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.

Effects of exercise preconditioning and HSP72 on diaphragm muscle function during mechanical ventilation

“…Preclinical models of MV provide important information regarding the signalling pathways required for VIDD. The rat model of MV is clinically significant because it greatly mimics the diaphragm weakness observed in mechanically ventilated patients, including during conditions where diaphragm weakness may be exacerbated as a result of ICU‐acquired comorbidities (i.e. sepsis) .…”

Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems

“…Under acute inflammation such as sepsis, the presence of muscular weakness including the dysfunction of respiratory muscles has been reported in animal models and patients . Under these conditions, the pathophysiology of muscle weakness such as proteolysis has been elucidated to a large extent using animal models .…”

Muscle wasting and sarcopenia in heart failure: a brief overview of the current literature

“…30 The human skeletal muscle proteome project is currently underway to characterize muscle proteins and the way they change during ageing and disease. 36 Cheung et al recently reported that testosterone deprivation selectively decreases lower limb muscle function, predominantly affecting muscles that support body weight and muscles that accelerate the body forward during walking and mediate balance. 33 Anorexia is likewise very prevalent in patients with HF as assessed using a 6-point Likert scale.…”