ELECTRO-BOOST: Electroencephalography for cerebral trauma recovery and oxygenation

ELECTRO-BOOST：用于脑外伤恢复和氧合的脑电图

• 批准号: 10033586
• 负责人: KAN DING
• 金额: $ 70.78万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10033586
• 关键词: Acute; Acute Brain Injuries; Address; Advocate; Aftercare; Anesthetics; Biological Markers; Brain; Brain Hypoxia; Brain Injuries; Cerebrum; Clinical; Clinical Treatment; Clinical Trials; Clinical Trials Network; Complex; Coupled; Critical Care; Delirium; Detection; Deterioration; Early Mobilizations; Electroencephalography; Electrographic Status Epilepticus; Emergency Care; Energy Supply; Epilepsy; Event; Exposure to; Failure; Frequencies; Future; Glasgow Coma Scale; Glasgow Outcome Scale; Goals; Hospitals; Hypoxia; Infrastructure; Infusion procedures; Injury; Intervention; Intervention Trial; Intracranial Hypertension; Intracranial Pressure; Knowledge; Length of Stay; Link; Measurable; Measures; Mechanical ventilation; Metabolic; Metabolism; Modeling; Monitor; Multi-Institutional Clinical Trial; Neurologic; Neurons; Outcome; Outcome Measure; Oxygen; Partial Pressure; Patient Monitoring; Patient-Focused Outcomes; Patients; Periodicity; Pharmaceutical Preparations; Pharmacotherapy; Phase; Population; Post-Traumatic Epilepsy; Randomized Controlled Trials; Research; Risk; Sedation procedure; Seizures; Site; Structure; TBI treatment; Therapeutic Intervention; Tissues; Trauma recovery; Traumatic Brain Injury; Treatment Protocols; Work; base; brain tissue; cerebral atrophy; clinical effect; clinical efficacy; cohort; density; design; experience; functional disability; functional outcomes; improved; improved outcome; innovation; multimodality; neurophysiology; phase III trial; pressure; programs; prospective test; response; signal processing; standard of care; tissue oxygenation; treatment guidelines; treatment strategy; treatment trial; trend

PROJECT SUMMARY Electrographic seizures (ESz) and high-frequency periodic discharges (HF-PD) are present in approximately 30% of severe traumatic brain injury (sTBI) patients and are associated with poor outcomes across a range of acute brain injuries. ESz and HF-PD are associated with hypermetabolism that demands more energy than supplied, particularly in patients vulnerable from acute brain injury. A gap in knowledge exists regarding whether ESz and HF-PD result in secondary brain injury in sTBI and are treatment-responsive. To date, no existing treatment guidelines are available regarding which epileptiform abnormalities result in secondary brain injury or respond to treatment after sTBI. Thus, our central hypothesis is that ESz and HF- PD represent a treatable biomarker of metabolic crisis and secondary brain injury in at-risk tissue. The long- range goal of our research program is to improve the outcomes of sTBI patients by developing treatment strategies that reduce acute secondary brain injury. The proposed project is significant because it will 1) establish if ESz and HF-PD exposure is linked with metabolic crisis, 2) quantify the impact of ESz and HF-PD on clinical outcome, and 3) investigate the effect of clinical treatment on ESz and HF-PD exposure in a large, generalizable population of sTBI patients. BOOST-3 (Brain Oxygen Optimization in Severe TBI Phase 3 trial, U01 NS099946) is a multicenter clinical trial to evaluate the clinical efficacy of a treatment strategy using invasively monitoring to optimize PbtO2 and ICP compared to ICP alone. It offers a unique infrastructure in a codified cohort to quantify the complex relationship between EEG abnormalities, PbtO2, ICP, clinical outcomes, and treatment. We will evaluate our central hypothesis in 250 BOOST-3 patients from selected BOOST-3 sites performing continuous EEG (cEEG) as standard of care in sTBI patients undergoing invasive multimodality monitoring. We will address the following specific aims: Specific Aim 1: Demonstrate the influence of ESz and HF-PD on brain tissue oxygenation after sTBI. We will establish the relationship between ESz, HF-PD, brain hypoxia, and elevated ICP to determine if ESz and HF-PD are a dynamic biomarker of secondary brain injury related to metabolic crisis after sTBI. Specific Aim 2: Quantify the effect of ESz and HF-PD exposure on functional outcome after sTBI. We will determine the effect of elevations in the peak exposure to ESz and HF-PD on functional outcome measured by Glasgow Outcome Scale – Extended (GOSE) 6 months after sTBI. Specific Aim 3: Quantify the effect of ESz and HF-PD exposure on functional outcome after sTBI. We will evaluate the change in ESz and HF-PD exposure after anti-seizure drug intervention. Further, we will measure the change in quantitative measures of EEG frequency and networks as well as Glasgow Coma Scale (GCS) score trends before and after the administration of anti-seizure drugs. The findings from this study will lead to future clinical trials of interventions targeting disrupted metabolism associated with ESz and HF-PD, in order to improve patient outcomes after sTBI.

