Breath synchronized electrical stimulation of the abdominal wall muscles to prevent respiratory muscle atrophy during the acute stages of mechanical ventilation therapy

Approximately 30-40% of intubated patients at the intensive care unit (ICU)
take more than one attempt to wean from
mechanical ventilation (MV) and approximately 6-14% of intubated patients take
longer than 7 days to wean from MV.[1]-[5]
While MV can be lifesaving, patients requiring prolonged time on the ventilator
are susceptible to a wide range of clinical
complications and excess mortality.[1], [3], [4], [6] It is therefore
imperative for them to wean at the earliest possible time.

Although the pathophysiology of weaning failure is complex and multifaceted,
respiratory muscle dysfunction is a major
underlying factor for many patients and already occurs during the first five
days of MV [7]-[11] Weakness of the diaphragm,
abdominal, and intercostal muscles may result in to decreased cough function,
poor breathing force, and results in low blood
oxygen/elevated carbon dioxide levels. Consequently, patients are susceptible
to ICU acquired pneumonia and have difficulties
weaning.

Recent evidence suggests that neuromuscular electrical stimulation (NMES) can
be used as a safe therapy to maintain skeletal
muscle function in critically ill patients, e.g. by stimulating quadriceps
muscles in patients receiving MV.[12]-[20] This is a noninvasive
method, which incorporates the use of electrical current to activate skeletal
muscles and produce contractions without
active participation of the patient.[13], [14], [21]-[23] It thus follows that
a similar approach could be applied to the respiratory
muscles, in particular to the expiratory muscles, during MV therapy.

To test this hypothesis, a bedside transcutaneous electrical muscle stimulator
that applies NMES to the abdominal wall muscles
in synchrony with exhalation will be used. It has been demonstrated that this
technique acutely improves minute ventilation,
while not affecting the inspiratory load in healthy subjects, COPD patients and
patients receiving prolonged MV.[24]-[26]
This study will build upon this previous work and test the hypothesis that
exhalation synchronized NMES of the abdominal-wall
muscles can prevent expiratory muscle atrophy during the acute stages of MV.
The long-term goal of this study is to determine
whether this approach can improve lung function and thereby reduce the amount
of time it takes to wean patients from MV,
which could have a promising impact in critical care.

The primary objective of this study is to investigate whether electrical
stimulation applied to the abdominal wall muscles in synchrony with exhalation
can be feasible to prevent the development of atrophy of the abdominal wall
muscles during the acute stages of MV therapy. The secondary objectives of this
study are to analyse whether this intervention also affects: (1) the thickness
of the diaphragm, (2) functional respiratory measurements, (3) markers for
systemic inflammation, and (4) weaning outcome.
Other objectives are to study recruitment rate and time to collect data.

This data will be used to assess the feasibility, and estimate the sample size,
of a follow up fully powered study, which assesses clinically relevant
endpoints.

This study is a multicentre, randomized, sham-controlled intervention pilot
trial with patients, caregivers and outcome
assessors blinded to the treatment allocation.
The rationale of performing sham stimulation, and blinding of caregivers and
outcome assessors is to ensure that there will be
no difference in care provided between the intervention group and other
patients.

The intervention will be NMES (versus a sham [control] intervention) applied to
the abdominal wall muscles for 30 minutes per
session, twice a day, 5 days per week, for 6 weeks or until the patient is
weaned from MV, whichever occurs sooner.
The sham-controlled group will receive the stimlulation as well, however the
stimulus intensity will be too low to induce muscle
contraction.

The study setting will be a mixed ICU. In addition to standard care, the
patients participating in this study will additionally receive two 30-minute
sessions of transcutaneous NMES therapy per day. The risks associated with
participation are negligible, since other studies have demonstrated the safety
of this intervention in ICU and non-ICU patients.[7-15],[22] Furthermore, NMES
is already used in the Radboudumc for physiotherapeutic purposes, which means
that we are familiar with the equipment.

Ultrasound measurements will be performed every other day to study the effect
of NMES. There are no risks associated with this assessment. After the patient
is weaned from MV, data from lung function measurements will be obtained. Since
these measurements are performed within routine care, this will not induce any
risks for participation in this study.

Two venous blood samples will be collected during enrolment and after the third
NMES session. This will be taken out of the intravenous catheter the patient
already has. Therefore this will not cause any further harm. Next to the fact
that all participants receive standard intensive care, each participant will be
monitored intensively to avoid any burden or risks.

Finally, all other measurements will be collected from chart review, in which
the patient is not directly involved.


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