Introduction: Critically ill patients are characterized by increased loss of muscle mass, partially attributed to sepsis and multiple organ failure, as well as immobilization. Recent studies have shown that electrical muscle stimulation (EMS) may be an alternative to active exercise in chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) patients with myopathy. The aim of our study was to investigate the EMS effects on muscle mass preservation of critically ill patients with the use of ultrasonography (US). Methods: Forty-nine critically ill patients (age: 59 ± 21 years) with an APACHE II admission score ≥13 were randomly assigned after stratification upon admission to receive daily EMS sessions of both lower extremities (EMS-group) or to the control group (control group). Muscle mass was evaluated with US, by measuring the cross sectional diameter (CSD) of the vastus intermedius and the rectus femoris of the quadriceps muscle. Results: Twenty-six patients were finally evaluated. Right rectus femoris and right vastus intermedius CSD decreased in both groups (EMS group: from 1.42 ± 0.48 to 1.31 ± 0.45 cm, P = 0.001 control group: from 1.59 ± 0.53 to 1.37 ± 0.5 cm, P = 0.002; EMS group: from 0.91 ± 0.39 to 0.81 ± 0.38 cm, P = 0.001 control group: from 1.40 ± 0.64 to 1.11 ± 0.56 cm, P = 0.004, respectively). However, the CSD of the right rectus femoris decreased significantly less in the EMS group (-0.11 ± 0.06 cm, -8 ± 3.9%) as compared to the control group (-0.21 ± 0.10 cm, -13.9 ± 6.4%; P < 0.05) and the CSD of the right vastus intermedius decreased significantly less in the EMS group (-0.10 ± 0.05 cm, -12.5 ± 7.4%) as compared to the control group (-0.29 ± 0.28 cm, -21.5 ± 15.3%; P < 0.05). Conclusions: EMS is well tolerated and seems to preserve the muscle mass of critically ill patients. The potential use of EMS as a preventive and rehabilitation tool in ICU patients with polyneuromyopathy needs to be further investigated. Trial Registration: clinicaltrials.gov: NCT00882830

Neuromuscular electrical stimulation (NMES) therapy may be useful in early musculoskeletal rehabilitation during acute critical illness. The objective of this systematic review was to evaluate the effectiveness of NMES for preventing skeletal-muscle weakness and wasting in critically ill patients, in comparison with usual care. We searched PubMed, CENTRAL, CINAHL, Web of Science, and PEDro to identify randomized controlled trials exploring the effect of NMES in critically ill patients, which had a well-defined NMES protocol, provided outcomes related to skeletal-muscle strength and/or mass, and for which full text was available. Two independent reviewers extracted data on muscle-related outcomes (strength and mass), and participant and intervention characteristics, and assessed the methodological quality of the studies. Owing to the lack of means and standard deviations (SDs) in some studies, as well as the lack of baseline measurements in two studies, it was impossible to conduct a full meta-analysis. When means and SDs were provided, the effect sizes of individual outcomes were calculated, and otherwise, a qualitative analysis was performed. The search yielded 8 eligible studies involving 172 patients. The methodological quality of the studies was moderate to high. Five studies reported an increase in strength or better preservation of strength with NMES, with one study having a large effect size. Two studies found better preservation of muscle mass with NMES, with small to moderate effect sizes, while no significant benefits were found in two other studies. NMES added to usual care proved to be more effective than usual care alone for preventing skeletal-muscle weakness in critically ill patients. However, there is inconclusive evidence for its benefit in prevention of muscle wasting.

Peripheral myopathy consists of a hallmark of heart failure (HF). Exercise enhanced skeletal muscle angiogenesis, and thus, it can be further beneficial towards the HF-induced myopathy. However, there is limited evidence regarding the exercise type that elicits optimum angiogenic responses of skeletal muscle in HF patients. This study aimed to (a) compare the effects of a high-intensity-interval-training (HIIT) or combined HIIT with strength training (COM) exercise protocol on the expression of angiogenesis-related factors in skeletal muscle of HF patients, and (b) examine the potential associations between the expression of those genes and capillarization in the trained muscles. Thirteen male patients with chronic HF (age: 51 ± 13 y; BMI: 27 ± 4 kg/m²) were randomly assigned to a 3-month exercise program that consisted of either HIIT (N = 6) or COM training (N = 7). Vastus lateralis muscle biopsies were performed pre- and post-training. RT-PCR was used to quantify the fold changes in mRNA expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia-inducible factor 1 alpha (HIF-1α), angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2), angiopoietin receptor (Tie2), and matrix metallopeptidase 9 (MMP-9), and immunohistochemistry to assess capillarization in skeletal muscle post-training. There was an overall increase in the expression levels of VEGF, VEGFR-2, HIF-1α, Ang2, and MMP9 post-training, while these changes were not different among groups. Changes in capillary-to-fibre ratio were found to be strongly associated with Tie2 and HIF-1α expression. This was the first study demonstrating that both HIIT and combined HIIT with strength training enhanced similarly the expression profile of angiogenic factors in skeletal muscle of HF patients, possibly driving the angiogenic program in the trained muscles, although those gene expression increases were found to be only partially related with muscle capillarization.

Intensive care unit-acquired weakness (ICUAW) is a common complication, associated with significant morbidity. Neuromuscular electrical stimulation (NMES) has shown promise for prevention. NMES acutely affects skeletal muscle microcirculation; such effects could mediate the favorable outcomes. However, optimal current characteristics have not been defined. This study aimed to compare the effects on muscle microcirculation of a single NMES session using medium and high frequency currents.

Endothelial progenitor cells (EPCs) have been suggested to constitute a restoration index of the disturbed endothelium in ICU patients. Neuromuscular electric stimulation (NMES) is increasingly employed in ICU to prevent comorbidities such as ICU-acquired weakness, which is related to endothelial dysfunction. The role of NMES to mobilize EPCs has not been investigated yet. The purpose of this study was to explore the NMES-induced effects on mobilization of EPCs in septic ICU patients. Thirty-two septic mechanically ventilated patients (mean ± SD, age 58 ± 14 years) were randomized to one of the two 30-min NMES protocols of different characteristics: a high-frequency (75 Hz, 6 s on–21 s off) or a medium-frequency (45 Hz, 5 s on–12 s off) protocol both applied at maximally tolerated intensity. Blood was sampled before and immediately after the NMES sessions. Different EPCs subpopulations were quantified by cytometry markers CD34+/CD133+/CD45−, CD34+/CD133+/CD45−/VEGFR2 + and CD34+/CD45−/VEGFR2 +. Overall, CD34+/CD133+/CD45− EPCs increased from 13.5 ± 10.2 to 20.8 ± 16.9 and CD34+/CD133+/CD45−/VEGFR2 + EPCs from 3.8 ± 5.2 to 6.4 ± 8.5 cells/106 enucleated cells (mean ± SD, p < 0.05). CD34+/CD45−/VEGFR2 + EPCs also increased from 16.5 ± 14.5 to 23.8 ± 19.2 cells/106 enucleated cells (mean ± SD, p < 0.05). EPCs mobilization was not affected by NMES protocol and sepsis severity (p > 0.05), while it was related to corticosteroids administration (p < 0.05). NMES acutely mobilized endothelial progenitor cells, measures of the endothelial restoration potential, in septic ICU patients.