Role of Spontaneous Effort During Mechanical Ventilation on Lung Injury in Preterm Lambs.

Abstract

<b>Rationale:</b> The lung protective and injurious potential of spontaneous breathing effort during positive pressure ventilation (PPV) in adults is well-understood but has never been defined in the preterm lung. <b>Objectives:</b> To determine the role of synchronous and asynchronous breathing during PPV on lung injury. <b>Methods:</b> Steroid-exposed intubated preterm lambs (n=59; 126-130d gestation) were randomly allocated to receive 1) fully <b>synchronised PPV</b>, 2) <b>asynchronous PPV</b> or <b>apnoeic PPV</b> for 90-min from birth using an otherwise standardised lung protective PPV strategy. Breathing was supported with caffeine, doxapram and stimulation. <b>Measurements and Main Results:</b> Lung mechanics, gas exchange and regional ventilation and aeration characteristics were measured during PPV. Lung tissue and bronchoalveolar fluid was taken for histology and proteomic analysis. Clinical characteristics and gas exchange were similar. Each PPV strategy generated unique flow and pressure characteristics that were associated with different lung proteome expression. Overall, asynchronous breathing created the most injury, least developed alveolar morphology and 5-fold more dependent lung differentially expressed proteins (compared to synchronous and apnoeic PPV). Synchronous and apnoeic PPV resulted in similar morphology and minimal acute injury. At study completion, dynamic compliance and gravity-dependent centre of ventilation were better in the synchronous PPV group compared to apnoeic PPV; mean (95% CI) difference 0.26 (0.08, 0.43) ml/kg/min and 3.6 (1.0, 6.1)% respectively (ANOVA). <b>Conclusions:</b> Different breathing efforts during PPV support of the preterm lung creates complex lung states, each with unique and measurable injury events. This offers the potential to develop lung protective strategies that target minimising breathing-related injury.