Effect PEEP on Diaphragm

Study Overview
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Brief Summary
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This study evaluates the effect of positive end-expiratory pressure on the position, length and function of the diaphragm. During the first part of the study, physiological measurements of the diaphragm will be performed while participants receive non-invasive ventilation at different PEEP levels. During the second part of the study, MRI measurements of the diaphragm will be performed during a change in PEEP level.

Detailed Description
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In almost all mechanically ventilated patients, positive end-expiratory pressure (PEEP) is used. Its function is to prevent alveolar collapse and to maintain oxygenation. However, it has recently been found that PEEP may contribute to diaphragm weakness, which is an important problem in the intensive care unit (ICU). This study showed that mechanical ventilation with PEEP resulted in a caudal displacement of the diaphragm, since PEEP increases the end-expiratory volume. Furthermore, their study in rats showed that this displacement resulted in a reduced fiber length and sarcomere length on the short term. After rats were ventilated with PEEP for 18 hours, it was found that adaptation of the diaphragm occurred; i.e. the number of sarcomeres were decreased. It is hypothesized that this adaptation may also occur in mechanically ventilated patients. This could lead to problems in weaning a patient off the ventilator, as PEEP is abruptly removed during a spontaneous breathing trial (SBT). This leads to a reduction in end-expiratory volume which would mean that the newly-adapted diaphragm fibers are being stretched. These stretched muscle fibers are not working at their optimal length of the force-length relation, thereby contributing to diaphragm weakness.

Official Title
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The Effects of Positive End-expiratory Pressure on the Position, Length and Contractibility of the Diaphragm.

Conditions
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Diaphragm Disease

Intervention / Treatment
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* Other: PEEP: 5 cmH2O
* Other: PEEP: 10 cmH2O
* Other: PEEP: 15 cmH2O


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age ≥ 18 years Exclusion Criteria: Symptoms relating to respiratory or cardiovascular disease History of pneumothorax or family history of primary pneumothorax Obesity (defined as BMI > 30kg/m²) Known pregnancy Contraindications for the placement of a nasogastric tube (upper airway/esophageal/gastric/mouth or face pathology (e.g. recent surgery, esophageal varices, diaphragmatic hernia), nasal bleeding within the last 2 weeks or use of anticoagulants) Contraindications for MRI (electrical/metallic implants, claustrophobia or history in metalworking) Subjects who are employed at the department of intensive care adults, directly involved in the study and/or family from staff of the ICU.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All participants will receive the same protocol with different levels of PEEP ventilation during the first part of the study (physiological part), so the interventional study model for this part is single group. During the second part (MRI), participants are randomized for one of the three available PEEP levels (5, 10 or 15 cmH2O), so the study model for this part is parallel.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PEEP level of 5 cmH2O<br>During second part of the study (MRI) Diaphragm position | Other: PEEP: 5 cmH2O<br>* During second part of the study (MRI)<br>|
| Active Comparator: PEEP level of 10 cmH2O<br>During second part of the study (MRI) Diaphragm position | Other: PEEP: 10 cmH2O<br>* During second part of the study (MRI)<br>|
| Active Comparator: PEEP level of 15 cmH2O<br>During second part of the study (MRI) Diaphragm position | Other: PEEP: 15 cmH2O<br>* During second part of the study (MRI)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in diaphragm's position | Changes in the position of the diaphragm during different PEEP levels, as measured with both ultrasound and MRI | 2 hours | 
| Changes in diaphragm's shape and length | Changes of the diaphragm's shape and length during different PEEP levels, as measured with MRI | 2 hours | 
| Changes in diaphragm's efficiency | Changes in the neuro-mechanical efficiency of the diaphragm (ratio between pressure and electrical muscle activity) during different PEEP levels, as measured with a nasogastric catheter | 2 hours | 
| Change in twitch transdiaphragmatic pressures | Twitch transdiaphragmatic pressures during different PEEP levels, as measured with magnetic stimulation of the phrenic nerves. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between MRI and ultrasound | The difference between diaphragm parameters obtained by ultrasound and parameters obtained by MRI | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PEEP, Diaphragm