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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要接受治疗的所有危重成人中，多达四分之一发生急性呼吸窘迫综合征 (ARDS) 机械通气与 ARDS 患者的高死亡风险相关。由于肺泡水肿和肺不张，肺相对于健康肺的大小大幅减小。 “婴儿肺”因其可用于通气的通气量减少而被称为“婴儿肺”，需要较小的潮气量 (Vt) 低于健康肺部所需的量，以防止局部通气过度膨胀。诱导性肺损伤（VILI）并提高 ARDS 患者的生存率。将 Vt 缩放至估计的健康肺大小，即 6 mL/kg 预测体重 (PBW)，并限制最终吸气平台气道压力≤ 30 cmH2O 然而，肺压力和应变之间差异很大。由于婴儿肺部大小和胸壁的个体差异，ARDS 患者每 PBW 接受相同的 Vt 理想情况下，ARDS 中 Vt 策略的精准医学方法将考虑到这些个体。通过使用食管测压法更好地限制患者的差异以限制吸气末的最大肺膨胀。为了估计胸膜压，可以在床边测量整个肺部的机械应力，独立的胸壁力学，如跨肺压（肺压力=气道压力-胸膜压力）。之前的一项研究，我们发现吸气末测量的峰值肺压力与“婴儿肺”高度相关体积（患病肺大小），但 Vt 也独立缩放至 PBW（健康肺大小）。该提案旨在 (1) 提高肺应激峰值的生物学合理性。尽管 Vt 较低，但仍可作为持续 VILI 的床边标志物，并且 (2) 验证其预测患者的预后效用 ARDS 的中心结果是 ARDS 患者的肺应激峰值较高。尽管 Vt 通气量较低，但仍会经历更多的 VILI 和更高的死亡率，我们将通过对 II 期 EPVent-2 试验的临床、生理和生物标志物数据进行二次分析食管压力引导呼气末正压 (PEEP) 滴定的多中心随机试验 ARDS。每天根据所有试验中记录的呼吸生理波形测量峰值肺压力。肺泡上皮损伤（sRAGE、表面活性蛋白-D）和全身的血浆生物标志物。炎症（IL-6、IL-8）以及明显的气压伤（气胸、纵隔气肿、皮下气肿）肺气肿），将用作 VILI 的生物学和临床指标以及无呼吸机天数。用于确定肺应激峰值的预后效用，以预测患有以下疾病的患者的临床结果这项研究将阐明接受当前标准护理的患者发生隐匿性 VILI 的机制。最终，结果可能会为个体化新策略的开发提供信息。 Vt 基于肺应激峰值，旨在降低 ARDS 的发病率和死亡率。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lung protection in acute respiratory distress syndrome: what should we target?

急性呼吸窘迫综合征的肺部保护：我们应该瞄准什么？

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Beitler; Jeremy R
通讯作者：
Jeremy R

Reverse Triggering, the Rhythm Dyssynchrony: Potential Implications for Lung and Diaphragm Protection.

反向触发，节律不同步：对肺和隔膜保护的潜在影响。

DOI：
发表时间：
2021
期刊：
影响因子：
24.7
作者：
Telias, Irene;Beitler, Jeremy R
通讯作者：
Beitler, Jeremy R

Emerging concepts in ventilation-induced lung injury.

通气引起的肺损伤的新兴概念。

DOI：
发表时间：
2020
期刊：
影响因子：
0
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：
发表时间：
2019
期刊：
影响因子：
6.5
作者：
Eng, Kevin J;Yang, Jenny Z;Tyagi, Sanjeev;Odish, Mazen F;Rosen, Sheri;Sell, Rebecca E;Beitler, Jeremy R
通讯作者：
Beitler, Jeremy R

Transpulmonary Pressure-guided Ventilation to Attenuate Atelectrauma and Hyperinflation in Acute Lung Injury.

跨肺压力引导通气可减轻急性肺损伤中的肺不张和过度充气。