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)估计每年有250-350,000人在医院外，250-750,000人在医院内- 美国的医院事件，存活率分别低至5%和20%。缺氧性脑损伤残留 对于那些活到出院的人来说，这是一个主要的健康负担。这些结果反映了两步损伤。 过程包括a)全身缺氧/缺血和b)二次再灌流和炎症损伤 自主循环恢复(ROSC)后。因为继发性损伤是由以下因素决定的 CA期间的缺血，通过提高复苏质量和增加氧气来改善缺血的能力 实时传输对于减少缺血和继发性损伤至关重要。当前复苏 方法只能提供心输出量的25%-30%，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%。作为回应，美国人的心 美国心脏协会(AHA)建议采用两种反馈方式来提高心肺复苏质量：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(Etco2)。 使用NEAR监测局部脑氧合(RSO2)，开创了无创脑监测的先河 红外光谱作为心肺复苏期间的生理反馈，并表明它们反映了两个 心肺复苏的互补方面：i)循环质量(ETCO2)和ii)脑/重要器官灌注(RSO2)。我们 也表明rSO2与存活和良好的神经学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 心肺复苏术中的反馈系统是否能预测无神经损伤的CA存活期尚不清楚。在 目前的研究，我们建议分析从正在进行的20个现场观察中收集的数据和血液样本。 对院内心脏骤停(IHCA)的研究(复苏期间的意识[AWARE II])以识别大脑 复苏“黄金标准”，然后测试生理反馈指导使用rSO2进行CPR的假设 或者ETCO2或其组合在预测CA存活期方面将比非生理性反馈CPR更好 以及通过减轻脑损伤和炎症而达到的神经状态。目前的申请提出了 三个目标：对于目标1，使用来自500个IHCA的前瞻性数据，我们建议确定最佳的生理 复苏靶点(rSO2和/或ETCO2)在预测CA存活和神经状态中的作用。对于目标2，血清 在CPR期间和CA后时期收集的数据将被分析，以测量脑损伤的生物标志物和 确定心肺复苏期间rSO2和ETCO2水平与炎症指标的相关性 继发性损伤。在确定了最佳生理目标后，目标3将随机选择150名受试者 比较实时生理反馈心肺复苏与非生理反馈心肺复苏对ROSC的影响， 一项先导性随机对照试验的存活率和神经结局。