Preemptive application of airway pressure release ventilation prevents development of acute respiratory distress syndrome in a rat traumatic hemorrhagic shock model

Abstract

Background: Once established, the acute respiratory distress syndrome (ARDS) is highly resistant to treatment and retains a high mortality. We hypothesized that preemptive application of airway pressure release ventilation (APRV) in a rat model of trauma/hemorrhagic shock (T/HS) would prevent ARDS.

Methods: Rats were anesthetized, instrumented for hemodynamic monitoring, subjected to T/HS, and randomized into two groups: (a) volume cycled ventilation (VC) (n = 5, tidal volume 10 mL/kg; positive end-expiratory pressure 0.5 cmH(2)O) or (b) APRV (n = 4, P(high) = 15-20 cmH(2)O; T(high) = 1.3-1.5 s to achieve 90% of the total cycle time; T(low) = 0.11-0.14 s, which was set to 75% of the peak expiratory flow rate; P(low) = 0 cmH(2)O). Study duration was 6 h.

Results: Airway pressure release ventilation prevented lung injury as measured by PaO(2)/FIO(2) (VC 143.3 ± 42.4 vs. APRV 426.8 ± 26.9, P < 0.05), which correlated with a significant decrease in histopathology as compared with the VC group. In addition, APRV resulted in a significant decrease in bronchoalveolar lavage fluid total protein, increased surfactant protein B concentration, and an increase in epithelial cadherin tissue expression. In vivo microscopy demonstrated that APRV significantly improved alveolar patency and stability as compared with the VC group.

Conclusions: Our findings demonstrate that preemptive mechanical ventilation with APRV attenuates the clinical and histologic lung injury associated with T/HS. The mechanism of injury prevention is related to preservation of alveolar epithelial and endothelial integrity. These data support our hypothesis that preemptive APRV, applied using published guidelines, can prevent the development of ARDS.

Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1

Time Line of experimental protocol. The experiment is broken into two Sections: Phase 1 – Preparation/Shock/Resuscitation: surgical preparation followed by Baseline measurements (BL) and an equilibrium period (EQ) to stabilize hemodynamics and body temperature. Following EQ, hemorrhagic shock (HS) is induced for 40min, followed by resuscitation (RES) with shed blood and Ringers Lactate. It takes approximately 70 min from the beginning of HS to the end of RES; Phase 2 – Ventilator Strategy: animals are randomized to their ventilation strategy (VC or APRV). Hemodynamics, blood gas and lung function measurements are made every 30 minutes until the end of the study at 360 minutes (T360) following RES. See Methods for detailed procedures.

Figure 2

(A–D) – A: PaO2/FiO2 ratio (P/F) over time in the volume cycled ventilation (VC=▲) and airway pressure release ventilation (APRV=■) groups. There was a significant fall in P/F in the VC as compared with APRV group, with the P/F falling below 200 at T300 indicating the development of ARDS. B: Peak airway pressure (PIP) over time in the volume cycled ventilation (VC=▲) and airway pressure release ventilation (APRV=■) groups. C: Mean arterial blood pressure (MAP) over time in the volume cycled ventilation (VC=▲) and airway pressure release ventilation (APRV=■) groups. D: Airway Pressure/Time Profile (P/TP) over time in the volume cycled ventilation (VC=▲) and airway pressure release ventilation (APRV=■) groups. P/TP was significantly elevated in the APRV as compared with VC group throughout the entire experiment. BL=Baseline, EQ=Equilibrium, HS=Hemorrhagic Shock, RES=Resuscitation. Data±SEM. *=p<0.05 vs. VC group.

Figure 3

In vivo photomicrographs and image analysis of inflated subpleural alveoli in the VC (A, B) and APRV (C, D) groups. Measurement of the % Air Space was accomplished by circling the inflated alveoli using computer image analysis. All inflated alveoli were then assigned the color yellow and noninflated areas were assigned the color red generating a sharp contrast for the image analysis software to identify and measure the % of inflated alveoli/microscopic field. Arrows (A, C) identify a single alveolus.

Figure 4

Histological comparison of a rats receiving Volume Cycled Ventilation (VC) vs. airway pressure release ventilation (APRV). The VC animal exhibits hallmarks of ARDS, including alveolar flooding (stars), fibrinous deposits in the air compartment (arrowheads) and high cellularity (between arrows). The APRV animal shows patent alveoli with notable preservation of nearly normal histology.