We tested the hypothesis that collapsed alveoli opened by a recruitment maneuver would be unstable or recollapse without adequate positive end-expiratory pressure (PEEP) after recruitment. Surfactant deactivation was induced in pigs by Tween instillation. An in vivo microscope was placed on a lung area with significant atelectasis and the following parameters measured: (1) the number of alveoli per field and (2) alveolar stability (i.e., the change in alveolar size from peak inspiration to end expiration). We previously demonstrated that unstable alveoli cause lung injury. A recruitment maneuver (peak pressure = 45 cm H2O, PEEP = 35 cm H2O for 1 minute) was applied and alveolar number and stability were measured. Pigs were then separated into two groups with standard ventilation plus (1) 5 PEEP or (2) 10 PEEP and alveolar number and stability were again measured. The recruitment maneuver opened a significant number of alveoli, which were stable during the recruitment maneuver. Although both 5 PEEP and 10 PEEP after recruitment demonstrated improved oxygenation, alveoli ventilated with 10 PEEP were stable, whereas alveoli ventilated with 5 PEEP showed significant instability. This suggests recruitment followed by inadequate PEEP permits unstable alveoli and may result in ventilator-induced lung injury despite improved oxygenation.
Intratracheal instillation of Tween causes a heterogeneous surfactant deactivation in the lung, with areas of unstable alveoli directly adjacent to normal stable alveoli. We employed in vivo video microscopy to directly assess alveolar stability in normal and surfactant-deactivated lung and tested our hypothesis that alveolar instability causes a mechanical injury, initiating an inflammatory response that results in a secondary neutrophil-mediated proteolytic injury. Pigs were mechanically ventilated (VT 10 cc/kg, positive end-expiratory pressure [PEEP] 3 cm H2O), randomized to into three groups, and followed for 4 hours: Control group (n = 3) surgery only; Tween group (n = 4) subjected to intratracheal Tween (surfactant deactivator causing alveolar instability); and Tween + PEEP group (n = 4) subjected to Tween with increased PEEP (15 cm H2O) to stabilize alveoli. The magnitude of alveolar instability was quantified by computer image analysis. Surfactant-deactivated lungs developed significant histopathology only in lung areas with unstable alveoli without an increase in neutrophil-derived proteases. PEEP stabilized alveoli and significantly reduced histologic evidence of lung injury. Thus, in this model, alveolar instability can independently cause ventilator-induced lung injury. To our knowledge, this is the first study to directly confirm that unstable alveoli are subjected to ventilator-induced lung injury whereas stable alveoli are not.
Introduction One potential mechanism of ventilator-induced lung injury (VILI) is due to shear stresses associated with alveolar instability (recruitment/derecruitment). It has been postulated that the optimal combination of tidal volume (Vt) and positive end-expiratory pressure (PEEP) stabilizes alveoli, thus diminishing recruitment/derecruitment and reducing VILI. In this study we directly visualized the effect of Vt and PEEP on alveolar mechanics and correlated alveolar stability with lung injury.
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