Early stabilizing alveolar ventilation prevents acute respiratory distress syndrome

Abstract

Background Established ARDS is often refractory to treatment. Clinical trials have demonstrated modest treatment effects, and mortality remains high. Ventilator strategies must be developed to prevent ARDS. Hypothesis Early ventilatory intervention will block progression to ARDS if the ventilator mode: 1) maintains alveolar stability and 2) reduces pulmonary edema formation. Methods Yorkshire Pigs (38–45kg) were anaesthetized and subjected to "2-hit" Ischemia-Reperfusion and Peritoneal Sepsis. Following injury, animals were randomized into two groups: Early Preventative Ventilation (Airway Pressure Release Ventilation- APRV) vs. Non-Preventative Ventilation (NPV) and followed for 48hr. All animals received anesthesia, antibiotics, and fluid/vasopressor therapy per Surviving Sepsis Campaign. Ventilation parameters: 1) NPV Group - Tidal volume (Vt): 10cc/kg + PEEP- 5 cm/H2O volume-cycled mode, 2) APRV Group - Vt: 10–15 cc/kg; Phigh, Plow, Thigh, Tlow were titrated for optimal alveolar stability. Physiologic data and plasma were collected throughout the 48hr study period, followed by BAL and necropsy. Results APRV prevented development of ARDS (p<0.001 vs NPV) by PaO2/FiO2 ratio. Quantitative histological scoring showed APRV prevented lung tissue injury (p<0.001 vs. NPV). BALF showed APRV lowered total protein and IL-6, while preserving surfactant proteins A & B (p<0.05 vs. NPV). APRV significantly lowered lung water (p<0.001 vs. NPV). Plasma IL-6 concentrations were similar between groups. Conclusions Early preventative mechanical ventilation with APRV blocked ARDS development, preserved surfactant proteins, and reduced pulmonary inflammation and edema, despite systemic inflammation similar to NPV. These data suggest early preventative ventilation strategies stabilizing alveoli and reducing pulmonary edema can attenuate ARDS after ischemia-reperfusion-sepsis.

RETRACTED: Mechanical Ventilation as a Therapeutic Tool to Reduce ARDS Incidence

“…32 In addition, we have demonstrated nearcomplete lung protection in a high-fi delity clinically applicable porcine ARDS model, 31,33 which was associated with high PTI ( Fig 5B ). Th ese studies thus confi rm, perhaps somewhat counterintuitively, that increasing PTI is actually protective, at least in the context of APRV, and reduces both alveolar and alveolar duct m -strain ( Figs 3, 4 ).…”

“…24,[31][32][33][34] In other words, protection against the development of ALI is conferred by much more than simply the values of V t , plateau pressure, and PEEP that are used; the durations over which these parameters are applied also determine whether lung injury will progress. Mode acronyms such as APRV or CMV, thus, do not encompass all the features of a mechanical breath that determine its injurious or protective impact because the temporal details of the mechanical breath can be critical to this impact.…”

“…Th e APRV groups in these studies demonstrate preservation of normal preinjury lung compliance, while accommodating 12 mL/kg V t throughout the 48-h experiment. 31,33 Th ere is reason to expect that future studies will identify other parameters of the mechanical breath with a substantial protective role.…”

“…48 Th ese studies suggest that the optimally protective breath involves the appropriate combination of multiple parameters, with the durations that these components are applied to the lung during each breath playing a key role in lung protection. 30,33,44 In a recent study, Amato et al 49 reveal that the protective mechanical breath is complex and not just a function of LV t . 49 In a retrospective meta-analysis of ARDSnet data, the authors demonstrated that lower driving pressure (ie, Vt/respiratory compliance) was strongly associated with increased survival.…”

“…Given that APRV is superior to CMV for the most severely injured lungs (ie, rescue mode) and that the MBP of APRV is theoretically ideal for minimizing ventilator injury cost function, we chose to study the effi cacy of this mechanical breath at reducing ARDS incidence. We hypothesized that the mechanism by which APRV protected the lung 24,[30][31][32][33][34]44,45 was reduced alveolar microstrain ( m -strain). We found that appropriately set APRV with an extended duration at plateau pressure (duration at high pressure [THigh]) and a very brief duration at pressure release (duration at low pressure [TLow]) is essential to minimizing m -strain in the alveoli and the alveolar ducts ( Figs 3 , 4 ).…”