Clinical trial NCT04658498: Improving Our Understanding of Respiratory Muscle Training to Facilitate Weaning From Mechanical Ventilation in the ICU
Official title: Improving Our Understanding of Respiratory Muscle Training to Facilitate Weaning From Mechanical Ventilation in the ICU
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Weaning Failure
Keywords: ICU acquired muscle weakness
IMT
Weaning outcomes
Maximal inspiratory pressure
Diaphragm EMG
Surface EMG
Diaphragm ultrasounds
Microbiopsies
Difficult to wean patients
Respiratory muscles
Lead sponsor: KU Leuven
Sponsor class: OTHER
First posted: 2020-12-08
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, three arms parallel group randomized controlled trial with 1:1:1 allocation ratio
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Maximal Inspiratory Pressure (PImax)
timeFrame: Maximal duration of IMT treatment: 28 days
Secondary outcomes:
measure: Diaphragm mobility, thickness and thickening fraction by ultrasounds
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in contractile material and structural alteration of sternocleidomastoid muscle
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in fiber proportion of sternocleidomastoid muscle fibers
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in size of sternocleidomastoid muscle fibers
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in amount of satellite cells of sternocleidomastoid muscle
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in amount of fibrotic tissue of sternocleidomastoid muscle
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change of gene expression of atrophy/hypertrophy related pathways of sternocleidomastoid muscle
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in cell proliferation of sternocleidomastoid muscle
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in cell differentiation of sternocleidomastoid muscle
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in Blood Flow Index (BFI) of extra-diaphragmatic respiratory muscles
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in Tissue Oxygenation Index (TOI) of ex of extra-diaphragmatic respiratory muscles
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in signal amplitude of diaphragm electromyography
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Change in signal amplitude of electromyography of extra-diaphragmatic respiratory muscles
timeFrame: Maximal duration of IMT treatment: 28 days
measure: Esophageal and gastric pressure
timeFrame: Maximal duration of IMT treatment: 28 days
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospital Leuven
Study officials:
References:
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