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.

该项目的目标是提供增强的床边微透析，以监测严重创伤性脑损伤神经外科手术后重症监护患者的脑间质葡萄糖和 K+ 水平。最终目标是实时量化由扩散去极化 (SD) 引起的代谢危机的严重程度和持续时间，这种情况在受伤的大脑中普遍存在，是导致患者预后不良的继发性损伤的基础，包括严重残疾、植物人状态和死亡。 皮质电图 (ECoG) 显示受伤的大脑对 SD 高度敏感，但 ECoG 的目的并不是检测或量化 SD 对大脑代谢的影响。 SD 后组织的复极化需要大量能量，导致葡萄糖水平可能降至危险的低水平，尤其是在受损组织中，补充葡萄糖的血流可能受到损害。通过量化损伤半暗带中低血糖发作的程度和持续时间，我们将对继发性损伤进行诊断。目前缺乏诊断技术是控制继发性损伤的治疗策略的障碍。尽管临床微透析已被证明能够量化 SD 后的代谢危机，但仍迫切需要实质性的技术改进。手术后需要对患者进行 10 天的监测，但由于探针轨道处有神经胶质增生，传统的微透析在 2-3 天后的价值有限。 Michael 实验室的临床前研究表明，地塞米松（一种有效的抗炎剂）的逆透析是一种简单而高效的方法，可将功能性微透析时间延长至少 10 天。 Boutelle 集团开发的新技术将进一步增强微透析技术，以 1 分钟的时间分辨率连续、快速、在线、无线、自动地检测葡萄糖和 K+。在神经外科医生专家的帮助下，我们建议将增强型微透析应用于严重创伤性脑损伤患者，以确定化学记录与患者结果之间相关性的统计显着性，并继续对增强型微透析方法进行临床前改进。