Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study. Randomised controlled trial of transcutaneous electrical muscle stimulation of the lower extremities in patients with chronic obstructive pulmonary disease. Randomized controlled pilot study of neuromuscular electrical stimulation of the quadriceps in patients with non-small cell lung cancer. Skeletal muscle structure and function in response to electrical stimulation in moderately impaired COPD patients. Home based neuromuscular electrical stimulation as a new rehabilitative strategy for severely disabled patients with chronic obstructive pulmonary disease (COPD). Neuromuscular electrical stimulation improves exercise tolerance in chronic obstructive pulmonary disease patients with better preserved fat-free mass. Beneficial effects of chronic low-frequency stimulation of thigh muscles in patients with advanced chronic heart failure. Improvement of thigh muscles by neuromuscular electrical stimulation in patients with refractory heart failure: a single-blind, randomized, controlled trial. Functional and muscular effects of neuromuscular electrical stimulation in patients with severe COPD: a randomized clinical trial. Improvement in quadriceps strength and dyspnea in daily tasks after 1 month of electrical stimulation in severely deconditioned and malnourished COPD. Peripheral muscle strength training in bed-bound patients with COPD receiving mechanical ventilation: effect of electrical stimulation.
Muscle dysfunction is a major problem in chronic obstructive pulmonary disease (COPD), particularly after exacerbations. We thus asked whether neuromuscular electrostimulation (NMES) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and/or alters muscle fibre distribution. A pilot randomised controlled study of NMES lasting 6 weeks was carried out in 15 in-patients (n=9 NMES; n=6 sham) following a COPD exacerbation. Stimulation was delivered to the quadriceps and hamstring muscles (35 Hz). Primary outcomes were quadriceps force and muscle oxidative stress. At the end of the study, quadriceps force improvement was statistically different between groups (p=0.02), with a significant increase only in the NMES group (median (interquartile range) 10 (4.7-11.5) kg; p=0.01). Changes in the 6-min walking distance were statistically different between groups (p=0.008), with a significant increase in the NMES group (165 (125-203) m; p=0.003). NMES did not lead to higher muscle oxidative stress, as indicated by the decrease in total protein carbonylation (p=0.02) and myosin heavy chain carbonylation (p=0.01) levels. Finally, we observed a significant increase in type I fibre proportion in the NMES group. Our study shows that following COPD exacerbation, NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress. Although exercise training improves exercise tolerance in most patients with chronic obstructive pulmonary disease (COPD), some patients with severe disease may not be able to tolerate exercise training due to incapacitating breathlessness. Transcutaneous electrical muscle stimulation (TCEMS) has been shown to improve muscle strength, muscle mass, and performance in paraplegics, patients with knee ligament injury, and patients with peripheral vascular disease. We hypothesised that TCEMS of the lower extremities can improve muscle strength and exercise tolerance in patients with moderate to severe COPD.
                A randomised controlled trial of TCEMS of the lower extremities was performed in 18 medically stable patients of mean (SD) age 60.0 (1.5) years with a mean forced expiratory volume in 1 second (FEV(1)) of 1.03 (0.10) l (38% predicted) and residual volume/total lung capacity (RV/TLC) of 59 (2)%. Stimulation of the lower extremities was performed three times a week, 20 minutes each session, for six continuous weeks. Quadriceps and hamstring muscle strength, exercise capacity, and peak oxygen uptake were measured at baseline and after 6 weeks of stimulation.
                TCEMS improved both the quadriceps strength (by 39.0 (20.4)% v 9.0 (8.1)%, p=0.046) and hamstring muscle strength (by 33.9 (13.0)% v 2.9 (4.7)%, p=0.038) in the treated (n=9) and sham treated (n=9) groups, respectively. The improvement in muscle strength carried over to better performance in the shuttle walk test in the treated group (36.1% v 1.6% in the treated and sham groups respectively, p=0.007, Mann-Whitney U test). There was no significant change in lung function, peak workload, or peak oxygen consumption in either group. Muscle stimulation was well tolerated by the patients with no dropouts and better than 95% compliance with the protocol.
