventilation | 
| Tidal esophageal pressure swing (∆Pes) - D6 | Our primary endpoint is the amount of total inspiratory muscle activity as represented by ∆Pes, measured at least once daily during the first 8 days of mechanical ventilation. | ∆Pes (average over 1 minute recording) at day 6 of mechanical ventilation | 
| Tidal esophageal pressure swing (∆Pes) - D7 | Our primary endpoint is the amount of total inspiratory muscle activity as represented by ∆Pes, measured at least once daily during the first 8 days of mechanical ventilation. | ∆Pes (average over 1 minute recording) at day 7 of mechanical ventilation | 
| Tidal esophageal pressure swing (∆Pes) - D8 | Our primary endpoint is the amount of total inspiratory muscle activity as represented by ∆Pes, measured at least once daily during the first 8 days of mechanical ventilation. | ∆Pes (average over 1 minute recording) at day 8 of mechanical ventilation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transpulmonary driving pressure (ΔPL) - D1 | ∆PL is calculated as change in airway pressure minus change in esophageal pressure | ∆PL (average over 1 minute recording) at day 1 of mechanical ventilation | 
| Transpulmonary driving pressure (ΔPL) - D2 | ∆PL is calculated as change in airway pressure minus change in esophageal pressure | ∆PL (average over 1 minute recording) at day 2 of mechanical ventilation | 
| Transpulmonary driving pressure (ΔPL) - D3 | ∆PL is calculated as change in airway pressure minus change in esophageal pressure | ∆PL (average over 1 minute recording) at day 3 of mechanical ventilation | 
| Transpulmonary driving pressure (ΔPL) - D4 | ∆PL is calculated as change in airway pressure minus change in esophageal pressure | ∆PL (average over 1 minute recording) at day 4 of mechanical ventilation | 
| Transpulmonary driving pressure (ΔPL) - D5 | ∆PL is calculated as change in airway pressure minus change in esophageal pressure | ∆PL (average over 1 minute recording) at day 5 of mechanical ventilation | 
| Transpulmonary driving pressure (ΔPL) - D6 | ∆PL is calculated as change in airway pressure minus change in esophageal pressure | ∆PL (average over 1 minute recording) at day 6 of mechanical ventilation | 
| Transpulmonary driving pressure (ΔPL) - D7 | ∆PL is calculated as change in airway pressure minus change in esophageal pressure | ∆PL (average over 1 minute recording) at day 7 of mechanical ventilation | 
| Transpulmonary driving pressure (ΔPL) - D8 | ∆PL is calculated as change in airway pressure minus change in esophageal pressure | ∆PL (average over 1 minute recording) at day 8 of mechanical ventilation | 
| Occlusion pressure (P0.1) - D1 | P0.1 is measured during the first 100 milliseconds of a breath | P0.1 (average of 3 breaths) at day 1 of mechanical ventilation | 
| Occlusion pressure (P0.1) - D2 | P0.1 is measured during the first 100 milliseconds of a breath | P0.1 (average of 3 breaths) at day 2 of mechanical ventilation | 
| Occlusion pressure (P0.1) - D3 | P0.1 is measured during the first 100 milliseconds of a breath | P0.1 (average of 3 breaths) at day 3 of mechanical ventilation | 
| Occlusion pressure (P0.1) - D4 | P0.1 is measured during the first 100 milliseconds of a breath | P0.1 (average of 3 breaths) at day 4 of mechanical ventilation | 
| Occlusion pressure (P0.1) - D5 | P0.1 is measured during the first 100 milliseconds of a breath | P0.1 (average of 3 breaths) at day 5 of mechanical ventilation | 
| Occlusion pressure (P0.1) - D6 | P0.1 is measured during the first 100 milliseconds of a breath | P0.1 (average of 3 breaths) at day 6 of mechanical ventilation | 
| Occlusion pressure (P0.1) - D7 | P0.1 is measured during the first 100 milliseconds of a breath | P0.1 (average of 3 breaths) at day 7 of mechanical ventilation | 
| Occlusion pressure (P0.1) - D8 | P0.1 is measured during the first 100 milliseconds of a breath | P0.1 (average of 3 breaths) at day 8 of mechanical ventilation | 
| End-expiratory diaphragm thickness (DTee) - D1 | Measured with ultrasound. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTee (average of 3 breaths) at day 1 of mechanical ventilation | 
| End-expiratory diaphragm thickness (DTee) - D2 | Measured with ultrasound. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTee (average of 3 breaths) at day 2 of mechanical ventilation | 
| End-expiratory diaphragm thickness (DTee) - D3 | Measured with ultrasound. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTee (average of 3 breaths) at day 3 of mechanical ventilation | 
| End-expiratory diaphragm thickness (DTee) - D4 | Measured with ultrasound. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTee (average of 3 breaths) at day 4 of mechanical ventilation | 
