Diaphragm Injury, Mechanical Ventilation Complication, Respiratory Failure
Conditions
Keywords
Diaphragm Dysfunction, Acute Respiratory Failure, Mechanical Ventilation
Brief summary
This study is designed to characterize the changes in diaphragm structure, function and biology during bridging to lung transplant by mechanical ventilation or extracorporeal life support.
Detailed description
Mechanical ventilation has been linked to diaphragm injury and dysfunction. During mechanical ventilation, the amount of breathing work done by the diaphragm is unpredictable: the diaphragm could be completely rested, or it could be overworked. Either of these possibilities may cause injury to the diaphragm. Patients with an injured and dysfunctional diaphragm have greater difficulty weaning from mechanical ventilation - they become too weak to breathe. However, little is known about the relationship between changes in the diaphragm and the histological (structure of cells and tissue) basis of these changes. The investigators have developed a new technique employing beside ultrasound to measure diaphragm thickness. This allows them to observe changes in diaphragm muscle structure and function. The goal of the study is to determine whether different forms of respiratory support (mechanical ventilation vs extracorporeal life support) lead to different degrees of diaphragm injury and to compare changes in the diaphragm seen on ultrasound to changes in the diaphragm tissues under a microscope. This will help the investigators to confirm the best way to avoid diaphragm injury and to understanding the meaning of diaphragm ultrasound images.
Interventions
DEVICERespiratory support
Mechanical ventilation or extracorporeal life support
Sponsors
The Hospital for Sick Children
University Health Network, Toronto
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Cases): * Receiving a respiratory support modality as a bridge to lung transplantation * Formally listed for transplantation Inclusion Criteria (Control Group 1): \- Undergoing lung transplantation for either obstructive or restrictive lung disease Inclusion Criteria (Control Group 2): \- Undergoing elective thoracic surgery without any prior history of chronic pulmonary parenchymal disease
Exclusion criteria
(Cases and Controls): * Previously diagnosed with neuromuscular disorder * Received invasive mechanical ventilation for \>48 hours in the preceding four weeks * Thoracic cage deformity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in diaphragm thickness and thickening fraction in patients using MV and patients using ECLS | Change from baseline diaphragm thickness and thickening fraction at 7 days after lung transplant | Diaphragm thickness and injury score will be tested for an interaction between the bridging modality (MV vs. ECLS) and the duration of exposure to the modality on the degree of diaphragm injury and atrophy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlate changes in diaphragm thickness and histological features of diaphragm dysfunction | Assessed immediately after transplantation | Histological features to be assessed are: myofibril cross-sectional area, muscle fiber type, presence of cellular infiltrates, myofiber necrosis and regeneration, autophagy and fibro-fatty infiltration |
| Biomarkers for diaphragm dysfunction | Assessed immediately before transplantation | Biomarkers to be assessed are: skeletal troponin-I and markers of systemic inflammation (IL-1, IL-6, Tumor Necrosis Factor (TNF)-alpha) |
Countries
Canada
Contacts
Primary ContactRongyu (Cindy) Jin
Outcome results
None listed