Early neuromuscular electrical stimulation reduces the loss of muscle mass in critically ill patients – A within subject randomized controlled trial
Introduction
Critically ill patients admitted to the intensive care unit (ICU) often suffer from a dramatic loss of muscle mass and strength, known as intensive care unit-acquired weakness (ICUAW) [1]. On average, patients lose about 11% of their muscle mass in the first week after ICU admission and this loss is more pronounced in patients with multiple organ failure [2,3]. It appears attractive to counteract this muscle mass loss before the patient is even able to cooperate [4]. Therefore, the effects of neuromuscular electrical stimulation (NMES) have been investigated in acutely critically ill patients [[5], [6], [7], [8], [9], [10], [11], [12], [13]]. Both Gerovasili [5] and Meesen [10] concluded that muscle mass was better preserved in groups receiving NMES as compared to control groups. However, other studies [[7], [8], [9],11] could not confirm these results. These studies are difficult to compare, mostly due to methodological heterogeneity in the assessment of muscle mass. Various outcome measures were used, including circumference measures, CT-scan and ultrasound. Other studies focused on the effect of NMES on muscle strength [6,9,11,13,14]. Routsi et al. [6] and Rodriguez et al. [9] showed that NMES resulted in a significantly better preserved muscle strength. Fischer et al. [11] showed that muscle strength was higher in the NMES group at ICU discharge, but not at hospital discharge. Kho et al. [13] and Grunow et al. [14] did not find any difference in strength between the NMES and sham treated group. A few studies investigated the effect of NMES in muscle biopsies. Dirks et al. showed that muscle fibre cross-sectional area (CSA) did not decrease in the stimulated muscles, compared to ~20% decrease in fibre CSA in the unstimulated muscles [15]. Wollersheim et al. confirmed this preservation of fibre CSA and showed a higher gene expression for myosin heavy chains in the NMES treated muscles [16]. Weber-Carstens et al. showed attenuation of atrophy in type II fibres only [17]. In addition, Strasser et al. observed signs of more synthesis and less degradation of proteins in the muscles treated with NMES [18]. None of the aforementioned studies investigated the effects of NMES on muscle thickness, muscle strength and morphological and molecular markers of muscle atrophy simultaneously.
The primary aim of this study was to investigate the effect of 7 days of unilateral NMES on quadriceps muscle thickness. The combined thickness of the rectus femoris and intermedius were used for this analysis. Secondary outcomes were muscle strength and morphological and molecular markers of muscle atrophy. In addition, factors associated with changes in muscle thickness were explored.
Section snippets
Study design
The effect of unilateral NMES in critically ill patients was assessed in a randomized controlled design. Patients were included between day 2 and day 4 after their admission to the ICU. The attending intensivist judged whether the patient was expected to stay at least 7 more days in the ICU before the patient was considered for inclusion in the study.
Randomisation
Opaque sealed envelopes were used to randomize which quadriceps muscle was selected for stimulation. Five envelopes contained a paper with
Patient characteristics and quality of NMES
Between May 2014 and September 2016, 1710 critically ill patients were screened. The consolidated standards of reporting trials (CONSORT) flow chart is depicted in Fig. 1. Fifty patients were included in the study. Three patients did not complete the study period as consent was withdrawn. Patient characteristics are shown in Table 1. The online supplement shows the patient characteristics of the subgroups (Table S1 shows the data for the patients that performed a strength test and the data for
Discussion
This study showed that NMES can attenuate muscle mass loss in critically ill patients. No differences in strength were observed. A shift towards larger myofibers and significantly higher gene expression for MyHC-I in the stimulated muscle was observed, while no differences in signs of muscle fibre necrosis or inflammation were observed in both muscles. Preservation of muscle mass was more likely in patients who received opioids, who had a poorer muscle contraction during NMES, or who were more
Limitations of the study
Our study has some limitations to address. First, our patients were not blinded for the intervention as the control muscle did not receive any sham stimulation. However, most patients were not cooperative during the intervention period. In addition, as our primary outcome is an effort-independent measure of muscle thickness performed by a blinded investigator, this is not considered to induce bias. Second, no long-term consequences or functional outcomes were investigated. Our focus was on the
Conclusions
Muscle mass was better preserved in the muscle treated with NMES as compared to the control muscle, coinciding with a shift towards larger type 1 and type 2 myofibers in the stimulated muscle as compared with the non-stimulated muscle. Muscle strength was not different between the stimulated and control muscle. Patients receiving opioids and those who exhibited more pronounced loss of muscle mass in the non-stimulated muscle benefitted most of NMES, while a good muscle contraction in all
Author contributions
Conceptualization: Gosselink, Hermans, Vanhorebeek
Data curation: Segers, Vanhorebeek
Formal analysis: Segers, Hermans, Vanhorebeek, Langer
Investigation: Segers, Charususin, Clerckx, Frickx, Demeyere, Wei, Casaer, Derde, Derese, Pauwels
Methodology: Segers, Gosselink, Hermans, Vanhorebeek, Van den Berghe
Supervision: Gosselink, Hermans, Vanhorebeek
Validation: Segers, Gosselink, Hermans, Vanhorebeek, Langer
Writing - original draft: Segers, Gosselink, Hermans, Vanhorebeek
Writing - review & editing:
Declaration of Competing Interest
None of the authors have declared any conflict of interest related to the subject of this study. The authors acknowledge DJO Global (Herentals, Belgium) for providing the neuromuscular stimulation equipment used in this study.
References (30)
- et al.
Neuromuscular electrical stimulation in mechanically ventilated patients: a randomized, sham-controlled pilot trial with blinded outcome assessment
J Crit Care
(2015) - et al.
Feasibility of neuromuscular electrical stimulation in critically ill patients
J Crit Care
(2014) - et al.
Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial
Lancet Respir Med
(2013) - et al.
Safety and feasibility of a neuromuscular electrical stimulation chronaxie-based protocol in critical ill patients: a prospective observational study
J Crit Care
(2017) - et al.
An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults
Am J Respir Crit Care Med
(2014) - et al.
Assessment of quadriceps muscle mass with ultrasound in critically ill patients: intra- and inter-observer agreement and sensitivity
Intensive Care Med
(2015) - et al.
Acute skeletal muscle wasting in critical illness
JAMA
(2013) - et al.
Physiotherapy in the Intensive Care Unit
Netherlands J Crit Care (NJCC)
(2011) - et al.
Electrical muscle stimulation preserves the muscle mass of critically ill patients: a randomized study
Crit Care
(2009) - et al.
Electrical muscle stimulation prevents critical illness polyneuromyopathy: a randomized parallel intervention trial
Crit Care
(2010)