| End-expiratory diaphragm thickness (DTee) - D5 | Measured with ultrasound. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTee (average of 3 breaths) at day 5 of mechanical ventilation | 
| End-expiratory diaphragm thickness (DTee) - D6 | Measured with ultrasound. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTee (average of 3 breaths) at day 6 of mechanical ventilation | 
| End-expiratory diaphragm thickness (DTee) - D7 | Measured with ultrasound. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTee (average of 3 breaths) at day 7 of mechanical ventilation | 
| End-expiratory diaphragm thickness (DTee) - D8 | Measured with ultrasound. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTee (average of 3 breaths) at day 8 of mechanical ventilation | 
| Diaphragm thickening fraction (DTF) measured with ultrasound - D1 | DTF is calculated as (Thickness at end-inspiration [DTei] - Thickness at end-expiration [DTee])/Thickness at end-expiration [DTee] × 100. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTF (average of 3 breaths) at day 1 of mechanical ventilation | 
| Diaphragm thickening fraction (DTF) measured with ultrasound - D2 | DTF is calculated as (Thickness at end-inspiration [DTei] - Thickness at end-expiration [DTee])/Thickness at end-expiration [DTee] × 100. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTF (average of 3 breaths) at day 2 of mechanical ventilation | 
| Diaphragm thickening fraction (DTF) measured with ultrasound - D3 | DTF is calculated as (Thickness at end-inspiration [DTei] - Thickness at end-expiration [DTee])/Thickness at end-expiration [DTee] × 100. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTF (average of 3 breaths) at day 3 of mechanical ventilation | 
| Diaphragm thickening fraction (DTF) measured with ultrasound - D4 | DTF is calculated as (Thickness at end-inspiration [DTei] - Thickness at end-expiration [DTee])/Thickness at end-expiration [DTee] × 100. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTF (average of 3 breaths) at day 4 of mechanical ventilation | 
| Diaphragm thickening fraction (DTF) measured with ultrasound - D5 | DTF is calculated as (Thickness at end-inspiration [DTei] - Thickness at end-expiration [DTee])/Thickness at end-expiration [DTee] × 100. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTF (average of 3 breaths) at day 5 of mechanical ventilation | 
| Diaphragm thickening fraction (DTF) measured with ultrasound - D6 | DTF is calculated as (Thickness at end-inspiration [DTei] - Thickness at end-expiration [DTee])/Thickness at end-expiration [DTee] × 100. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTF (average of 3 breaths) at day 6 of mechanical ventilation | 
| Diaphragm thickening fraction (DTF) measured with ultrasound - D7 | DTF is calculated as (Thickness at end-inspiration [DTei] - Thickness at end-expiration [DTee])/Thickness at end-expiration [DTee] × 100. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTF (average of 3 breaths) at day 7 of mechanical ventilation | 
| Diaphragm thickening fraction (DTF) measured with ultrasound - D8 | DTF is calculated as (Thickness at end-inspiration [DTei] - Thickness at end-expiration [DTee])/Thickness at end-expiration [DTee] × 100. The ultrasound probe will be positioned perpendicular to the skin at the right zone of apposition. | DTF (average of 3 breaths) at day 8 of mechanical ventilation | 
| Duration of mechanical ventilation | Cumulative duration of mechanical ventilation in days (excluding non-invasive ventilation) | From date of intubation until the date of extubation or date of death from any cause, whichever came first, assessed up to 4 months | 
| Maximal inspiratory pressure (MIP) - D1 | MIP is a measure of inspiratory function. Measured once daily during an expiratory hold (± 30 seconds) | MIP at day 1 of mechanical ventilation | 
| Maximal inspiratory pressure (MIP) - D2 | MIP is a measure of inspiratory function. Measured once daily during an expiratory hold (± 30 seconds) | MIP at day 2 of mechanical ventilation | 
| Maximal inspiratory pressure (MIP) - D3 | MIP is a measure of inspiratory function. Measured once daily during an expiratory hold (± 30 seconds) | MIP at day 3 of mechanical ventilation | 
| Maximal inspiratory pressure (MIP) - D4 | MIP is a measure of inspiratory function. Measured once daily during an expiratory hold (± 30 seconds) | MIP at day 4 of mechanical ventilation | 
| Maximal inspiratory pressure (MIP) - D5 | MIP is a measure of inspiratory function. Measured once daily during an expiratory hold (± 30 seconds) | MIP at day 5 of mechanical ventilation | 
| Maximal inspiratory pressure (MIP) - D6 | MIP is a measure of inspiratory function. Measured once daily during an expiratory hold (± 30 seconds) | MIP at day 6 of mechanical ventilation | 
