Role of spontaneous effort during mechanical ventilation on lung injury in preterm lambs.

Abstract

RATIONALE: 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. OBJECTIVES: To determine the role of synchronous and asynchronous breathing during PPV on lung injury. METHODS: Steroid-exposed intubated preterm lambs (n = 59; 126-130 days gestation) were randomly allocated to receive (1) fully synchronized PPV or (2) asynchronous PPV or apnoeic PPV for 90 minutes from birth using an otherwise standardized lung-protective PPV strategy. Breathing was supported with caffeine, doxapram, and stimulation. MEASUREMENTS AND MAIN RESULTS: Lung mechanics, gas exchange, and regional ventilation and aeration characteristics were measured during PPV. Lung tissue and bronchoalveolar fluid were 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, the 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 center of ventilation were better in the synchronous PPV group compared to the apnoeic PPV group, with a mean (95% CI) difference of 0.26 (0.08-0.43) mL/kg/min and 3.6% (1.0%-6.1%), respectively (analysis of variance). CONCLUSIONS: Different breathing efforts during PPV support of the preterm lung create complex lung states, each with unique and measurable injury events. This offers the potential to develop lung-protective strategies that target minimizing breathing-related injury.