                TCEMS of peripheral muscles can be a useful adjunct to the comprehensive pulmonary rehabilitation of patients with COPD. Patients with lung cancer experience muscle wasting and weakness. Therapeutic exercise may be beneficial but is not always practical. An alternative approach may be neuromuscular electrical stimulation (NMES) of the quadriceps muscles, but this has not been formally examined in patients with cancer. Thus, we have undertaken this pilot study to assess feasibility and inform the design of future studies. Sixteen patients were randomized to receive usual care (control group) or usual care plus NMES for four weeks. NMES consisted of daily stimulation to both thighs for up to 30minutes (frequency 50Hz, "on" cycle 11%-25%). Adherence was assessed by a self-report diary and a semistructured evaluation form. Quadriceps muscle strength, exercise endurance, and free-living physical activity were assessed using a Cybex NORM dynamometer, an endurance shuttle walk test, and an ActivPAL accelerometer (mean daily step count), respectively. Changes in outcome from baseline were compared between groups by mean differences and their 95% confidence intervals using independent t-test (P=0.05). Median (range) adherence to the program was 80% (69%-100%). All patients found the NMES device easy to use. Changes in outcome favored the NMES group, with mean differences of 9.4 Nm (21%) in quadriceps muscle strength, 768 steps (15%) in free-living activity, and 138 m (8%) in exercise endurance, but none of the differences were statistically significant. In conclusion, NMES warrants further study in patients with lung cancer. To determine the structural and functional consequences of high-frequency neuromuscular electrical stimulation (hf-NMES) in a group of moderately impaired outpatients with chronic obstructive pulmonary disease (COPD).
                A prospective, cross-over randomized trial.
                An university-based, tertiary center.
                Seventeen patients (FEV(1)=49.6+/-13.4% predicted, Medical Research Council dyspnoea grades II-III) underwent 6-weeks hf-NMES (50Hz) and sham stimulation of the quadriceps femoris in a randomized, cross-over design. Knee strength was measured by isokinetic dynamometry (peak torque) and leg muscle mass (LMM) by DEXA; in addition, median cross-sectional area (CSA) of type I and II fibres and capillary-fibre ratio were evaluated in the vastus lateralis. The 6-min walking distance (6MWD) was also determined.
                At baseline, patients presented with well-preserved functional capacity, muscle strength and mass: there was a significant relationship between strength and type II CSA (P<0.05). NMES was not associated with significant changes in peak torque, LMM or 6MWD as compared to sham (P>0.05). At micro-structural level, however, electrical stimulation increased type II, but decreased type I, CSA; no change, however, was found in the relative fibre distribution or capillary:fibre ratio (P<0.05). There was no significant association between individual changes in structure and function with training (P>0.05). Post-NMES increase in type II CSA was inversely related to baseline mass and strength (P<0.05).
                NMES may promote a modest degree of type II muscle fibre hypertrophy in COPD patients with well-preserved functional status. These micro-structural changes, however, were not translated into increased volitional strength in this sub-population. Passive training of specific locomotor muscle groups by means of neuromuscular electrical stimulation (NMES) might be better tolerated than whole body exercise in patients with severe chronic obstructive pulmonary disease (COPD). It was hypothesised that this novel strategy would be particularly effective in improving functional impairment and the consequent disability which characterises patients with end stage COPD.
                Fifteen patients with advanced COPD (nine men) were randomly assigned to either a home based 6 week quadriceps femoris NMES training programme (group 1, n=9, FEV(1)=38.0 (9.6)% of predicted) or a 6 week control period before receiving NMES (group 2, n=6, FEV(1)=39.5 (13.3)% of predicted). Knee extensor strength and endurance, whole body exercise capacity, and health related quality of life (Chronic Respiratory Disease Questionnaire, CRDQ) were assessed.
                All patients were able to complete the NMES training programme successfully, even in the presence of exacerbations (n=4). Training was associated with significant improvements in muscle function, maximal and endurance exercise tolerance, and the dyspnoea domain of the CRDQ (p<0.05). Improvements in muscle performance and exercise capacity after NMES correlated well with a reduction in perception of leg effort corrected for exercise intensity (p<0.01).
                For severely disabled COPD patients with incapacitating dyspnoea, short term electrical stimulation of selected lower limb muscles involved in ambulation can improve muscle strength and endurance, whole body exercise tolerance, and breathlessness during activities of daily living. High-frequency neuromuscular electrical stimulation increases exercise tolerance in patients with advanced chronic obstructive pulmonary disease (COPD patients). However, it is conceivable that its benefits are more prominent in patients with better-preserved peripheral muscle function and structure.
                To investigate the effects of high-frequency neuromuscular electrical stimulation in COPD patients with better-preserved peripheral muscle function. Design: Prospective and cross-over study.
                Thirty COPD patients were randomly assigned to either home-based, high-frequency neuromuscular electrical stimulation or sham stimulation for six weeks. The training intensity was adjusted according to each subject's tolerance. Fat-free mass, isometric strength, six-minute walking distance and time to exercise intolerance (Tlim) were assessed.