| Maximal inspiratory pressure (MIP) - D7 | MIP is a measure of inspiratory function. Measured once daily during an expiratory hold (± 30 seconds) | MIP at day 7 of mechanical ventilation | 
| Maximal inspiratory pressure (MIP) - D8 | MIP is a measure of inspiratory function. Measured once daily during an expiratory hold (± 30 seconds) | MIP at day 8 of mechanical ventilation | 
| Need for tracheal reintubation after tracheal extubation |  | From date of inclusion until the date of reintubation or date of hospital discharge or date of death from any cause, whichever came first, assessed up to 4 months. | 
| Lung ultrasound scores (LUSS) - D1 | Measured once daily for the first 8 days of mechanical ventilation | LUSS at day 1 of mechanical ventilation | 
| Lung ultrasound scores (LUSS) - D2 | Measured once daily for the first 8 days of mechanical ventilation | LUSS at day 2 of mechanical ventilation | 
| Lung ultrasound scores (LUSS) - D3 | Measured once daily for the first 8 days of mechanical ventilation | LUSS at day 3 of mechanical ventilation | 
| Lung ultrasound scores (LUSS) - D4 | Measured once daily for the first 8 days of mechanical ventilation | LUSS at day 4 of mechanical ventilation | 
| Lung ultrasound scores (LUSS) - D5 | Measured once daily for the first 8 days of mechanical ventilation | LUSS at day 5 of mechanical ventilation | 
| Lung ultrasound scores (LUSS) - D6 | Measured once daily for the first 8 days of mechanical ventilation | LUSS at day 6 of mechanical ventilation | 
| Lung ultrasound scores (LUSS) - D7 | Measured once daily for the first 8 days of mechanical ventilation | LUSS at day 7 of mechanical ventilation | 
| Lung ultrasound scores (LUSS) - D8 | Measured once daily for the first 8 days of mechanical ventilation | LUSS at day 8 of mechanical ventilation | 
| ICU length of stay | Duration to live discharge from the ICU | From date of ICU admission until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 4 months | 
| ICU mortality |  | From date of inclusion until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 4 months | 
| Hospital length of stay | Duration to live discharge from hospital | From date of hospital admission until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 4 months | 
| Duration to decease | Cumulative time to death counting from the day of intubation | From date of intubation until the date of death from any cause, whichever came first, assessed up to 4 months | 
| Hospital mortality |  | From date of inclusion until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 4 months | 
| Presence of clinical signs of muscle weakness at ICU discharge |  | From date of inclusion until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 4 months | 
| Presence of clinical signs of muscle weakness at hospital discharge |  | From date of inclusion until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 4 months | 
| ICU readmission rate within 48 hours |  | From date of ICU discharge until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 4 months | 
| Inspiratory muscle pressure (Pmus) - D1 | Measured at least once daily for the first 8 days of mechanical ventilation | Pmus at day 1 of mechanical ventilation | 
| Inspiratory muscle pressure (Pmus) - D2 | Measured at least once daily for the first 8 days of mechanical ventilation | Pmus at day 2 of mechanical ventilation | 
| Inspiratory muscle pressure (Pmus) - D3 | Measured at least once daily for the first 8 days of mechanical ventilation | Pmus at day 3 of mechanical ventilation | 
| Inspiratory muscle pressure (Pmus) - D4 | Measured at least once daily for the first 8 days of mechanical ventilation | Pmus at day 4 of mechanical ventilation | 
| Inspiratory muscle pressure (Pmus) - D5 | Measured at least once daily for the first 8 days of mechanical ventilation | Pmus at day 5 of mechanical ventilation | 
| Inspiratory muscle pressure (Pmus) - D6 | Measured at least once daily for the first 8 days of mechanical ventilation | Pmus at day 6 of mechanical ventilation | 
| Inspiratory muscle pressure (Pmus) - D7 | Measured at least once daily for the first 8 days of mechanical ventilation | Pmus at day 7 of mechanical ventilation | 
| Inspiratory muscle pressure (Pmus) - D8 | Measured at least once daily for the first 8 days of mechanical ventilation | Pmus at day 8 of mechanical ventilation | 
| Occlusion pressure (∆Pocc) - D1 | Measured at least once daily for the first 8 days of mechanical ventilation | ∆Pocc at day 1 of mechanical ventilation | 
| Occlusion pressure (∆Pocc) - D2 | Measured at least once daily for the first 8 days of mechanical ventilation | ∆Pocc at day 2 of mechanical ventilation | 
