Background
Muscle wasting and intensive care unit-acquired weakness (ICU-AW) are common complications in ICU patients, leading to longer ICU and hospital stay, higher morbidity and mortality, as well as a poor long-term prognosis [
1‐
3]. Sepsis, multiple organ failure, muscle inactivity, hyperglycemia, as well as the use of corticosteroids and neuromuscular blocking agents were identified as risk factors [
1,
4,
5]. ICU-AW diagnosis is often delayed during the ICU stay, usually after a reduction of analgesics and anxiolytics, as the patients first become fully alert. Decreased muscle protein synthesis and increased protein degradation are involved in the pathomechanism, and occur very early during critical illness [
6,
7]. Early mobilization of alert patients reduces the length of mechanical ventilation and ICU and hospital stay [
8,
9], and leads to better functional independence at hospital discharge [
8]. These results only relate to patients who are able to participate in active physiotherapy. Hence follows the idea of closing the gap between onset of critical illness and active muscle training, using external devices during immobilization and sedation phases to evoke muscle contractions [
10‐
13]. During this time course of disease there are further options for intensified passive mobilization by physiotherapists, such as passive cycling or motorized continuous passive motion for different conditions, which we separate from treatment options for active muscle training indicated by patients initiating muscle contraction or from external evoked ones. A series of investigations with electrical muscle stimulation (EMS) in critically ill patients therefore commenced, and while some EMS studies showed promising results [
11,
14], others could not [
13]. From our own experience we know that application of EMS is time consuming, if feasible at all, and effectiveness is inconsistent [
15]. As an alternative, we propose the use of whole-body vibration (WBV) for muscle activation in the ICU. First investigations of human tolerance when exposed to vibration date back to the 1960s [
16], and to this day the use of vibration has become more and more interesting in many different approaches and popular in the fitness world. Companies offer devices starting at around €1000. WBV is used as a countermeasure to muscle atrophy and bone loss during the absence of gravity in space, as well as a training option for professional athletes [
17,
18] and patients with various underlying diseases [
19]. The spinal cord reflex function means that WBV may be suitable for unconscious patients, because muscle contraction occurs at a spinal level and not at a cerebral level [
20‐
22]. There is evidence that prolonged application of WBV helps to maintain muscular mass and strength, increases bone density, improves outcome, and increases glucose metabolism, as shown in healthy volunteers, athletes, older people, or non-ICU patients in the short term [
17,
18,
23‐
30]. These benefits correspond to the needs of critically ill patients and may support ICU patient recovery, although thus far there are no WBV investigations in mechanically ventilated ICU patients. Our aim is to transfer the application of WBV to the ICU.
We hypothesize that the use of WBV in mechanically ventilated ICU patients is safe, feasible, and effective in inducing skeletal muscle activation.
Discussion
To the best of our knowledge, this is the first report about safety and feasibility of WBV in critically ill, mechanically ventilated patients. We found that WBV is safely applicable even to critically ill patients in severe condition, as indicated by high SOFA and SAPS-II scores in addition to mechanical ventilation.
Our approach is to induce muscle activation during early critical illness, when patients are unable to participate in active physiotherapy due to sedation or unconsciousness due to neurological reasons. WBV might be an option to evoke muscle activation within a protocol-based physiotherapy and mobilization plan during the course of disease. Additionally, WBV may be a treatment option throughout the ICU stay; that is, may be continued when patients are awake.
The beneficial effect of physiotherapy and early mobilization, which has been shown to be safe and feasible, has been shown in several clinical studies [
8,
9,
36,
37]. There are still phases in which patients are not available for active physiotherapy, and these intervals often coincide with intervals of severe illness, acute systemic inflammation, or dependency on norepinephrine for hemodynamic stability. These early periods of critical illness and inflammation are particularly significant in the development of muscle wasting and ICU-AW, as we [
6,
14] and others [
7] could recently show. Evoked muscle training to avoid immobilization due to EMS can be an option [
10‐
12,
14], but application is labored, often not feasible [
15], and in general EMS therapy for ICU patients remains controversial [
38]. Alternatively WBV may be able to close the gap between immobilization and active physiotherapy, hypothesizing that frequently applied early muscle activation evoked by WBV may support patient recovery.
