Clinical trial NCT05857774: Respiratory Muscle Structure and Function in Mechanically Ventilated Patients and Long-term Outcomes
Official title: Respiratory Muscle Structure and Function in Mechanically Ventilated Patients and Long-term Outcomes
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Mechanical Ventilation Complication
Diaphragm Injury
Lung Injury
Respiratory Insufficiency
Abdominal Muscle Strained
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2023-05-15
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be enrolled in the Medical-Surgical ICU at Toronto General Hospital.

Brief summary: Air is normally pumped in and out of the lungs by the muscles that contribute to inhalation and exhalation, called the respiratory muscles. The abdominal muscles help by forcing air out of your lungs during exhalation; whereas the diaphragm, the main muscle used for breathing, contracts to get air into the lungs during inhalation. With mechanical ventilation, respiratory muscles are able to rest and recover while the breathing machine takes over; however, this may cause respiratory muscle weakness. Patients who develop weakness of these muscles may require more assistance from the ventilator and take longer to recover their ability to breathe without assistance. The impact of this phenomenon on long-term outcomes is uncertain.

The RESPIRE study is designed to characterize how respiratory muscles change during mechanical ventilation and to evaluate the impact on long term quality of life. An additional objective of this study is to examine novel measures obtained from automated functions of a ventilator, that may better predict success from weaning from mechanical ventilation.

Detailed description: Previous work has established that diaphragm atrophy during mechanical ventilation is associated with adverse clinical outcomes. Abdominal muscles, which are engaged during breathing also undergo atrophy during mechanical ventilation. However, the relationship between these muscles and how they relate to long term function status is known and warrants further investigation.

Mechanical ventilation is a life-saving technique in patients with respiratory failure, however reasons why some patients require long term ventilation and are unsuccessful from weaning from ventilators are not fully elucidated. Respiratory muscle dysfunction as a result of mechanical ventilation is only recently being understood. Diaphragm atrophy is associated with adverse clinical outcomes, but the same is unknown if this holds true with abdominal muscle atrophy. Properly understanding the natural progression of diaphragm and abdominal muscle atrophy and dysfunction, and how they relate to each other, is critical to identifying markers or factors that may put particular patients at risk for long durations of mechanical ventilation and adverse clinical outcomes.

This study will provide important insights into the relationship between inspiratory and expiratory muscle function, and the evolution of functional impairments in critical care patients undergoing weaning from invasive mechanical ventilation. Further understanding of the pathophysiological processes of how these muscle groups interact in this context is important in moving forward with potential therapeutic strategies aimed at mitigating injury.

Eligibility criteria: Cases Inclusion Criteria:

• Adult patients ≥18 years of age undergoing invasive mechanical ventilation in the ICU for any reason within 36 hours of intubation

Control condition A Inclusion Criteria:

• Non-invasively ventilated patients in the ICU within 36 hours of initiating non-invasive ventilation

Control condition B Inclusion Criteria

• Non-ventilated patients admitted to the ICU receiving no respiratory support or oxygen therapy alone, including high flow nasal cannula

Exclusion Criteria:

* Patients expected to be extubated within 24 hours of screening for eligibility
* Patients who have already undergone a SBT at time of screening
* Patients with a previously diagnosed neuromuscular disorder
* Patients receiving long-term invasive mechanical ventilation (prior to current hospitalization)
* Patients who have required previously (during current hospitalization) a period of invasive ventilation in ICU of more than 24 hours
* Patients who have previously been enrolled in the study
* Patients for whom post-hospital follow-up may be challenging, e.g. those who reside overseas or who have no fixed address

Primary outcomes:
measure: Quality of life at home
timeFrame: Day 180
measure: Quality of life at home
timeFrame: Day 180
Secondary outcomes:
measure: Duration of ventilation
timeFrame: Until hospital discharge (up to 6 months)
measure: Muscle research council score
timeFrame: Until day 14
measure: Airway occlusion pressure (P0.1)
timeFrame: First spontaneous breathing trial (within 5 minutes of onset)
measure: Expiratory occlusion pressure (Pocc)
timeFrame: First spontaneous breathing trial (within 5 minutes of onset)
measure: Maximal inspiratory pressure (MIP)
timeFrame: First spontaneous breathing trial within 30 minutes of onset
measure: Days alive and at home at 180 days post ICU discharge
timeFrame: Day 180
measure: Changes in abdominal muscle thickening fraction during cough
timeFrame: At first spontaneous breathing trial within 30 minutes of onset and at ICU discharge, an average of 7 days
measure: Maximal diaphragm thickening fraction
timeFrame: At first spontaneous breathing trial within 30 minutes of onset and at ICU discharge, an average of 7 days
measure: Changes in resting abdominal muscle thickening
timeFrame: Until Day 14
measure: Changes in resting thickening fraction
timeFrame: Until Day 14
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Ewan Goligher, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: