Clinical trial NCT03539640: Effect PEEP on Diaphragm
Official title: The Effects of Positive End-expiratory Pressure on the Position, Length and Contractibility of the Diaphragm.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diaphragm Disease
Keywords: PEEP
Diaphragm
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2018-05-29
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All participants will receive the same protocol with different levels of PEEP ventilation during the first part of the study (physiological part), so the interventional study model for this part is single group. During the second part (MRI), participants are randomized for one of the three available PEEP levels (5, 10 or 15 cmH2O), so the study model for this part is parallel.
Primary purpose: BASIC_SCIENCE

Brief summary: This study evaluates the effect of positive end-expiratory pressure on the position, length and function of the diaphragm. During the first part of the study, physiological measurements of the diaphragm will be performed while participants receive non-invasive ventilation at different PEEP levels. During the second part of the study, MRI measurements of the diaphragm will be performed during a change in PEEP level.

Detailed description: In almost all mechanically ventilated patients, positive end-expiratory pressure (PEEP) is used. Its function is to prevent alveolar collapse and to maintain oxygenation. However, it has recently been found that PEEP may contribute to diaphragm weakness, which is an important problem in the intensive care unit (ICU). This study showed that mechanical ventilation with PEEP resulted in a caudal displacement of the diaphragm, since PEEP increases the end-expiratory volume. Furthermore, their study in rats showed that this displacement resulted in a reduced fiber length and sarcomere length on the short term.

After rats were ventilated with PEEP for 18 hours, it was found that adaptation of the diaphragm occurred; i.e. the number of sarcomeres were decreased. It is hypothesized that this adaptation may also occur in mechanically ventilated patients. This could lead to problems in weaning a patient off the ventilator, as PEEP is abruptly removed during a spontaneous breathing trial (SBT). This leads to a reduction in end-expiratory volume which would mean that the newly-adapted diaphragm fibers are being stretched. These stretched muscle fibers are not working at their optimal length of the force-length relation, thereby contributing to diaphragm weakness.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Age ≥ 18 years

Exclusion Criteria:

* Symptoms relating to respiratory or cardiovascular disease
* History of pneumothorax or family history of primary pneumothorax
* Obesity (defined as BMI \> 30kg/m²)
* Known pregnancy
* Contraindications for the placement of a nasogastric tube (upper airway/esophageal/gastric/mouth or face pathology (e.g. recent surgery, esophageal varices, diaphragmatic hernia), nasal bleeding within the last 2 weeks or use of anticoagulants)
* Contraindications for MRI (electrical/metallic implants, claustrophobia or history in metalworking)
* Subjects who are employed at the department of intensive care adults, directly involved in the study and/or family from staff of the ICU.

Primary outcomes:
measure: Changes in diaphragm's position
timeFrame: 2 hours
measure: Changes in diaphragm's shape and length
timeFrame: 2 hours
measure: Changes in diaphragm's efficiency
timeFrame: 2 hours
measure: Change in twitch transdiaphragmatic pressures
timeFrame: 2 hours
Secondary outcomes:
measure: Difference between MRI and ultrasound
timeFrame: 2 hours
Other outcomes:
measure: Expiratory abdominal muscle activity
timeFrame: 2 hours
measure: Flow
timeFrame: 2 hours
Locations:
city: Amsterdam
country: Netherlands
facility: VU Medical Center
state: Noord-Holland
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Leo Heunks, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: