Ventilator-induced diaphragmatic dysfunction: pathophysiology, monitoring and advances in potential treatment and prevention.

Mechanical ventilation is a life-saving method for those critically ill patients with acute or chronic respiratory failure without assistance. However, even short-term mechanical ventilation can lead to alterations in the fibrous structure and reduced contraction force of the diaphragm, which is defined as ventilator-induced diaphragmatic dysfunction (VIDD). This condition is associated with various risks of adverse clinical outcomes. Research on mechanical ventilation-related respiratory mechanics helps us to understand the macroscopic myotrauma mechanisms of VIDD. Ongoing clinical trials into comprehensive management strategies for lung- and diaphragm-protective ventilation are continually refining respiratory therapy protocols in clinical practice. Although the cellular and molecular mechanisms are not fully defined, pathways involving mitochondrial oxidative stress have been identified as key contributors to disease progression, leading to both accelerated proteolysis and depressed protein synthesis. Additionally, research on the ubiquitin-proteasome pathway, lysosomal autophagy, calpain, caspase-3 and dysfunction of the ryanodine receptor-1 pathway is enhancing our understanding of the downstream mechanisms involved. Promising interventions based on these findings have yielded hopeful results in animal models for preventing VIDD. This review summarises the epidemiology and pathophysiological mechanisms of VIDD and advances in potential treatment and prevention.