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: 10698018
• 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/10698018
• 关键词: Address; American Heart Association; Anoxia; Anoxic Encephalopathy; Awareness; Biological Markers; Blood specimen; Brain; Brain Injuries; Carbon Dioxide; Cardiac Output; Cardiopulmonary Resuscitation; Caring; Categories; Cerebrum; Cessation of life; Circulation; Clinical Trials; Conscious; Data; Dose; Encephalitis; Enzyme-Linked Immunosorbent Assay; Event; Exhibits; Feedback; Goals; 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; functional status; 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.

项目总结/摘要 心脏骤停（CA）的估计年发病率为250- 350，000例院外病例和250- 750，000例院内病例。 美国的医院事件，存活率分别低至5%和20%。厌食症脑损伤仍然存在 这对那些存活到出院的人来说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 恢复自主循环（ROSC）。由于二次伤害是由 CA期间的缺血，通过改善复苏质量和增加氧气来改善缺血的能力 实时输送对于减少局部缺血和随后的二次损伤是至关重要的。当前复苏 方法仅提供25-30%的心输出量 心肺复苏（CPR）的有效性高达50%的时间。作为回应，美国心脏 美国心脏协会（AHA）推荐了两种反馈选择，以提高心肺复苏术质量：i）生理或ii） 非生理系统。通过多点研究，我们研究了潮气末二氧化碳（ETCO 2） 监测，并开创了非侵入性脑监测局部脑氧合（rSO 2）使用近 红外光谱作为CPR期间的生理反馈，并证明它们反映了两个 CPR的补充方面：i）循环质量（ETCO 2）和ii）脑/重要器官灌注（rSO 2）。我们 还表明rSO 2与存活率和良好的神经功能表现出剂量反应关系， 结果。尽管有这些数据和AHA的建议，生理目标和最佳的 心肺复苏术中的反馈系统来预测无神经损伤的CA存活率仍然是未知的。在 目前的研究，我们建议分析数据和血液样本收集从一个正在进行的20个网站的观察 一项旨在识别大脑的院内心脏骤停（IHCA）研究（复苏期间的意识[AWARE II]） 复苏“金标准”，然后使用rSO 2测试生理反馈指导CPR的假设 或ETCO 2或其组合在预测CA存活率方面将比非生理反馈CPR表现更好 以及通过减轻脑损伤和炎症来改善神经系统状态。本申请提出 三个目标：对于目标1，使用来自500个IHCA的前瞻性数据，我们建议确定最佳生理 复苏目标（rSO 2和/或ETCO 2）预测CA生存和神经状态。对于目标2，血清 将分析在CPR期间和CA后期间收集的数据，以测量脑损伤的生物标志物， 炎症，以确定CPR期间rSO 2和ETCO 2水平与 二次伤害在确定了最佳生理目标后，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， 生存率和神经系统结局的初步随机对照试验。