The contribution of mechanical ventilation to critical illness-associated diaphragm dysfunction: a critical appraisal

Although diaphragm dysfunction is increasingly recognized as a major contributor to morbidity and mortality in the intensive care unit, the physiological mechanisms leading to its development in mechanically ventilated patients are incompletely understood. Mechanical ventilation is often recognized as the main cause of the problem, delineating a paradigm known as ventilator-induced diaphragm dysfunction (VIDD). Yet, evidence on this causal relationship in ventilated critically ill patients is scarce, with direct experimental data mostly coming from animal models or brain-dead organ donors. In this narrative review, we provide a critical appraisal on the contribution of mechanical ventilation to diaphragm dysfunction and an integration with other major mechanisms involved in its development and trajectory over time. Examining this complex interplay is important, as it may support clinicians in adhering to expert consensus on diaphragm protective mechanical ventilation. First, the evidence for mechanisms potentially caused by mechanical ventilation, such as disuse atrophy, under- and over-assistance, PEEP and asynchronies is analyzed. Secondly, important contributors not directly explained by ventilator support, such as inflammation and sepsis, muscle hibernation and impaired calcium sensitivity of force are addressed. Finally, a summary of this complex scenario is provided together with clinical and research-oriented key messages, highlighting the reasons for which the term critical illness-associated diaphragm dysfunction may be more appropriate.