Нейромышечная электрическая стимуляция при мышечной слабости у взрослых с прогрессированием заболеваний
Referencias
References to studies included in this review
References to studies excluded from this review
Additional references
References to other published versions of this review
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Ir a:
| Methods | 2‐arm parallel RCT (n = 17) | |
| Participants | Inclusion criteria: acute exacerbation of COPD, age < 75 years, body mass index < 30 kg/m2 Exclusion criteria: locomotor or neurological condition or disability that could limit ability to exercise, implanted cardiac pacemaker Gender: 13 male, 2 female (2 unknown due to attrition) Age: median (IQR) 59 (57, 69) and 67 (59, 72) years Illness severity: median (IQR) FEV1 15 (10, 27) and 25 (17, 41) % predicted | |
| Interventions | NMES: bilateral quadriceps and hamstrings stimulation (35 Hz, 400 µs, duty cycle 33%) for 1 hour, 5 times each week for 6 weeks. Amplitude set to elicit visible contraction to maximum tolerated intensity. Control: parameters as per NMES arm, amplitude set to avoid visible or palpable muscle contraction | |
| Outcomes | Isometric quadriceps strength (hand‐held dynamometry), submaximal exercise capacity (6MWT) | |
| Notes | Standard deviations for laboratory outcomes derived from standard errors reported in original report and from authors by request | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Block randomisation |
| Allocation concealment (selection bias) | Low risk | Sealed, opaque envelopes prepared independently |
| Blinding of participants and personnel (performance bias) | Low risk | Placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | High risk | Assessors not blinded to group allocation |
| Incomplete outcome data (attrition bias) | Low risk | All appropriate participants included in analysis, all attrition accounted for, similar across groups (1 participant each), and not related to study intervention (disease‐related readmission and family refusal) |
| Selective reporting (reporting bias) | Low risk | Full results provided in online supplement |
| Study sizes | High risk | < 50 participants |
| Methods | 3‐arm parallel RCT (n = 30) | |
| Participants | Inclusion criteria: intubated COPD patients, GOLD stage C or D, concious, without deep vein thrombosis (examined with bilateral lower extremity Doppler ultrasonography) Exclusion criteria: patients monitored on mechanical ventilation for less than 24 h and discharged from intensive care unit within 48 h, concurrent comorbidities (e.g. renal failure, congestive heart failure, cerebrovascular diseases, neuromuscular diseases, diabetes mellitus, malignancy), haemodynamically unstable patients Gender: 15 male, 15 female Age: mean (SD) 67 (12) years Illness severity: GOLD stage C or D | |
| Interventions | NMES: bilateral quadriceps and deltoid muscle stimulation (50 Hz, pulse width and duty cycle not reported) for 4 weeks, 5 times per week. NMES intensity was adjusted to individual toleration. NMES plus active mobilisation: bilateral quadriceps and deltoid muscle stimulation as above, plus active mobilisation using joint range of motion exercises for the upper and lower limbs. Passive or active‐assisted exercises used in participant unable to perform active exercises. Control: active mobilisation using joint range of motion exercises for the upper and lower limbs. Passive or active‐assisted exercises used in participant unable to perform active exercises. | |
| Outcomes | Lower and upper extremity muscle strength (manual muscle testing), days to demonstrate abilty to sit up in bed, at the bedside, get into standing, and transfer from bed to chair, and intensive care unit stay in days | |
| Notes | Lower extremity muscle strength outcomes were not clearly limited to quadriceps and were excluded from meta‐analysis. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "Randomised", but no further details reported. |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding of participants and personnel (performance bias) | High risk | No placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | Low risk | Assessors blinded to group allocation. |
| Incomplete outcome data (attrition bias) | Low risk | All participants included in analysis. |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 18) | |
| Participants | Inclusion criteria: moderate to severe COPD FEV1< 65% predicted, age < 70 years, limited exercise tolerance Exclusion criteria: cardiovascular or neurological condition, active or debilitating joint disease, pulmonary rehabilitation previous 2 years Gender: 10 male, 8 female Age: mean (SD) 59 (2) and 62 (2) years Illness severity: GOLD stage III/IV | |
| Interventions | NMES: bilateral quadriceps, hamstrings, and calve stimulation (50 Hz, 200 µs, duty cycle 13%) for 1 hour (20 min each muscle), 3 times each week for 6 weeks. Amplitude set to maximum tolerated intensity Control: set up as per NMES arm but no active stimulation | |
| Outcomes | Isokinetic quadriceps and hamstring strength (dynamometry), maximal exercise capacity (incremental shuttle walk test) | |
| Notes | Standard deviation derived from standard errors reported. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomised |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding of participants and personnel (performance bias) | Unclear risk | Placebo/sham model used but with no output. |
| Blinding of outcome assessment (detection bias) | Low risk | Assessors blinded to group allocation. |
| Incomplete outcome data (attrition bias) | Low risk | All participants included in analysis. |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm cross‐over RCT (n = 17) | |
