Electromyography for Diaphragm Effort

Study Overview
=================
Brief Summary
-----------------
Mechanical ventilation may be necessary to save the life of a patient due to an accident, pneumonia or surgery. The ventilator then temporarily takes over the function of the respiratory muscles. During treatment in the Intensive Care, the amount of support provided by the ventilator is usually lowered gradually, until the point that the patient can breathe unassisted once again. However, in a large fraction of patients (up to 40%) it takes days to weeks before the patient is able to breathe unassisted, even after the initial disease has been treated. This is called prolonged weaning. A possible cause of prolonged weaning is weakness of the respiratory muscles. The diaphragm, the largest respiratory muscle, can become weakened if it is used too little, much like all other muscles in the body. Additionally, damage and weakness of the diaphragm can occur when the diaphragm has to work excessively. Therefore, it is important that the diaphragm works enough; not so little that it becomes weakened, but not too much either. Measurements of pressure generated by the diaphragm are needed to determine the current level of diaphragm activity in a patient on mechanical ventilation. However, these measurements are rarely performed, because they are time-consuming and require placement of two additional nasogastric catheters. This is a shame, as adequate loading of the diaphragm might prevent development of weakness, leading to shorter duration of mechanical ventilation. Finding alternative measurements of diaphragm effort might be a solution to this problem. It has been hypothesized that the electrical activity of the diaphragm provides a reliable indication of diaphragm effort. This study aims to determine whether there is a correlation between pressure generation by the diaphragm and electrical activity of the diaphragm over a wide range of respiratory activity, from low effort to extreme effort, in healthy volunteers.

Official Title
-----------------
Diaphragm Electromyography to Estimate Breathing Effort: a Physiological Study

Conditions
-----------------
Diaphragm Injury, Muscle Weakness, Weaning Failure, Physiological Stress

Intervention / Treatment
-----------------
* Other: Inspiratory threshold loading protocol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed Consent Age >18 years Exclusion Criteria: History of cardiac and/or pulmonary disease or current medication use History of pneumothorax Contra-indications for nasogastric tube placement (recent epistaxis, severe coagulopathy, current upper airway pathology) Contra-indication for magnetic stimulation (cardiac pacemakers or metal in cervical area)

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

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intervention group, receiving Inspiratory threshold loading protocol. | Other: Inspiratory threshold loading protocol<br>* Subjects will be instrumented with catheters that measure electrical activity of the diaphragm and transdiaphragmatic pressure. Subjects will perform a stepwise inspiratory threshold loading protocol to induce a wide range of diaphragm activity.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electrical activity of the diaphragm | Diaphragm electromyography will be obtained with multiple electrode pairs situated on specialized esophageal catheters. The raw diaphragm electromyography will be filtered and integrated to obtain the compound mean action potential reported in microvolts (μV) as described in ref 1 (Sinderby et al.). | Electrical activity of the diaphragm will be assessed at multiple levels of breathing effort in each subject for two hours. | 
| Transdiaphragmatic pressure | The pressure gradient over the diaphragm will be obtained by subtracting the esophageal pressure from the pressure in the stomach, measured with specialized catheters, and will be reported in centimeters of water (cmH2O) as described in ref 3, American Thoracic Society (ATS) statement on respiratory muscle testing. | Transdiaphragmatic pressure will be assessed at multiple levels of breathing effort in each subject for two hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Work of breathing | Work of breathing will be obtained by integrating the pressure-volume loops of esophageal pressure and tidal volume, and will be reported in Joule per minute as described in ref 3, ATS statement on respiratory muscle testing.. | Work of breathing will be assessed at multiple levels of breathing effort in each subject for two hours. | 
| Pressure-time product of the diaphragm | Pressure-time product of the diaphragm will be obtained by dividing the time-integral of transdiaphragmatic pressure (described above) over time, and will be reported as cmH20*s per minute as described in ref 3, ATS statement on respiratory muscle testing.. | Pressure-time product of the diaphragm will be assessed at multiple levels of breathing effort in each subject for two hours. | 
| Pressure-time product of the respiratory muscles | Pressure-time product of the respiratory muscles will be obtained by dividing the time-integral of esophageal pressure over time, and will be reported as cmH20*s per minute as described in ref 3, ATS statement on respiratory muscle testing.. | Pressure-time product of the respiratory muscles will be assessed at multiple levels of breathing effort in each subject for two hours. | 
| Mechanical power | Mechanical power will be obtained by multiplying the work of breathing (described above) by the number of breaths per minute, and will be reported in Watt (joule/minute) as described in ref 3, ATS statement on respiratory muscle testing.. | Mechanical power will be assessed at multiple levels of breathing effort in each subject for two hours. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Monitoring, Breathing effort, Intensive Care, Diaphragm weakness