Effects of High Positive End-expiratory Pressure Over Abdominal Venous Congestion, Visceral Edema, and Organ Dysfunction, in Mechanically Ventilated ARDS Patients: a Randomized Cross-over Study

Acute respiratory distress syndrome (ARDS), ventilation-induced lung injury (VILI), and protective mechanical ventilation (MV) are key aspects of respiratory failure management. ARDS is an inflammatory pulmonary edema caused by alveolar and endothelial injury, characterized by a breakdown in the alveolar-capillary barrier that results in the collapse of alveolar spaces. Clinically, ARDS manifests as acute hypoxemia, bilateral X-ray infiltrates, and decreased lung compliance. A global epidemiological study identified a 10.4% prevalence of ARDS among ICU admissions, with ICU and hospital mortality rates of 35.3% and 40.0%, respectively. ARDS survivors often experience long-term morbidity affecting the cardiovascular system, nerves, muscles, and the central nervous system. During the SARS-CoV-2 pandemic, ARDS statistics surged, placing an unprecedented burden on healthcare systems worldwide.

Mechanical ventilation serves as the primary supportive therapy for ARDS but can also exacerbate lung damage, a phenomenon referred to as VILI. VILI is primarily caused by alveolar overdistension (volutrauma) due to high tidal volumes and repeated opening and closing of unstable alveoli (atelectrauma) associated with insufficient positive end-expiratory pressure (PEEP). The late 1990s saw the first clinical trials definitively showing that lower tidal volumes improved survival rates in ARDS patients, highlighting the importance of VILI in determining ARDS outcomes. VILI also triggers a biological response characterized by lung and systemic inflammation, as well as damage to distant organs (biotrauma), which explains the role of protective ventilatory strategies in preventing organ failure and mortality.

In ARDS, a significant portion of lung units becomes unstable, collapses, and is excluded from ventilation. The collapse reduces the aerated lung size, resembling what is referred to as the "baby lung." Consequently, only this small "baby lung" receives the tidal volume, making it prone to overstretching and excessive strain. Moreover, lung infiltrates are unevenly distributed, concentrating exaggerated tensions in the healthy alveoli surrounding collapsed regions. To prevent VILI, two main ventilatory strategies have been employed: reducing tidal volume to mitigate volutrauma and optimizing PEEP to decrease atelectrauma, strain, and the uneven distribution of forces. While the protective role of low tidal volume is well-established, the role of PEEP remains a subject of ongoing debate.

The Role of PEEP in Protective Mechanical Ventilation

PEEP is defined as the maintenance of positive pressure at the airway opening at the end of expiration. Since the initial description of ARDS in 1967, PEEP has been observed to improve hypoxemia in ARDS patients by preventing alveolar collapse and recruiting collapsed lung regions, thus reducing intrapulmonary shunt. Another significant effect of PEEP is the reduction of the primary mechanisms responsible for VILI: 1) increasing the size of the "baby lung" through lung recruitment, reducing lung strain and stress; 2) keeping unstable alveoli open at end-expiration, thereby reducing opening and closing; and 3) promoting more uniform ventilation to decrease lung inhomogeneities and reduce injury at the interfaces between aerated and collapsed lung tissue.