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.

项目总结/文摘