Physiologically variable ventilation in a rabbit model of asthma exacerbation.

Abstract

Mechanical ventilation during status asthmaticus is challenging and increases the risk of severe complications. We recently reported the value of physiologically variable ventilation (PVV) in healthy and acutely injured lungs. We investigated whether PVV provides benefits compared with pressure-controlled ventilation (PCV) in an experimental model of severe acute asthma. Allergen-sensitised rabbits were anaesthetised and randomised to either PCV (n=10) or PVV (n=12) during sustained bronchoconstriction induced by allergen and cholinergic stimuli for 6 h. The PVV pattern was generated from pre-recorded spontaneous breathing. Ventilation parameters, oxygenation index (PaO₂/FiO₂), and respiratory mechanics were measured hourly. Histological injury and inflammation were quantified after 6 h of ventilation. PVV resulted in lower driving pressures (13.7 cm H₂O [12.5-14.9], mean [95% confidence interval]), compared with pressure-controlled ventilation (17.6 cm H₂O [15.4-19.8]; P=0.002). PVV improved PaO₂/FiO₂ (PVV: 55.1 kPa [52-58.2]; PCV: 45.6 kPa [39.3-51.9]; P=0.018) and maintained tissue elastance (PVV: +8.7% [-0.6 to 18]; PCV: -11.2% [-17.3 to -5.1]; P=0.03). PVV resulted in less lung injury as assessed by lower histological injury score (PVV: 0.65 [0.62-0.65]; PCV: 0.71 [0.69-0.73]; P=0.003), cell count (PVV: 247 10⁴ ml^-1 [189-305]; PCV: 447 10⁴ ml^-1 [324-570]; P=0.005), and protein concentration in bronchoalveolar lavage fluid (PVV: 0.14 μg ml^-1 [0.10-0.18]; PCV: 0.21 μg ml^-1 [0.15-0.27]; P=0.035). Applying physiological variable ventilation in a model of asthma exacerbation led to improvements in gas exchange, ventilatory pressures, and respiratory tissue mechanics, and reduced lung injury. A global reduction in lung shear stress and recruitment effects may explain the benefits of PVV in status asthmaticus.