Neuromuscular electrical stimulation for preventing skeletal-muscle weakness and wasting in critically ill patients: a systematic review.
ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Project description:Background:Critically ill traumatic brain injury (TBI) patients experience extensive muscle damage during their stay in the intensive care unit. Neuromuscular electrical stimulation (NMES) has been considered a promising treatment to reduce the functional and clinical impacts of this. However, the time needed for NMES to produce effects over the muscles is still unclear. This study primarily aimed to assess the time needed and effects of an NMES protocol on muscle architecture, neuromuscular electrophysiological disorder (NED), and muscle strength, and secondarily, to evaluate the effects on plasma systemic inflammation, catabolic responses, and clinical outcomes. Methods:We performed a randomized clinical trial in critically ill TBI patients. The control group received only conventional physiotherapy, while the NMES group additionally underwent daily NMES for 14 days in the lower limb muscles. Participants were assessed at baseline and on days 3, 7, and 14 of their stay in the intensive care unit. The primary outcomes were assessed with muscle ultrasound, neuromuscular electrophysiology, and evoked peak force, and the secondary outcomes with plasma cytokines, matrix metalloproteinases, and clinical outcomes. Results:Sixty participants were randomized, and twenty completed the trial from each group. After 14?days, the control group presented a significant reduction in muscle thickness of tibialis anterior and rectus femoris, mean of -?0.33?mm (-?14%) and -?0.49?mm (-?21%), p?<?0.0001, respectively, while muscle thickness was preserved in the NMES group. The control group presented a higher incidence of NED: 47% vs. 0% in the NMES group, p?<?0.0001, risk ratio of 16, and the NMES group demonstrated an increase in the evoked peak force (2.34 kg/f, p?<?0.0001), in contrast to the control group (-?1.55 kg/f, p?<?0.0001). The time needed for the NMES protocol to prevent muscle architecture disorders and treat weakness was at least 7 days, and 14 days to treat NED. The secondary outcomes exhibited less precise results, with confidence intervals that spanned worthwhile or trivial effects. Conclusions:NMES applied daily for fourteen consecutive days reduced muscle atrophy, the incidence of NED, and muscle weakness in critically ill TBI patients. At least 7 days of NMES were required to elicit the first significant results. Trial registration:The trial was registered at ensaiosclinicos.gov.br under protocol RBR-8kdrbz on 17 January 2016.
Project description:The 'obesity paradox' of critical illness refers to better survival with a higher body mass index. We hypothesized that fat mobilized from excess adipose tissue during critical illness provides energy more efficiently than exogenous macronutrients and could prevent lean tissue wasting.In lean and premorbidly obese mice, the effect of 5?days of sepsis-induced critical illness on body weight and composition, muscle wasting, and weakness was assessed, each with fasting and parenteral feeding. Also, in lean and overweight/obese prolonged critically ill patients, markers of muscle wasting and weakness were compared.In mice, sepsis reduced body weight similarly in the lean and obese, but in the obese with more fat loss and less loss of muscle mass, better preservation of myofibre size and muscle force, and less loss of ectopic lipids, irrespective of administered feeding. These differences between lean and obese septic mice coincided with signs of more effective hepatic fatty acid and glycerol metabolism, and ketogenesis in the obese. Also in humans, better preservation of myofibre size and muscle strength was observed in overweight/obese compared with lean prolonged critically ill patients.During critical illness premorbid obesity, but not nutrition, optimized utilization of stored lipids and attenuated muscle wasting and weakness.