| Participants | Inclusion criteria: COPD FEV1:FVC < 70%, MRC breathlessness score II/III, stable medication previous 3 months Exclusion criteria: locomotor or neurological condition, malignancy, severe endocrine, hepatic, or renal disease, cardiac failure, implanted cardiac pacemaker, distal arteriopathy, recent surgery, use of anticoagulant medication Gender: 16 male, 1 female Age: mean (SD) 66 (9) years Illness severity: GOLD stage III/IV | |
| Interventions | NMES: bilateral quadriceps stimulation (50 Hz, 400 µs, duty cycle 16% to 33%) for 1 hour, 5 times each week for 6 weeks. Amplitude set to elicit visible contraction to maximum tolerated intensity Control: bilateral quadriceps stimulation (10 Hz, 50 µs, duty cycle 16% to 33%) for 1 hour, 5 times each week for 6 weeks. Amplitude limited to 10 mA set to avoid muscle contraction | |
| Outcomes | Isokinetic quadriceps strength (dynamometry), submaximal exercise capacity (6MWT), body composition (DEXA) | |
| Notes | Participants included in Nápolis 2011 clinical outcomes (excluded from meta‐analysis to avoid multiplicity). Laboratory outcomes included separately. The wash‐out period was deemed sufficient to include both study phases in the meta‐analysis. Results from paired analyses were used as recommended by Elbourne 2002. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomly allocated |
| Allocation concealment (selection bias) | Unclear risk | Not reported |
| Blinding of participants and personnel (performance bias) | Low risk | Placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | High risk | Muscle biopsies only taken in NMES arm. |
| Incomplete outcome data (attrition bias) | Low risk | All participants included in analysis. |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 389) | |
| Participants | Inclusion criteria: admitted to hospital with an exacerbation of chronic respiratory disease, diagnosis of chronic respiratory disease (COPD, asthma, bronchiectasis, or ILD), self reported breathlessness on exertion (MRC grade 3 or worse), and age ≥ 40 years Exclusion criteria: inability to provide consent, concomitant acute cardiac event, musculoskeletal, neurological, or psychiatric comorbidities, more than 4 emergency admissions for any cause in the previous 12 months Gender: 173 male, 216 female Age: mean (SD) 71.1 (9.7) years Illness severity: mean (SD) FEV1 54.7 (24.5) (82% of participants had COPD) | |
| Interventions | Early rehabilitation: bilateral NMES of the quadriceps (50 Hz, 300 ms, 15 s on and 5 s off) for 30 minutes daily for 6 weeks. The intensity was increased by therapist or participant in accordance with tolerance. NMES used in addition to strength and aerobic training. Usual care: no intervention other than usual care from the ward | |
| Outcomes | Isometric quadriceps strength (dynamometer), maximal exercise capacity (ISWT), submaximal exercise capacity (ESWT), health‐related quality of life (SGRQ) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomised on a 1:1 basis |
| Allocation concealment (selection bias) | Low risk | Automated |
| Blinding of participants and personnel (performance bias) | High risk | Blinding of participants was not possible. No placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | Low risk | All investigators performing outcome measures blinded to treatment allocation. |
| Incomplete outcome data (attrition bias) | Low risk | Intention‐to‐treat analysis |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | Unclear risk | 50 to 200 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 16) | |
| Participants | Inclusion criteria: non‐small cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 1, < 10% weight loss Exclusion criteria: chemotherapy or radiotherapy previous 4 weeks, change in medication previous week, ischaemic heart disease, implanted cardiac pacemaker Gender: 9 male, 7 female Age: mean (SD) 64 (5) and 56 (9) years Illness severity: locally advanced or metastatic, stage III/IV | |
| Interventions | NMES: bilateral quadriceps stimulation (50 Hz, 350 µs, duty cycle 11% to 25%) for 30 minutes daily for 4 weeks. Amplitude set to elicit visible contraction to maximum tolerated intensity Control: no intervention | |
| Outcomes | Isokinetic quadriceps strength (dynamometry), submaximal exercise capacity (endurance shuttle walk test), physical activity level (accelerometer) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Permuted block generated independently. |
| Allocation concealment (selection bias) | Low risk | Using sealed, opaque envelopes |
| Blinding of participants and personnel (performance bias) | High risk | No placebo/sham model |
| Blinding of outcome assessment (detection bias) | High risk | Assessors not blinded to group allocation |
| Incomplete outcome data (attrition bias) | Low risk | All participants included in analysis. Data on 1 participant (NMES group) missing for each quadriceps strength and physical activity level due to technical problems |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 49) | |
| Participants | Inclusion criteria: adults with advanced (stage IV) NSCLC confirmed by histology or cytology, Eastern Cooperative Oncology Group performance status 0 to 2 scheduled to receive first‐line palliative chemotherapy Exclusion criteria: spinal cord compression, epilepsy, cardiac pacemaker Gender: 28 male, 21 female Age: mean (SD) 69.1 (9.4) years Illness severity: advanced stage IV NSCLC | |
