title: Dysfunction of respiratory muscles in critically ill patients on the intensive care unit.
abstract: Muscular weakness and muscle wasting may often be observed in critically ill patients on intensive care units (ICUs) and may present as failure to wean from mechanical ventilation. Importantly, mounting data demonstrate that mechanical ventilation itself may induce progressive dysfunction of the main respiratory muscle, i.e. the diaphragm. The respective condition was termed 'ventilator-induced diaphragmatic dysfunction' (VIDD) and should be distinguished from peripheral muscular weakness as observed in 'ICU-acquired weakness (ICU-AW)'. Interestingly, VIDD and ICU-AW may often be observed in critically ill patients with, e.g. severe sepsis or septic shock, and recent data demonstrate that the pathophysiology of these conditions may overlap. VIDD may mainly be characterized on a histopathological level as disuse muscular atrophy, and data demonstrate increased proteolysis and decreased protein synthesis as important underlying pathomechanisms. However, atrophy alone does not explain the observed loss of muscular force. When, e.g. isolated muscle strips are examined and force is normalized for cross-sectional fibre area, the loss is disproportionally larger than would be expected by atrophy alone. Nevertheless, although the exact molecular pathways for the induction of proteolytic systems remain incompletely understood, data now suggest that VIDD may also be triggered by mechanisms including decreased diaphragmatic blood flow or increased oxidative stress. Here we provide a concise review on the available literature on respiratory muscle weakness and VIDD in the critically ill. Potential underlying pathomechanisms will be discussed before the background of current diagnostic options. Furthermore, we will elucidate and speculate on potential novel future therapeutic avenues.
authors.affiliation: Department of Intensive Care Medicine, Inselspital University Hospital of Bern Bern Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Berger
authors.affiliation: Department of Intensive Care Medicine, Inselspital University Hospital of Bern Bern Switzerland; Department of Clinical Cardiology, Inselspital University Hospital of Bern Bern Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bloechlinger
authors.affiliation: Department of Cardiology and Center for Innovative Clinical Trials University of Göttingen Göttingen Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.affiliation: Center for Stroke Research Berlin Charite Universitätsmedizin Berlin Berlin Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.affiliation: Department of Intensive Care Medicine, Inselspital University Hospital of Bern Bern Switzerland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Takala
authors.affiliation: Department of Neurosurgery and Dept. of Neurology, Inselspital University Hospital of Bern Bern Switzerland.
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Z'Graggen
authors.affiliation: Department of Intensive Care Medicine, Inselspital University Hospital of Bern Bern Switzerland.
authors.forename: Joerg C
authors.initials: JC
authors.lastname: Schefold
keywords: Cachexia; Diaphragm; ICU‐acquired weakness; Mechanical ventilation; Sepsis; VIDD; Weakness; weaning failure