Impact of Autonomic Dysfunction on Multi-Organ Dysfunction following Severe TBI: The AUTO-BOOST Study

严重 TBI 后自主神经功能障碍对多器官功能障碍的影响：AUTO-BOOST 研究

基本信息

批准号：
10607731
负责人：
Vijay Krishnamoorthy
金额：
$ 71.43万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10607731
关键词：
Address Admission activity Adult Affect Age Ancillary Study Autonomic Dysfunction Autonomic nervous system Biological Markers Brain Brain Injuries Cardiac Cephalic Cerebrum Cessation of life Clinical Clinical Data Clinical Trials Cohort Studies Complex Critical Care Data Development Emergency department visit Frequencies Functional disorder Future Glasgow Outcome Scale Goals Guidelines Heart Injuries Hospitalization Hour Hypoxia Incidence Individual Inflammatory Infrastructure Injury Injury to Kidney Intracranial Hypertension Intracranial Pressure Managed Care Metabolic Multi-Institutional Clinical Trial Neurological outcome Organ Organ failure Outcome Oxygen Patient-Focused Outcomes Patients Performance Pilot Projects Pressoreceptors Prevalence Public Health Research Secondary to Sedation procedure Signal Transduction Standardization Sympathetic Nervous System TBI Patients Telemetry Testing Traumatic Brain Injury Troponin United States brain tissue cerebral hypoperfusion clinical care clinical efficacy cohort functional outcomes heart rate variability hemodynamics high risk improved improved outcome indexing injury-related death lung injury mortality risk organ injury participant enrollment phase III trial post gamma-globulins predictive modeling pressure prevent receptor for advanced glycation endproducts risk prediction sex therapy development treatment strategy

项目摘要

PROJECT SUMMARY/ABSTRACT Traumatic brain injury (TBI) is a major public health concern, affecting more than 1.5 million individuals annually in the United States. Extracranial multi-organ dysfunction (MODS) occurs in approximately 60% of severe TBI patients and contributes to secondary brain injuries, increased risk for mortality, and poor functional outcomes over the year following TBI. Our prior research has demonstrated that the prevalence of early autonomic nervous system dysfunction is high following severe TBI and associated with cerebral metabolic crisis and MODS development. Although treatments for autonomic dysfunction following severe TBI are readily available, a complete characterization of the course of autonomic dysfunction following severe TBI that would be adequate to guide therapy is lacking. Therefore, a comprehensive characterization of autonomic dysfunction after TBI and an understanding of how early autonomic dysfunction contributes to episodes of cerebral metabolic crisis and extracranial organ injury are urgently needed to guide the development of therapies to improve patient outcomes following TBI. To address this, we propose the following specific aims using unique and granular waveform data from the BOOST-3 (Brain Oxygen Optimization in Severe TBI Phase 3 trial, U01 NS099946) clinical trial: 1) Determine the burden of early autonomic dysfunction and its relationship to cerebral metabolic crisis following severe TBI, 2) Determine the relationship of early autonomic dysfunction with extracranial MODS and functional neurologic outcomes following severe TBI, and 3) Assess the uniqueness and added value of cardiac waveform data in predicting risk for MODS and functional neurologic outcomes following severe TBI. Successful completion of this study will solidify our understanding of the effects of autonomic dysfunction after severe TBI, and inform trials to determine the impact of modulating autonomic dysfunction on the development of MODS and poor outcomes following severe TBI. Our long-term goal is to develop strategies to personalize critical care management in order to improve clinical outcomes after severe TBI in adults.

项目概要/摘要创伤性脑损伤 (TBI) 是一个重大的公共卫生问题，每年影响超过 150 万人在美国。大约 60% 的严重 TBI 发生颅外多器官功能障碍 (MODS) 患者并导致继发性脑损伤、死亡风险增加和功能结果不佳 TBI 后一年内。我们之前的研究表明，早期自主神经症的患病率严重 TBI 后系统功能障碍严重，并与脑代谢危象和 MODS 相关发展。尽管严重 TBI 后自主神经功能障碍的治疗方法很容易获得，但严重 TBI 后自主神经功能障碍过程的完整表征就足够了缺乏指导治疗。因此，TBI 和 TBI 后自主神经功能障碍的综合表征了解早期自主神经功能障碍如何导致脑代谢危机的发生迫切需要颅外器官损伤来指导治疗方法的开发，以改善患者的预后 TBI 后。为了解决这个问题，我们使用独特且精细的波形数据提出以下具体目标来自 BOOST-3（严重 TBI 中的脑氧优化 3 期试验，U01 NS099946）临床试验：1) 确定早期自主神经功能障碍的负担及其与术后脑代谢危象的关系严重TBI，2）确定早期自主神经功能障碍与颅外MODS和功能的关系严重 TBI 后的神经系统结果，以及 3) 评估心脏波形的独特性和附加值预测严重 TBI 后 MODS 风险和功能性神经系统结果的数据。顺利完成这项研究将巩固我们对严重 TBI 后自主神经功能障碍影响的理解，并为我们提供信息确定调节自主神经功能障碍对 MODS 和穷人的发展影响的试验严重 TBI 后的结果。我们的长期目标是制定个性化重症监护策略管理以改善成人严重 TBI 后的临床结果。