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: 8536932
• 负责人: STEPHEN H LORING
• 金额: $ 176.52万
• 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/8536932
• 关键词: Accounting; Acute Lung Injury; Adult Respiratory Distress Syndrome; Advanced Glycosylation End Products; Alveolar; Ancillary Study; Atelectasis; Biological Markers; Blood; Catheters; Cessation of life; Chest wall structure; Clinical Data; Clinical Management; Clinical Research; Clinical Trials; Control Groups; Critical Illness; Data; Databases; Enrollment; Environmental air flow; Esophageal; Factor VIII-Related Antigen; Health Resources; Hospitals; Hypoxemia; Individual; Infection; Intercellular adhesion molecule 1; Interleukin-6; Intervention; Investigation; Lead; Lung; Lung Inflammation; Measurement; Mechanical ventilation; Mechanics; Medical; Medical center; Methods; Modeling; Morbidity - disease rate; Outcome; Oxygen; Pathogenesis; Patients; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Physiological; Plasminogen Activator Inhibitor 1; Pleural; Positive-Pressure Respiration; Procedures; Protein C; Proteins; Protocols documentation; Public Health; Pulmonary Surfactant-Associated Protein D; Randomized; Randomized Controlled Trials; Recruitment Activity; Research; Specific qualifier value; Testing; Tidal Volume; Trauma; Tumor Necrosis Factor Receptor; Ventilator; Volutrauma; X-Ray Computed Tomography; abdominal pressure; atelectrauma; base; design; esophagus pressure; group intervention; hemodynamics; improved; lung injury; mortality; pressure; prospective; randomized trial; receptor; standard of care; surfactant; trend

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（由申请人提供）：急性呼吸窘迫综合征（ARDS）和急性肺损伤（AL 1）给公众健康带来沉重负担，仅在美国每年就有超过190，000人受到折磨。相关死亡率超过30%，每年有74，500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，因此具有重要的公共卫生影响。低潮气量通气策略对ALI/ARDS患者明显有益。然而，应用呼气末正压（PEEP）的最佳水平是不确定的。我们提出了一个II期多中心，随机对照试验的机械通气指导食管压力测量。主要假设是，调整PEEP以在整个呼吸周期内维持正的经肺动脉压将导致28天时临床上重要的改善。在使用传统呼吸机的高胸膜压患者中，充气不足导致肺不张、低氧血症和通过“肺不张”加重肺损伤。在这类患者中，提高PEEP以维持经肺正压可能会改善通气和氧合，而不会导致过度扩张。相反，在低胸膜压的患者中，维持低PEEP将使经胸膜压保持较低，避免过度扩张和随后的“体积创伤”。因此，目前推荐的不考虑经尿道压力的PEEP设置策略可能会使一些患者受益，同时伤害其他患者。我们的初步研究表明，旨在优化经肺压力的呼吸机策略显著改善了氧合和肺力学，并有改善生存率的趋势。我们建议在6个大型医疗中心的多中心试验中确认这些结果，该试验招募了200例ALI/ARDS患者。我们将使用食管压力来估计经尿道压力（PTP）。然后将受试者随机分配至对照组（根据ARDSnet方案进行通气管理）或EPVent组（调整呼吸机设置以达到指定的PTP）。主要假设是，在整个治疗周期内使用维持阳性PTP的策略将导致28天时死亡率和无呼吸机天数的综合分层结局改善。这项研究对公众的健康具有重要意义。强有力的初步数据表明，这是一个积极的结果，可能会改变医疗实践。