• Respiratory Muscles

Mechanical ventilation is a life-saving ‘therapeutic’ intervention for patients with respiratory failure. The vast majority of critically ill patients are mechanically ventilated (MV) and a significant part of time is spent in weaning patients from mechanical ventilation. It is during weaning that the diaphragm becomes so important becoming a major pathophysiological determinant of weaning failure or success.1 ,2

Various insults can render the diaphragm weak in critically ill patients such as sepsis, multiorgan failure and/or inflammation, electrolyte disturbances, hyperinflation, to name a few out of a long list.3 Extensive animal research4 and few human studies5–8 have provided evidence that controlled mechanical ventilation (CMV), a form of ventilation where the ventilator assumes all the work of breathing and the respiratory muscles are theoretically completely unloaded, can also cause dysfunction of the diaphragm, an entity named ventilator-induced diaphragm dysfunction (VIDD).9

VIDD has been described in the laboratory in previously healthy animals subjected to CMV4 and in brain-dead patients free of infection and other derangements so as to be eligible for organ donation.5–8 The mechanisms of VIDD are not fully elucidated, but include muscle atrophy (lysosomal, autophagy, cysteine protease and ubiquitin–proteasome activation having all been described), oxidative stress, structural injury (disrupted myofibrils, lipid vacuoles and abnormally small and disrupted mitochondria), myofibre remodelling and mitochondrial dysfunction. The animal data have shown that these insults result in the decline of the pressure-generating capacity of the diaphragm, that is, reduced diaphragmatic contractility. The extent to which this happens in humans and thus is clinically relevant is largely unknown.

Much of the uncertainty in proving the concept that mechanical ventilation per se can cause contractile dysfunction of the diaphragm derives from the difficulty in accurately studying the performance of the diaphragm in critically ill patients. Diaphragm contractility in MV …