Optimising Postnatal Transition: effects of gradual aeration on IMmature Animal Lungs- a PEEP-based approach (OPTIMAL PEEP)

优化产后过渡：逐渐通气对未成熟动物肺的影响 - 基于 PEEP 的方法 (OPTIMAL PEEP)

• 批准号: 399182194
• 负责人: Dr. Anja Demel
• 金额: --
• 依托单位: The Ritchie Centre
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/399182194?language=en
• 关键词: Optimising; Postnatal; Transition; effects; gradual

The recommendation of the current European Resuscitation Council Guidelines of 2015 suggests respiratory support with the use of continuous positive airway pressure as a non-invasive approach being superior to mechanical ventilation in preterm infants. Non-invasive ventilation, applied via a facemask is accepted as the first choice respiratory care provided to preterm infants in the delivery room.There are different ways of non-invasive aeration modes after birth in comparison to ventilation like using continuous positive airway pressure support, sustained inflation or nasal high-flow-devise to aerate the lung if the preterm infant is not breathing appropriate or spontaneously. Despite many years of intense research in this field, aerating lung strategies relating to the best timing, needed opening pressure, tidal volume or positive end-expiratory pressure level remain controversial.Nevertheless, both methods have not been able to reduce adequately neonatal chronic lung disease, also known as bronchopulmonary dysplasia. Bronchopulmonary dysplasia is the most common complication in premature infants, which highly influences the later neuro-developmental outcome in child- and adulthood and mortality. The following health costs have a huge economic impact and present therefore a global health issue.The respiratory transitional period at birth involves much more than lung aeration, changes in glottic function and breathing activity. Postnatal airway liquid clearance and sustained prevention of liquid efflux into the lungs is one of the major challenges during the first hours of life. Little or no scientific knowledge is available to assess the effectiveness of this approach, how it integrates with the preterm infant’s physiological state and why it sometimes fails. Gradually increasing and continuously sustaining PEEP-based lung recruitment strategies will be investigated comparing different respiratory support devices (Benveniste Valve, Sustained Inflation, High-Flow-Therapy) in well-characterised preterm animal models as intermediate step of translational research.The Benveniste Valve might be superior to establish optimal non-invasive aeration and respiratory support by applying gradually an increasing end-expiratory positive pressure that will lead to reduced cell inflammation followed by a reduction of long-term damage of the immature lung. This may be more the result of considering the postnatal (patho-)physiological mechanisms of lung aeration and successful fluid clearance.Visualising the spatial relationships between fluid clearance and lung aeration after birth through phase-contrast X-ray imaging and histologically analysed lung sections will be mandatory to assess inflammation and injury.The results of the study will influence the future resuscitation guideline recommendation of respiratory support in preterm infants around the world.

目前的欧洲复苏理事会2015年指南的建议建议，在早产儿中使用持续气道正压作为一种非侵入性方法的呼吸支持优于机械通气。经口罩实施的无创通气被认为是在产房为早产儿提供呼吸护理的首选。与机械通气相比，出生后有不同的非侵入性通风模式，如使用持续正压支持、持续充气或鼻腔高流量装置为肺充气，如果早产儿呼吸不适当或自发。尽管在这一领域进行了多年的密集研究，但有关最佳时机、所需开放压力、潮气量或呼气末正压水平的充气策略仍然存在争议。然而，这两种方法都不能充分减少新生儿慢性肺部疾病，也称为支气管肺发育不良。支气管肺发育不良是早产儿最常见的并发症，严重影响儿童和成人以后的神经发育结局和死亡率。以下医疗费用具有巨大的经济影响，因此是一个全球性的健康问题。出生时的呼吸过渡期涉及的不仅仅是肺部充气、声门功能和呼吸活动的改变。出生后呼吸道液体清除和持续防止液体外流到肺是生命最初几小时的主要挑战之一。很少或根本没有科学知识来评估这种方法的有效性，它是如何与早产儿的生理状态结合在一起的，以及为什么它有时会失败。作为翻译研究的中间步骤，将在具有良好特征的早产动物模型中比较不同的呼吸支持装置(Benveniste瓣膜、持续充气、高流量疗法)，研究逐步增加和持续维持基于PEEP的肺招募策略。Benveniste瓣膜可能更好地建立最佳的非侵入性通气和呼吸支持，通过逐渐增加呼气末正压，从而减少细胞炎症，继而减少对未成熟肺的长期损害。这可能更多地是考虑到出生后肺部充气和成功清除液体的(病理)生理机制的结果。通过相位对比X射线成像和组织学分析肺切片来可视化出生后液体清除和肺充气之间的空间关系将是强制性的，以评估炎症和损伤。这项研究的结果将影响未来世界各地早产儿呼吸支持的复苏指南推荐。