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

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.

journal_name

Chest

journal_title

Chest

authors

Petrof BJ

doi

10.1016/j.chest.2018.08.1028

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1395-1403

issue

6

eissn

0012-3692

issn

1931-3543

pii

S0012-3692(18)32242-6

journal_volume

154

pub_type

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