Relevance of Ventilator-induced Diaphragm Dysfunction in ICU Patients

Abstract

Mechanical ventilation (MV), the most frequently used life-saving therapy in the intensive care unit (ICU) may, among other adverse effects, induce diaphragmatic dysfunction, or ventilator-induced diaphragm dysfunction (VIDD). The objective of the present review is to discuss the data that demonstrate the presence of VIDD, to detail the main pathologic findings and mechanisms of VIDD, and to discuss the relevance of VIDD in patients as well as the potential targets to prevent VIDD. In various animal species, <12 hours of controlled MV results in a dramatic reduction of diaphragm force production. Pathologic examination of ventilated diaphragms shows clear slow and fast muscle fiber atrophy as well as ultrastructural cell abnormalities involving myofibrillar and mitochondrial damage. The 2 main mechanisms involved in VIDD are oxidative stress as well as downregulation of proteosynthesis associated with the activation of major proteolytic systems (calpain, proteasome, caspase, and to a lesser extent, lysosome). Pathologic studies and biochemical analysis performed on the diaphragms of brain-dead organ donors, who are not per se ICU patients, undergoing prolonged MV have found similar features. Nonetheless, small-scale studies in ICU patients suggest that controlled MV might be associated with a certain level of diaphragm dysfunction in ICU patients. Although VIDD is a well-demonstrated phenomenon in animal models for controlled MV, its relevance in MV patients in the ICU remains questionable. Large-scale studies in humans are needed to establish the actual role of MV in the pathogenesis of an ICU-acquired diaphragm dysfunction.