Project description:BACKGROUND:Neuromuscular electrical stimulation (NMES) has been investigated as a preventative measure for intensive care unit-acquired weakness. Trial results remain contradictory and therefore inconclusive. As it has been shown that NMES does not necessarily lead to a contractile response, our aim was to characterise the response of critically ill patients to NMES and investigate potential outcome benefits of an adequate contractile response. METHODS:This is a sub-analysis of a randomised controlled trial investigating early muscle activating measures together with protocol-based physiotherapy in patients with a SOFA score ≥ 9 within the first 72 h after admission. Included patients received protocol-based physiotherapy twice daily for 20 min and NMES once daily for 20 min, bilaterally on eight muscle groups. Electrical current was increased up to 70 mA or until a contraction was detected visually or on palpation. Muscle strength was measured by a blinded assessor at the first adequate awakening and ICU discharge. RESULTS:One thousand eight hundred twenty-four neuromuscular electrical stimulations in 21 patients starting on day 3.0 (2.0/6.0) after ICU admission were included in this sub-analysis. Contractile response decreased from 64.4% on day 1 to 25.0% on day 7 with a significantly lower response rate in the lower extremities and proximal muscle groups. The electrical current required to elicit a contraction did not change over time (day 1, 50.2 [31.3/58.8] mA; day 7, 45.3 [38.0/57.5] mA). The electrical current necessary for a contractile response was higher in the lower extremities. At the first awakening, patients presented with significant weakness (3.2 [2.5/3.8] MRC score). When dividing the cohort into responders and non-responders (> 50% vs. ≤ 50% contractile response), we observed a significantly higher SOFA score in non-responders. The electrical current necessary for a muscle contraction in responders was significantly lower (38.0 [32.8/42.9] vs. 54.7 [51.3/56.0] mA, p < 0.001). Muscle strength showed higher values in the upper extremities of responders at ICU discharge (4.4 [4.1/4.6] vs. 3.3 [2.8/3.8] MRC score, p = 0.036). CONCLUSION:Patients show a differential contractile response to NMES, which appears to be dependent on the severity of illness and also relevant for potential outcome benefits. TRIAL REGISTRATION:ISRCTN ISRCTN19392591 , registered 17 February 2011.
Project description:The effects of neuromuscular electrical stimulation (NMES) in critically ill patients after cardiothoracic surgery are unknown. The objectives were to investigate whether NMES prevents loss of muscle layer thickness (MLT) and strength and to observe the time variation of MLT and strength from preoperative day to hospital discharge.In this randomized controlled trial, 54 critically ill patients were randomized into four strata based on the SAPS II score. Patients were blinded to the intervention. In the intervention group, quadriceps muscles were electrically stimulated bilaterally from the first postoperative day until ICU discharge for a maximum of 14 days. In the control group, the electrodes were applied, but no electricity was delivered. The primary outcomes were MLT measured by ultrasonography and muscle strength evaluated with the Medical Research Council (MRC) scale. The secondary functional outcomes were average mobility level, FIM score, Timed Up and Go Test and SF-12 health survey. Additional variables of interest were grip strength and the relation between fluid balance and MLT. Linear mixed models were used to assess the effect of NMES on MLT, MRC score and grip strength.NMES had no significant effect on MLT. Patients in the NMES group regained muscle strength 4.5 times faster than patients in the control group. During the first three postoperative days, there was a positive correlation between change in MLT and cumulative fluid balance (r = 0.43, P = 0.01). At hospital discharge, all patients regained preoperative levels of muscle strength, but not of MLT. Patients did not regain their preoperative levels of average mobility (P = 0.04) and FIM score (P = 0.02) at hospital discharge, independent of group allocation.NMES had no effect on MLT, but was associated with a higher rate in regaining muscle strength during the ICU stay. Regression of intramuscular edema during the ICU stay interfered with measurement of changes in MLT. At hospital discharge patients had regained preoperative levels of muscle strength, but still showed residual functional disability and decreased MLT compared to pre-ICU levels in both groups.Clinicaltrials.gov identifier NCT02391103. Registered on 7 March 2015.
Project description:Skeletal muscle weakness is a prominent feature in patients with rheumatoid arthritis (RA). In this study, we investigated whether neuromuscular electrical stimulation (NMES) training protects against skeletal muscle dysfunction in rats with adjuvant-induced arthritis (AIA). AIA was produced by intraarticular injection of complete Freund's adjuvant into the knees of Wistar rats. For NMES training, dorsiflexor muscles were stimulated via a surface electrode (0.5 ms pulse, 50 Hz, 2 s on/4 s off). NMES training was performed every other day for three weeks and consisted of three sets produced at three min intervals. In each set, the electrical current was set to achieve 60% of the initial maximum isometric torque and the current was progressively increased to maintain this torque; stimulation was stopped when the 60% torque could no longer be maintained. After the intervention period, extensor digitorum longus (EDL) muscles were excised and used for physiological and biochemical analyses. There was a reduction in specific force production (i.e. force per cross-sectional area) in AIA EDL muscles, which was accompanied by aggregation of the myofibrillar proteins actin and desmin. Moreover, the protein expressions of the pro-oxidative enzymes NADPH oxidase, neuronal nitric oxide synthase, p62, and the ratio of the autophagosome marker LC3bII/LC3bI were increased in AIA EDL muscles. NMES training prevented all these AIA-induced alterations. The present data suggest that NMES training prevents AIA-induced skeletal muscle weakness presumably by counteracting the formation of actin and desmin aggregates. Thus, NMES training can be an effective treatment for muscle dysfunction in patients with RA.
