Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial

Objectives: As the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass. Design: Randomized controlled trial. Setting: Tertiary mixed ICU. Patients: Adult patients admitted for septic shock within the first 72 hours. Interventions: Patients were assigned randomly into two groups. The control group benefited from manual mobilization once a day. The intervention group had twice daily sessions of both manual mobilization and 30-minute passive/active cycling therapy. Measurements and Main Results: Skeletal muscle biopsies and electrophysiology testing were performed at day 1 and day 7. Muscle biopsies were analyzed for histology and molecular components of signaling pathways regulating protein synthesis and degradation as well as inflammation markers. Hemodynamic values and patient perception were collected during each session. Twenty-one patients were included. Three died before the second muscle biopsy. Ten patients in the control and eight in the intervention group were analyzed. Markers of the catabolic ubiquitin-proteasome pathway, muscle atrophy F-box and muscle ring finger-1 messenger RNA, were reduced at day 7 only in the intervention group, but without difference between groups (muscle atrophy F-box: –7.3% ± 138.4% in control vs –56.4% ± 37.4% in intervention group; p = 0.23 and muscle ring finger-1: –30.8% ± 66.9% in control vs –62.7% ± 45.5% in intervention group; p = 0.15). Muscle fiber cross-sectional area (µm2) was preserved by exercise (–25.8% ± 21.6% in control vs 12.4% ± 22.5% in intervention group; p = 0.005). Molecular regulations suggest that the excessive activation of autophagy due to septic shock was lower in the intervention group, without being suppressed. Markers of anabolism and inflammation were not modified by the intervention, which was well tolerated by the patients. Conclusions: Early physical therapy during the first week of septic shock is safe and preserves muscle fiber cross-sectional area. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. This work was performed at ICU, Saint Luc university hospital, Université catholique de Louvain (UCL), Brussels, Belgium. Clinical trial registered with www.clinicaltrials.gov (NCT01787045). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by funds from the "Department of Critical Care Medicine of Saint Luc University Hospital." During study inclusions, the ICU received a lending from RECK-Technik GmbH & Co. (KG, 88422 Betzenweiler, Germany) of the motorized cycling device MOTOmed Viva2 with MOTOmed sam2 training analysis program. Drs. Hickman and Laterre disclosed that, during study inclusions, the ICU received a lending from RECK-Technik GmbH & Co. (KG, 88422 Betzenweiler, Germany) of the motorized cycling device MOTOmed Viva2 with MOTOmed sam2 training analysis program (the company RECK-Technik GmbH & Co had no role in the study design, conduction of the study, analyses, and article preparation). The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Pierre-François Laterre, MD, ICU, Department of Critical Care Medicine, Saint Luc University Hospital, Université catholique de Louvain (UCL), Avenue Hippocrate 10, 1200 Brussels, Belgium. E-mail: pierre-francois.laterre@uclouvain.be Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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