Goal directed cardiopulmonary resuscitation in cardiac arrest using a novel physiological target: A pilot mechanistic randomized control trial

使用新型生理目标进行心脏骤停的目标导向心肺复苏：一项试点机械随机对照试验

• 批准号: 10471231
• 负责人: Sam Parnia
• 金额: $ 34.6万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-04 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10471231
• 关键词: Address; American Heart Association; Anoxia; Anoxic Encephalopathy; Attenuated; Awareness; Biological Markers; Blood Circulation; Blood specimen; Brain; Brain Injuries; Carbon Dioxide; Cardiac; Cardiac Output; Cardiopulmonary Resuscitation; Categories; Cerebrum; Cessation of life; Clinical Trials; Conscious; Data; Dose; Encephalitis; Enzyme-Linked Immunosorbent Assay; Event; Exhibits; Feedback; Goals; Gold; Grant; Health; Heart; Heart Arrest; Hospitals; Hour; Impairment; Incidence; Inflammation; Inflammatory; Injury; Ischemia; Measures; Meta-Analysis; Methods; Monitor; Morbidity - disease rate; Near-Infrared Spectroscopy; Nervous System Physiology; Nervous System Trauma; Neurologic; Neurological outcome; Neurological status; Observational Study; Organ; Outcome; Outcome Measure; Oxygen; Patients; Performance; Perfusion; Physiological; Process; Randomized; Randomized Controlled Trials; Recommendation; Reperfusion Injury; Reperfusion Therapy; Resuscitation; Serum; Site; Survival Rate; System; Testing; Time; Tissues; attenuation; cerebral oxygenation; cost; diagnostic accuracy; improved; mortality; novel; outcome prediction; pilot trial; primary outcome; prospective; recruit; response; secondary outcome; survival outcome

Project Summary/Abstract Cardiac arrest (CA) has an estimated annual incidence of 250-350,000 out-of-hospital and 250-750,000 in- hospital events in the U.S., with survival rates as low as 5% and 20% respectively. Anoxic brain injury remains a major health burden for those who survive to hospital discharge. These outcomes reflect a two-step injury process including a) whole body anoxia/isquemia and b) secondary reperfusion and inflammation injury following return of spontaneous circulation (ROSC). As secondary injuries are determined by the magnitude of ischemia during CA, the ability to ameliorate ischemia by improving resuscitation quality and increasing oxygen delivery in real-time is vital to reducing ischemic and subsequent secondary injuries. Current resuscitation methods only provide 25-30% of cardiac output and are limit by the inability of clinicians to deliver cardiopulmonary resuscitation (CPR) effectively up to 50% of the time. In response, the American Heart Association (AHA) has recommended two options of feedback to improve CPR quality: i) physiological or ii) non-physiological systems. Through a multi-site study, we have studied end tidal carbon dioxide (ETCO2) monitoring, and pioneered non-invasive brain monitoring of regional cerebral oxygenation (rSO2) using near infra-red spectroscopy as physiological feedback during CPR and demonstrated that they reflect two complementary aspects of CPR: i) circulation quality (ETCO2) and ii) brain/vital organ perfusion (rSO2). We have also shown that rSO2 exhibits a dose response relationship with survival and favorable neurological outcomes. In spite of these data and the AHA recommendations, the physiological target and the optimal feedback system during CPR to predict CA survival without neurological impairment remains unknown. In the present study, we propose to analyze data and blood samples collected from an ongoing 20 site observational study (AWAreness during Resuscitation [AWARE II]) of in-hospital cardiac arrests (IHCAs) to identify a brain resuscitation “gold standard,” and then test the hypothesis that physiological feedback guided CPR using rSO2 or ETCO2 or a combination will perform better than non-physiological feedback CPR in predicting CA survival and neurological status through attenuation of brain injury and inflammation. The current application proposes three aims: For Aim 1, using prospective data from 500 IHCAs, we propose to identify the optimal physiological resuscitation target (rSO2 and/or ETCO2) in predicting CA survival and neurological status. For Aim 2, serum collected during CPR and in the post-CA period will be analyzed to measure biomarkers of brain injury and inflammation to determine the association between rSO2 and ETCO2 levels during CPR and markers of secondary injury. Having determined the optimal physiological target, Aim 3 will randomize 150 subjects to compare the impact of real-time physiological feedback CPR with non-physiological feedback CPR on ROSC, survival and neurological outcomes in a pilot randomized control trial.

项目摘要/摘要 心脏骤停（CA）的年发病率估计为250-350,000院外，250-750,000 美国的医院事件，生存率分别低至5％和20％。缺氧脑损伤仍然存在 对于那些在医院出院生存的人来说，重大健康烧伤。这些结果反映了两步损伤 过程包括a）全身缺氧/静期权和b）继发性再灌注和感染损伤 发起人自发循环（ROSC）返回之后。由于继发损伤是由 CA期间缺血，通过改善复苏质量和增加氧气来改善缺血的能力 实时交付对于减少缺血性和随后的继发损伤至关重要。当前的复苏 方法仅提供25-30％的心输出量，并且由于临床医生无法交付而受到限制 心肺复苏（CPR）有效多达50％。作为回应，美国心脏 协会（AHA）建议提高CPR质量的两种反馈选择：i）物理或II） 非生理系统。通过多站点的研究，我们研究了末端潮汐二氧化碳（ETCO2） 监测和开创性的非侵入性大脑监测区域大脑氧合（RSO2） 在心肺复苏期间，红外光谱作为物理反馈，并证明它们反映了两个 CPR的互补方面：i）循环质量（ETCO2）和II）大脑/重要器官灌注（RSO2）。我们 还表明RSO2表现出与生存和有利神经系统的剂量反应关系 结果。尽管有这些数据和AHA建议，但物理目标和最佳目标 CPR期间的反馈系统预测没有神经系统损害的CA生存率仍然未知。在 目前的研究，我们建议分析从正在进行的20个现场观察性的数据和血液样本 研究（在复苏期间意识[意识到II]）对院内心脏骤停（IHCAS）以识别大脑 复苏“黄金标准”，然后检验以下假设：物理反馈使用RSO2指导CPR 或ETCO2或组合在预测CA存活时的性能优于非生理反馈CPR 通过脑损伤和炎症衰减神经状态。当前的申请建议 三个目标：对于AIM 1，使用500 IHCA的前瞻性数据，我们建议识别最佳生理学 复苏靶标（RSO2和/或ETCO2）在预测CA存活和神经系统状态方面。对于目标2，序列号 在CPR期间和CA后期收集的时期将进行分析，以测量脑损伤的生物标志物 炎症以确定CPR期间RSO2与ETCO2水平之间的关联和标记 继发伤害。确定了最佳生理目标后，AIM 3将将150名受试者随机 比较实时物理反馈心肺复苏与非生理反馈CPR对ROSC的影响， 在一项试验随机对照试验中的生存和神经结局。