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      Effects of early, combined endurance and resistance training in mechanically ventilated, critically ill patients: A randomised controlled trial

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          Abstract

          Introduction

          Neuromuscular weakness resulting in severe functional impairment is common in critical care survivors. This study aimed to evaluate effects of an early progressive rehabilitation intervention in mechanically ventilated adults at risk.

          Methods

          This was a parallel, two-arm, assessor-blinded, randomised controlled trial with 6-months follow-up that was conducted in a mixed ICU of an academic centre in Switzerland. Previously independent, mechanically ventilated, critically ill adults with expected critical care stay ≥72 hours (n = 115) were randomised to a control group receiving standard physiotherapy including early mobilisation or to an experimental group with early endurance and resistance training combined with mobilisation. Primary endpoints were functional capacity (6-Minute Walk Distance) and functional independence (Functional Independence Measure) at hospital discharge. Secondary endpoints including muscle strength were assessed at critical care discharge. Safety was monitored closely by standard monitoring and predefined adverse events.

          Results

          Physiotherapy started within 48 hours of critical care admission while 97% of participants were still ventilated and 68% on inotropes. Compared to the control group (n = 57), the experimental group (n = 58) received significantly more physiotherapy (sessions: 407 vs 377, p<0.001; time/session: 25min vs 18min, p<0.001) and had less days with sedation (p<0.001). Adverse events were rare (0.6%) and without consequences. There were no significant between-group differences in 6-Minute Walk Distance (experimental 123m (IQR 25–280) vs control 100m (IQR 0–300); p = 0.542) or functional independence (98 (IQR 66–119) vs 98 (IQR 18–115); p = 0.308). Likewise, no differences were found for the secondary outcomes, except a trend towards improved mental health in the experimental group after 6 months (84 (IQR 68–88) vs 70 (IQR 64–76); p = 0.023).

          Conclusions

          Early endurance and resistance training in mechanically ventilated, intensive care patients does not improve functional capacity or independence at hospital discharge compared to early standard physiotherapy but may improve mental health 6-months after critical care discharge.

          Trial registration

          German Clinical Trials Register (DRKS): DRKS00004347, registered on 10 September 2012.

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          Most cited references35

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          Pulmonary rehabilitation for chronic obstructive pulmonary disease.

          Widespread application of pulmonary rehabilitation (also known as respiratory rehabilitation) in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function (health-related quality of life, functional and maximal exercise capacity) attributable to the programmes. This review updates the review reported in 2006.
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            Paresis acquired in the intensive care unit: a prospective multicenter study.

            Although electrophysiologic and histologic neuromuscular abnormalities are common in intensive care unit (ICU) patients, the clinical incidence of ICU-acquired neuromuscular disorders in patients recovering from severe illness remains unknown. To assess the clinical incidence, risk factors, and outcomes of ICU-acquired paresis (ICUAP) during recovery from critical illness in the ICU and to determine the electrophysiologic and histologic patterns in patients with ICUAP. Prospective cohort study conducted from March 1999 to June 2000. Three medical and 2 surgical ICUs in 4 hospitals in France. All consecutive ICU patients without preexisting neuromuscular disease who underwent mechanical ventilation for 7 or more days were screened daily for awakening. The first day a patient was considered awake was day 1. Patients with severe muscle weakness on day 7 were considered to have ICUAP. Incidence and duration of ICUAP, risk factors for ICUAP, and comparative duration of mechanical ventilation between ICUAP and control patients. Among the 95 patients who achieved satisfactory awakening, the incidence of ICUAP was 25.3% (95% confidence interval [CI], 16.9%-35.2%). All ICUAP patients had a sensorimotor axonopathy, and all patients who underwent a muscle biopsy had specific muscle involvement not related to nerve involvement. The median duration of ICUAP after day 1 was 21 days. Mean (SD) duration of mechanical ventilation after day 1 was significantly longer in patients with ICUAP compared with those without (18.2 [36.3] vs 7.6 [19.2] days; P =.03). Independent predictors of ICUAP were female sex (odds ratio [OR], 4.66; 95% CI, 1.19-18.30), the number of days with dysfunction of 2 or more organs (OR, 1.28; 95% CI, 1.11-1.49), duration of mechanical ventilation (OR, 1.10; 95% CI, 1.00-1.22), and administration of corticosteroids (OR, 14.90; 95% CI, 3.20-69.80) before day 1. Identified using simple bedside clinical criteria, ICUAP was frequent during recovery from critical illness and was associated with a prolonged duration of mechanical ventilation. Our findings suggest an important role of corticosteroids in the development of ICUAP.
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              Physical complications in acute lung injury survivors: a two-year longitudinal prospective study.