| Occlusion pressure (∆Pocc) - D3 | Measured at least once daily for the first 8 days of mechanical ventilation | ∆Pocc at day 3 of mechanical ventilation | 
| Occlusion pressure (∆Pocc) - D4 | Measured at least once daily for the first 8 days of mechanical ventilation | ∆Pocc at day 4 of mechanical ventilation | 
| Occlusion pressure (∆Pocc) - D5 | Measured at least once daily for the first 8 days of mechanical ventilation | ∆Pocc at day 5 of mechanical ventilation | 
| Occlusion pressure (∆Pocc) - D6 | Measured at least once daily for the first 8 days of mechanical ventilation | ∆Pocc at day 6 of mechanical ventilation | 
| Occlusion pressure (∆Pocc) - D7 | Measured at least once daily for the first 8 days of mechanical ventilation | ∆Pocc at day 7 of mechanical ventilation | 
| Occlusion pressure (∆Pocc) - D8 | Measured at least once daily for the first 8 days of mechanical ventilation | ∆Pocc at day 8 of mechanical ventilation | 
| Esophageal pressure-time product (PTPes) - D1 | Area under the curve (AUC) of the Pes-time plot during inspiration. Measured at least once daily for the first 8 days of mechanical ventilation. | PTPes at day 1 of mechanical ventilation | 
| Esophageal pressure-time product (PTPes) - D2 | Area under the curve (AUC) of the Pes-time plot during inspiration. Measured at least once daily for the first 8 days of mechanical ventilation. | PTPes at day 2 of mechanical ventilation | 
| Esophageal pressure-time product (PTPes) - D3 | Area under the curve (AUC) of the Pes-time plot during inspiration. Measured at least once daily for the first 8 days of mechanical ventilation. | PTPes at day 3 of mechanical ventilation | 
| Esophageal pressure-time product (PTPes) - D4 | Area under the curve (AUC) of the Pes-time plot during inspiration. Measured at least once daily for the first 8 days of mechanical ventilation. | PTPes at day 4 of mechanical ventilation | 
| Esophageal pressure-time product (PTPes) - D5 | Area under the curve (AUC) of the Pes-time plot during inspiration. Measured at least once daily for the first 8 days of mechanical ventilation. | PTPes at day 5 of mechanical ventilation | 
| Esophageal pressure-time product (PTPes) - D6 | Area under the curve (AUC) of the Pes-time plot during inspiration. Measured at least once daily for the first 8 days of mechanical ventilation. | PTPes at day 6 of mechanical ventilation | 
| Esophageal pressure-time product (PTPes) - D7 | Area under the curve (AUC) of the Pes-time plot during inspiration. Measured at least once daily for the first 8 days of mechanical ventilation. | PTPes at day 7 of mechanical ventilation | 
| Esophageal pressure-time product (PTPes) - D8 | Area under the curve (AUC) of the Pes-time plot during inspiration. Measured at least once daily for the first 8 days of mechanical ventilation. | PTPes at day 8 of mechanical ventilation | 
| Dead space ventilation (VD) - D1 | Measured with volumetric capnography (Capnostat 5, Philips) in adults only. Measured at least once daily for the first 8 days of mechanical ventilation. | VD at day 1 of mechanical ventilation | 
| Dead space ventilation (VD) - D2 | Measured with volumetric capnography (Capnostat 5, Philips) in adults only. Measured at least once daily for the first 8 days of mechanical ventilation. | VD at day 2 of mechanical ventilation | 
| Dead space ventilation (VD) - D3 | Measured with volumetric capnography (Capnostat 5, Philips) in adults only. Measured at least once daily for the first 8 days of mechanical ventilation. | VD at day 3 of mechanical ventilation | 
| Dead space ventilation (VD) - D4 | Measured with volumetric capnography (Capnostat 5, Philips) in adults only. Measured at least once daily for the first 8 days of mechanical ventilation. | VD at day 4 of mechanical ventilation | 
| Dead space ventilation (VD) - D5 | Measured with volumetric capnography (Capnostat 5, Philips) in adults only. Measured at least once daily for the first 8 days of mechanical ventilation. | VD at day 5 of mechanical ventilation | 
| Dead space ventilation (VD) - D6 | Measured with volumetric capnography (Capnostat 5, Philips) in adults only. Measured at least once daily for the first 8 days of mechanical ventilation. | VD at day 6 of mechanical ventilation | 
| Dead space ventilation (VD) - D7 | Measured with volumetric capnography (Capnostat 5, Philips) in adults only. Measured at least once daily for the first 8 days of mechanical ventilation. | VD at day 7 of mechanical ventilation | 
| Dead space ventilation (VD) - D8 | Measured with volumetric capnography (Capnostat 5, Philips) in adults only. Measured at least once daily for the first 8 days of mechanical ventilation. | VD at day 8 of mechanical ventilation |