项目摘要 电描记癫痫发作（ESz）和高频周期性放电（HF-PD）存在于 约 百分之三十 的 严重 创伤性 大脑 损伤 （sTBI） 患者 和 是 关联 与 贫困 成果 跨 一 范围 的 急性 大脑 受伤 ESz和HF-PD与高代谢有关， 能量超过供应量，特别是在易受急性脑损伤的患者中。知识上的差距 关于ESz和HF-PD是否导致sTBI中的继发性脑损伤以及是否对治疗有反应存在争议。 到目前为止，没有现有的治疗指南是关于癫痫样异常导致 继发性脑损伤或对sTBI后的治疗有反应。因此，我们的中心假设是ESz和HF- PD是代谢危象和高危组织继发性脑损伤的可治疗生物标志物。很长的- 我们研究项目的一系列目标是通过开发治疗方法来改善sTBI患者的预后 减少急性继发性脑损伤的策略。该项目之所以重要，是因为：（1） 确定ESz和HF-PD暴露是否与代谢危机有关，2）量化ESz和HF-PD的影响 临床结果，和3）研究临床治疗对ESz和HF-PD暴露的影响， sTBI患者的可推广人群。BOOST-3（重度TBI 3期试验中的脑氧优化， U 01 NS 099946）是一项多中心临床试验，旨在评价使用以下药物的治疗策略的临床疗效： 有创监测，以优化PbtO 2和ICP相比，单独的ICP。它提供了一个独特的基础设施， 编码队列，以量化EEG异常、PbtO 2、ICP、临床结局 和治疗。我们将在来自选定BOOST-3研究中心的250名BOOST-3患者中评估我们的中心假设 将连续EEG（cEEG）作为接受侵入性多模态治疗的sTBI患者的标准治疗 监测.具体目标1：展示ESz的影响力 和HF-PD对sTBI后脑组织氧合的影响。我们将建立ESz，HF-PD， 脑缺氧和ICP升高，以确定ESz和HF-PD是否是继发性脑损伤的动态生物标志物。 sTBI后代谢危象相关损伤。具体目标2：量化ESz和HF-PD暴露的影响 sTBI后的功能结果。我们将确定ESz峰值暴露升高的影响， HF-PD对sTBI后6个月通过格拉斯哥结局量表-扩展（GOSE）测量的功能结局的影响。 具体目标3：量化ESz和HF-PD暴露对sTBI后功能结局的影响。我们 将评价抗癫痫药物干预后ESz和HF-PD暴露量的变化。此外，我们将 测量EEG频率和网络以及格拉斯哥昏迷定量测量的变化 抗癫痫药物给药前后的GCS评分趋势。这一发现 这项研究将导致未来的临床试验的干预措施，目标是破坏代谢相关的 ESz和HF-PD，以改善sTBI后的患者结局。