1/2: PREcision VENTilation to attenuate Ventilation-Induced Lung Injury (PREVENT VILI)

1/2：精确通气以减轻通气引起的肺损伤（预防 VILI）

• 批准号: 10738958
• 负责人: Jeremy R. Beitler
• 金额: $ 144.57万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10738958
• 关键词: Acute; Acute Respiratory Distress Syndrome; Adipose tissue; Admission activity; Adult; Alveolar; Anatomy; Atelectasis; Attenuated; Automobile Driving; Blinded; Body Weight; Breathing; COVID-19; COVID-19 mortality; COVID-19 pandemic; Cause of Death; Chest wall structure; Clinical; Clinical Management; Cognitive; Cohort Studies; Edema; Esophagus; Etiology; Fibrosis; Grant; Healthcare Systems; Heterogeneity; Histologic; Hospitalization; Human; Hypoxemia; Impairment; Injury; Insufflation; Intensive Care; Intra-abdominal; Life; Lung; Manometry; Measures; Mechanical Stress; Mechanical ventilation; Mechanics; Modeling; Morbidity - disease rate; Multi-Institutional Clinical Trial; National Heart, Lung, and Blood Institute; Normal Range; Outcome; Pancreatitis; Patient-Focused Outcomes; Patients; Periodicity; Phase; Pleural; Pleural effusion disorder; Pneumonia; Positioning Attribute; Positive-Pressure Respiration; Pre-Clinical Model; Predisposition; Public Health; Pulmonary Edema; Randomized, Controlled Trials; Recovery; Relaxation; Research; Risk; Role; Safety; Sepsis; Shapes; Shock; Stress; Structure of parenchyma of lung; Survivors; Testing; Tidal Volume; Time; Titrations; Trauma; Ventilator; Ventilator-induced lung injury; abdominal pressure; arm; atelectrauma; circulating biomarkers; cost; experience; expiration; hemodynamics; improved; lung injury; lung volume; mortality; novel; personalized approach; personalized strategies; pre-clinical; pre-pandemic; pressure; prevent; psychologic; randomized trial; receptor for advanced glycation endproducts; recruit; soft tissue; standard care; standard of care; stress reduction; surfactant; systemic inflammatory response; treatment as usual; usual care arm; ventilation; volunteer

PROJECT SUMMARY / ABSTRACT Acute respiratory distress syndrome (ARDS) is a severe form of lung injury requiring hospitalization in intensive care and often invasive mechanical ventilation in effort to sustain life. ARDS can result from a variety of insults (e.g. pneumonia, sepsis, trauma, and pancreatitis), posing broad risk to the public health. With the COVID-19 pandemic, ARDS has become a leading cause of death in the US and globally. Yet, even pre-pandemic, ARDS occurred in 10% of US ICU admissions and had an associated mortality of 30-45%. Regardless of ARDS etiology, many survivors experience cognitive, psychological, and physical impairments persisting years after the acute illness resolves. Thus, there remains an urgent need to identify effective ARDS therapies. Invasive mechanical ventilation is potentially life-saving, but can worsen lung injury and patient outcomes if not precisely titrated to attenuate lung stress, which varies by patient with overdistension and atelectrauma (repetitive opening/closure of potentially recruitable lung). Alveolar edema and atelectasis reduce the functional aerated lung volume, such that tidal volume scaled to estimated healthy lung size (i.e. 6 mL/kg predicted body weight) may not always prevent overdistension. Similarly, positive end-expiratory pressure (PEEP) is routinely increased to recruit lung in patients with more severe hypoxemia, an approach that may exacerbate overdistension injury in patients most susceptible. An integrated strategy that mitigates the competing risks of atelectrauma and overdistension is needed. The range of lung stress observed in patients with ARDS receiving standard-of-care ventilation is often larger than that observed in healthy adults due to perturbed lung and chest wall mechanics, increasing risk of both atelectrauma and overdistension. In preclinical models and human cohort studies, lung injury and mortality are less when the ventilator is set to maintain lung stress in the healthy normal range. PREcision VENTilation to attenuate Ventilation-Induced Lung Injury (PREVENT VILI) is a phase III multicenter randomized trial for adults with moderate-severe ARDS that tests whether precise ventilator titration to maintain lung stress within 0-12 cm H2O, the healthy normal range during relaxed breathing, will improve patient outcomes compared to guided usual care. In the precision ventilation arm, PEEP will be individualized to achieve lung stress of 0 cm H2O at end-expiration, and tidal volume individualized to achieve driving pressure of 12 cm H2O or the lowest possible. In the guided usual care arm, PEEP will be adjusted per usual care within limits set to avoid practice extremes; tidal volume of 6-8 mL/kg predicted body weight will be targeted unless plateau pressure exceeds 30 cm H2O, in which case tidal volume will be lowered. We will evaluate the effect of ventilator strategy on 60-day mortality (Aim 1), lung injury (Aim 2), and hemodynamic instability (Aim 3). Findings will help determine the role for individualizing ventilator support to reduce lung stress in ARDS and have potential to improve survival from this leading cause of death worldwide.