| Interventions | NMES: bilateral quadriceps stimulation (50 Hz, 350 μs, duty cycle 11% to 25%) for 30 minutes daily, at a minimum of 3 times per week, commencing 1 week after chemotherapy started and continued for 8 or 11 weeks. Amplitude was set to elicit visible contraction to maximum tolerated intensity. Control: no intervention | |
| Outcomes | Isometric quadriceps strength (dynamometry), body composition (DEXA), physical activity level (accelerometer), fatigue (Multidimensional Fatigue Inventory), quality of life (EORTC QLQ‐C30) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomly allocated |
| Allocation concealment (selection bias) | Low risk | Permuted block generated independently. |
| Blinding of participants and personnel (performance bias) | High risk | No placebo/sham model |
| Blinding of outcome assessment (detection bias) | High risk | Outcome assessors were not blinded to the participant group allocation. |
| Incomplete outcome data (attrition bias) | High risk | All appropriate participants included in the analysis, all attrition accounted for. Data were missing in 8 participants for body composition due to inability to scan before chemotherapy (n = 5) and participant choice (n = 3). 3 further participants withdrew due to NMES‐related muscle discomfort. |
| Selective reporting (reporting bias) | Low risk | Full results reported. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 52) | |
| Participants | Inclusion criteria: aged 18 years or older, diagnosis of severe COPD consistent with GOLD criteria (FEV1% predicted ≤ 50) and incapacitating breathlessness (MRC dyspnoea scale 4 or 5) Exclusion criteria: implanted cardiac pacemaker, coexisting neurological condition, had changes to their medication, or had experienced an acute exacerbation requiring hospitalisation or systemic corticosteroids in the preceding 4 weeks, regular exercisers (defined as those enrolled in pulmonary rehabilitation or undertaking structured exercise training ≥ 3 times per week within the past month) | |
| Interventions | NMES: bilateral quadriceps stimulation (50 Hz, 350 μs, duty cycle 13% to 66%) for 30 minutes daily. Amplitude was set to elicit visible contraction to maximum tolerated intensity. Placebo: parameters as per NMES arm, however amplitude was set between 0 mA and 20 mA to provide a sensory stimulus that was detectable by the participant. | |
| Outcomes | Submaximal exercise capacity (6MWT), voluntary and involuntary isometric quadriceps strength (dynamometer), body composition (BIA), health‐related quality of life (SGRQ, CRQ, and EQ‐5D), physical activity level (accelerometer) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomly assigned (1:1) at the individual level |
| Allocation concealment (selection bias) | Low risk | Randomised using an independent, web‐based randomisation system |
| Blinding of participants and personnel (performance bias) | Low risk | Placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | Low risk | Outcome assessors blinded to the participant group allocation |
| Incomplete outcome data (attrition bias) | Low risk | All attrition accounted for. Data analysed by intention to treat, and missing data were handled by a multiple imputation approach. |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 15) | |
| Participants | Inclusion criteria: severe COPD FEV1 < 50% predicted, MRC breathlessness score IV/V Exclusion criteria: locomotor or neurological condition, change in medication or exacerbation in previous 4 weeks Gender: 9 male, 6 female Age: mean (SD) 67 (8) and 65 (5) years Illness severity: GOLD stage IV | |
| Interventions | NMES: bilateral quadriceps stimulation (50 Hz, 300 µs to 400 µs, duty cycle 11% to 25%) for 30 minutes, 5 times each week for 6 weeks. Amplitude set to elicit visible contraction to maximum tolerated intensity Control: no intervention | |
| Outcomes | Isokinetic and isometric quadriceps strength (dynamometry), quadriceps endurance (constant load), maximal exercise capacity (CPET cycle ergometry), quality of life (CRQ) | |
| Notes | Control participants received NMES after the first study period, and pre‐post changes reported. These data were not used in meta‐analysis. Change score for the meta‐analysis for quadriceps strength and exercise capacity were estimated using the difference between pre‐ and post‐intervention groups means the widest standard deviations as per a previous review (Roig 2009). | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomised |
| Allocation concealment (selection bias) | Low risk | "Referers" blinded to sequence allocation |
| Blinding of participants and personnel (performance bias) | High risk | No placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Not reported |
| Incomplete outcome data (attrition bias) | Low risk | All participants included in analysis |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 34) | |
| Participants | Inclusion criteria: symptomatic left ventricular fraction < 35%, optimised medication Exclusion criteria: acute heart failure, angina, arrhythmia, implanted cardiac pacemaker Gender: 29 male, 5 female Age: mean (SD) 53 (10) years Illness severity: NYHA stage II to IV | |
| Interventions | NMES: bilateral quadriceps and hamstrings stimulation (15 Hz, 500 µs, duty cycle 33%) for 4 hours, daily for 10 weeks. Amplitude set to elicit visible contraction to maximum tolerated intensity. Control: parameters as per NMES arm, amplitude set to avoid visible or palpable muscle contraction | |
| Outcomes | Maximal exercise capacity (CPET cycle ergometry), submaximal exercise capacity (6MWT), quality of life (Minnesota Living With Heart Failure Questionnaire) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation list |
| Allocation concealment (selection bias) | Low risk | Sealed envelopes |
