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 需要入侵通气的急性呼吸衰竭（ARF）发生在重症监护病房的三分之一（ICU） 患者，与高死亡风险有关。通风引起的肺损伤（VILI）是可修改的 当高风险肺部经历过多的全球或区域性时，ARF结果的决定因素 压力/应变。 VILI可能是由于呼吸机和/或呼吸肌肉施加的过量力所致。 广泛研究了优化呼吸机滴定，而对的贡献知之甚少 自发的呼吸努力为vili在ARF中。高呼吸驱动会导致有害的潮汐量， 通过同步努力或呼气堆叠异步的增加来增加全球压力/应变 呼吸机模式。高驱动器还会导致暂时的异质不足，增加了潮汐内区域 给定潮汐体积的应变。两种与呼吸驱动有关的模式增加了应力/应变恶化的肺 临床前模型的损伤，在ARF患者中观察到，但它们是否在临床上贡献 患者有意义的肺损伤尚不清楚。极端的驱动器，高或低，也可能引起临床相关的 膜片损伤。高驱动风险会导致负载引起的伤害，尤其是在流动限制的呼吸机模式或某些方面 患者 - 视频症患者的异步性相对于患者的努力过早结束。低的 驱动风险会隔膜消除萎缩，事实证明，一些患者在几天内发生在呼吸机上。 ARF驱动异质性的原因尚未确定。化学感受器，机械感受器和皮质 输入（例如疼痛，焦虑）是呼吸驱动的良好调节剂，但仅它们并没有完全 解释ARF中的驱动异质性。尽管深层镇静通常会抑制健康的呼吸驱动 个人，我们最近发现，镇静深度和呼吸驱动与ARF相关。许多 患者表现出高驱动力对深镇静的难治性，而在其他情况下，即使是轻度镇静也可以完全 消除驱动器。我们的初步数据表明系统性炎症的差异可能解释了这一动力 异质性。这项研究将加深对驱动异质性及其基础机制的理解 ARF患者的临床结局的关系。我们的总体假设是系统性炎症是 呼吸道驱动的关键决定因素，极端造成临床上重要的肺和隔膜损伤。 我们将组装一个前瞻性的两院，多ICU队列 生物标志物被串行确定。 AIM 1评估循环炎症标记作为潜在的贡献者 驱动异质性。 AIM 2决定了极端呼吸驱动可能有助于的机制 肺和膜片损伤。 AIM 3评估呼吸驱动和拔管时间之间的关系。 这项工作的发现将为制定精确通风策略提供信息，并结合呼吸系统 在以后的临床试验中进行评估，以优化肺和隔膜保护。