The primary goal is to evaluate the difference between diaphragm tissue characteristics and movement in extubated COVID-ICU patients after >72 hours of invasive mechanical ventilation compared to other ICU-patients and healthy controls. Secondary…
ID
Source
Brief title
Condition
- Muscle disorders
- Thoracic disorders (excl lung and pleura)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are the configuration of the diaphragm and chest wall
during tidal breathing and tissue characteristics (amount of fat and/or water
infiltration, presence of fibrosis or inflammation) of the diaphragm. Secondary
parameters include function of the diaphragm, quantified by mean inspiratory
and expiratory pressure and clinical parameters such as mode and duration of
ventilation and inflammatory markers. The primary study parameters (MRI
measurements) will be compared between case and control group and tested for
correlation with secondary outcomes.
Secondary outcome
1. To relate the primary study parameters to clinical parameters, such as mode
and duration of mechanical ventilation and inflammatory parameters.
2. To relate the primary study parameters to respiratory muscle function,
namely maximum inspiratory (MIP) and expiratory pressure (MEP).
3. To relate the primary study parameters to thickness and intensity of the
muscle on ultrasound images
Background summary
COVID-19-infection has a large impact on the respiratory system and possibly on
the diaphragm, the main respiratory muscle. In ICU-patients, diaphragm weakness
is associated with prolonged ICU-stay, difficult weaning and increased
mortality. Our research group recently found evidence for fibrosis and
expression of genes involved in fibrosis as well as viral infiltration of the
SARS-CoV-2 virus in diaphragm biopsies from COVID-19 ICU patients (article
published). This finding suggests a unique manifestation of diaphragm injury in
COVID-19 patients after mechanical ventilation. However, it remains unclear
what the exact nature and location of diaphragm injury is.
Additionally, it is largely unknown whether this injury affects the movement of
the diaphragm, but this might have important clinical implications. Therefore,
we aim at visualizing the tissue characteristics and movement of the diaphragm
in COVID-19 patients who recently received long-term mechanical ventilation,
other ICU patients and healthy controls, using magnetic resonance imaging
(MRI). MRI of the diaphragm was already shown feasible in previous research
from our group (article currently under review).
New insights in the characteristics of diaphragm weakness or injury in COVID-19
patients and control ICU-patients will contribute to strategies to prevent this
and monitor the diaphragm of patients under mechanical ventilation, which can
contribute to better patient outcomes
Study objective
The primary goal is to evaluate the difference between diaphragm tissue
characteristics and movement in extubated COVID-ICU patients after >72 hours of
invasive mechanical ventilation compared to other ICU-patients and healthy
controls. Secondary objectives include exploring the associations between MRI
measurements of the diaphragm and clinical parameters and functional
measurements, such as strength of the respiratory muscles and thickness and
intensity of the muscle on ultrasound.
Study design
The study is a physiological proof-of-concept study
Intervention
MRI measurements will be performed for every subject. In the case group, also a
contrast agent (Dotarem ® 0.5 mmol) will be used to enhance visualization of
the diaphragm. Next to that, subjects are asked to perform manoeuvres to
determine the maximum inspiratory and expiratory pressure for every subject.
Study burden and risks
We do not expect high risks for participating in this study, because all
techniques used (MRI, spirometry and ultrasound) are non-invasive and performed
according to clinical protocol. MRI is in principle a non-invasive imaging
modality that does not use any radiation and spirometry is a non-invasive
technique for measuring respiratory muscle strength. Although the
administration of a Gadolinium contrast agent is associated with adverse
events, the risk of severe adverse events is extremely low (<1 in 10.000 users
endure a severe allergic reaction). Also, subjects are excluded in case of
contraindications for either MRI or the contrast agent. The burden of subjects
is mainly in the form of time investment and performing breathing manoeuvres.
There are no direct benefits from participating in the study, but subjects
contribute to gaining crucial knowledge on critical illness associated
diaphragm weakness, important for developing diaphragm protective ventilation.
The study will be partially performed in patients because we want to study the
effects of critical illness and mechanical ventilation. This would not be
possible in healthy humans, making the study group related.
de Boelelaan 10
Amsterdam 1007MB
NL
de Boelelaan 10
Amsterdam 1007MB
NL
Listed location countries
Age
Inclusion criteria
Invasive mechanical ventilation > 72 hours during current hospital admission
(only patients)
Discharged from the ICU <= 14 days ago (only patients)
Admitted for COVID-19-infection (n = 10)
Currently negative COVID-19 PCR test (only previously infected subjects)
Age 50-70 years (only healthy volunteers)
Signed informed consent
Age >= 18 years (only patients)
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
• Known history of:
o Diaphragmatic injury or weakness
o COPD (GOLD IV)
o Neuromuscular disease (including pathology of the n. phrenicus)
o Connective tissue disease
o Chronic use of corticosteroids (>7.5 mg/day for at least 3 months before
hospital admission)
o >10% weight loss within last 6 months (before hospital admission)
o COVID-19-infection, confirmed with positive test (except for subset of
infected patients)
• Known pregnancy
• Contraindications for MRI
o Electrical/metallic implants
o Claustrophobia
• Hierarchical relation with one of the collaborating investigators
• Incapacitation
• Contraindications for the use of a Gadolinium based contrast agent for MRI
o eGFR < 30 ml/min/1.73m2
o Known history of allergic reactions to a MRI contrast medium
o Known history of atopy
o Unstable Asthma
Additional exclusion criteria for the control group are:
• History of mechanical ventilation > 24 hours
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL72271.029.19 |