| Blinding of participants and personnel (performance bias) | Low risk | Placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Not reported |
| Incomplete outcome data (attrition bias) | Low risk | All attrition accounted for, small number of participants (n = 2) and not related to study intervention (urgent heart transplantation). |
| Selective reporting (reporting bias) | High risk | Under adverse events subheading "maximum voluntary strength of the stimulated muscle groups did not differ from baseline data" |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm cross‐over RCT (n = 30) | |
| Participants | Inclusion criteria: COPD FEV1:FVC < 70%, MRC breathlessness score I/III Exclusion criteria: locomotor or neurological condition, malignancy, severe endocrine, hepatic, or renal disease, cardiac failure, implanted cardiac pacemaker, distal arteriopathy, recent surgery, use of anticoagulant medication, change in medication or exacerbation in previous 4 weeks, regular physical activity, previous pulmonary rehabilitation Gender: 26 male, 4 female Age: mean (SD) 64 (7) years Illness severity: GOLD stage II/III | |
| Interventions | NMES: bilateral quadriceps stimulation (50 Hz, 300 µs to 400 µs, duty cycle 16% to 33%) for up to 1 hour, 5 times each week for 6 weeks. Amplitude set to elicit visible contraction to maximum tolerated intensity Control: bilateral quadriceps stimulation (50 Hz, 200 µs, duty cycle 16%) for 15 minutes, 3 times each week for 6 weeks. Amplitude limited to 10 mA set to avoid muscle contraction | |
| Outcomes | Isokinetic quadriceps strength (dynamometry), maximal exercise capacity (CPET cycle ergometry), submaximal exercise capacity (6MWT) | |
| Notes | Participants from Dal Corso 2007 were included in this study (for clinical outcomes Nápolis 2011 data were used in meta‐analysis to avoid multiplicity). The wash‐out period was deemed sufficient to include both study phases in the meta‐analysis. Results from paired analyses were used as recommended by Elbourne 2002. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | After randomisation |
| Allocation concealment (selection bias) | Unclear risk | As per Dal Corso 2007 |
| Blinding of participants and personnel (performance bias) | Low risk | Placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | Low risk | Assessors blinded to participant treatment sequence |
| Incomplete outcome data (attrition bias) | Low risk | All participants included in analysis. Data on 2 and 4 participants were missing for maximal and submaximal exercise capacity, respectively due to technical problems (group allocation unknown). |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 42) | |
| Participants | Inclusion criteria: severe chronic heart failure, optimised drug therapy Exclusion criteria: unstable disease, peripheral oedema, implanted cardiac pacemaker Gender: 21 male, 12 female Age: mean (SD) 59 (6) and 57 (8) years Illness severity: NYHA stage II to IV | |
| Interventions | NMES: bilateral quadriceps and hamstrings stimulation (50 Hz, 700 µs, duty cycle 25%) for up to 1 hour, 5 times each week for 8 weeks. Amplitude set to elicit visible contraction to maximum tolerated intensity Control: encouraged to continue engagement in usual activities of daily living recorded in diary | |
| Outcomes | Isokinetic and isometric quadriceps and hamstrings strength (dynamometry), quadriceps endurance (interval fixed load), body composition (computed tomography), lower limb functional activities (stair climb, rise from chair, rise from supine), quality of life (SF‐36) | |
| Notes | Standard deviations for outcomes of quadriceps and hamstrings strength, quadriceps endurance, and body composition were derived from reported 95% confidence intervals. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Block‐wise randomisation using list provided by independent staff |
| Allocation concealment (selection bias) | Low risk | Randomisation code locked until the end of the study |
| Blinding of participants and personnel (performance bias) | High risk | No placebo/sham model |
| Blinding of outcome assessment (detection bias) | Low risk | Assessors were not aware of the participants' group allocation |
| Incomplete outcome data (attrition bias) | Low risk | All attrition accounted for, similar numbers across groups (NMES n = 2, control n = 5) and not related to study intervention (urgent heart transplantation n = 6, pacemaker implanted n = 1, renal failure n = 1, died (control) n = 1) |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 3‐arm parallel RCT (n = 120) | |
| Participants | Inclusion criteria: primary diagnosis of COPD, baseline MRC dyspnoea grade 3 or 4, quadriceps weakness (peak torque ≤ 80% predicted) Exclusion criteria: neuromuscular diseases, joint disorders in hip/leg and/or knees, metal implants in hip, leg, and/or knee, cardiac pacemaker or internal cardiac defibrillator, and/or outpatient pulmonary rehabilitation programme Gender: 62 male, 58 female Age: mean (SD) 64.8 (8.8) years Illness severity: mean (SD) FEV1 33 (11) % predicted | |
| Interventions | High‐frequency NMES: bilateral quadriceps and calf muscle stimulation (75 Hz, 400 μs, duty cycle was 38%) for 8 weeks, twice per day, 5 times per week. After a 3‐minute warm‐up at 5 Hz, intensity was adjusted to individual toleration during each 18‐minute session. Low‐frequency NMES: same as the high‐frequency NMES protocol, however the frequency used was 15 Hz Control: strength training consisting of bilateral leg extension and bilateral leg press exercises at 70% 1 RPM, 4 sets of 8 for each exercise with at least 2 minutes of recovery between sets. Training load was set to increase by 5% every 2 weeks. | |
