Diaphragm paralysis: Surgery or mechanical ventilation?

The diaphragm is a dome-shaped muscle which separates the thoracic cavity from
the abdomen. It is the most important muscle of respiration innervated by the
phrenic nerves. While many diseases might interfere with its function(1), in
the intended pilot study we will focus on diaphragm paralysis due to phrenic
nerve injury. Two types of diaphragm paralysis can be distinguished: unilateral
and bilateral. Patients with unilateral paralysis perceive exertional dyspnea,
have an impaired exercise capacity and orthopnea(2). Patients with a bilateral
paralysis usually have more symptoms and might even develop respiratory
failure(3). In addition, all patients with a diaphragm paralysis may have poor
sleep quality, as the diaphragm is the only active respiratory muscle during
REM sleep(4). Currently, two treatment approaches for patients with diaphragm
paralysis are used in clinical practice: surgical diaphragm plication and
nocturnal non-invasive ventilation (NIV). Plication is a minimal invasive
surgical procedure that aims to stiffen the diaphragm and such limits
dysfunctional (paradoxical movement) excursions of the paralytic diaphragm. The
procedure is performed in ±70 patients per year in the Netherlands. NIV is a
non-invasive mode of positive pressure ventilatory assistance; through a facial
mask the ventilator supports patient breathing effort. Patients with diaphragm
paralysis use their ventilator mainly during night time, to improve quality of
sleep and such to reduce day time symptoms. In the Netherlands, home mechanical
ventilation is very well organized, as care is delivered by only 4 specialized
centers. NIV for diaphragm paralysis is started in around 50 patients yearly.

Currently, both plication and nocturnal NIV appear beneficial, are standard
care and are covered by health care insurance. However, it is unknown which
intervention is most beneficial from a patient perspective. For instance,
comparison on patient relevant outcome measures and complications between these
treatment approaches is unknown. In addition, patients with diaphragm paralysis
may develop severe symptoms, limiting daily activities including ability to
perform their professional work. To assess the overall impact of this a
detailed cost analysis is necessary to compare both treatments from a societal
perspective. A solid cost effectiveness / cost utility study will reveal which
therapy is the best option from a societal perspective.

In this pilot study we will describe the effect of both plication and
non-invasive ventilation. To know what clinical effect, of both therapies is
relevant, the EQ-5D-5L is used(5). It is unknown whether there is a significant
difference on the outcome between both therapies. A search in trial registries
did not reveal any study with similar research questions. Due to the acute
origin of a diaphragm paralysis, patients get suddenly severely impaired which
is interfering enormously with their lives. As this is often happening in
middle aged patients they often have to discontinue professional activities.
This means that the potential impact of this disorder is huge from patient and
societal perspective and needs to be assessed.
As both therapies are completely different for invasiveness, we need to compare
the side effects and possible complications. Possible complications of the
surgery are infection, bleeding and abdominal pain while the well know side
effects of ventilatory support are leakage of the mask, aerophagia and
a-synchrony between breathing pattern of the patient and the ventilator.
Participants will be monitored from the start of therapy and there will be a
follow-up after 3 months in group 1 and 2 and after 6 months in group 2.

The following questions will be addressed in the PARASOL study

• What is the effect of plication or non-invasive mechanical ventilation on the
EQ-5D-5L?
o The pilot study is needed as we do not know the clinical relevant effect of
both therapies on EQ-5D-5L. Moreover, it is unknown whether there is a
significant difference on the outcomes between both therapies. A search in
trial registries did not reveal any study with similar research questions as
the current proposal.
• What are the costs of both therapies from a societal perspective?
o Due to the acute origin of a diaphragm paralysis patients get suddenly
severely impaired which is interfering enormously in their lives. As this is
often happening in middle aged patients they often have to discontinue
professional activities. This means that the potential impact of this disorder
is huge from patient and societal perspective needs to be assessed.
• What are the side effects - complications of both interventions?
o As both therapies are completely different for invasiveness, we need to
compare the side effects and possible complications. Possible complications of
the surgery are infection, bleeding and abdominal pain while the well know side
effects of ventilatory support are leakage of the mask, aerophagia and
a-synchrony between breathing pattern of the patient and the ventilator. As
this is also an important outcome of this pilot study patients will be
monitored from the start of therapy until follow-up.

Patient: Patients with a symptomatic unilateral diaphragm paralysis
Intervention: Surgical diaphragm-plication
Comparator: Non-invasive mechanical ventilation
Outcome: The goal is to describe the effect of both surgical plication and NIV
on the secondary endpoints: quality of life measured by the EQ-5D-5L
questionnaire. six minute walk test(6), spirometry both in sitting and supine
position, polysomnography, transcutaneous carbon dioxide and oxygen saturation
at night(7), other questionnaires as Diaphragmatic Paralysis Questionnaire (8)
MRC dyspnoea scale (9), Borg dyspnoea scores in both sitting and supine
position (10), Short Form-36 questionnaire(11)
Follow-up Time: 3 and 6 Months
Study design: Multi center intervention pilot study

Two treatment approaches for patients with diaphragm paralysis are used in
clinical practice: surgical diaphragm plication and nocturnal non-invasive
ventilation (NIV). Plication is a minimal invasive surgical procedure that aims
to stiffen the diaphragm and such limits dysfunctional (paradoxical movement)
excursions of the paralytic diaphragm. NIV is a non-invasive mode of positive
pressure ventilatory assistance; through a facial mask the ventilator supports
patient breathing effort. Both plication and nocturnal NIV appear beneficial,
are standard care and are covered by health care insurance
The following questions will be addressed in this study:
- What is the effect on surgical plication or non-invasive mechanical
ventilation on the EQ-5D-5L?
- What are the costs of both therapies from a societal perspective?
- What are the side effects - complications of both interventions?

As both therapies are standard care no risk is is associated with
participation.