Diaphragm Atrophy and Dysfunction in Mechanical Ventilation

Study Overview
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Brief Summary
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The gold standard of twitch transdiaphragmatic pressure recordings would ultimately clear the fog around the rate of development of Ventilator induced Diaphragm Dysfunction (VIDD) in mechanically ventilated patients over time. Through measurements made even after mechanical ventilation (MV) it could be clarified to what extent patients recover from VIDD. Paired with cortical stimulation and electromyographic recordings of diaphragm muscle potentials, it could be explored to what extent decreased diaphragm excitability due to long term MV contributes to VIDD on the level of motor cortex. Against that background the present project aims at determining the rate of decline in diaphragm function, strength and control in patients undergoing MV (including measurements after extubation).

Detailed Description
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Evidence both from animal and human studies support the development of ventilator induced diaphragm dysfunction (VIDD) from as early as 24 hours of mechanical ventilation (MV) in the intensive care unit (ICU). However, while the concept of VIDD seems to be proven now, several questions remain unanswered regarding its actual rate of development and (potentially) recovery after MV. The gold standard of twitch transdiaphragmatic pressure recordings would ultimately clear the fog around the rate of development of VIDD over time. Through measurements made even after MV it could be clarified to what extent patients recover from VIDD. Paired with cortical stimulation and electromyographic recordings of diaphragm muscle potentials, it could be explored to what extent decreased diaphragm excitability due to long term MV contributes to VIDD on the level of motor cortex. Against that background the present project aims at determining the rate of decline in diaphragm function, strength and control in patients undergoing MV (including measurements after extubation).

Official Title
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Development of Diaphragm Atrophy, Dysfunction and Inhibited Cortical Control in Mechanical Ventilation

Conditions
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Diaphragm Issues, Mechanical Ventilation Complication, Respiratory Failure, Intensive Care (ICU) Myopathy

Intervention / Treatment
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* Diagnostic Test: Respiratory Muscle Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Initiation of invasive mechanical ventilation in the Intensive Care Unit within 48 hours. Expected duration of invasive mechanical ventilation of at least 5 days. Exclusion Criteria: Body-mass-index (BMI) >40 Expected absence of active participation of the patient in study-related measurements after extubation Alcohol or drug abuse Non MRI compatible implant in the body Slipped disc Epilepsy Patients in an interdependence or with an employment contract with the principal investigator, Co-PI or his deputy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Invasively ventilated patients (n=15)<br>First measurement (comprehensive protocol) within 48 hours from initiation of MV. Serial measurements every third day including 2 measurements after extubation. | Diagnostic Test: Respiratory Muscle Testing<br>* Comprehensive assessment of respiratory muscle function. Comprehensive assessment of respiratory muscle function to the point of its invasive assessment with recordings of twitch transdiaphragmatic pressure in response to magnetic phrenic nerve stimulation and stimulation of the lower thoracic nerve roots.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Twitch transdiaphragmatic pressure in response to supramaximal magnetic stimulation of the phrenic nerve roots. |  | 2 years | 
| Cortical control of diaphragm function | Amplitude of the diaphragm motor evoked potentials (measured by surface electrodes attached to the diaphragm) following cortical magnetic stimulation of the phrenic nerve roots. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diaphragm ultrasound | Diaphragm thickening fraction on ultrasound | 2 years | 
| Systemic inflammation | Concentration of circulating Interleukin, high-sensitivity C-reactive protein (analyzed quantitatively based on a Levels venous blood sample). | 2 years |