Measuring lung stress to identify occult ventilation-induced lung injury in ARDS

测量肺应激以识别 ARDS 患者隐匿性通气引起的肺损伤

• 批准号: 9918972
• 负责人: Jeremy R. Beitler
• 金额: $ 12.15万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-20 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9918972
• 关键词: Acute respiratory failure; Adult; Adult Respiratory Distress Syndrome; Alveolar; Atelectasis; Automobile Driving; Biological; Biological Markers; Body Weight; Breathing; Chest wall structure; Clinical; Critical Illness; Data; Development; Disease; Dysbarism; Edema; Esophagus; IL8 gene; Individual Differences; Inflammation; Inflammatory; Interleukin-6; Lung; Lung diseases; Manometry; Measures; Mechanical Stress; Mechanical ventilation; Mechanics; Mediastinal Emphysema; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Participant; Patient-Focused Outcomes; Patients; Phase; Physiological; Plasma; Pleural; Pneumothorax; Positive-Pressure Respiration; Protocols documentation; Pulmonary Surfactant-Associated Protein D; Reporting; Research; Risk; Safety; Stress; Subcutaneous Emphysema; Testing; Tidal Volume; Time; Tissues; Titrations; Validation; Ventilator; Vital Status; alveolar epithelium; base; cohort; cytokine; epithelial injury; esophagus pressure; experience; high risk; improved; individual patient; lung injury; lung volume; mortality; mortality risk; novel; novel strategies; personalized approach; personalized strategies; precision medicine; predict clinical outcome; pressure; prevent; prognostic value; public health relevance; randomized trial; rate of change; respiratory; secondary analysis; soluble RAGE; standard of care; ventilation

PROJECT SUMMARY/ABSTRACT Acute respiratory distress syndrome (ARDS) occurs in up to one-quarter of all critically ill adults receiving mechanical ventilation and is associated with high risk of death. In patients with ARDS, the volume of aerated lung is reduced substantially relative to healthy lung size due to alveolar edema and atelectasis. This smaller “baby lung,” so-called for its reduced aerated volume available for ventilation, requires smaller tidal volume (Vt) than would be needed in healthy lungs to prevent regional overdistension. Low Vt ventilation limits ventilation- induced lung injury (VILI) and improves survival in patients with ARDS. Current standard of care involves scaling Vt to estimated healthy lung size, i.e. 6 mL/kg predicted body weight (PBW), and limiting end- inspiratory plateau airway pressure to ≤ 30 cmH2O. Yet, lung stress and strain vary considerably between ARDS patients receiving the same Vt per PBW due to individual differences in baby lung size and chest wall mechanics. Ideally, a precision medicine approach to Vt strategy in ARDS would account for these individual patient differences to better limit maximum lung distension at end-inspiration. By using esophageal manometry to estimate pleural pressure, one can measure at bedside the mechanical stress across the lung, independent of chest wall mechanics, as the transpulmonary pressure (lung stress = airway pressure – pleural pressure). In a prior study, we found peak lung stress measured at end-inspiration was highly correlated with “baby lung” volume (diseased lung size) but not Vt scaled to PBW (healthy lung size). Peak lung stress also independently predicted mortality in this cohort. This proposal seeks to (1) advance biological plausibility of peak lung stress as a bedside marker of ongoing VILI despite low Vt and (2) validate its prognostic utility for predicting patient- centered outcomes in ARDS. Our central hypothesis is that ARDS patients with higher peak lung stress experience more VILI and higher mortality despite low Vt ventilation. We will test this hypothesis via a secondary analysis of clinical, physiological, and biomarker data from the EPVent-2 Trial, a phase-II multicenter randomized trial of esophageal pressure-guided positive end-expiratory pressure (PEEP) titration in ARDS. Peak lung stress will be measured daily from respiratory physiological waveforms recorded in all trial participants. Plasma biomarkers for alveolar epithelial injury (sRAGE, surfactant protein-D) and systemic inflammation (IL-6, IL-8), as well as overt barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema), will be used as biological and clinical measures of VILI. Vital status and ventilator-free days will be used to determine prognostic utility of peak lung stress for predicting clinical outcomes in patients with ARDS. This research will elucidate mechanisms of occult VILI in patients receiving the current standard-of-care “lung-protective” Vt strategy. Ultimately, results may inform development of novel strategies for individualizing Vt based on peak lung stress in effort to reduce morbidity and mortality from ARDS.

