EPVent 2-A Phase II Trial Esophageal Pressure Guided Ventilation

EPVent 2-A II 期试验食管压力引导通气

• 批准号: 8283454
• 负责人: STEPHEN H LORING
• 金额: $ 106.45万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8283454
• 关键词: EPVent; Phase; II; Trial; Esophageal

DESCRIPTION (provided by applicant): Acute Respiratory Distress Syndrome (ARDS) and acute lung injury (ALl) place heavy burdens on the health of the public, afflicting over 190,000 people annually in the US alone. The associated mortality exceeds 30% and accounts for 74,500 deaths annually. Improvements in ventilator management have reduced both the mortality and morbidity associated with ALI/ARDS, and thus have an important public health impact. Low tidal volume ventilation strategies are clearly beneficial in patients with ALI/ARDS. However, the optimal level of applied positive end-expiratory pressure (PEEP) is uncertain. We propose a phase II multicenter, randomized controlled trial of mechanical ventilation directed by esophageal pressure measurements. The primary hypothesis is that adjusting PEEP to maintain a positive transpulmonary pressure throughout the ventilatory cycle will lead to clinically important improvements at 28 days. In patients with high pleural pressure on conventional ventilator settings, underinflation leads to atelectasis, hypoxemia, and exacerbation of lung injury through "atelectrauma". In such patients, raising PEEP to maintain a positive transpulmonary pressure might improve aeration and oxygenation without causing overdistension. Conversely, in patients with low pleural pressure, maintaining a low PEEP would keep transpulmonary pressure low, avoiding over-distension and consequent "volutrauma". Thus, the currently recommended strategy of setting PEEP without regard to transpulmonary pressure could benefit some patients while harming others. Our preliminary study demonstrated that a ventilator strategy designed to optimize transpulmonary pressure significantly improved oxygenation and lung mechanics, and there was a trend toward improved survival. We propose to confirm these results in a multi-centered trial at 6 large medical centers enrolling 200 patient with ALI/ARDS. We will use esophageal pressure to estimate transpulmonary pressure (PTP). Subjects will then be randomized to the control group, in which ventilation will be managed according to the ARDSnet protocol, or the EPVent group, in which ventilator settings will be adjusted to achieve a specified PTP. The primary hypothesis is that using a strategy of maintaining a positive PTP throughout the ventilatory cycle will lead to improvement in a combined hierarchical outcome of mortality and ventilator free days at 28 days. This study has important implications for the health of the public. Strong preliminary data suggest a positive result, potentially changing medical practice.

描述(申请人提供)：急性呼吸窘迫综合症(ARDS)和急性肺损伤(ALL)对公众健康造成沉重负担，仅在美国每年就有超过19万人受到影响。相关死亡率超过30%，每年占7.45万人死亡。呼吸机管理的改进降低了与ALI/ARDS相关的死亡率和发病率，因此对公共卫生产生了重要影响。低潮气量机械通气策略对ALI/ARDS患者明显有益。然而，应用呼气末正压(PEEP)的最佳水平尚不确定。我们提出了一项以食道压力测量为指导的机械通气II期多中心随机对照试验。基本的假设是，调整PEEP以在整个呼吸周期中保持正的经肺压力将在28天时导致临床上重要的改善。在传统呼吸机上胸膜压力较高的患者，低充气会导致肺不张、低氧血症，并通过“肺不张创伤”加重肺损伤。在这类患者中，增加PEEP以维持正的跨肺压可能会改善充气和氧合，而不会引起过度扩张。相反，在胸膜压力低的患者中，保持低PEEP将使经肺压力保持在低水平，从而避免过度扩张和随之而来的“蜗牛创伤”。因此，目前推荐的不考虑经肺压力而设置PEEP的策略可能会使一些患者受益，同时也会损害另一些患者。我们的初步研究表明，旨在优化跨肺压力的呼吸机策略显著改善了氧合和肺力学，并有提高存活率的趋势。我们建议在6个大型医学中心的多中心试验中证实这些结果，该试验招募了200名ALI/ARDS患者。我们将使用食道压力来估算经肺压力(PTP)。然后，受试者将被随机分配到对照组或EPVent组，在对照组中，将根据ARDSNet协议进行通风管理，在EPVent组中，将调整呼吸机设置以实现指定的PTP。主要的假设是，采用在整个呼吸机周期中保持积极的PTP的策略将导致28天死亡率和无呼吸机天数的综合分级结果的改善。这项研究对公众的健康具有重要影响。强劲的初步数据表明，这是一个积极的结果，可能会改变医疗实践。