Inflating Pressure and Not Expiratory Pressure Initiates Lung Injury at Birth in Preterm Lambs.

Rationale: Inflation is essential for aeration at birth, but current inflating pressure settings are without an evidence base. Objectives: To determine the role of inflating pressure (ΔP), and relationship with positive end-expiratory pressure (PEEP), in initiating early lung injury pathways in the preterm lamb lung. Methods: 124-127d steroid exposed preterm lambs (n=45) were randomly allocated (8-10/gp) to 15 min of respiratory support with placental circulation and 20 or 30 cmH 2 O ΔP, with an initial high PEEP (maximum 20 cmH 2 O) recruitment manoeuvre known to facilitate aeration (dynamic PEEP), and compared to dynamic PEEP with no ΔP or 30 cmH 2 O ΔP and low (4 cmH 2 O) PEEP. Lung mechanics and aeration were measured throughout. after an additional 30 min of apnoeic placental support, lung tissue and bronchoalveolar fluid were analysed for regional lung injury, including proteomics. Results: 30 cmH 2 O ΔP and dynamic PEEP resulted in quicker aeration, better compliance, but higher tidal volumes (often >8 ml/kg, all p<0.0001; mixed effects) and injury. ΔP 20 cmH 2 O with dynamic PEEP resulted in the same lung mechanics and aeration, but less energy transmission (tidal mechanical power), as ΔP 30 cmH 2 O with low PEEP.. Dynamic PEEP without any tidal inflations resulted in the least lung injury. Use of any tidal inflating pressures altered metabolic, coagulation and complemented protein pathways within the lung. Conclusions: Inflating pressure is essential for the preterm lung at birth, but also the primary mediator of lung injury. Greater focus is needed on strategies that identify safest application of pressure in the delivery room.