Ventilator-Induced Lung Injury: The Unseen Challenge in Acute Respiratory Distress Syndrome Management

Summary of “Ventilator-Induced Lung Injury: The Unseen Challenge in Acute Respiratory Distress Syndrome Management” (Merola et al.)

Abstract Summary: Merola et al. comprehensively review ventilator-induced lung injury (VILI) within acute respiratory distress syndrome (ARDS) management, underscoring the complex interplay of pathophysiological mechanisms. The authors discuss traditional and emerging concepts such as volutrauma, barotrauma, atelectrauma, biotrauma, ergotrauma, and heterogeneous lung mechanics, highlighting current lung-protective strategies and novel personalized ventilation approaches aimed at reducing VILI and improving patient outcomes.

Mechanisms of Barotrauma and Volutrauma: The Role of Transpulmonary Pressure. This figure illustrates how transpulmonary pressure (Ptp)—the difference between alveolar pressure (Palv) and pleural pressure (Ppl)—determines the risk of alveolar overdistension in different clinical and physiological scenarios. (A) illustrates end-inspiration in a spontaneously breathing individual with healthy lungs. At this point, Palv remains at 0 cm H2O, while Ppl is negative (−10 cm H2O), resulting in a transpulmonary pressure (Ptp) of +10 cm H2O. (B) depicts the same spontaneously breathing individual with healthy lungs during passive positive-pressure ventilation, using the same tidal volume as in Panel A. Despite the change in ventilation mode, the degree of lung inflation is comparable, with a Palv of +10 cm H2O and a Ppl of 0 cm H2O, resulting in a Ptp of +10 cm H2O. (C) depicts the same healthy lung under active positive-pressure ventilation. Palv reaches +10 cm H2O, while the marked negative Ppl (−15 cm H2O) generated by the patient’s effort results in a Ptp of +25 cm H2O. (D) shows an intubated patient with acute respiratory distress syndrome (ARDS) and stiff lungs under passive positive-pressure MV. Despite a high Palv of +20 cm H2O, the Ppl rises to +15 cm H2O due to reduced lung compliance, resulting in a Ptp of only +15 cm H2O. (E) shows an intubated ARDS patient with a stiff chest wall (such as one with a pleural effusion, massive ascites, or severe obesity). In these patients, a significant portion of the ventilator-delivered pressure is used to inflate the chest wall rather than the lungs. As a result, the plateau pressure may be high, but so will the pleural pressure, maintaining the transpulmonary pressure at values that avoid the risk of alveolar overdistension. (F) shows an ARDS patient with marked dyspnea on mechanically assisted ventilation (e.g., pressure support ventilation). In such cases, a marked inspiratory effort causes a large negative pleural pressure swing, increasing transpulmonary pressure to potentially injurious levels, even if the airway pressure remains low (e.g., 20 cmH2O). These examples highlight the importance of assessing transpulmonary pressure—not just airway pressure—when evaluating the risk of ventilator-induced lung injury (VILI).

Key Points:

Introduction to VILI: Mechanical ventilation (MV) is essential in ARDS but can cause significant harm (VILI), historically known but clearly demonstrated clinically only after recognizing reduced mortality with lung-protective strategies.
Mechanisms of VILI (Barotrauma and Volutrauma): VILI occurs via multiple mechanisms, including barotrauma (high pressure), volutrauma (overdistension), and excessive transpulmonary pressure, which are closely interrelated rather than distinct entities.
Atelectrauma: The cyclic opening and collapse of alveoli (atelectrauma), exacerbated by surfactant dysfunction and dependent edema, significantly contributes to lung damage. Strategies that minimize repetitive alveolar collapse (e.g., higher PEEP) are protective but require careful titration.
Biotrauma: Mechanical ventilation can trigger inflammatory cascades (“biotrauma”), causing systemic inflammation and multiorgan failure. Clinical trials demonstrate lung-protective strategies significantly reduce systemic inflammation and multiorgan dysfunction.
Ergotrauma and Mechanical Power (MP): Mechanical power, incorporating tidal volume (VT), respiratory rate (RR), and inspiratory pressures, provides a comprehensive marker for ventilatory-induced stress. Excessive MP (>17 J/min) is linked to higher mortality rates, suggesting potential use in personalizing ventilation settings.
Personalized Ventilation: Lung-protective ventilation with low VT (4–6 mL/kg predicted body weight [PBW]) and tailored positive end-expiratory pressure (PEEP) is standard but may not suit all patients. Emerging approaches involve esophageal pressure measurements, electrical impedance tomography (EIT), and individualized ventilatory strategies.
Prone Positioning: Prone positioning redistributes lung aeration, reduces regional lung strain, improves oxygenation, and significantly reduces mortality in severe ARDS, particularly with prolonged sessions (>12–16 hours/day).
Ultra-Protective Ventilation and Extracorporeal Support: Ultra-protective ventilation strategies (VT <4 mL/kg PBW) facilitated by extracorporeal life support (ECLS), including extracorporeal carbon dioxide removal (ECCO₂R) and ECMO, show potential benefits but require careful management to avoid complications.
Biological Subphenotypes and Pharmacological Interventions: Distinct ARDS biological subphenotypes (hyperinflammatory vs. hypoinflammatory) respond differently to interventions. Emerging therapies like mesenchymal stem cells and targeted anti-inflammatory agents, though promising, require further validation.
Future Directions and Precision Medicine: Future ARDS management should integrate advanced monitoring (MP, transpulmonary pressure), biological phenotyping, and artificial intelligence tools. Personalized ventilation strategies, guided by patient-specific lung mechanics and real-time monitoring, hold promise for further reducing VILI and improving survival.

Biotrauma: The Inflammatory Cascade Triggered by Mechanical Lung Injury. This figure illustrates the pathophysiological mechanisms underlying biotrauma, a form of ventilator-induced lung injury (VILI) resulting from the mechanical stress of ventilation. Mechanical forces damage alveolar and airway structures, leading to the release of intracellular mediators from epithelial, endothelial, and immune cells. These mediators exert multiple effects: some directly injure lung tissue, while others activate intracellular signaling pathways that amplify inflammation and promote fibrotic remodeling. Key inflammatory mediators—such as tumor necrosis factor (TNF-a), interleukins (IL), and transforming growth factor (TGF)—serve as homing signals that recruit immune cells (e.g., neutrophils and macrophages) to the lungs. Once activated, these cells release additional proinflammatory and cytotoxic molecules, perpetuating tissue damage and inflammation. In acute respiratory distress syndrome (ARDS), increased alveolar–capillary permeability allows the translocation of harmful substances, including cytokines, bacteria, and lipopolysaccharides, into the bloodstream. This systemic spread contributes to multiorgan dysfunction and may ultimately result in organ failure and death. The figure emphasizes how localized mechanical injury can evolve into a self-sustaining and system-wide inflammatory process with life-threatening consequences.

Conclusion: Despite advances in understanding and managing VILI, significant challenges persist in identifying universally optimal ventilation strategies. A shift from standardized ventilation protocols to personalized, physiology-based, and phenotype-driven approaches, leveraging advanced monitoring technologies and precision medicine frameworks, is essential to further mitigate lung injury and enhance patient outcomes.

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Ventilator-Induced Lung Injury: The Unseen Challenge in Acute Respiratory Distress Syndrome Management

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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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