• Cheryl E Hickmann, Diego Castanares-Zapatero, Louise Deldicque, Peter Van den Bergh, Gilles Caty, Annie Robert, Jean Roeseler, Marc Francaux, and Pierre-François Laterre.
• Department of Critical Care Medicine, Saint Luc University hospital, Université catholique de Louvain (UCL), Brussels, Belgium.
• Crit. Care Med. 2018 Sep 1; 46 (9): 1436-1443.

ObjectivesAs 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.DesignRandomized controlled trial.SettingTertiary mixed ICU.PatientsAdult patients admitted for septic shock within the first 72 hours.InterventionsPatients 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 ResultsSkeletal 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 (µm) 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.ConclusionsEarly physical therapy during the first week of septic shock is safe and preserves muscle fiber cross-sectional area.

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