Improving Our Understanding of Respiratory Muscle Training to Facilitate Weaning From Mechanical Ventilation in the ICU

Weaning Failure Clinical Trial

— TrainToWean  

Official title:

Improving Our Understanding of Respiratory Muscle Training to Facilitate Weaning From Mechanical Ventilation in the ICU

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04658498
• Other study ID #: S64871
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2023
• Est. completion date: October 2026

Study information

• Verified date: February 2023
• Source: KU Leuven
• Contact: Daniel Langer, PT, PhD
• Phone: +3216330192
• Email: daniel.langer[@]kuleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: October 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Weaning Failure

Intervention

Other:
• Procedure: Usual Care (UC)
Intermittent spontaneous breathing periods
• Procedure: UC + HI-IMT
UC + Supervised daily sessions of training including 4 sets of 6-10 full vital capacity breaths against an external load using a tapered flow resistive device (POWERbreathe KH2, HaB International, UK). The maximum tolerable resistance allowing patients to inhale at least 70% of their inspiratory vital capacity will be chosen and progressively increased throughout the training period.
• Procedure: UC + LI-IMT (sham IMT)
UC + superrvised daily sessions of training including 4 sets of 6-10 breaths at the lowest external imposable load with the tapered flow resistive device (POWERbreathe KH2, HaB International, UK) (i.e. 3 cmH2O).

Locations

Country	Name	City	State
Belgium	University Hospital Leuven	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
KU Leuven

Country where clinical trial is conducted

Belgium, 

References & Publications (8)

Dres M, Goligher EC, Dube BP, Morawiec E, Dangers L, Reuter D, Mayaux J, Similowski T, Demoule A. Diaphragm function and weaning from mechanical ventilation: an ultrasound and phrenic nerve stimulation clinical study. Ann Intensive Care. 2018 Apr 23;8(1):53. doi: 10.1186/s13613-018-0401-y. — View Citation

Dres M, Goligher EC, Heunks LMA, Brochard LJ. Critical illness-associated diaphragm weakness. Intensive Care Med. 2017 Oct;43(10):1441-1452. doi: 10.1007/s00134-017-4928-4. Epub 2017 Sep 15. — View Citation

Elkins M, Dentice R. Inspiratory muscle training facilitates weaning from mechanical ventilation among patients in the intensive care unit: a systematic review. J Physiother. 2015 Jul;61(3):125-34. doi: 10.1016/j.jphys.2015.05.016. Epub 2015 Jun 16. — View Citation

Hoffman M, Van Hollebeke M, Clerckx B, Muller J, Louvaris Z, Gosselink R, Hermans G, Langer D. Can inspiratory muscle training improve weaning outcomes in difficult to wean patients? A protocol for a randomised controlled trial (IMweanT study). BMJ Open. 2018 Jun 30;8(6):e021091. doi: 10.1136/bmjopen-2017-021091. — View Citation

Langer D, Charususin N, Jacome C, Hoffman M, McConnell A, Decramer M, Gosselink R. Efficacy of a Novel Method for Inspiratory Muscle Training in People With Chronic Obstructive Pulmonary Disease. Phys Ther. 2015 Sep;95(9):1264-73. doi: 10.2522/ptj.20140245. Epub 2015 Apr 9. — View Citation

Laveneziana P, Albuquerque A, Aliverti A, Babb T, Barreiro E, Dres M, Dube BP, Fauroux B, Gea J, Guenette JA, Hudson AL, Kabitz HJ, Laghi F, Langer D, Luo YM, Neder JA, O'Donnell D, Polkey MI, Rabinovich RA, Rossi A, Series F, Similowski T, Spengler CM, Vogiatzis I, Verges S. ERS statement on respiratory muscle testing at rest and during exercise. Eur Respir J. 2019 Jun 13;53(6):1801214. doi: 10.1183/13993003.01214-2018. Print 2019 Jun. — View Citation

Supinski GS, Callahan LA. Diaphragm weakness in mechanically ventilated critically ill patients. Crit Care. 2013 Jun 20;17(3):R120. doi: 10.1186/cc12792. — View Citation

Vorona S, Sabatini U, Al-Maqbali S, Bertoni M, Dres M, Bissett B, Van Haren F, Martin AD, Urrea C, Brace D, Parotto M, Herridge MS, Adhikari NKJ, Fan E, Melo LT, Reid WD, Brochard LJ, Ferguson ND, Goligher EC. Inspiratory Muscle Rehabilitation in Critically Ill Adults. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2018 Jun;15(6):735-744. doi: 10.1513/AnnalsATS.201712-961OC. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal Inspiratory Pressure (PImax)	Using a unidirectional valve which will be connected to the patient's tracheostomy tube or endotracheal tube for an uninterrupted period of 25 seconds.	Maximal duration of IMT treatment: 28 days
Secondary	Diaphragm mobility, thickness and thickening fraction by ultrasounds	Assessment by diaphragm ultrasounds	Maximal duration of IMT treatment: 28 days
Secondary	Change in contractile material and structural alteration of sternocleidomastoid muscle	By analyzing muscle microbiopsies using Hematoxylin & Eosin (H&E) staining.	Maximal duration of IMT treatment: 28 days
Secondary	Change in fiber proportion of sternocleidomastoid muscle fibers	By analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.	Maximal duration of IMT treatment: 28 days
Secondary	Change in size of sternocleidomastoid muscle fibers	By analyzing muscle microbiopsies with immunostaining of the myosin heavy chain.	Maximal duration of IMT treatment: 28 days
Secondary	Change in amount of satellite cells of sternocleidomastoid muscle	By analyzing muscle microbiopsies with Pax7 immunostaining	Maximal duration of IMT treatment: 28 days
Secondary	Change in amount of fibrotic tissue of sternocleidomastoid muscle	By analyzing muscle microbiopsies with Masson staining	Maximal duration of IMT treatment: 28 days
Secondary	Change of gene expression of atrophy/hypertrophy related pathways of sternocleidomastoid muscle	By analyzing muscle microbiopsies with RT2 profiler PCR array skeletal muscle, Qiagen	Maximal duration of IMT treatment: 28 days
Secondary	Change in cell proliferation of sternocleidomastoid muscle	By analyzing muscle microbiopsies cell proliferation assays	Maximal duration of IMT treatment: 28 days
Secondary	Change in cell differentiation of sternocleidomastoid muscle	By analyzing muscle microbiopsies cell differentiation assays	Maximal duration of IMT treatment: 28 days
Secondary	Change in Blood Flow Index (BFI) of extra-diaphragmatic respiratory muscles	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.	Maximal duration of IMT treatment: 28 days
Secondary	Change in Tissue Oxygenation Index (TOI) of ex of extra-diaphragmatic respiratory muscles	Measured by near-infrared spectroscopy with optodes transcutaneously positioned on the scalene, sternocleidomastoid and upper rectus abdominis muscles	Maximal duration of IMT treatment: 28 days
Secondary	Change in signal amplitude of diaphragm electromyography	Diaphragm electromyography will be collected with an esophageal electrode catheter	Maximal duration of IMT treatment: 28 days
Secondary	Change in signal amplitude of electromyography of extra-diaphragmatic respiratory muscles	Electromyography of scalene, sternocleidomastoid, parasternal intercostal and rectus abdominis muscles will be collected through surface electromyography electrodes	Maximal duration of IMT treatment: 28 days
Secondary	Esophageal and gastric pressure	Using a multifunction nasogastric catheter	Maximal duration of IMT treatment: 28 days