Ancillary Study

辅助研究

• 批准号: 8309670
• 负责人: STEPHEN H LORING
• 金额: $ 6.16万
• 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/8309670
• 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; Instruction; 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

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 nnortality exceeds 30% and accounts for 74,500 deaths annually. Improvennents 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 patients 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.

急性呼吸窘迫综合征（ARDS）和急性肺损伤（AL 1）给患者带来了沉重的负担。 公众健康，仅在美国每年就有超过19万人受到影响。相关的nnorality 超过30%，每年造成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，从而对公众产生了重要影响 健康影响。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 食管压力导向机械通气的II期、多中心、随机对照试验 测量.主要假设是调整PEEP以维持积极的经肺通气 在整个治疗周期中的压力将导致在28天时的临床上重要的改善。 在常规呼吸机设置的高胸膜压患者中，充气不足导致肺不张， 低氧血症和通过“肺损伤不全”加重肺损伤。对于此类患者，提高PEEP至 保持正的经肺压力可以改善通气和氧合，而不会引起 过度膨胀相反，在低胸膜压的患者中，维持低PEEP将保持 经肺动脉压低，避免过度扩张和随之而来的“体积创伤”。因此，目前 建议的策略，设置PEEP不考虑经尿道压力可能有利于一些 患者，同时伤害他人。我们的初步研究表明，一个呼吸机策略，旨在 优化的经肺压力显著改善了氧合和肺力学， 提高生存率的趋势我们建议在6个大样本的多中心试验中证实这些结果。 医学中心招募了200名ALI/ARDS患者。我们将使用食管压力来估计 穿髓压（PTP）。然后将受试者随机分配至对照组，其中通气 将根据ARDSNet方案或EPVent组进行管理，其中呼吸机设置将 调整以实现指定的PTP。主要的假设是，使用保持积极的策略， 在整个治疗周期中，PTP将导致以下综合分层结局的改善： 28天时的死亡率和无呼吸机天数。 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， 积极的结果，可能会改变医疗实践。