P109: Late application of protective mechanical ventilation does not reduce lung injury in a porcine ARDS model

Abstract

Introduction: Proper ventilatory management is critical to patients with acute respiratory distress syndrome (ARDS). Non-protective ventilation can result in ventilator-induced lung injury (VILI), a contributing factor in the morbidity and mortality of ARDS patients. Recent human and animal studies have shown that the implementation of protective ventilator strategies such as low tidal volume (N Engl J Med 2000; 342: 1301-1308) or high frequency oscillatory ventilation (HFOV) (Imai et al J Appl Physiol 2001; 91: 1836-1844) can reduce VILI and improve outcome, especially if applied early in the course of ARDS. However, it has been demonstrated that if protective ventilation is applied late in the course of ARDS it will be much less effective. We hypothesized that if ARDSnet or HFOV were applied late, following 30minutes of non-protective ventilation, that these strategies would be ineffective at reducing VILI in our porcine ARDS model. Methods: Lung injury was caused by Tween-20 lung lavage followed by a 30 minute period of non-protective ventilation (end-expiratory pressure of 3 cm H20 and 12cc/kg tidal volume) in Yorkshire pigs. Swine (n=20) were separated into four groups: Control (n=6; no injury + Vt 12 cc/kg / PEEP 3 cm H20), Non-Protective Ventilation: NPV (NPV; n=7; Vt 12 cc/kg / PEEP 3), Two Protective Ventilation Groups: 1) ARDSNet (n=4; Vt 6cc/kg, PEEP per ARDSNet protocol), and 2) HFOV (n=3; mean airway pressure 30cm H20, inspiratory time 33%, frequency 6Hz, ΔP 50cmH2O). After lung injury, animals were ventilated for 6hrs in each group. The primary endpoints were lung function (oxygenation) and edema. Lung edema was assessed from bronchoalveolar lavage fluid protein concentrations and wet-dry lung weight ratios. Results: HFOV showed a significant improvement in oxygenation when compared to the NPV group as seen by the PF (PaO2/FiO2) ratio (Table). However, there was no significant reduction in lung injury as suggested by pulmonary edema or BAL protein concentration. Conclusion: Neither ARDSnet or HFOV reduced lung injury when applied after 30 minutes of NPV in our porcine ARDS model. These data suggest that these protective ventilation strategies must be applied early in the course of ARDS to be effective. Table 1 Group Oxygenation (PF ratio) Wet/dry lung weight ratio BALF [proteinμg/μl] Control 507.67±12.21 ‡ p<0.05 significance between control and NPV/ARDSnet groups 5.57±0.02 ⁎ p<0.05 significance between control and other groups 0.08±0.03 NPV 172.71±59.06 7.82±0.21 0.67±0.39 ARDSnet 243.50±31.06 8.65±0.64 0.67±0.30 HFOV 387.17±87.25 † p<0.05 significance between HFOV and NPV 8.37±0.23 0.41±0.07 All means expressed ± SEM and calculated using student’s t-test p<0.05 significance between control and other groups † p<0.05 significance between HFOV and NPV ‡ p<0.05 significance between control and NPV/ARDSnet groups Open table in a new tab All means expressed ± SEM and calculated using student’s t-test