项目总结/摘要 急性呼吸窘迫综合征（ARDS）发生在所有重症成人中的四分之一， 机械通气并与高死亡风险相关。在ARDS患者中， 由于肺泡水肿和肺不张，肺相对于健康肺的大小显著减小。这个较小 所谓的“婴儿肺”是因为其可用于通气的通气量减少，需要较小的潮气量（Vt） 比健康肺防止局部过度扩张所需的量要多。低Vt通气限制通气- 诱导的肺损伤（VILI），并改善ARDS患者的生存率。目前的护理标准包括 将Vt按比例缩放至估计的健康肺大小，即6 mL/kg预测体重（PBW），并限制终末- 吸气平台气道压≤ 30 cmH 2 O。然而，肺的应力和应变在以下两种情况之间变化很大： 由于婴儿肺大小和胸壁的个体差异，每个PBW接受相同Vt的ARDS患者 力学理想情况下，ARDS中Vt策略的精确医学方法将解释这些个体 患者差异，以更好地限制吸气末的最大肺扩张。通过食管测压 为了估计胸腔压，可以在床边独立测量整个肺部的机械应力 胸壁力学，如经肺压力（肺应力=气道压力-胸膜压力）。在 在先前的研究中，我们发现在吸气末测量的峰值肺应力与“婴儿肺”高度相关。 体积（患病肺大小），但Vt未缩放至PBW（健康肺大小）。峰值肺应力也独立于 预测死亡率。该建议旨在（1）提高峰值肺应力的生物相容性 作为进行性VILI的床旁标志物，尽管Vt较低;（2）验证其预测患者预后的实用性， 以ARDS为中心的结局。我们的中心假设是，具有较高峰值肺应力的ARDS患者 尽管有低Vt通气，VILI和死亡率仍较高。我们将通过一个 对EPVent-2试验（II期）的临床、生理和生物标志物数据进行二次分析 食管压力引导的呼气末正压（PEEP）滴定治疗食管癌的多中心随机试验 ARDS。每天根据所有试验中记录的呼吸生理波形测量峰值肺应力 参与者肺泡上皮损伤的血浆生物标志物（sIgA，表面活性蛋白-D）和全身性 炎症（IL-6，IL-8），以及明显的气压伤（气胸，肺气肿，皮下 肺气肿）将用作VILI的生物学和临床测量。生命状态和无呼吸机天数将 用于确定峰值肺应力预测患者临床结局的预后效用， ARDS。这项研究将阐明接受当前标准治疗的患者中隐匿性VILI的机制 “肺保护”VT策略。最终，研究结果可能会为个性化的新策略的发展提供信息。 以肺压力峰值为基础的Vt，旨在降低ARDS的发病率和死亡率。

项目成果

Emerging concepts in ventilation-induced lung injury.

• DOI: 10.12688/f1000research.20576.1
• 发表时间: 2020-01-01
• 期刊: F1000Research
• 作者: Madahar, Purnema;Beitler, Jeremy R
• 通讯作者: Beitler, Jeremy R

Incorporating baseline functional status to improve validity of neurological outcome assessments following cardiac arrest.

纳入基线功能状态以提高心脏骤停后神经系统结果评估的有效性。

• DOI: 10.1016/j.resuscitation.2019.07.006
• 发表时间: 2019
• 期刊: Resuscitation
• 影响因子: 6.5
• 作者: Eng,KevinJ;Yang,JennyZ;Tyagi,Sanjeev;Odish,MazenF;Rosen,Sheri;Sell,RebeccaE;Beitler,JeremyR
• 通讯作者: Beitler,JeremyR

Strategies to Adjust Positive End-Expiratory Pressure in Patients With ARDS-Reply.

调整 ARDS-Reply 患者呼气末正压的策略。

• DOI: 10.1001/jama.2019.7888
• 发表时间: 2019
• 期刊: JAMA
• 作者: Beitler,JeremyR;Talmor,Daniel
• 通讯作者: Talmor,Daniel