| Outcomes | Isokinetic quadriceps muscle strength (dynamometry), isokinetic quadriceps endurance (constant load), submaximal exercise capacity (6MWT), endurance (constant work rate cycle endurance test), anxiety and depression (HADS), health‐related quality of life (SGRQ), problematic activities of daily living (COPM) | |
| Notes | Standard deviations for laboratory outcomes derived from standard errors reported in the original paper. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation schedule generated by a computer. |
| Allocation concealment (selection bias) | Low risk | Sequence was concealed. |
| Blinding of participants and personnel (performance bias) | High risk | Participants randomly assigned to one of the NMES groups were blinded for stimulation frequency, however no placebo/sham in the control group (the main comparison for this review). |
| Blinding of outcome assessment (detection bias) | Low risk | Randomisation schedule was maintained centrally, and the investigator was not involved in the assessment and treatment of participants. Investigators supervising the interventions were blinded for initial results, and were not involved in the initial or outcome assessments. |
| Incomplete outcome data (attrition bias) | Unclear risk | No imputations. Attrition accounted for but not similar between the groups, highest attrition in the low‐frequency group |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 34) | |
| Participants | Inclusion criteria: aged between 40 and 75 years, eligible to participate in exercise, no acute exacerbations within the past month, and no drug or antibiotic usage within the past 4 weeks Exclusion criteria: suffering from orthopaedic or neuromuscular disorders, metal implants in the lower limb, suffered from advanced heart failure, aortic stenosis, or deep vein thrombosis, required cardiac pacemaker, had a pulmonary artery pressure > 50 mmHg, suffered an acute exacerbation within the past 4 weeks, unable to understand the questionnaires, and were unable to co‐operate Gender: 24 male, 3 female Age: mean (SD) 62.1 (7.9) and 62.9 (7.5) years Illness severity: GOLD stages 1 = 0, II = 9, III = 9, IV = 9 | |
| Interventions | NMES: bilateral quadriceps stimulation (50 Hz, 300 μs, duty cycle was 50%) for 20 minutes, 2 days per week, for 10 weeks. Intensity was increased to each participant's maximum individual tolerance level. Control: parameters as per NMES arm, with the exception of stimulation frequency of 5 Hz, which caused a visible twitch All participants undertook a pulmonary rehabilitation programme consisting of exercise training and additional intervention such as education and nutritional and psychological support. Exercise training consisted of 10 weeks of endurance training, quadriceps resistance training, and low‐level resistance training for the upper limbs. | |
| Outcomes | Maximal exercise capacity (ISWT), submaximal exercise capacity (ESWT), body composition (BIA), quadriceps function (1‐repetition maximum and 30‐second sit‐to‐stand test), quadriceps endurance (squat test and 2‐minute step‐in‐place test), health‐related quality of life (SGRQ) | |
| Notes | Mean and standard deviation values were estimated from reported median and range values using the formulae published by Hozo 2005. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation list |
| Allocation concealment (selection bias) | Low risk | Sealed envelopes |
| Blinding of participants and personnel (performance bias) | Low risk | Placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | High risk | Assessors were not blinded for the final evaluation assessment. |
| Incomplete outcome data (attrition bias) | Low risk | All attrition accounted for, similar across groups (NMES n = 4, control n = 3) and not related to study intervention |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 30) | |
| Participants | Inclusion criteria: diagnosis of COPD with FEV1 < 50% predicted, self reported dyspnoea and/or arm fatigue during at least 1 activity of daily living that required arm exercise Exclusion criteria: musculoskeletal or neurological condition that could affect exercise performance, symptomatic cardiac disease or previous lung surgery, an acute exacerbation of COPD that required a change in pharmacological management within the preceding 2 months, use of oral corticosteroids, a change in medication dosage or exacerbation of symptoms in the preceding 12 weeks, implantable electrical devices Gender: 24 male, 0 female Age: mean (SD) 56.4 (11.8) years Illness severity: GOLD stage III/IV, mean (SD) 38.1 (12.4)% predicted | |
| Interventions | NMES: bilateral quadriceps stimulation (50 Hz, 300 μs to 400 μs, duty cycle 10% to 33%) for 60 minutes per session, 5 times per week, twice per day for 8 weeks. Amplitude was set to elicit visible contraction to maximum tolerated intensity. Control: parameters as per NMES arm, but no active stimulation All participants received respiratory physiotherapy, i.e. breathing and stretching exercises. | |
| Outcomes | Submaximal exercise capacity (6MWT), cardiopulmonary exercise testing (constant work test at 80% peak workload), body composition (BIA), quality of life (SGRQ) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomly allocated |
| Allocation concealment (selection bias) | Low risk | 2 investigators were blinded to the order of participant allocation. |
| Blinding of participants and personnel (performance bias) | Unclear risk | Active and sham devices were utilised, however the sham device produced no stimulation. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Within group health‐related quality of life reporting |
