The effects of positive end-expiratory pressure on the position, length and function of the diaphragm

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 by investigators of
the VUmc that PEEP may contribute to diaphragm weakness, which is an important
problem in the intensive care unit (ICU). Their 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. More insights in the role that PEEP could have on the development of
diaphragm weakness in mechanically ventilated patients are needed.

The objective of this study is to evaluate the acute effects of PEEP on the
position, length, and contractibility of the diaphragm.

Proof of concept study in healthy subjects

Participants will breathe with different levels of PEEP through a non-invasive
ventilation (NIV) face mask. During the first part of the study, a nasogastric
tube will be inserted and EMG surface electrodes are placed, after which
measurement with magnetic stimulation and ultrasound are made during different
levels of PEEP. During the second part of the study, MRI measurements are
performed during different levels of PEEP.

We do not expect high risks for participating in this study, as measurements
will be performed on healthy subjects.
PEEP ventilation may be experienced as slightly uncomfortable but is generally
well tolerated by a healthy individual. The burden to the subject of placement
of a nasogastric catheter used in this study is similar to placement of a
regular nasogastric feeding tube. From our clinical and researchexperience, we
consider these risks minimal, especially when *high risk subjects* are excluded
(upper airway / esophageal pathology, nasal bleeding disorders) and insertion
is performed by well-trained nurses or physicians. The insertion of the
catheter will take place at a safe environment (research room at the ICU),
where potential risks can be anticipated immediately. Therefore, we believe
that the risk of the nasogastric catheter is minimal. Furthermore, All other
study measurements (ultrasound, magnetic stimulation and MRI) are non-invasive
and performed according to clinical protocol. As subjects with possible
contraindications for these measurements are excluded from study participation,
we believe that risks are minimal. Subjects do not have direct benefits from
participating in this study. However, participation will lead to further
knowledge of the effects of PEEP on diaphragm weakness, which can lead to
better mechanical ventilation strategies.