Abstract
The accepted protocol to ventilate patients with acute lung injury is to use low tidal volume (VT) in combination with recruitment maneuvers or positive end-expiratory pressure (PEEP). However, an important aspect of mechanical ventilation has not been considered: the combined effects of PEEP and ventilation modes on the integrity of the epithelium. Additionally, it is implicitly assumed that the best PEEP-VT combination also protects the epithelium. We aimed to investigate the effects of ventilation mode and PEEP on respiratory mechanics, peak airway pressures and gas exchange as well as on lung surfactant and epithelial cell integrity in mice with acute lung injury. HCl-injured mice were ventilated at PEEPs of 3 and 6 cmH2O with conventional ventilation (CV), CV with intermittent large breaths (CVLB) to promote recruitment, and a new mode, variable ventilation, optimized for mice (VVN). Mechanics and gas exchange were measured during ventilation and surfactant protein (SP)-B, proSP-B and E-cadherin levels were determined from lavage and lung homogenate. PEEP had a significant effect on mechanics, gas exchange and the epithelium. The higher PEEP reduced lung collapse and improved mechanics and gas exchange but it also down regulated surfactant release and production and increased epithelial cell injury. While CVLB was better than CV, VVN outperformed CVLB in recruitment, reduced epithelial injury and, via a dynamic mechanotransduction, it also triggered increased release and production of surfactant. For long-term outcome, selection of optimal PEEP and ventilation mode may be based on balancing lung physiology with epithelial injury.
Highlights
In acute respiratory distress syndrome (ARDS), the currently accepted protocol is to use low tidal volume (VT) in combination with a procedure that helps keep the lung open such as a recruitment maneuver (RM) or adding positive end-expiratory pressure (PEEP) [1]
At PEEPs of 3 cmH2O (PEEP3), R in the conventional ventilation (CV) group was significantly higher than in the VVN and CV with intermittent large breaths (CVLB) groups (p = 0.002 and p = 0.028, respectively) whereas at PEEP6, R during CV was significantly higher than during VVN (p = 0.012), but not during CVLB. Both H and DH during CV was higher than during VVN and CVLB (p,0.001) at both PEEPs while there was no difference between DH during VVN and CVLB
Chiumello et al [37] showed that VT and airway pressure are not adequate surrogates of lung stress and strain due to the large heterogeneity of lung stiffness in ARDS patients in agreement with the above notion that regional heterogeneity is not reflected in the total P-V curve
Summary
In acute respiratory distress syndrome (ARDS), the currently accepted protocol is to use low tidal volume (VT) in combination with a procedure that helps keep the lung open such as a recruitment maneuver (RM) or adding positive end-expiratory pressure (PEEP) [1]. When a high PEEP is required to maintain an open lung, normal lung regions will be overinflated. An inadequate PEEP can result in cyclic recruitment/derecruitment during ventilation with high non-physiologic shear and normal stresses on the epithelium which can generate epithelial injury [7,8]. A moderate PEEP together with regular delivery of large breaths as RMs might be able to keep the lung open while minimizing the risk of VILI. This approach works in mice [14,15,16] but clinical studies showed mixed results [10,17,18]
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