Enhanced Bedside Microdialysis for TBI

针对 TBI 的增强型床边微透析

• 批准号: 9981842
• 负责人: Adrian C Michael
• 金额: $ 53.31万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9981842
• 关键词: Animal Model; Animals; Anti-Inflammatory Agents; Bedside Technology; Biological Assay; Blood flow; Brain; Brain Injuries; Cessation of life; Chemicals; Child; Clinical; Dangerousness; Devices; Dexamethasone; Diagnostic; Electrocorticogram; Electrodes; Electroencephalography; Epidemic; Female; Fluorescence Microscopy; Gender; Gliosis; Glucose; Goals; Hospitalization; Hypoglycemia; Immunohistochemistry; Incidence; Informed Consent; Injury; Institutional Review Boards; Institutionalized Persons; Intensive Care; Intracranial Pressure; Knowledge; Laboratories; Lead; Lesion; Liquid substance; Metabolic; Microdialysis; Monitor; Neurosciences; Neurosurgeon; Operative Surgical Procedures; Patient-Focused Outcomes; Patients; Performance; Perfusion; Persons; Physicians; Pregnant Women; Race; Rattus; Reporting; Research Personnel; Risk; Technology; Therapeutic; Time; Tissues; Translating; Traumatic Brain Injury; Vegetative States; Ventriculostomy; Wireless Technology; brain metabolism; brain tissue; clinical translation; controlled cortical impact; disability; injured; interstitial; male; medically necessary care; neurosurgery; new technology; postoperative recovery; pre-clinical; preclinical development; preclinical study; pressure sensor; prevent; recruit; temporal measurement

The goal of this project is to deliver enhanced bedside microdialysis for monitoring interstitial brain glucose and K+ levels in patients in intensive care after neurosurgery for severe traumatic brain injury. The ultimate objective is to quantify, in real time, the magnitude and duration of metabolic crises caused by spreading depolarization (SD), which are prevalent in the injured brain and underlie the secondary injury responsible for poor patient outcomes, including severe disability, vegetative state, and death. Electrocorticography (ECoG) shows that the injured brain is highly susceptible to SD but ECoG is not designed to detect or quantify the impact of SD on brain metabolism. Repolarization of tissues after SD requires such vast amounts of energy that glucose levels can be driven dangerously low, especially in injured tissue where blood flow to resupply glucose may be compromised. By quantifying the magnitude and duration of hypoglycemic episodes in the injury penumbra, we will deliver a diagnostic for secondary injury. The present absence of diagnostic technology is a roadblock to therapeutic strategies for managing secondary injury. Although clinical microdialysis has the demonstrated ability to quantify metabolic crisis after SD, substantial technical enhancements are urgently needed. Patients need to be monitored for 10 days after surgery but, due to gliosis at the probe track, conventional microdialysis is of limited value after 2-3 days. Preclinical studies in the Michael laboratory have demonstrated that retrodialysis of dexamethasone, a potent anti-inflammatory agent, is a simple yet highly effective means of extending functional microdialysis to at least 10 days. Microdialysis will be further enhanced by new technology, developed by the Boutelle group, for continuous, rapid, on-line, wireless, automated assays of glucose and K+ with 1-min temporal resolution. With the aid of expert neurosurgeons, we propose to translate enhanced microdialysis to patients with severe traumatic brain injury, to determine the statistical significance of correlations between chemical recordings and patient outcomes, and to continue the preclinical refinement of our enhanced microdialysis approaches.

该项目的目的是提供增强的床边微透析，以监测神经外科治疗后重症监护患者的间隙脑葡萄糖和K+水平的严重创伤性脑损伤。最终目标是实时量化由扩散去极化（SD）引起的代谢危机的幅度和持续时间，这些危机在受伤的大脑中普遍存在，并构成了导致患者不良结果的继发性损伤，包括严重的残疾，营养状态和死亡。 电皮质学（ECOG）表明，受伤的大脑对SD高度敏感，但ECOG并非旨在检测或量化SD对脑代谢的影响。 SD后组织的重极化需要大量的能量，以至于葡萄糖水平可以危险地驱动，尤其是在受伤的组织中，可能会损害血液流动以补充葡萄糖的血液。通过量化损伤阴影中降血糖发作的大小和持续时间，我们将提供继发性损伤的诊断。目前缺乏诊断技术是治疗次要伤害的治疗策略的障碍。尽管临床微透析具有量化SD后代谢危机的能力，但迫切需要大量的技术增强。需要在手术后10天监测患者，但是由于探针轨道上的神经胶质病，常规微透析在2-3天后的价值有限。迈克尔实验室中的临床前研究表明，有效的抗炎药的逆转录透析是将功能性微透析扩展到至少10天的一种简单而高效的方法。由Boutelle Group开发的新技术将进一步增强微透析，用于连续，快速，在线，无线，无线，自动化测定，对葡萄糖和K+进行1分钟的时间分辨率。借助专家神经外科医生，我们建议将增强的微透析转化为严重的脑损伤患者，以确定化学记录与患者结局之间相关性的统计学意义，并继续对我们增强的微透析方法的临时性进行精炼。