| Incomplete outcome data (attrition bias) | High risk | 17% attrition, causing an imbalance between the groups. Increased dropouts due to an exacerbation in the control group compared to the NMES group |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 17) | |
| Participants | Inclusion criteria: severe COPD, COPD FEV1:FVC < 70%, FEV1 < 50% predicted, body mass index < 22 kg/m2, quadriceps maximum voluntary strength < 50% predicted Exclusion criteria: cardiovascular, renal, or hepatic disease, acute respiratory failure Gender: 11 male, 6 female Age: mean (SD) 59 (15) and 68 (12) years Illness severity: GOLD stage IV | |
| Interventions | NMES: bilateral quadriceps stimulation (35 Hz, 400 µs, duty cycle 47%) for 30 minutes, 4 times each week for 4 weeks. Amplitude set to elicit visible contraction to maximum tolerated intensity. Additional usual rehabilitation as described below. Control: usual rehabilitation limb mobilisations, slow treadmill walking, light upper limb resistance training for ˜30 minutes, 4 times each week for 4 weeks | |
| Outcomes | Isometric quadriceps strength (dynamometry), submaximal exercise capacity (6MWT), body composition (anthropometry), quality of life (Maugeri Foundation Respiratory Failure Questionnaire) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomised into 2 groups |
| Allocation concealment (selection bias) | Unclear risk | Inadequately described to judge |
| Blinding of participants and personnel (performance bias) | High risk | No placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Not reported |
| Incomplete outcome data (attrition bias) | Low risk | Body composition assessments optional |
| Selective reporting (reporting bias) | Low risk | Full results provided, body composition assessments optional, similar numbers across groups (NMES n = 6, control n = 5). |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 22) | |
| Participants | Inclusion criteria: severe COPD FEV1:FVC < 70%, FEV1 < 50% predicted, 6‐minute walking distance < 400 metres, > 20‐year smoking pack‐year history, sedentary lifestyle, < 1 hour from hospital Exclusion criteria: acute exacerbation or systemic steroids in previous 4 weeks, condition associated with muscle wasting including active inflammatory illness, heart failure, or diabetes Gender: 13 male, 7 female Age: mean (SD) 68 (9) and 70 (3) years Illness severity: GOLD stage IV | |
| Interventions | NMES: bilateral quadriceps and calve stimulation (50 Hz, 400 µs, duty cycle 27%) for 1 hour (35 minutes quadriceps and 25 minutes calves), 5 times each week for 6 weeks. Amplitude set to elicit visible contraction to maximum tolerated intensity Control: bilateral quadriceps stimulation (5 Hz, 100 µs, continuous) for 1 hour (35 minutes quadriceps and 25 minutes calves), 5 times each week for 6 weeks | |
| Outcomes | Isometric quadriceps strength (dynamometry), quadriceps endurance (constant load test), body composition (computed tomography), submaximal exercise capacity (endurance shuttle walk test) | |
| Notes | Standard deviations for all outcomes derived from standard errors reported in original report and from authors by request. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomly assigned |
| Allocation concealment (selection bias) | Unclear risk | Inadequately described to judge |
| Blinding of participants and personnel (performance bias) | Low risk | Placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Inadequately described to judge |
| Incomplete outcome data (attrition bias) | Low risk | All participants included in analysis |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
| Methods | 2‐arm parallel RCT (n = 24) | |
| Participants | Inclusion criteria: chronic hypercapnic respiratory failure, COPD FEV1:FVC < 70%, mechanically ventilated, severe peripheral muscle atrophy, bed‐bound > 30 days Exclusion criteria: condition or disease other than COPD, change in medication within previous 4 weeks, corticosteroid use > 5 days whilst on intensive care unit Gender: 17 male, 7 female Age: mean (SD) 68 (8) and 65 (4) years Illness severity: respiratory failure due to COPD | |
| Interventions | NMES: bilateral quadriceps and glutei stimulation (35 Hz, 350 µs, duty cycle not reported) for 30 minutes, 5 times each week for 4 weeks. Amplitude not reported. Used as adjunct to active limb mobilisation described below Control: active limb mobilisation of upper and lower limbs for up to 30 minutes within participant tolerance, 5 times each week for 4 weeks | |
| Outcomes | Peripheral muscle strength (manual muscle testing), number of days to transfer from bed to chair | |
| Notes | Peripheral muscle strength outcome not clearly limited to quadriceps and excluded from meta‐analysis | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomly assigned |
| Allocation concealment (selection bias) | Unclear risk | Inadequately described to judge |
| Blinding of participants and personnel (performance bias) | High risk | No placebo/sham model used. |
| Blinding of outcome assessment (detection bias) | Low risk | Assessors blinded to group allocation |
| Incomplete outcome data (attrition bias) | Low risk | All participants included in analysis |
| Selective reporting (reporting bias) | Low risk | Full results provided. |
| Study sizes | High risk | < 50 participants per study arm |
