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

基本信息

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
项目类别：
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

项目摘要

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) 的发生率为 250-350,000 例，院内心脏骤停 (CA) 的发生率为 250-750,000 例。在美国，缺氧性脑损伤的存活率仍然分别低至 5% 和 20%。对于那些幸存到出院的人来说，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，继发性损伤取决于恢复的程度。 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。方法只能提供 25-30% 的心输出量，并且由于上级无法提供而受到限制美国心脏协会 (American Heart) 的心肺复苏 (CPR) 有效率高达 50%。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) 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）的无创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)。还表明 rSO2 与生存和有利的神经系统表现出剂量反应关系尽管有这些数据和 AHA 建议，生理目标和最佳结果。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。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预测 CA 存活和神经状态的复苏目标（rSO2 和/或 ETCO2）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，以测量脑损伤和炎症以确定 CPR 期间 rSO2 和 ETCO2 水平与标记物之间的关联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，试点随机对照试验中的生存率和神经学结果。