Project description:Impaired skeletal muscle function has important clinical outcome implications for survivors of critical illness. Previous studies employing volitional manual muscle testing for diagnosing intensive care unit-acquired weakness (ICU-AW) during the early stages of critical illness have only provided limited data on outcome. This study aimed to determine inter-observer agreement and clinical predictive value of the Medical Research Council sum score (MRC-SS) test in critically ill patients.Study 1: Inter-observer agreement for ICU-AW between two clinicians in critically ill patients within ICU (n = 20) was compared with simulated presentations (n = 20). Study 2: MRC-SS at awakening in an unselected sequential ICU cohort was used to determine the clinical predictive value (n = 94) for outcomes of ICU and hospital mortality and length of stay.Although the intra-class correlation coefficient (ICC) for MRC-SS in the ICU was 0.94 (95% CI 0.85-0.98), ? statistic for diagnosis of ICU-AW (MRC-SS <48/60) was only 0.60 (95% CI 0.25-0.95). Agreement for simulated weakness presentations was almost complete (ICC 1.0 (95% CI 0.99-1.0), with a ? statistic of 1.0 (95% CI 1.0-1.0)). There was no association observed between ability to perform the MRC-SS and clinical outcome and no association between ICU-AW and mortality. Although ICU-AW demonstrated limited positive predictive value for ICU (54.2%; 95% CI 39.2-68.6) and hospital (66.7%; 95% CI 51.6-79.6) length of stay, the negative predictive value for ICU length of stay was clinically acceptable (88.2%; 95% CI 63.6-98.5).These data highlight the limited clinical applicability of volitional muscle strength testing in critically ill patients. Alternative non-volitional strategies are required for assessment and monitoring of muscle function in the early stages of critical illness.
Project description:Skeletal muscle aging is a multifactorial process strictly related to progressive weakness. One of the results that were focused on was the fiber phenotype modification and their loss. The physiological muscle recruitment to contraction, basically prosecuted under volitional control, can also be engaged by means of Neuromuscular Electrical Stimulation (NMES). Knowing that the NMES is effective in improving muscle strength in active healthy elderly, the aim was to investigate which physiological modifications were able to produce in the Vastus lateralis muscle and the pathways involved. It was found that NMES increased the cross sectional area and the isometric strength of type II myofibers together with the activated myogenic pathway in order to shift glycolytic toward the oxidative phenotype II myofibers, at a molecular level and with an increase of maximal voluntary contraction (MVC) at a functional level. Using the TaqMan low density array on 48 different genes, we found that NMES specific gene regulation highlighted: (i) increased protein synthesis with respect to protein degradation; (ii) the activation of an apoptotic pathway involved in the differentiation process; (iii) increased regeneration signals; (iv) oxidative enzyme regulation. These pathways were validated via confirmatory RT-PCR for genes involved in the regeneration process as well as Myosin isoforms. We also investigated the oxidative stress status analyzing superoxide anion levels, the protein expression of two different superoxide dismutase and the activity of both catalase and superoxide anion dismutase, being two main antioxidant enzymes. In conclusion, data demonstrates that NMES is effective in producing physiological adaptation on Vastus Lateralis of active healthy elderly as well as providing new insights for further research on elderly who experienced muscle detriment for periodic or permanent immobility.
