Improving Our Understanding of Respiratory Muscle Training to Facilitate Weaning From Mechanical Ventilation in the ICU
- Conditions
- Weaning Failure
- Registration Number
- NCT04658498
- Lead Sponsor
- KU Leuven
- Brief Summary
Mechanical ventilation is a life-saving treatment frequently applied in intensive care unit (ICU). Nonetheless, by putting at rest the respiratory muscles, it can lead to respiratory muscle weakness and atrophy, which are accompanied by prolonged duration of mechanical ventilation, difficult weaning and increased ICU mortality. Despite a strong theoretical rationale and some evidence supporting the use of inspiratory muscle training (IMT) to address respiratory muscle weakness and atrophy, the optimal approach to IMT remains largely uncertain. In fact, mechanistic studies evaluating physiological adaptations that occur in respiratory muscles of mechanically ventilated patients in response to different training regimens have not been conducted so far.
The aim of this study is to comprehensively investigate changes in respiratory muscle function in response to three different conditions that patients will be exposed to during their period of weaning from mechanical ventilation.
- Detailed Description
A majority of mechanically ventilated patients develop respiratory muscle weakness during critical illness.
The potential value of implementing rehabilitative interventions for respiratory muscle conditioning are supported by observations showing that respiratory muscle weakness is associated with prolonged duration of mechanical ventilation, difficult weaning, and increased ICU mortality.
Despite a strong theoretical rationale and some evidence supporting its use, mechanistic studies evaluating physiological adaptations that occur in respiratory muscles of mechanically ventilated patients in response to different training regimens have not been performed so far. Consequently, the characterization of IMT modalities and of the optimal approach to IMT remain largely uncertain.
To date, the great part of the studies on the topic employed an external mechanical threshold device to perform trainings, in general adopting loads ranging between 10-50% of maximal inspiratory strength (i.e. maximal inspiratory pressure (PImax)). Intermittent spontaneous breathing periods (e.g. using partially assisted or spontaneous modes of ventilation) are also frequently applied as an activating stimulus to the respiratory muscles during periods of mechanical ventilation.
A tapered flow resistive load (TFRL) device (POWERbreathe KH2, HaB International, UK) has been already tested and implemented at University Hospital Leuven as a way of loading respiratory muscles in ICU patients. The TFRL approach represents a potential more optimal way of loading the respiratory muscles in patients on prolonged mechanical ventilation. Such a loading approach allows higher inspiratory tidal volumes to be reached and higher work and power generation during trainings, by adapting to changes in length-tension characteristics of the inspiratory muscles during inspiration.
With regards to training modalities, high-intensity IMT modalities by applying loads ranging between 30 and 50 %PImax, have not yet been proven to be associated with better improvements in respiratory muscle strength compared to low-intensity (sham) IMT modalities at loads not exceeding 10 %PImax.
On the other hand, no studies are available that assessed changes in respiratory muscle function beyond assessments of respiratory muscle strength in response to training.
Additionally, no training studies have tried to quantify the intrinsic loading of the patients (i.e. elastic and resistive resistances of the chest wall and the lungs) that muscles are exposed to in between periods of additional loading applied during IMT sessions.
The aim of this study is to comprehensively investigate changes in respiratory muscle function in response to three different conditions that difficult to wean patients will be exposed to during their weaning period. The complementary quantification of the entity of loading that respiratory muscles are bearing during assisted, spontaneous and resistive breathing would provide important novel insights on the optimization of IMT stimulus in different patients on prolonged mechanical ventilation.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- Difficult and prolonged weaning patients
- Adequate oxygenation
- Febrile temperature < 38ºC
- Hemodynamic stability
- Stable blood pressure
- No or minimal vasopressors
- No myocardial ischemia
- Adequate hemoglobin and mentation
- Resolution of disease acute phase
- Able to follow simple verbal commands related to IMT
- Mechanically ventilated via a tracheostomy or endotracheal tube
- Pre-existing neuromuscular disease
- Agitation
- Hemodynamically instable (arrhythmia, decompensated heart failure, coronary insufficiency)
- Hemoptysis
- Diaphoresis
- Spinal cord injury above T8
- Use of any type of home MV support prior to hospitalization
- Skeletal pathology that impairs chest wall movements
- Poor general prognosis or fatal outcome
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Maximal Inspiratory Pressure (PImax) Maximal duration of IMT treatment: 28 days Using a unidirectional valve which will be connected to the patient's tracheostomy tube or endotracheal tube for an uninterrupted period of 25 seconds.
- Secondary Outcome Measures
Name Time Method Change in cell differentiation of sternocleidomastoid muscle Maximal duration of IMT treatment: 28 days By analyzing muscle microbiopsies cell differentiation assays
Change in amount of fibrotic tissue of sternocleidomastoid muscle Maximal duration of IMT treatment: 28 days By analyzing muscle microbiopsies with Masson staining
Change in signal amplitude of electromyography of extra-diaphragmatic respiratory muscles Maximal duration of IMT treatment: 28 days Electromyography of scalene, sternocleidomastoid, parasternal intercostal and rectus abdominis muscles will be collected through surface electromyography electrodes
Change in contractile material and structural alteration of sternocleidomastoid muscle Maximal duration of IMT treatment: 28 days By analyzing muscle microbiopsies using Hematoxylin \& Eosin (H\&E) staining.
Change in fiber proportion of sternocleidomastoid muscle fibers Maximal duration of IMT treatment: 28 days By analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.
Change in cell proliferation of sternocleidomastoid muscle Maximal duration of IMT treatment: 28 days By analyzing muscle microbiopsies cell proliferation assays
Change in Tissue Oxygenation Index (TOI) of ex of extra-diaphragmatic respiratory muscles Maximal duration of IMT treatment: 28 days Measured by near-infrared spectroscopy with optodes transcutaneously positioned on the scalene, sternocleidomastoid and upper rectus abdominis muscles
Esophageal and gastric pressure Maximal duration of IMT treatment: 28 days Using a multifunction nasogastric catheter
Change in amount of satellite cells of sternocleidomastoid muscle Maximal duration of IMT treatment: 28 days By analyzing muscle microbiopsies with Pax7 immunostaining
Change of gene expression of atrophy/hypertrophy related pathways of sternocleidomastoid muscle Maximal duration of IMT treatment: 28 days By analyzing muscle microbiopsies with RT2 profiler PCR array skeletal muscle, Qiagen
Change in signal amplitude of diaphragm electromyography Maximal duration of IMT treatment: 28 days Diaphragm electromyography will be collected with an esophageal electrode catheter
Diaphragm mobility, thickness and thickening fraction by ultrasounds Maximal duration of IMT treatment: 28 days Assessment by diaphragm ultrasounds
Change in size of sternocleidomastoid muscle fibers Maximal duration of IMT treatment: 28 days By analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.
Change in Blood Flow Index (BFI) of extra-diaphragmatic respiratory muscles Maximal duration of IMT treatment: 28 days Measured by near-infrared spectroscopy in combination with injections of the tracer indocyanine green dye (ICG), with optodes transcutaneously positioned on the scalene, sternocleidomastoid and upper rectus abdominis muscles.
Trial Locations
- Locations (1)
University Hospital Leuven
🇧🇪Leuven, Belgium