WBV represents a strong stimulus to the skeletal muscle, leading to physiological growth adaption in bone and muscle [
39,
40]. Clinically, it was shown that WBV improves average velocity, average force, and average power [
41] in volunteers and not critically ill patients. The activation on spinal linkage by WBV is evident, as published in a recent investigation showing increased EMG activity on the paretic and nonparetic sides of stroke patients, independent of the intensity of the stimulus [
19].
The physiological principal behind WBV is a mechanical stretch and reflex mechanism by the peripheral nerve [
20]. Dependent on the frequency of the vibration stimulus, WBV leads to much more than 1000 muscle contractions per minute, leading to increased muscle strength and mass, seen as muscle hypertrophy. This principle of muscle activation agrees with the metabolic findings and expected benefits for ICU patients. Our data show that passive range of motion via physiotherapy increases carbon dioxide elimination, which can be explained by the mobilization of resting blood in the capacity vessels. Absence of active muscle contraction in passive mobilization is reflected by a missing increase in oxygen uptake. In contrast, WBV in critically ill patients increases both carbon dioxide elimination and oxygen uptake in our patients. This has been shown by others in overweight and obese women [
42]. The physiotherapist had the subjective impression that, in single cases, patients had an arousal reaction due to the intervention, which was not measurable by RASS scoring but may have an impact on their energy expenditure. We interpret this increased energy turnover as the result of muscular activation. That the increased energy expenditure is caused by actual muscle activation, and not by metabolic dysregulation, is confirmed by steady-state levels for pO2, pCO2, pH, HCO
3
–, and base excess. Time delay between intervention and measurement of the indirect calorimetry may occur but is improbable due to the selected time frame and no significant changes over time within each phase (see Additional file
1). Serum potassium levels were significantly increased only during WBV, probably due to muscle contraction, and unchanged serum sodium levels underline our interpretation.
Besides the mechanical stretch and reflex mechanism by the peripheral nerve caused by the vibration stimuli, there is evidence for an additional, direct impact on different tissues. This could be demonstrated by molecular findings showing beneficial effects of vibration in vivo and in vitro on separated stem cells, myoblasts, and muscle tissue [
40,
43,
44]. Ceccarelli et al. [
40] showed an increased synthesis and decreased activation of the ubiquitin–proteasome pathway with myostatin and Atrogin-1 suppression in vitro due to vibration. These findings imply that vibration could have a significant impact on maintaining muscle in ICU patients because decreased myosin synthesis and increased myosin degradation is an established mechanism in the development of ICU-AW [
6].
Repetitive WBV was shown to have a positive effect on glucose metabolism in type II diabetes patients [
27,
28]. We showed recently that EMS has an impact on maintaining muscular mass by improving glucose metabolism in the critically ill [
14]. Future studies could investigate whether a similarly positive effect can be achieved by WBV.
We also did not find a serum lactate elevation, which might be expected during extensive muscle training. Thus, WBV does not result in substantial anaerobic muscle activity, which would presumably not be favorable in critically ill patients. Small changes were probably not measurable in an intervention of this scale. Small changes would also explain why we could not find any significant changes in the hormonal regulation of IGF-1 and cortisol, which were shown earlier for both hormones [
31,
32].
This pilot study was limited to investigate safety, feasibility, and metabolic response of WBV in critically ill patients, focusing on hemodynamic stability. Thus it was outside the scope of the study to evaluate aspects such as patient comfort, staff workload, and staff acceptance. Further investigations are also needed to assess the most favorable type, intensity, frequency, and duration of WBV in ICU treatment. For the first time in critically ill patients, we could show a safe feasibility of WBV, as well as measure indicators for muscle activation and induced metabolism. These results could be further improved by measuring the muscle activity by electromyography. The next step would be an investigation to determine whether WBV could improve short-term and long-term outcome for ICU patients, by prevention or treatment, as already shown for non-ICU patients.