Abbreviations: 6MWT = 6‐minute walk test, BIA = bioelectrical impedance analysis, COPD = chronic obstructive pulmonary disease, COPM = Canadian Occupational Performance Measure, CPET = cardiopulmonary exercise testing, CRQ = Chronic Respiratory Questionnaire, DEXA = dual energy X‐ray absorptiometry, EORTC QLQ‐C30 = European Organisation for the Research and Treatment of Cancer Quality of Life Core 30, ESWT = endurance shuttle walk test, FEV1 forced expiratory volume in 1 second, FVC = forced vital capacity, HADS = Hospital Anxiety and Depression Scale, ILD = interstitial lung disease, IQR = interquartile range, ISWT = incremental shuttle walk test, mA = maximum amplitude, MRC = Medical Research Council, NMES = neuromuscular electrical stimulation, NSCLC = non‐small cell lung cancer, NYHA = New York Heart Association, RCT = randomised controlled trial, RPM = revolutions per minute, SD = standard deviation, SF‐36 = 36‐Item Short Form Health Survey, SGRQ = St George's Respiratory Disease Questionnaire
Characteristics of excluded studies [ordered by study ID]
Ir a:
| Study | Reason for exclusion |
| Review, perspective | |
| Review, perspective | |
| Review, perspective | |
| The majority of participants (9/10) had early‐stage (NYHA II) disease. | |
| Review, perspective | |
| Review, meta‐analysis | |
| Review, perspective | |
| Review, perspective | |
| The intervention studied involved magnetic rather than electrical stimulation to elicit a muscular contraction. | |
| Acute‐effects study | |
| The study compared high‐frequency and low‐frequency NMES, no comparison to an inactive control or an active control such as exercise present. | |
| Poststroke | |
| Observation | |
| Difficult to define advanced disease in multiple sclerosis | |
| Case series | |
| Case series | |
| Case report | |
| Review, perspective | |
| The majority of participants (18/24) had early‐stage (NYHA II) disease. | |
| Observational | |
| The majority of participants (22/30) had early‐stage (NYHA II) disease. | |
| Observational | |
| Review, perspective | |
| Spinal cord injury | |
| Group allocation reportedly occurred according to level of illness severity and muscle dysfunction: "due to illness severity and muscle dysfunction 8 patients were included in NMES and 11 patients were included in endurance program". | |
| Osteoarthritis | |
| Critically ill patient including sepsis and trauma | |
| Randomisation occurred at the level of the limb, with one leg stimulated and the other acting as a control. | |
| Total hip replacement | |
| Critically ill patient including sepsis and trauma | |
| The majority of participants (35/46) had early‐stage (NYHA II) disease. | |
| Acute‐effects study | |
| Acute‐effects study | |
| Observational | |
| Frequency‐matched case‐control | |
| Observational | |
| Review, perspective | |
| The majority of participants (28/35) had early‐stage (NYHA II) disease. | |
| Review, perspective | |
| Assessment using ES not intervention | |
| Review, perspective | |
| Observational | |
| Compared 2 intensity protocols | |
| Spinal cord injury, paralysis | |
| Review, perspective | |
| Observational | |
| Review, perspective | |
| Osteoarthritis | |
| Review, perspective | |
| Case series | |
| Observational | |
| Review, meta‐analysis | |
| Critically ill patient including sepsis and trauma | |
| Review, meta‐analysis | |
| Compared 2 NMES frequencies | |
| Assessment using ES not intervention | |
| Review, perspective | |
| Acute‐effects study | |
| Review, meta‐analysis | |
| Acute‐effects study | |
| Acute‐effects study | |
| Measurements made following 1 session/acute‐effects study. | |
| Total knee replacement | |
| Abdominal surgery | |
| Repeat report | |
| The majority of participants (99/101) had early‐stage disease. | |
| Repeat report | |
| Osteoarthritis | |
| Post‐cardiac transplantation | |
| Review, perspective | |
| Review, perspective | |
| Repeat report | |
| Repeat report | |
| Total knee replacement | |
| Observational |
NMES = neuromuscular electrical stimulation, NYHA = New York Heart Association
Data and analyses
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Quadriceps muscle strength Show forest plot | 12 | 781 | Std. Mean Difference (IV, Random, 95% CI) | 0.53 [0.19, 0.87] |
| Analysis 1.1  Comparison 1 Neuromuscular electrical stimulation versus control, Outcome 1 Quadriceps muscle strength. | ||||
| 2 Muscle mass Show forest plot | 8 | Std. Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| Analysis 1.2  Comparison 1 Neuromuscular electrical stimulation versus control, Outcome 2 Muscle mass. | ||||
| 2.1 Anthropometry | 2 | 31 | Std. Mean Difference (IV, Random, 95% CI) | 0.69 [‐0.05, 1.42] |
| 2.2 Dual energy X‐ray absorptiometry (DEXA) | 3 | 179 | Std. Mean Difference (IV, Random, 95% CI) | 0.09 [‐0.20, 0.38] |
| 2.3 Ultrasound | 1 | 52 | Std. Mean Difference (IV, Random, 95% CI) | 0.82 [0.26, 1.39] |
| 2.4 Computed tomography | 2 | 52 | Std. Mean Difference (IV, Random, 95% CI) | 1.01 [0.42, 1.60] |
| 3 Exercise performance Show forest plot | 13 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| Analysis 1.3  Comparison 1 Neuromuscular electrical stimulation versus control, Outcome 3 Exercise performance. | ||||
| 3.1 6‐minute walk test (m) (6MWT) | 7 | 317 | Mean Difference (IV, Random, 95% CI) | 34.78 [13.52, 56.05] |
| 3.2 Incremental shuttle walk test (m) (ISWT) | 3 | 434 | Mean Difference (IV, Random, 95% CI) | 8.72 [‐34.87, 52.31] |
| 3.3 Endurance shuttle walk test (m) (ESWT) | 4 | 452 | Mean Difference (IV, Random, 95% CI) | 64.13 [‐17.79, 146.05] |
| 3.4 Cardiopulmonary exercise testing (mL/min) (CPET) | 4 | 109 | Mean Difference (IV, Random, 95% CI) | 44.82 [‐7.34, 96.99] |
Study flow diagram.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Forest plot of quadriceps muscle strength for NMES versus control.
