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）

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要急性呼吸窘迫综合征 (ARDS) 是一种严重的肺损伤，需要住院治疗护理和经常有创机械通气以努力维持生命。 ARDS 可能由多种侮辱引起（例如肺炎、败血症、创伤和胰腺炎），对公众健康构成广泛风险。随着新冠肺炎 (COVID-19) 大流行期间，ARDS 已成为美国和全球的主要原因。然而，即使在大流行前，ARDS 10% 的美国 ICU 入院患者发生这种情况，相关死亡率为 30-45%。无论ARDS 由于病因学原因，许多幸存者在多年后仍经历认知、心理和身体损伤急性疾病痊愈。因此，仍然迫切需要确定有效的 ARDS 疗法。侵入性机械通气有可能挽救生命，但如果不准确，可能会加重肺损伤和患者的预后滴定以减轻肺应激，肺应激因过度扩张和肺不张（重复性肺不张）患者而异潜在可复张肺的打开/关闭）。肺泡水肿和肺不张降低功能通气量肺容量，使潮气量适应估计的健康肺大小（即 6 mL/kg 预测体重）可能并不总能防止过度膨胀。同样，呼气末正压（PEEP）通常会增加对严重低氧血症患者进行肺复张，这种方法可能会加剧过度扩张损伤最易受影响的患者。减轻肺不张和肺不张的竞争风险的综合策略需要过度扩张。在接受标准护理的 ARDS 患者中观察到的肺应激范围由于肺部和胸壁力学受到干扰，通气量通常大于健康成人观察到的通气量，肺不张和过度扩张的风险增加。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内时，伤害和死亡率会减少。 PREcision VENTilation 减轻通气引起的肺损伤 (PREVENT VILI) 是一项 III 期多中心研究针对中重度 ARDS 成人的随机试验，测试精确的呼吸机滴定是否能够维持肺压力在 0-12 cm H2O 范围内（轻松呼吸时的健康正常范围）将改善患者的治疗结果与指导性常规护理相比。在精准通气臂中，PEEP将个体化以实现肺呼气末压力为 0 cm H2O，潮气量个性化以实现 12 cm H2O 的驱动压力或最低的可能。在指导性常规护理组中，PEEP 将根据常规护理在设定的限度内进行调整避免练习极端；潮气量的目标是 6-8 mL/kg 预测体重，除非平台压超过 30 cm H2O，在这种情况下潮气量将会降低。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 肺应激方面的作用并有可能提高生存率来自这一全球主要死亡原因。