NMES to Prevent Respiratory Muscle Atrophy in Mechanically Ventilated Patients

Study Overview
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Brief Summary
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Patients requiring prolonged time on the ventilator are susceptible to a wide range of clinical complications and excess mortality. It is therefore imperative for them to wean at the earliest possible time. Respiratory muscle weakness due to disuse of these muscles is a major underlying factor for weaning failure. Surprisingly, there is not much known about the impact of critical illness and MV on the expiratory abdominal wall muscles.These muscles are immediately activated as ventilation demands increase and are important in supporting respiratory function in patients with diaphragm weakness. Weakness of expiratory abdominal wall muscles will result in a decreased cough function and reduced ventilatory capacity. These are considerable causes of weaning failure and (re)hospitalisation for respiratory complications such as pneumonia. Recent evidence shows that neuromuscular electrical stimulation (NMES) can be used as a safe therapy to maintain skeletal muscle function in critically ill patients. This study will be the first to test the hypothesis that breath-synchronized NMES of the abdominal wall muscles can prevent expiratory muscle atrophy during the acute stages of MV.

Detailed Description
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Approximately 30-40% of intubated patients at the intensive care unit (ICU) take more than one attempt to wean from mechanical ventilation (MV). 6-14% of intubated patients take longer than 7 days to wean from MV. Patients requiring prolonged time on the ventilator are susceptible to a wide range of clinical complications and excess mortality. It is therefore imperative for them to wean at the earliest possible time. Respiratory muscle weakness due to disuse of these muscles is a major underlying factor for weaning failure. It is known that diaphragm strength rapidly declines within a few days after the initiation of MV. Surprisingly, there is not much known about the impact of critical illness and MV on the expiratory abdominal wall muscles.These muscles are immediately activated as ventilation demands increase and are important in supporting respiratory function in patients with diaphragm weakness. Weakness of expiratory abdominal wall muscles will result in a decreased cough function and reduced ventilatory capacity. These are considerable causes of weaning failure and (re)hospitalisation for respiratory complications such as pneumonia. Recent evidence shows that neuromuscular electrical stimulation (NMES) can be used as a safe therapy to maintain skeletal muscle function in critically ill patients, e.g. by stimulating quadriceps muscles in patients receiving MV. This study will be the first to test the hypothesis that exhalation synchronized NMES of the abdominal wall muscles can prevent expiratory muscle atrophy during the acute stages of MV. The investigators hypothesize that this approach will improve respiratory function and thereby will reduce the amount of time it takes to wean patients from mechanical ventilation.

Official Title
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Breath Synchronized Electrical Stimulation of the Abdominal Wall Muscles to Prevent Respiratory Muscle Atrophy During the Acute Stages of Mechanical Ventilation Therapy

Conditions
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Mechanical Ventilation Complication, Neuromuscular Electrical Stimulation, Muscle Weakness

Intervention / Treatment
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* Device: VentFree prototype (VF03-K) active stimulation
* Device: VentFree prototype (VF03-K) sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 year invasive mechanical ventilation less than 72 hours expected duration of MV after inclusion > 72 hours Exclusion Criteria: no clearly visible separate layers of the abdominal wall muscles (external oblique, internal oblique and transverse abdominal muscles), assessed with ultrasound during routine care cardiac pacemaker congenital myopathies and/or existing central or peripheral neuropathies refractory epilepsy recent abdominal surgery within four weeks prior to study inclusion body mass index (BMI) greater than 35 kg/m2 pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VF03-K active stimulation<br>NMES applied to the abdominal wall muscles using the VentFree prototype (VF03-K). Stimulation is applied twice daily for 30 minutes, 5 days per week, for 6 weeks or until the patient is weaned from mechanical ventilation, whichever occurs sooner. | Device: VentFree prototype (VF03-K) active stimulation<br>* Abdominal wall muscle stimulation synchronised with mechanical ventilation. Stimulation frequency: 30 Hz, pulse width: 352us, max. intensity: 100mA (threshold intensity determined using ultrasound)<br>|
| Sham Comparator: VF03-K sham stimulation<br>Sham stimulation applied to the abdominal wall muscles using the VentFree prototype (VF03-K). Sham stimulation is applied twice daily for 30 minutes, 5 days per week, for 6 weeks or until the patient is weaned from mechanical ventilation, whichever occurs sooner. | Device: VentFree prototype (VF03-K) sham stimulation<br>* Abdominal wall muscle sham-stimulation synchronised with mechanical ventilation. Stimulation frequency: 10 Hz, pulse width: 352us, intensity: 15 mA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thickness of the abdominal wall muscles | Thickness of the abdominal wall muscles over time, for both groups, as measured by ultrasound. | Until study completion, up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thickness of the diaphragm | Thickness of the diaphragm over time, for both groups, as measured by ultrasound. | Until study completion, up to 6 weeks | 
| Thickness of the rectus abdominis muscle | Thickness of the rectus abdominis mucle over time, for both groups, as measured by ultrasound. | Until study completion, up to 6 weeks | 
| Maximum expiratory pressure (MEP) | Maximum expiratory pressure (MEP) to assess expiratory muscle function | Within 24 hours after extubation | 
| Maximum inspiratory pressure (MIP) | Maximum inspiratory pressure (MIP) to assess inspiratory muscle function | Within 24 hours after extubation | 
| Vital capacity (Vc) | Vital capacity (Vc) to assess respiratory muscle strength | Within 24 hours after extubation | 
| Peak expiratory flow | Peak expiratory flow (PEF) to assess cough strength | Within 24 hours after extubation | 
| Number of patients with extubation failure | Weaning failure defined as the failure to pass a spontaneous-breathing trial or the need for reintubation within 48 hours following extubation | Within 24 hours after extubation | 
| Systemic inflammatory markers | Among others, cytokines IL-6 and IL-1 will be determined from blood sample analysis | Within 24 hours after extubation | 
| Number of patients with respiratory complications after ICU discharge | Number of patients with development of pneumonia, and readmission to the ICU due to atelectasis or respiratory problems that require mechanical ventilation. | Up to 6 weeks after ICU discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Expiratory muscles, Mechanically ventilated patients, Neuromuscular electrical stimulation, Respiratory function, Ventilator-acquired muscle atrophy