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

• 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
• 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

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）仍然是美国的主要死亡原因之一。即使采用了最佳的临床记录的心肺复苏方法（CPR）和震荡后护理方法，其中35万美国人的OHCA死亡或严重的神经系统缺陷中，超过85-90％以上。尽管进行了深入的研究，但半个多世纪以来的结果几乎没有改善。该应用的重点是治疗在弹性后阶段成功除颤的心脏骤停患者。在最大的血液动力学不稳定的时间内，以及当神经系统损害的结果开始影响最终的结果时，仍有一个巨大的机会来优化和改善对这些患者的护理。在此应用中，我们建议检验以下假设：在心脏停滞后的前12个小时，通过非侵入性调节脑灌注和大脑特异性治疗，通过非侵入性调节脑灌注和脑电活动来改善神经系统恢复。 IPR疗法是由我们的研究小组开发的，依赖于从肺部积极撤出空气，以在典型的正压通气周期的呼气阶段产生小小的大气压。已经证明，在CPR期间使用时，可以增加休克和脑损伤状态的血液动力学，脑灌注和血流以及神经系统完整的生存。我们的目的是证明临床前概念的证据表明，颅内压和脑血流的非侵入性脑特异性IPR调节将改善加工后的EEG信号和心脏骤停后的神经功能性结果和自发循环返回（ROSC）（ROSC）。因此，该提案的具体目的是确定两种不同水平的知识产权疗法的安全性和功效，而不是在ROSC和ROSC之间进行12个小时之间进行血液动力学，脑血流量，ICP和EEG信号的IPR疗法，并在48小时以48小时的模型中与脑部病理学和神经组织的生存相关。如果成功，IPR疗法将导致新的复苏后治疗，并有效地弥合ROSC与长期神经功能的联系，从而显着改善神经系统生存和心脏骤停后生活质量。