Abstract / Summary
Abstract Rosà and colleagues recently proposed that mechanical ventilation (MV) may not be the primary driver of diaphragm dysfunction in critically ill patients, advocating the term “critical illness-associated diaphragm dysfunction” (CIADD) over “ventilator-induced diaphragm dysfunction” (VIDD). While we support distinguishing VIDD from CIADD, we contend that the review’s central conclusion underestimates the causal role of MV itself. This commentary addresses three questions in turn. First, does MV injure the diaphragm under controlled conditions? Here the evidence is strong: brain-dead donor studies—dismissed by the authors as a “unique patient category”—are a uniquely informative, though not pure, human model of controlled MV exposure, and their dismissal creates an unfalsifiable position. Second, how much does MV contribute to diaphragm dysfunction in critically ill patients? This is considerably less certain: the molecular abnormalities observed in critically ill patients (ubiquitin-proteasome activation, RyR1 calcium leak, mitochondrial oxidative stress) coincide with pathways that MV reliably induces in controlled animal experiments, providing biological plausibility—though not proof—that MV contributes to the molecular phenotype of critical illness. Third, do MV and critical illness interact? We propose that CIADD should serve as an umbrella term encompassing VIDD as a distinct mechanistic subtype—rather than replacing it—analogous to how “pneumonia” subsumes VAP, HAP, and CAP, and we propose three differentiated model types for future research: pure VIDD models, pure CIADD models, and combined models with factorial design. VIDD and CIADD are mechanistically distinct but interacting entities. Future research should employ models that minimize confounding from critical illness to isolate ventilation-specific injury pathways. Importantly, establishing that VIDD exists is not equivalent to establishing that preventing VIDD is beneficial; clinical trials are needed to demonstrate the feasibility and benefit of diaphragm-protective strategies. Diminishing MV’s role risks undermining the mechanistic foundation of diaphragm-protective ventilation strategies.