Critically ill patients hospitalized at Intensive Care Units (ICU) are characterized by
an accelerated muscle wasting, which leads to general muscle weakness and loss of
physical functions even after discharge. Particularly, muscle respiratory wasting will
occur early (18 to 69 hours) in up to 60% of patients with mechanical ventilation (MV),
leading rapidly to diaphragmatic weakness, which is associated with prolonged MV use,
longer ICU and hospital stay and higher mortality risk. Sepsis and muscle inactivity,
derived from sedation and MV use, are key driver mechanisms to developing these negative
consequences, which can be avoided through early physical activation. However, exercise
is limited at early stages of care, where sedation and MV are needed, delaying muscle
activation and favoring a vicious circle.
Neuromuscular electrical stimulation (NMES) represents an alternative to achieve early
muscle contraction in non-cooperative patients, being able to prevent local muscle
wasting and, according to some reports, has the potential to shorten the time on MV,
suggesting a systemic effect through myokines, a diverse range of cytokines and
chemokines secreted by myocytes during muscle contraction. These factors modulate the
function and metabolism of distant organs and can promote muscle cell proliferation and
growth in order to maintain muscle structure and function. However, no studies have
evaluated whether NMES applied to peripheral muscles can exert distant muscle effects
over the diaphragm, ameliorating its weakness, and if this protective profile is
associated to myokine's change in critically ill patients.
We hypothesize that in mechanical ventilated ICU patients NMES contributes to prevent
respiratory muscle weakness when initiated at an early phase of their critical illness,
and this effect is associated to acute changes in myokine profile, being able to
facilitate discontinuation of MV and decrease ICU length of stay.
This proposal comprises a randomized controlled study of NMES applied twice a day, for 3
days, in comparison to standard care (no NMES). Thirty-two patients will be recruited in
the first 48 hours after connection to MV, and randomly assigned to either control group
or stimulated group (16 subjects for each group). Muscle characterization of quadriceps
and diaphragm (Structural ultrasonography evaluation of muscle thickness and tracheal
twitch pressure assessment, derived from magnetic stimulation of phrenic nerve, for
diaphragmatic strength) will be performed at baseline (Day 1, prior to the first NMES
session) and after the last NMES session (morning of day 4). Myokine measurements (IL-1,
IL-6, IL-15, BDNF, Myostatin and Decorin), through blood serum obtained from peripheric
blood samples, will be performed at baseline 1 hour before NMES (T-1), just before
starting NMES (T0), at the end of NMES session (T0.5), and 2 and 6 hours later (T2 and
T6). This myokine curves will be repeated on days 1 and 3 at the first NMES session of
the day. Control group will be assessed in the same way and timing, with the exception
that blood samples will be performed at T0 and T6 of days 1 and 3. Additionally,
functional outcomes such as MV time and ICU length of stay will be registered for all
patients at ICU discharge. Standard care won´t be altered, performing passive
mobilization according to ICU procedures in both groups.