Project description:As the population ages and critical care advances, a growing number of survivors of critical illness will be at risk for intensive care unit (ICU)-acquired weakness. Bed rest, which is common in the ICU, causes adverse effects, including muscle weakness. Consequently, patients need ICU-based interventions focused on the muscular system. Although emerging evidence supports the benefits of early rehabilitation during mechanical ventilation, additional therapies may be beneficial. Neuromuscular electrical stimulation (NMES), which can provide some muscular activity even very early during critical illness, is a promising modality for patients in the ICU.The objectives of this article are to discuss the implications of bed rest for patients with critical illness, summarize recent studies of early rehabilitation and NMES in the ICU, and describe a protocol for a randomized, phase II pilot study of NMES in patients receiving mechanical ventilation.The study was a randomized, sham-controlled, concealed, phase II pilot study with caregivers and outcome assessors blinded to the treatment allocation.The study setting will be a medical ICU.The study participants will be patients who are receiving mechanical ventilation for 1 day or more, who are expected to stay in the ICU for an additional 2 days or more, and who meet no exclusion criteria.The intervention will be NMES (versus a sham [control] intervention) applied to the quadriceps, tibialis anterior, and gastrocnemius muscles for 60 minutes per day.Lower-extremity muscle strength at hospital discharge will be the primary outcome measure.Muscle strength is a surrogate measure, not a patient-centered outcome. The assessments will not include laboratory, genetic, or histological measures aimed at a mechanistic understanding of NMES. The optimal duration or dose of NMES is unclear.If NMES is beneficial, the results of the study will help advance research aimed at reducing the burden of muscular weakness and physical disability in survivors of critical illness.
Project description:ICU acquired weakness (ICUAW) is a common complication of critical illness characterized by structural and functional impairment of skeletal muscle. The resulting physical impairment may persist for years after ICU discharge, with few patients regaining functional independence. Elucidating molecular mechanisms underscoring sustained ICUAW is crucial to understanding outcomes linked to different morbidity trajectories as well as for the development of novel therapies. Quadriceps muscle biopsies and functional measures of muscle strength and mass were obtained at 7 days and 6 months post-ICU discharge from a cohort of ICUAW patients. Unsupervised co-expression network analysis of transcriptomic profiles identified discrete modules of co-expressed genes associated with the degree of muscle weakness and atrophy in early and sustained ICUAW. Modules were enriched for genes involved in skeletal muscle regeneration and extracellular matrix deposition. Collagen deposition in persistent ICUAW was confirmed by histochemical stain. Modules were further validated in an independent cohort of critically ill patients with sepsis-induced multi-organ failure and a porcine model of ICUAW, demonstrating disease-associated conservation across species and peripheral muscle type. Our findings provide a pathomolecular basis for sustained ICUAW, implicating aberrant expression of distinct skeletal muscle structural and regenerative genes in early and persistent ICUAW.
Project description:ICU acquired weakness (ICUAW) is a complication of critical illness characterized by structural and functional impairment of skeletal muscle that may persist for years after ICU discharge with many survivors developing protracted courses with few regaining functional independence. Elucidating molecular mechanisms underscoring sustained ICUAW is crucial to understanding outcomes linked to different morbidity trajectories as well as for the development of novel therapies. Quadriceps muscle biopsies and functional measures of muscle strength and mass were obtained at 7 days and 6 months post-ICU discharge from a cohort of ICUAW patients. Unsupervised co-expression network analysis of transcriptomic profiles identified discrete modules of co-expressed genes associated with the degree of muscle weakness and atrophy in early and sustained ICUAW. Modules were enriched for genes involved in skeletal muscle regeneration and extracellular matrix deposition. Collagen deposition in persistent ICUAW was confirmed by histochemical stain. Modules were further validated in an independent cohort of critically ill patients with sepsis-induced multi-organ failure and a porcine model of ICUAW, demonstrating disease-associated conservation across species and peripheral muscle type. Our findings provide a pathomolecular basis for sustained ICUAW, implicating aberrant expression of distinct skeletal muscle structural and regenerative genes in early and persistent ICUAW. Total RNA was extracted from approximately 200mg of quadriceps muscle (vastus lateralis) tissue in patients with Intensive care unit (ICU) acquired weakness (ICUAW) at day 7 post-ICU discharge (D7) and month 6 post-ICU discharge (M6), and from healthy controls (C)