                Thirteen (46.4%) patients responded to high-frequency neuromuscular electrical stimulation; that is, they had a post/pre Δ Tlim >10% after stimulation (unimproved after sham stimulation). Responders had a higher baseline fat-free mass and six-minute walking distance than their seventeen (53.6%) non-responding counterparts. Responders trained at higher stimulation intensities; their mean amplitude of stimulation during training was significantly related to their fat-free mass (r = 0.65; p<0.01). Logistic regression revealed that fat-free mass was the single independent predictor of Tlim improvement (odds ratio [95% CI] = 1.15 [1.04-1.26]; p<0.05).
                We conclude that high-frequency neuromuscular electrical stimulation improved the exercise capacity of COPD patients with better-preserved fat-free mass because they tolerated higher training stimulus levels. These data suggest that early training with high-frequency neuromuscular electrical stimulation before tissue wasting begins might enhance exercise tolerance in patients with less advanced COPD. Patients with chronic heart failure (CHF) exhibit detrimental changes in skeletal muscle that contribute to their impaired physical performance. This study investigates the possibility of counteracting these changes by chronic low-frequency electrical stimulation (CLFS) of left and right thigh muscles.
                (mean+/-SD) 32 CHF patients (53+/-10 years) with an LVEF of 22+/-5%, NYHA II-IV, undergoing optimized drug therapy, were randomized in a CLFS group (CLFSG) or a control group (controls). The groups differed in terms of the intensity of stimulation, which elicited strong muscle contractions only in the CLFSG, whereas the controls received current input up to the sensory threshold without muscle contractions. Functional capacity was assessed by peak VO(2), work capacity, and a 6-min-walk (6-MW). Muscle biopsies were analyzed for myosin heavy chain (MHC) isoforms, citrate synthase (CS) and glyceraldehydephosphate dehydrogenase (GAPDH) activities. Peak VO(2)(mlmin(-1)kg -1) increased from 9.6+/-3.5 to 11.6+/-2.8 (P<0.001) in the CLFSG, and decreased from 10.6+/-2.8 to 9.4+/-3.2 (P<0.05) in the controls. The increase in the CLFSG was paralleled by increases in maximal workload (P<0.05) and oxygen uptake at the anaerobic threshold (P<0.01). The corresponding values of the controls were unchanged, as also the 6-MW values, the MHC isoform distribution, and both CS and GAPDH activities. In the CLFSG, the 6-MW values increased (P<0.001), CS activity was elevated (P<0.05), GAPDH activity decreased (P<0.01), and the MHC isoforms were shifted in the slow direction with increases in MHCI at the expense of MHCIId/x (P<0.01).
                Our results suggest that CLFS is a suitable treatment to counteract detrimental changes in skeletal muscle and to increase exercise capacity in patients with severe CHF. To determine the impact of an 8-wk neuromuscular stimulation program of thigh muscles on strength and cross-sectional area in patients with refractory heart failure listed for transplantation.
                Forty-two patients with a stable disease course were assigned randomly to a stimulation group (SG) or a control group (CG). The stimulation protocol consisted of biphasic symmetric impulses with a frequency of 50 Hz and an on/off regime of 2/6 sec.
                Primary outcome measures were isometric and isokinetic thigh muscle strength and muscle cross-sectional area. Our results showed an increase of muscle strength by mean 22.7 for knee extensor and by 35.4 for knee flexor muscles. The CG remained unchanged or decreased by -8.4 in extensor strength. Cross-sectional area increased in the SG by 15.5 and in the CG by 1.7.
                Activities of daily living as well as quality of life increased in the SG but not in the CG. Subscales of the SF-36 increased significantly in the SG, especially concerning physical functioning by +7.5 (1.3-30.0), emotional role by +33.3 (0-66.6), and social functioning by +18.8 (0-46.9), all P < 0.05. Neither a change nor a decrease was observed in the CG. Neuromuscular electrical stimulation of thigh muscles in patients with refractory heart failure is effective in increasing muscle strength and bulk and positively affects the perception of quality of life and activities of daily living. The mechanisms through which neuromuscular electrical stimulation (NMES) training may improve limb muscle function and exercise tolerance in COPD are poorly understood. We investigated the functional and muscular effects of NMES in advanced COPD.
                Twenty of 22 patients with COPD were randomly assigned to NMES (n = 12) or sham (n = 8) training in a double-blind controlled study. NMES was performed on quadriceps and calf muscles, at home, 5 days per week for 6 weeks. Quadriceps and calf muscle cross-sectional area (CSA), quadriceps force and endurance, and the shuttle-walking distance with cardiorespiratory measurements were assessed before and after training. Quadriceps biopsy specimens were obtained to explore the insulin-like growth factor-1/AKT signaling pathway (70-kDa ribosomal S6 kinase [p70S6K] , atrogin-1).
