Gradual Aeration at Birth is More Lung Protective than a Sustained Inflation in Preterm Lambs

RATIONALE: The preterm lung is susceptible to injury during transition to air-breathing at birth. It remains unclear whether rapid or gradual lung aeration at birth causes less lung injury. OBJECTIVES: To examine the effect of gradual and rapid aeration at birth on 1) the spatiotemporal volume conditions of the lung, and 2) resultant regional lung injury. METHODS: 125±1d gestation preterm lambs were randomised at birth to receive 1) tidal ventilation without an intentional recruitment (No-RM; n=19), 2) sustained inflation (SI) until full aeration (n=26), or 3) tidal ventilation with an initial escalating/de-escalating positive end-expiratory pressure (DynPEEP; n=26). Ventilation thereafter continued for 90 min at standardised settings including positive end-expiratory pressure 8 cmH2O. Lung mechanics and regional aeration and ventilation (electrical impedance tomography) were measured throughout and correlated with histological and gene markers of early lung injury. MEASUREMENTS AND MAIN RESULTS: DynPEEP significantly improved dynamic compliance (p<0.0001). A SI, but not DynPEEP or No-RM, resulted in preferential non-dependent lung aeration, that became less uniform with time (p=0.0006). The non-dependent lung was preferential ventilated by 5 min in all groups, with ventilation only becoming uniform with time in the No-RM and DynPEEP groups. All strategies generated similar non-dependent lung injury patterns. Only a SI caused greater upregulation of dependent lung gene markers compared to unventilated fetal controls (p<0.05). CONCLUSIONS: Rapidly aerating the preterm lung at birth creates heterogeneous volume states, producing distinct regional injury patterns that affect subsequent tidal ventilation. Gradual aeration with tidal ventilation and PEEP produced the least lung injury.