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.

项目摘要/摘要 需要有创呼吸机的急性呼吸衰竭(ARF)发生在三分之一的重症监护病房(ICU) 并与高死亡风险有关。呼吸机诱导的肺损伤(VILI)是一种可修改的 高危肺出现全局性或区域性过度时发生ARF结局的决定因素 应力/应变。VILI可能是呼吸机和/或呼吸肌用力过大所致。 优化呼吸机滴定已经得到了广泛的研究，但对其贡献还知之甚少 ARF中VILI的自主呼吸努力。高速呼吸驱动会导致有害的高潮气量， 以同步努力或呼吸堆叠不同步的方式增加全球压力/紧张，具体取决于 呼吸机模式。高驱动力还会导致时间上的不均匀注气，增加潮内区域 对给定潮气量的应变。两种与呼吸驱动相关的压力/应变增加模式都会使肺恶化 临床前模型中的损伤已经在ARF患者中观察到，但它们是否在临床上起作用 患者是否存在有意义的肺损伤尚不清楚。极端的驱动力，无论是高还是低，也可能导致临床相关 横隔膜损伤。高驾驶风险负荷导致的伤害，特别是在限流呼吸机模式或某些 患者-呼吸机不同步，吸气支持相对于患者努力提前结束。低 驾驶风险隔膜废用萎缩，证明在一些患者在几天内发生在呼吸机上。 ARF中驱动器异质性的原因还没有很好地确定。化学感受器、机械感受器和皮质 输入(如疼痛、焦虑)是公认的呼吸动力调节器，但它们本身并不能完全发挥作用 解释ARF中的驱动器异质性。尽管深度镇静通常会抑制健康人的呼吸动力 对于个体，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，即使是轻度镇静也可以完全镇静。 消除驱动力。我们的初步数据表明，全身炎症的差异可能解释了这种驱动力 异质性。这项研究将加深对驱动异质性背后的机制以及其 急性肾功能衰竭与临床结局的关系。我们的总体假设是全身性炎症是 呼吸驱动的关键决定因素，其极端情况会导致临床上重要的肺和横隔膜损伤。 我们将组建一个预期的两家医院、多个ICU的队列，在这些队列中，呼吸力学和血清 生物标志物是按顺序确定的。AIM 1评估循环炎症标志物作为潜在的贡献者 以推动异质性。目标2确定极端的呼吸驱动可能有助于 肺和横隔膜损伤。目的3评价呼吸驱动与拔管时间的关系。 这项工作的发现将为开发包括呼吸在内的精确通风策略提供参考 推动优化肺和横隔膜保护，以便在未来的临床试验中进行评估。