                NMES training improved muscle CSA (P < .05), force, and endurance (P < .03) when compared with sham training. Phosphorylated p70S6K levels (anabolism) were increased after NMES as compared with sham (P = .03), whereas atrogin-1 levels (catabolism) were reduced (P = .01). Changes in quadriceps strength and ventilation during walking contributed independently to variations in walking distance after training (r = 0.77, P < .001). Gains in walking distance were related to the ability to tolerate increasing current intensities during training (r = 0.95, P < .001).
                In patients with severe COPD, NMES improved muscle CSA. This was associated with a more favorable muscle anabolic to catabolic balance. Improvement in walking distance after NMES training was associated with gains in muscle strength, reduced ventilation during walking, and the ability to tolerate higher stimulation intensity. Trial registry: ClinicalTrials.gov; No.: NCT00874965; URL: www.clinicaltrials.gov. Low body weight in COPD patients is associated with worsening dyspnea, reduced leg strength, and poor prognosis. Classical rehabilitation strategies are then limited by reduced exercise tolerance. Thus, we proposed to evaluate whether electrostimulation (ES) was a beneficial technique in the rehabilitation programs for severely deconditioned COPD patients after an acute exacerbation.
                Randomized, controlled study.
                Pulmonary rehabilitation center.
                Seventeen patients with severe COPD (mean [ +/- SD] FEV(1), 30 +/- 3% predicted) and low body mass index (BMI) [18 +/- 2.5 kg/m(2)].
                Patients were randomly assigned either to usual rehabilitation (UR) alone or to a UR-plus-ES program for 4 weeks. Quadriceps muscle strength, total muscle mass (MM), exercise capacity, and health-related quality of life were measured before and after rehabilitation.
                The training with ES plus UR induced a significant twofold improvement in the mean number of maximal voluntary contraction (MVC) compared to UR alone (97 +/- 71 vs 36 +/- 34 contractions, respectively; p = 0.03) and resulted in a more significant improvement in dyspnea when performing daily tasks (decrease in the dyspnea domain score of the 28-item Maugeri Foundation Respiratory Failure questionnaire, -1.7 +/- 1.0 vs -0.2 +/- 1.2 points, respectively; p = 0.05). There was also a significant increase in walking distance (63 +/- 40 m; p = 0.01) and BMI (0.6 +/- 0.5 kg/m(2); p = 0.02) after training in the ES + UR group. A significant relationship was found between changes in MVC and changes in MM after training in the ES + UR group (r = 0.94; p = 0.03).
                The combination of ES and UR was associated with greater improvement in quadriceps strength and dyspnea during the performance of daily tasks than UR alone in severely disabled COPD patients with low BMI. In this population, ES has been revealed as a useful procedure, complementing the usual pulmonary rehabilitation. To compare the effects of active limb mobilization (ALM) with or without electrical stimulation (ES) on muscle strength, respiratory rate (RR), heart rate, oxygen saturation, and time needed to transfer from bed to chair in two groups of patients with COPD.
                Randomized, controlled study.
                Respiratory high-dependency care unit.
                Twenty-four bed-bound patients with chronic hypercapnic respiratory failure due to COPD who were receiving mechanical ventilation, with marked peripheral muscle hypotonia and atrophy.
                Patients were randomly assigned either to ALM alone or to ALM plus ES (ALM/ES). ES was applied using square-wave alternate, symmetric, and compensated impulses for 30 min bid. The duration of treatment was 28 days for all patients.
                Muscle strength improved significantly in the overall group of patients (from 1.75 +/- 0.73 to 3.44 +/- 0.65, p < 0.05). Comparing the change (end minus beginning) of the analyzed variables, ALM/ES significantly improved muscle strength (2.16 +/- 1.02 vs 1.25 +/- 0.75, p = 0.02) and RR (- 1.91 +/- 1.72 vs 0.41 +/- 1.88, p = 0.004), and decreased the number of days needed to transfer from bed to chair (10.75 +/- 2.41 days vs 14.33 +/- 2.53 days, p = 0.001).
                In bed-bound patients with COPD receiving mechanical ventilation, with marked peripheral muscle hypotonia and atrophy, application of ES in addition to classical ALM significantly improved muscle strength and decreased the number of days needed to transfer from bed to chair.
NMES appears an effective means of improving muscle weakness in adults with progressive diseases such as COPD, chronic heart failure and cancer. Further research is required to clarify its place in clinical practice, by determining the optimal parameters for a NMES programme, the patients most likely to benefit, and its impact on morbidity and service use.