Respiratory Drive in Acute Respiratory Failure

急性呼吸衰竭中的呼吸驱动

• 批准号: 10637245
• 负责人: Jeremy R. Beitler
• 金额: $ 75.05万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10637245
• 关键词: Acute Respiratory Distress Syndrome; Acute respiratory failure; Advanced Development; Angiopoietin-2; Anxiety; Attenuated; Automobile Driving; Biological Markers; Blood - brain barrier anatomy; Breathing; Carbon Dioxide; Carotid Body; Chemoreceptors; Clinical; Clinical Data; Clinical Trials; Critical Illness; Cytokine Receptors; Data; Development; Disuse Atrophy; Electronic Health Record; Esophagus; Evaluation; Exhalation; Exhibits; Future; Heterogeneity; Hospitals; IL8 gene; Individual; Inflammation; Inflammatory; Injury; Injury to Diaphragm; Insufflation; Intensive Care Units; Investigation; Knowledge; Light; Link; Lung; Manometry; Measures; Mechanical ventilation; Mechanics; Mechanoreceptors; Morbidity - disease rate; Muscle; Outcome; Oxygen; Pain; Pathway interactions; Patients; Pattern; Physicians; Pre-Clinical Model; Prevention; Receptor Signaling; Refractory; Reporting; Research; Residual state; Resolution; Respiratory Diaphragm; Respiratory Mechanics; Respiratory Muscles; Risk; Sampling; Sedation procedure; Serum; Stress; Structure; Syndrome; Testing; Tidal Volume; Time; Titrations; Ventilator; Ventilator-induced lung injury; Work; adjudication; circulating biomarkers; clinical diagnosis; clinically relevant; cohort; cytokine; electrical impedance tomography; experience; high risk; inflammatory marker; lung injury; mortality; mortality risk; multiorgan injury; premature; pressure; prospective; respiratory; systemic inflammatory response; ultrasound; ventilation

PROJECT SUMMARY/ABSTRACT Acute respiratory failure (ARF) requiring invasive ventilation occurs in one-third of intensive care unit (ICU) patients and is associated with a high risk of death. Ventilation-induced lung injury (VILI) is a modifiable determinant of ARF outcomes that develops when the at-risk lung experiences excessive global or regional stress/strain. VILI may result from excessive forces applied by the ventilator and/or respiratory muscles. Optimizing ventilator titration has been studied extensively, while far less is known about the contribution of spontaneous breathing effort to VILI in ARF. High respiratory drive can cause injuriously high tidal volumes, increasing global stress/strain either with synchronous effort or breath stacking dyssynchrony depending on ventilator mode. High drive also causes temporally heterogeneous insufflation, increasing intra-tidal regional strain for a given tidal volume. Both patterns of respiratory drive-related increase in stress/strain worsen lung injury in preclinical models and have been observed in patients with ARF, but whether they contribute clinically meaningful lung injury in patients is unclear. Extremes of drive, high or low, also may cause clinically relevant diaphragm injury. High drive risks load-induced injury, particularly in flow-limited ventilator modes or certain patient-ventilator dyssynchronies in which inspiratory support ends prematurely relative to patient effort. Low drive risks diaphragm disuse atrophy, proven to occur in some patients within a few days on the ventilator. Causes of drive heterogeneity in ARF are not well established. Chemoreceptor, mechanoreceptor, and cortical inputs (e.g. pain, anxiety) are well established modulators of respiratory drive, but they alone do not fully explain drive heterogeneity in ARF. Although deep sedation often suppresses respiratory drive in healthy individuals, we recently found that sedation depth and respiratory drive are not well correlated in ARF. Many patients exhibit high drive refractory to deep sedation, while in others even light sedation can completely eliminate drive. Our preliminary data suggest differences in systemic inflammation might explain this drive heterogeneity. This research will deepen understanding of mechanisms underlying drive heterogeneity and its relationship with clinical outcomes in patients with ARF. Our overall hypothesis is that systemic inflammation is a key determinant of respiratory drive, extremes of which cause clinically important lung and diaphragm injury. We will assemble a prospective two-hospital, multi-ICU cohort in whom respiratory mechanics and serum biomarkers are ascertained serially. Aim 1 evaluates circulating inflammatory markers as a potential contributor to drive heterogeneity. Aim 2 determines mechanisms by which extremes of respiratory drive may contribute to lung and diaphragm injury. Aim 3 evaluates the relationship between respiratory drive and time to extubation. Findings from this work will inform development of a precision ventilation strategy, incorporating respiratory drive to optimize lung and diaphragm protection, for evaluation in a future clinical trial.

项目概要/摘要 三分之一的重症监护病房 (ICU) 发生需要有创通气的急性呼吸衰竭 (ARF) 患者，并与高死亡风险相关。通气引起的肺损伤（VILI）是一种可改变的疾病 当有风险的肺部经历过度的全球或区域性的ARF结果时，ARF结果的决定因素 压力/应变。 VILI 可能是由于呼吸机和/或呼吸肌施加过大的力造成的。 优化呼吸机滴定已被广泛研究，但人们对优化呼吸机滴定的贡献知之甚少。 ARF 中自主呼吸努力至 VILI。高呼吸动力会导致有害的高潮气量， 通过同步努力或呼吸叠加不同步来增加整体压力/应变，具体取决于 呼吸机模式。高驱动力还会导致时间上不均匀的注入，增加潮内区域 给定潮气量的应变。两种与呼吸驱动相关的压力/应变增加模式都会使肺部恶化 临床前模型中存在损伤，并且已在 ARF 患者中观察到，但它们是否有助于临床 对患者有意义的肺损伤尚不清楚。极端的驱动力，无论高还是低，也可能导致临床相关的 膈肌损伤。高驱动力存在负载引起的伤害的风险，特别是在限流呼吸机模式或某些特定模式下 患者与呼吸机不同步，即吸气支持相对于患者的努力过早结束。低的 驱动风险 膈肌废用性萎缩，已被证明发生在一些使用呼吸机几天内的患者身上。 ARF 中驱动异质性的原因尚未明确。化学感受器、机械感受器和皮质 输入（例如疼痛、焦虑）是呼吸驱动的成熟调节剂，但它们本身并不能完全 解释 ARF 中的驱动异质性。尽管深度镇静通常会抑制健康人的呼吸驱动 我们最近发现在 ARF 中镇静深度和呼吸驱动没有很好的相关性。许多 患者表现出对深度镇静无效的高驱动力，而在其他患者中，即使轻度镇静也可以完全 消除驱动力。我们的初步数据表明，全身炎症的差异可能可以解释这种驱动力 异质性。这项研究将加深对驱动异质性及其背后机制的理解 与 ARF 患者临床结局的关系。我们的总体假设是全身性炎症是 呼吸动力的关键决定因素，极端情况会导致临床上重要的肺和膈肌损伤。 我们将组建一个前瞻性的两家医院、多 ICU 队列，其中呼吸力学和血清 生物标志物是连续确定的。目标 1 评估循环炎症标志物作为潜在贡献者 来驱动异质性。目标 2 确定极端呼吸驱动可能导致的机制 肺和膈肌损伤。目标 3 评估呼吸动力与拔管时间之间的关系。 这项工作的结果将为制定精准通气策略提供信息，其中包括呼吸系统 推动优化肺和膈肌保护，以便在未来的临床试验中进行评估。