项目摘要/摘要 急性呼吸窘迫综合征(ARDS)是一种严重的肺损伤，需要在重症监护病房住院治疗。 护理，经常是侵入性的机械通风，以努力维持生命。各种侮辱都可能导致不良反应。 (如肺炎、败血症、创伤和胰腺炎)，对公众健康构成广泛风险。与新冠肺炎合作 在大流行期间，ARDS已成为美国和全球主要的死亡原因。然而，即使在大流行之前，ARDS 发生在美国ICU住院患者的10%，相关死亡率为30%-45%。不考虑ARDS 病因学方面，许多幸存者在多年后仍会经历认知、心理和身体上的损伤 急病痊愈了。因此，仍然迫切需要确定有效的ARDS治疗方法。侵入性 机械通气有可能挽救生命，但如果不准确的话，可能会加重肺损伤和患者的预后 滴定以减轻肺压力，这种压力因过度扩张和非选择性创伤的患者而异(重复 打开/关闭潜在的可招募肺)。肺泡水肿和肺不张减少了功能性充气 肺容量，使潮气量达到估计的健康肺大小(即6毫升/公斤预测体重) 可能并不总是能防止过度膨胀。同样，呼气末正压(PEEP)也会常规增加。 在有更严重低氧血症的患者中重新招募肺，这一方法可能会加剧过度膨胀损伤 在最易感染的患者中。一种综合战略，可减轻非电击创伤和 过度膨胀是必要的。接受标准护理的ARDS患者的肺应激范围观察 由于肺部和胸壁机械结构的干扰，通气量通常比健康成年人的通气量大， 增加了非电击伤和过度膨胀的风险。在临床前模型和人类队列研究中，肺 当呼吸机设置为将肺压力维持在健康的正常范围时，损伤和死亡率较低。 精确呼吸机减轻呼吸机引起的肺损伤(预防VILI)是一项第三阶段多中心研究 成人中重度ARDS的随机试验，测试精确的呼吸机滴定是否能维持 在放松呼吸时，0-12厘米水的肺压力是健康的正常范围，将改善患者的预后。 与有指导的日常护理相比。在精准通气臂上，将PEEP个体化实现肺功能 呼气末压力为0 cm H2O，潮气量个性化，驱动压力为12 cm H2O 或者是最低的。在指导式常规护理臂中，PEEP将根据常规护理在设置为 避免极端练习；除非高原压力，否则潮气量将被设定为6-8毫升/公斤的预测体重 超过30厘米H2O，在这种情况下潮气量将降低。我们将评估呼吸机策略的效果 60天死亡率(目标1)、肺损伤(目标2)和血流动力学不稳定(目标3)。调查结果将有助于确定 个体化呼吸机支持在减轻ARDS患者肺应激和提高存活率中的作用 这是世界范围内的主要死因。