Improving neurological survival after cardiac arrest during post-resuscitation ca

提高心脏骤停后复苏后神经系统的存活率

基本信息

批准号：
8780929
负责人：
Anja Kohler Metzger
金额：
$ 22.42万
依托单位：
RESQSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8780929
关键词：
Affect Air American Animal Model Animals Atmospheric Pressure Back Blood Blood Circulation Blood Pressure Blood flow Brain Brain Injuries Bundling Cardiac Cardiopulmonary Resuscitation Cardiovascular system Caring Cause of Death Cerebral Edema Cerebral perfusion pressure Cerebrovascular Circulation Cerebrum Clinical Complex Data Development Devices Disease Disodium Salt Nitroprusside Electroencephalography Emergency Situation Environmental air flow Family suidae Funding Heart Heart Arrest Histopathology Hospitals Hour Human Injury Intervention Intracranial Pressure Light Link Lung Manuals Measures Medical Metabolism Methods Modeling Monitor Morbidity - disease rate Nervous System Physiology Nervous System Trauma Neurologic Neurological outcome New Agents Organ Outcome Patient Care Patients Perfusion Phase Physiological Play Population Process Process Measure Quality of life Regulation Relative (related person)Reperfusion Injury Research Resistance Resuscitation Safety Severities Shock Signal Transduction Small Business Innovation Research Grant Staging Survival Rate System Techniques Technology Testing Therapeutic Therapeutic Uses Time United States Venous Withdrawal Work base blood perfusion brain electrical activity brain metabolism electric impedance functional outcomes hemodynamics improved indexing injured mortality natural hypothermia neurological recovery novel pre-clinical pressure prevent public health relevance success

项目摘要

DESCRIPTION (provided by applicant): Out-of-hospital cardiac arrest (OHCA) remains one of the leading causes of death in the United States. Even with the best clinically documented methods of cardiopulmonary resuscitation (CPR) and post-resuscitation care, more than 85-90% of the 350,000 Americans with OHCA die or have severe neurological deficits. Despite intensive research, little or no improvement in outcomes has been observed for over half a century. This application is focused on treating cardiac arrest patients that have been successfully defibrillated during the post-resuscitation phase. There remains a tremendous opportunity to optimize and improve the care of these patients, during the period of time when there is maximal hemodynamic instability and when the processes the result in neurologic damage begin to impact the ultimately outcome. In this application we propose to test the hypothesis that neurological recovery during the post-resuscitation phase will improve by non-invasively modulating cerebral perfusion and brain electrical activity with brain-specific intrathoracic pressure regulation (IPR) therapy in the first 12 hours after cardiac arrest. IPR therapy was developed by our research group and relies on active withdrawal of air from the lungs to create a small sub-atmospheric pressure during the expiratory phase of the typical positive pressure ventilation cycle. It has been demonstrated to increase hemodynamics, cerebral perfusion and blood flow in shock and brain injured states, and neurologically intact survival when used during CPR. Our intent is to demonstrate proof of preclinical concept that non-invasive brain-specific-IPR modulation of intracranial pressure and cerebral blood flow will improve processed EEG signals and neurological functional outcomes after cardiac arrest and return of spontaneous circulation (ROSC). As such, the specific aim of this proposal is to determine the safety and efficacy of two different levels of IPR therapy compared to no IPR therapy on hemodynamics, cerebral blood flow, ICP and EEG signals during the interval between ROSC and 12 hours post-ROSC and to correlate findings with brain histopathology and neurologically intact survival at 48 hours in a porcine model. If successful, IPR therapy will result in a novel post- resuscitation treatment and will effectively bridge the link between ROSC and long-term neurological function, significantly improving neurological survival and quality of life post cardiac arrest.

描述（由申请人提供）：院外心脏骤停 (OHCA) 仍然是美国的主要原因之一。即使采用临床记录最好的心肺复苏 (CPR) 和复苏后护理方法，在 350,000 名患有 OHCA 的美国人中，仍有超过 85-90% 死亡或患有严重的神经功能缺损。尽管进行了深入的研究，但半个多世纪以来，观察到的结果很少或根本没有改善。该应用程序的重点是治疗在复苏后阶段已成功除颤的心脏骤停患者。在血流动力学最不稳定以及导致神经损伤的过程开始影响最终结果的时期，仍然存在巨大的机会来优化和改善这些患者的护理。在此应用中，我们建议测试以下假设：在心脏骤停后的前 12 小时内，通过脑特异性胸腔内压力调节 (IPR) 治疗，无创地调节脑灌注和脑电活动，可改善复苏后阶段的神经功能恢复。。 IPR 疗法由我们的研究小组开发，依靠主动从肺部排出空气，在典型正压通气周期的呼气阶段产生一个小的负压。已被证明可以增加休克和脑损伤状态下的血流动力学、脑灌注和血流量，以及在心肺复苏期间使用时神经系统完整的存活率。我们的目的是证明临床前概念的证据，即颅内压和脑血流的非侵入性大脑特异性 IPR 调节将改善心脏骤停和自主循环 (ROSC) 恢复后处理的脑电图信号和神经功能结果。因此，本提案的具体目的是确定两种不同水平的 IPR 治疗与无 IPR 治疗相比，在 ROSC 到 ROSC 后 12 小时的时间间隔内对血流动力学、脑血流、ICP 和 EEG 信号的安全性和有效性并将猪模型中的发现与脑组织病理学和 48 小时神经完整存活率相关联。如果成功，IPR 疗法将带来一种新型的复苏后治疗，并将有效地弥合 ROSC 和长期神经功能之间的联系，显着改善心脏骤停后的神经存活和生活质量。