Neurological and cognitive effects of hyperoxia after cardiac arrest

心脏骤停后高氧的神经和认知影响

• 批准号: 8438216
• 负责人: Stephen Walter Trzeciak
• 金额: $ 62.52万
• 依托单位: COOPER UNIVERSITY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8438216
• 关键词: Accident and Emergency department; Adult; American; Anoxic Encephalopathy; Biological Markers; Blood Circulation; Blood flow; Brain; Brain Injuries; Cardiopulmonary Resuscitation; Caring; Cause of Death; Cessation of life; Chemicals; Clinical; Clinical Protocols; Clinical Research; Cognitive; Data; Elements; Emergency Medicine; Emergency Situation; Energy Metabolism; Ensure; Exposure to; Gas Chromatography; Health Benefit; Heart Arrest; Histopathology; Hospitals; Hour; Hyperoxia; Impairment; Injury; Intervention; Ions; Isoprostanes; Knowledge; Lipid Peroxidation; Mass Spectrum Analysis; Measures; Medical; Memory; Methods; Multicenter Studies; Neurologic; Neurological outcome; Neuronal Injury; Neuropsychological Tests; Outcome; Outcome Assessment; Oxidative Stress; Oxygen; Partial Pressure; Patients; Phase; Plasma; Protocols documentation; Provider; Public Health; Reperfusion Injury; Reperfusion Therapy; Research; Resuscitation; Science; Semantics; Shock; Site; Survivors; Testing; Therapeutic; Urine; Ventricular Fibrillation; Work; base; disability; executive function; experience; functional outcomes; improved; in vivo; indexing; instrument; ionization; killings; lexical; member; natural hypothermia; neuropsychological; preclinical study; prospective; public health relevance; standard care

DESCRIPTION (provided by applicant): Sudden cardiac arrest is a leading cause of death and disability in the U.S. Even if resuscitation achieves return of spontaneous circulation (ROSC), >50% of patients suffer fatal or crippling brain injury. Recent data suggest that exposure to hyperoxia (i.e. supranormal arterial oxygen partial pressure due to an excessively high fraction of inspired oxygen [FiO2]) after ROSC may accelerate oxidative stress, worsen reperfusion injury in the brain, and contribute to poor outcome. Prolonged hyperoxia exposure is extremely common in post- resuscitation care; however, no clinical study has tested if rapidly reducing FiO2 after resuscitation reduces oxidative stress and improves outcomes. Our hypothesis is that rapid FiO2 de-escalation after ROSC reduces oxidative stress and is associated with improved neurological, neuropsychological, and functional outcomes. To test this hypothesis, we will pursue the following Specific Aims using an experienced six center Emergency Department (ED)-based research consortium (Emergency Medicine Shock Research Network). Our first aim is to test if a protocol for rapid FiO2 de-escalation after ROSC lowers in vivo oxidative stress during post- resuscitation care. We will conduct a multicenter prospective before-and-after protocol implementation study testing the effects of a protocol for rapid FiO2 de-escalation after ROSC among 266 adult ED patients resuscitated from out-of-hospital ventricular fibrillation cardiac arrest. All sites currently employ uniform methods of pos-resuscitation care including therapeutic hypothermia. In the "before" phase, patients will receive standard care. In the "after" phase, patients will receive standard care plus rapid FiO2 de-escalation after ROSC via implementation of a clinical protocol. We will compare the most sensitive and specific in vivo biomarkers of oxidative stress - plasma and urine isoprostanes and isofurans measured by mass spectroscopy - over the first 24 hours between groups. Our second aim is to test if the rapid FiO2 de- escalation protocol is associated with reduced neurological disability. We will determine the Modified Rankin Scale (mRS) (a well-validated scale of neurological disability ranging from 0=no disability/asymptomatic to 6=death) at hospital discharge, and compare the proportion of patients with good neurological outcome (defined as a mRS <3) between groups. Our third aim is to test if the rapid FiO2 de-escalation protocol is associated with improved neuropsychological and functional outcomes. We will compare neuropsychological and functional outcomes between groups among survivors at 90 days using validated instruments across five cognitive domains (memory, executive function, lexical-semantic, visuoperceptual, psychomotor) and ability to return to work. Significance: This project will generate new, critically important knowledge about a fundamental element of post-cardiac arrest care. Research on new methods to improve outcomes from this devastating condition is a crucial and urgent priority. Given the magnitude of death and disability that cardiac arrest imparts upon Americans, even modest improvements would provide a major public health benefit.

描述(由申请人提供)：在美国，心脏骤停是导致死亡和残疾的主要原因。即使复苏能够恢复自主循环(ROSC)，50%的患者也会遭受致命或严重的脑损伤。最近的数据表明，ROSC后暴露于高氧(即由于吸入氧[FiO2]含量过高而导致的超常动脉血氧分压)可能会加速氧化应激，加重脑内再灌注损伤，并导致不良预后。长时间的高氧暴露在复苏后护理中非常常见；然而，还没有临床研究测试复苏后迅速减少FiO2是否可以减少氧化应激并改善预后。我们的假设是，ROSC后快速降低FiO2水平可减少氧化应激，并与改善神经、神经心理和功能结局有关。为了验证这一假设，我们将利用一个经验丰富的六中心急诊科(ED)研究联盟(急诊医学休克研究网络)来实现以下具体目标。我们的第一个目标是测试ROSC后快速降低FiO2的方案是否降低了复苏后护理期间体内的氧化应激。我们将进行一项多中心前瞻性方案实施前后研究，在266名从院外室颤心脏骤停中复苏的成年ED患者中测试ROSC后快速降低FiO2方案的效果。所有地点目前都采用统一的复苏后护理方法，包括治疗性低温。在“之前”阶段，患者将接受标准护理。在“后”阶段，患者将接受标准护理，并通过实施临床方案在ROSC后快速降低FIO2。我们将比较氧化应激最敏感和最特异的体内生物标志物--血浆和尿液中的异前列腺素和异呋喃的质谱学测量--在最初的24小时内。我们的第二个目标是测试快速降低FiO2方案是否与减少神经功能障碍有关。我们将在出院时测定改良Rankin量表(MRS)(一个经过充分验证的神经功能障碍评分，范围从0=无残疾/无症状到6=死亡)，并比较两组之间神经预后良好的患者的比例(定义为MRS和lt；3)。我们的第三个目标是测试快速降低FiO2方案是否与改善神经心理和功能结果有关。我们将在90天后使用经过验证的工具，在五个认知领域(记忆、执行功能、词汇-语义、视觉操作、精神运动)和重返工作的能力上比较幸存者组之间的神经心理和功能结果。意义：这个项目将产生关于心脏骤停后护理的基本要素的新的、至关重要的知识。研究新的方法以改善这一毁灭性状况的结果是一项至关重要而紧迫的优先事项。考虑到心脏骤停给美国人带来的死亡和残疾的严重性，即使是轻微的改善也会带来重大的公共健康好处。