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.

项目概要/摘要 据估计，每年院外心脏骤停 (CA) 发生率为 250-350,000 例，院内心脏骤停 (CA) 发生率为 250-750,000 例。 美国发生医院事件，存活率分别低至 5% 和 20%。缺氧性脑损伤依然存在 对于出院后存活下来的人来说，这是一个重大的健康负担。这些结果反映了两步损伤 过程包括a）全身缺氧/缺血和b）继发性再灌注和炎症损伤 自主循环恢复（ROSC）后。由于二次伤害是由伤害的严重程度决定的 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 实时输送对于减少缺血和随后的继发性损伤至关重要。当前复苏 方法只能提供 25-30% 的心输出量，并且受到临床医生无法提供的限制 心肺复苏 (CPR) 的有效率高达 50%。对此，美国之心 协会 (AHA) 建议使用两种反馈选项来提高心肺复苏质量：i) 生理反馈或 ii) 非生理系统。通过多地点研究，我们研究了潮气末二氧化碳 (ETCO2) 监测，并开创了使用近处区域脑氧合（rSO2）的非侵入性大脑监测 红外光谱作为心肺复苏期间的生理反馈，并证明它们反映了两种 CPR 的互补方面：i) 循环质量 (ETCO2) 和 ii) 脑/重要器官灌注 (rSO2)。我们 还表明 rSO2 与生存和有利的神经系统表现出剂量反应关系 结果。尽管有这些数据和 AHA 建议，生理目标和最佳 心肺复苏期间预测 CA 存活且无神经功能损伤的反馈系统仍然未知。在 在本研究中，我们建议分析从正在进行的 20 个地点观察中收集的数据和血液样本 院内心脏骤停 (IHCA) 识别大脑的研究（复苏期间的意识 [AWARE II]） 复苏“黄金标准”，然后测试生理反馈使用 rSO2 指导心肺复苏的假设 或 ETCO2 或组合在预测 CA 存活方面比非生理反馈 CPR 表现更好 通过减轻脑损伤和炎症来改善神经状态。目前的申请建议 三个目标：对于目标 1，使用 500 个 IHCA 的前瞻性数据，我们建议确定最佳的生理学 复苏目标（rSO2 和/或 ETCO2）可预测 CA 存活率和神经系统状态。对于目标 2，血清 在 CPR 期间和 CA 后期间收集的数据将被分析，以测量脑损伤的生物标志物和 炎症以确定 CPR 期间 rSO2 和 ETCO2 水平与标记物之间的关联 二次伤害。确定最佳生理目标后，目标 3 将随机分配 150 名受试者 比较实时生理反馈 CPR 与非生理反馈 CPR 对 ROSC 的影响， 试点随机对照试验中的生存率和神经学结果。