Maintaining end-expiratory transpulmonary pressure prevents worsening of ventilator-induced lung injury caused by chest wall constriction in surfactant-depleted rats*

Abstract

Objective To see whether in acute lung injury (ALI) 1) compression of the lungs caused by thoracoabdominal constriction degrades lung function and worsens ventilator-induced lung injury (VILI), and 2) maintaining end-expiratory transpulmonary pressure (Pl) by increasing positive end-expiratory pressure (PEEP) reduces the deleterious effects of chest wall constriction. Design Experimental study in rats. Setting Physiology laboratory. Interventions ALI was induced in 3 groups of 9 rats by saline lavage. Nine animals immediately sacrificed served as control group. Group L had lavage only, group LC had the chest wall constricted with an elastic binder, and group LCP had the same chest constriction but with PEEP raised to maintain end-expiratory Pl. After lavage, all groups were ventilated with the same pattern for 1½ hr. Measurements and Main Results Pl, measured with an esophageal balloon-catheter, lung volume changes, arterial blood gasses and pH were assessed during mechanical ventilation (MV). Lung wet-to-dry ratio (W/D), albumin, TNF-α, IL-1β, IL-6, IL-10, and MIP-2 in serum and bronchoalveolar lavage fluid (BALF), and serum E-selectin and von Willebrand Factor (vWF) were measured at the end of MV. Lavage caused hypoxemia and acidemia, increased lung resistance and elastance, and decreased end-expiratory lung volume. With prolonged MV, lung mechanics, hypoxemia, and W/D were significantly worse in group LC. Pro-inflammatory cytokines except E-selectin were elevated in serum and BALF in all groups, with significantly greater levels of TNF-α, IL-1β, and IL-6 in group LC, which also exhibited significantly worse bronchiolar injury and greater heterogeneity of airspace expansion at a fixed Pl than other groups. Conclusions Chest wall constriction in ALI reduces lung volume, worsens hypoxemia, and increases pulmonary edema, mechanical abnormalities, pro-inflammatory mediator release, and histological signs of VILI. Maintaining end-expiratory Pl at preconstriction levels by adding PEEP prevents these deleterious effects.

Esophageal pressure: research or clinical tool?

“…This strategy resulted in significantly higher applied PEEP, improved oxygenation and compliance, and a strong trend towards improved survival and shorter duration of mechanical ventilation compared with standard low tidal volume lung protective ARDSnet ventilation strategies [18]. An animal study using surfactant-depleted rats agreed with the rationale behind this study, finding that a strategy targeting positive end-expiratory PL maintained lung volumes, improved compliance, reduced hypoxemia and pulmonary edema, and decreased pro-inflammatory mediator release as well as histological signs of ventilation-induced lung injury (VILI) [19]. The newer multi-center randomized controlled trial uses higher PEEP in control patients to better replicate current clinical practices [20].…”

Conservative fluid management prevents age-associated ventilator induced mortality

“…Increased airspace enlargement values are associated with both increased age and pathophysiological conditions such as emphysema (23) and VILI (20). In our case, the differences we observed in the airspace enlargement values for the experimental groups represent the extent of the alveolar barrier injury/destruction resulting from mechanical ventilation.…”

Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives

“…This rationale was confirmed in animals with lung injury and different degrees of Pes elevation due to chest wall restriction. Targeting a positive endexpiratory P L in chest-restricted animals maintained lung volume and lung compliance, reduced hypoxemia and decreased pulmonary edema, mechanical abnormalities, pro-inflammatory mediator release and histological signs of ventilator-induced lung injury [24].…”