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      Lactate production without hypoxia in skeletal muscle during electrical cycling: Crossover study of femoral venous-arterial differences in healthy volunteers

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          Abstract

          Background

          Aim of the study was to compare metabolic response of leg skeletal muscle during functional electrical stimulation-driven unloaded cycling (FES) to that seen during volitional supine cycling.

          Methods

          Fourteen healthy volunteers were exposed in random order to supine cycling, either volitional (10-25-50 W, 10 min) or FES assisted (unloaded, 10 min) in a crossover design. Whole body and leg muscle metabolism were assessed by indirect calorimetry with concomitant repeated measurements of femoral venous-arterial differences of blood gases, glucose, lactate and amino acids.

          Results

          Unloaded FES cycling, but not volitional exercise, led to a significant increase in across-leg lactate production (from -1.1±2.1 to 5.5±7.4 mmol/min, p<0.001) and mild elevation of arterial lactate (from 1.8±0.7 to 2.5±0.8 mM). This occurred without widening of across-leg veno-arterial (VA) O 2 and CO 2 gaps. Femoral SvO 2 difference was directly proportional to VA difference of lactate (R 2 = 0.60, p = 0.002). Across-leg glucose uptake did not change with either type of exercise. Systemic oxygen consumption increased with FES cycling to similarly to 25W volitional exercise (138±29% resp. 124±23% of baseline). There was a net uptake of branched-chain amino acids and net release of Alanine from skeletal muscle, which were unaltered by either type of exercise.

          Conclusions

          Unloaded FES cycling, but not volitional exercise causes significant lactate production without hypoxia in skeletal muscle. This phenomenon can be significant in vulnerable patients’ groups.

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          Most cited references43

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          The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill.

          Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca(2+) dysregulation is present through altered Ca(2+) homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.
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            Early mobilization and recovery in mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study

            Introduction The aim of this study was to investigate current mobilization practice, strength at ICU discharge and functional recovery at 6 months among mechanically ventilated ICU patients. Method This was a prospective, multi-centre, cohort study conducted in twelve ICUs in Australia and New Zealand. Patients were previously functionally independent and expected to be ventilated for >48 hours. We measured mobilization during invasive ventilation, sedation depth using the Richmond Agitation and Sedation Scale (RASS), co-interventions, duration of mechanical ventilation, ICU-acquired weakness (ICUAW) at ICU discharge, mortality at day 90, and 6-month functional recovery including return to work. Results We studied 192 patients (mean age 58.1 ± 15.8 years; mean Acute Physiology and Chronic Health Evaluation (APACHE) (IQR) II score, 18.0 (14 to 24)). Mortality at day 90 was 26.6% (51/192). Over 1,351 study days, we collected information during 1,288 planned early mobilization episodes in patients on mechanical ventilation for the first 14 days or until extubation (whichever occurred first). We recorded the highest level of early mobilization. Despite the presence of dedicated physical therapy staff, no mobilization occurred in 1,079 (84%) of these episodes. Where mobilization occurred, the maximum levels of mobilization were exercises in bed (N = 94, 7%), standing at the bed side (N = 11, 0.9%) or walking (N = 26, 2%). On day three, all patients who were mobilized were mechanically ventilated via an endotracheal tube (N = 10), whereas by day five 50% of the patients mobilized were mechanically ventilated via a tracheostomy tube (N = 18). In 94 of the 156 ICU survivors, strength was assessed at ICU discharge and 48 (52%) had ICU-acquired weakness (Medical Research Council Manual Muscle Test Sum Score (MRC-SS) score <48/60). The MRC-SS score was higher in those patients who mobilized while mechanically ventilated (50.0 ± 11.2 versus 42.0 ± 10.8, P = 0.003). Patients who survived to ICU discharge but who had died by day 90 had a mean MRC score of 28.9 ± 13.2 compared with 44.9 ± 11.4 for day-90 survivors (P <0.0001). Conclusions Early mobilization of patients receiving mechanical ventilation was uncommon. More than 50% of patients discharged from the ICU had developed ICU-acquired weakness, which was associated with death between ICU discharge and day-90. Clinical trial registration ClinicalTrials.gov NCT01674608. Registered 14 August 2012.
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              The impact of extended bed rest on the musculoskeletal system in the critical care environment

              Prolonged immobility is harmful with rapid reductions in muscle mass, bone mineral density and impairment in other body systems evident within the first week of bed rest which is further exacerbated in individuals with critical illness. Our understanding of the aetiology and secondary consequences of prolonged immobilization in the critically ill is improving with recent and ongoing research to establish the cause, effect, and best treatment options. This review aims to describe the current literature on bed rest models for examining immobilization-induced changes in the musculoskeletal system and pathophysiology of immobilisation in critical illness including examination of intracellular signalling processes involved. Finally, the review examines the current barriers to early activity and mobilization and potential rehabilitation strategies, which are being, investigated which may reverse the effects of prolonged bed rest. Addressing the deleterious effects of immobilization is a major step in treatment and prevention of the public health issue, that is, critical illness survivorship.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: Software
                Role: InvestigationRole: MethodologyRole: Project administrationRole: Software
                Role: InvestigationRole: SoftwareRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Software
                Role: ConceptualizationRole: Formal analysisRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 March 2019
                2019
                : 14
                : 3
                : e0200228
                Affiliations
                [1 ] Department of Anaesthesia and Intensive Care Medicine, Kralovske Vinohrady University Hospital and The Third Faculty of Medicine, Charles University, Prague, Czech Republic
                [2 ] 2 nd Department of Internal Medicine, Kralovske Vinohrady University Hospital and The Third Faculty of Medicine, Charles University, Prague, Czech Republic
                [3 ] Department of Rehabilitation, Kralovske Vinohrady University Hospital and The Third Faculty of Medicine, Charles University, Prague, Czech Republic
                [4 ] Department of Hygiene, The Third Faculty of Medicine, Charles University, Prague, Czech Republic
                University of Tennessee Health Science Center College of Graduate Health Sciences, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-7995-5947
                http://orcid.org/0000-0003-1617-0656
                Article
                PONE-D-18-18284
                10.1371/journal.pone.0200228
                6396965
                30822305
                6a6e0abd-f681-40e9-a6ec-461d49cdb2de
                © 2019 Gojda et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 June 2018
                : 11 February 2019
                Page count
                Figures: 4, Tables: 1, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003243, Ministerstvo Zdravotnictví Ceské Republiky;
                Award ID: 16-28663A
                Award Recipient :
                The study was supported by Ministry of Health of the Czech Rep. grant AZV 16-28663A ( http://www.azvcr.cz/en). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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