              Survivors of severe critical illness frequently develop substantial and persistent physical complications, including muscle weakness, impaired physical function, and decreased health-related quality of life. Our objective was to determine the longitudinal epidemiology of muscle weakness, physical function, and health-related quality of life and their associations with critical illness and ICU exposures.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 November 2018
                2018
                : 13
                : 11
                : e0207428
                Affiliations
                [1 ] Department of Physiotherapy, Inselspital, Bern University Hospital, Bern, Switzerland
                [2 ] Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
                University of Bern, SWITZERLAND
                Author notes

                Competing Interests: SE, MLV, GL declare that they have no competing interests. JT and SMJ report the following potential conflicts of interest: The Department of Intensive Care Medicine has, or has had in the past, research contracts with Orion Corporation, Abbott Nutrition International, B. Braun Medical AG, CSEM SA, Edwards Lifesciences Services GmbH, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical Research AG and research & development/consulting contracts with Edwards Lifesciences SA, Maquet Critical Care AB, and Nestlé. The money was paid into a departmental fund; JT and SMJ received no personal financial gain. The Department of Intensive Care Medicine has received unrestricted educational grants from the following organizations for organizing a quarterly postgraduate educational symposium, the Berner Forum for Intensive Care (until 2015): Fresenius Kabi, gsk, MSD, Lilly, Baxter, astellas, AstraZeneca, B | Braun, CSL Behring, Maquet, Novartis, Covidien, Nycomed, Pierre Fabre Pharma AG (formerly known as RobaPharm), Pfizer, Orion Pharma, Bard Medica S.A., Abbott AG, Anandic Medical Systems. The Department of Intensive Care Medicine has received unrestricted educational grants from the following organizations for organizing bi-annual postgraduate courses in the fields of critical care ultrasound, management of ECMO and mechanical ventilation: Pierre Fabre Pharma AG (formerly known as RobaPharm), Pfizer AG, Bard Medica S.A., Abbott AG, Anandic Medical Systems, PanGas AG Healthcare, Orion Pharma, Bracco, Edwards Lifesciences AG, Hamilton Medical AG, Fresenius Kabi (Schweiz) AG, Getinge Group Maquet AG, Dräger Schweiz AG, Teleflex Medical GmbH. No author was employed by any of these companies. None of the companies played a role in this study. Our relationship with the companies does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-7379-7343
                http://orcid.org/0000-0003-4742-4225
                Article
                PONE-D-18-17676
                10.1371/journal.pone.0207428
                6235392
                30427933
                3f5d1bf7-aeec-462d-807a-2b99ec39d100
                © 2018 Eggmann 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
                : 17 June 2018
                : 30 October 2018
                Page count
                Figures: 2, Tables: 5, Pages: 19
                Funding
                This study was self-funded and supported by the Departments of Physiotherapy and Intensive Care Medicine at the Inselspital, Bern University Hospital, Bern, Switzerland. None of the authors received funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Health Care
                Physiotherapy
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Intensive Care Units
                Medicine and Health Sciences
                Public and Occupational Health
                Physical Activity
                Physical Fitness
                Exercise
                Strength Training
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                Sports and Exercise Medicine
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                Biology and Life Sciences
                Sports Science
                Sports and Exercise Medicine
                Exercise
                Strength Training
                Medicine and Health Sciences
                Mental Health and Psychiatry
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                Pharmacology
                Sedation
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                Health Care
                Health Care Facilities
                Hospitals
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                Public and Occupational Health
                Physical Activity
                Physical Fitness
                Exercise
                Medicine and Health Sciences
                Sports and Exercise Medicine
                Exercise
                Biology and Life Sciences
                Sports Science
                Sports and Exercise Medicine
                Exercise
                Medicine and Health Sciences
                Clinical Medicine
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                Randomized Controlled Trials
                Medicine and Health Sciences
                Pharmacology
                Drug Research and Development
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                The minimal dataset has been anonymized and are within the Supporting Information files.

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