Forest plot of muscle mass for NMES versus control.
Forest plot of exercise performance for NMES versus control.
Comparison 1 Neuromuscular electrical stimulation versus control, Outcome 1 Quadriceps muscle strength.
Comparison 1 Neuromuscular electrical stimulation versus control, Outcome 2 Muscle mass.
Comparison 1 Neuromuscular electrical stimulation versus control, Outcome 3 Exercise performance.
| NMES for adults with advanced disease for muscle weakness | ||||
| Patient or population: adults with advanced disease for muscle weakness Control: no intervention (7 studies), placebo NMES (8 studies), or resistance training (1 study) | ||||
| Outcomes | Illustrative comparative risks* (95% CI) | No of Participants | Quality of the evidence | |
| Assumed risk | Corresponding risk | |||
| Control | NMES | |||
| Quadriceps muscle strength | The mean change was 0.43 standard deviations from baseline. | The mean change in the intervention groups was 0.53 standard deviations higher (ranging from 0.19 to 0.87 standard deviations higher). | 781 | ⊕⊕⊝⊝ |
| Safety | No serious adverse events related to control interventions reported. | No serious adverse events related to NMES reported. | 933 | ⊕⊕⊕⊝ |
| Safety Adverse events: Muscle discomfort | 0/415 (0%) participants reported muscle discomfort following control interventions. | 19/518 (3.7%) participants reported muscle discomfort following NMES. | 933 (18 studies) | ⊕⊕⊕⊝ |
| Muscle mass | The mean change in muscle mass ranged from 0.04 to 0.49 standard deviations from baseline across the different assessment modalities used. | The mean change in muscle mass ranged from 0.09 to 1.01 standard deviations higher across the different assessment modalities used. | 314 | ⊕⊝⊝⊝ |
| Exercise performance ‐ walking distance | The mean change in distance walked was 21, 36, and 37 metres from baseline across the different walking tests used. | The mean change in distance walked was 35, 9, and 64 metres further across the different walking tests used. | 788 | ⊕⊝⊝⊝ |
| Exercise performance ‐ peak oxygen uptake | The mean change in peak oxygen uptake was ‐0.4 mL/min from baseline. | The mean exercise performance ‐ peak oxygen uptake in the intervention groups was 44.8 mL/min higher (95% CI 7.3 lower to 97.0 higher) | 109 | ⊕⊕⊝⊝ |
| *The basis for the assumed risk is the mean change from baseline in the control groups. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||
| GRADE Working Group grades of evidence | ||||
| 1Downgraded once: the lower 95% CI for the estimate of effect was below what would be considered a small effect (standardised mean difference 0.2). | ||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Quadriceps muscle strength Show forest plot | 12 | 781 | Std. Mean Difference (IV, Random, 95% CI) | 0.53 [0.19, 0.87] |
| 2 Muscle mass Show forest plot | 8 | Std. Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 2.1 Anthropometry | 2 | 31 | Std. Mean Difference (IV, Random, 95% CI) | 0.69 [‐0.05, 1.42] |
| 2.2 Dual energy X‐ray absorptiometry (DEXA) | 3 | 179 | Std. Mean Difference (IV, Random, 95% CI) | 0.09 [‐0.20, 0.38] |
| 2.3 Ultrasound | 1 | 52 | Std. Mean Difference (IV, Random, 95% CI) | 0.82 [0.26, 1.39] |
| 2.4 Computed tomography | 2 | 52 | Std. Mean Difference (IV, Random, 95% CI) | 1.01 [0.42, 1.60] |
| 3 Exercise performance Show forest plot | 13 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 3.1 6‐minute walk test (m) (6MWT) | 7 | 317 | Mean Difference (IV, Random, 95% CI) | 34.78 [13.52, 56.05] |
| 3.2 Incremental shuttle walk test (m) (ISWT) | 3 | 434 | Mean Difference (IV, Random, 95% CI) | 8.72 [‐34.87, 52.31] |
| 3.3 Endurance shuttle walk test (m) (ESWT) | 4 | 452 | Mean Difference (IV, Random, 95% CI) | 64.13 [‐17.79, 146.05] |
| 3.4 Cardiopulmonary exercise testing (mL/min) (CPET) | 4 | 109 | Mean Difference (IV, Random, 95% CI) | 44.82 [‐7.34, 96.99] |
