Diaphragm Weakness in the Critically Ill: Basic Mechanisms Reveal Therapeutic Opportunities

Chest
Basil J Petrof

Abstract

The diaphragm is the primary muscle of inspiration. Its capacity to respond to the load imposed by pulmonary disease is a major determining factor both in the onset of ventilatory failure and in the ability to successfully separate patients from ventilator support. It has recently been established that a very large proportion of critically ill patients exhibit major weakness of the diaphragm, which is associated with poor clinical outcomes. The two greatest risk factors for the development of diaphragm weakness in critical illness are the use of mechanical ventilation and the presence of sepsis. Loss of force production by the diaphragm under these conditions is caused by a combination of defective contractility and reduced diaphragm muscle mass. Importantly, many of the same molecular mechanisms are implicated in the diaphragm dysfunction associated with both mechanical ventilation and sepsis. This review outlines the primary cellular mechanisms identified thus far at the nexus of diaphragm dysfunction associated with mechanical ventilation and/or sepsis, and explores the potential for treatment or prevention of diaphragm weakness in critically ill patients through therapeutic manipulation of these final common pathway targets.

Citations

Feb 12, 2019·Intensive Care Medicine·Ewan C Goligher
Jan 17, 2020·Journal of Applied Physiology·Gerald S SupinskiLeigh Ann P Callahan
Jun 10, 2020·American Journal of Respiratory and Critical Care Medicine·Ewan C GoligherLaurent Brochard
May 3, 2020·Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society·Michael Swash, Mamede de Carvalho
May 17, 2019·Anesthesiology·Emmanuel VivierArmand Mekontso Dessap
Apr 13, 2021·Frontiers in Physiology·Justine Frija-MassonMarie-Pia d'Ortho
Jun 22, 2021·SN Comprehensive Clinical Medicine·Abdallah FayssoilBenjamin Davido
Jul 2, 2021·Critical Care : the Official Journal of the Critical Care Forum·Benjamin CrulliGuillaume Emeriaud
Jul 4, 2021·Annals of Intensive Care·Sebastien PreauPeter Radermacher
Jul 14, 2021·American Journal of Respiratory and Critical Care Medicine·Yassir AarabBoris Jung

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