Normobaric O2 in Ischemic Stroke

在常压下呼吸高流量氧气(常压氧疗，NBO)可能是一种 维持脑缺血组织(‘争取时间’)直到自发或治疗性再灌流的简单策略 发生，从而改善中风的结局。通过防止早期缺血细胞死亡，NBO可能是一种有用的 延长静脉注射组织型纤溶酶原激活剂(TPA)狭窄(3小时)时间窗的辅助治疗 心理治疗。我们最近的啮齿动物和试点人类中风研究提供了令人信服的证据，表明早期NBO 提供强大的神经保护。虽然这种好处似乎是暂时的，与之前观察到的类似 高压氧研究表明，如果NBO治疗的缺血组织稍后再灌流，确实会产生持续的好处。 在这项提案(SPOTRIAS项目1)中，我们的目标是将我们的初步工作扩展到双盲、随机、 安慰剂对照临床试验，纳入5年内240名急性(9小时)缺血性中风患者。病人 将接受NBO或Room Air 8小时治疗，并接受一系列临床评估和CT扫描。 NBO的治疗潜力将通过对NIHSS的变化进行“意向治疗”统计分析来评估 治疗期间的分数。NBO与再灌注的潜在协同效益将在患者中进行评估 作为项目2(LEV)的一部分，他们接受基线和24小时CT灌注扫描以评估再灌注。 其他二级分析将包括对治疗后临床功能评分、大脑 CT上的出血率和病变体积的增长。在第一年，我们将排除接受tPA治疗的患者和 研究NBO联合tPA在栓塞性(基于血栓)啮齿动物卒中模型中的安全性和有效性。如果 联合疗法在啮齿动物中似乎是安全的，如果第一年的人类数据没有引起安全问题，我们 将把接受tPA治疗的患者纳入NBO的临床试验。从这些研究中，我们希望收集到初步的 为未来由EMS在现场发起的NBO多中心试验提供数据和获得试点经验。 从公共健康的角度来看，这些研究意义重大，因为它们将评估呼吸是否 高流量氧气是一种潜在的简单、实用、可广泛使用、便携和成本效益高的疗法，可以 独立或通过延长静脉注射tPA的时间窗来改善卒中结果。

Breathing high-flow oxygen at normal atmospheric pressure (Normobaric Oxygen Therapy, NBO) may be a simple strategy to sustain ischemic brain tissue ('buy time') until spontaneous or therapeutic reperfusion occurs, and thereby improve stroke outcome. By preventing early ischemic cell death, NBO may be a useful adjunctive therapy that extends the narrow (3-hour) time window for IV tissue plasminogen activator (tPA) therapy. Our recent rodent and pilot human stroke studies provide compelling evidence that early NBO confers potent neuroprotection. While the benefit appears to be transient, similar to that observed in prior hyperbaric oxygen studies, sustained benefit does occur if NBO-treated ischemic tissue is later reperfused. In this proposal (Spotrias Project 1), we aim to extend our preliminary work in a double blind, randomized, placebo-controlled clinical trial enrolling 240 acute (< 9 hours) ischemic stroke patients over 5 years. Patients will receive either NBO or Room Air for 8 hours and undergo serial clincial assessments and CT scans. NBO's therapeutic potential will be assessed in an "intention to treat" statistical analysis of change in NIHSS scores during therapy. The potential synergistic benefit of NBO with reperfusion will be assesed in patients who undergo a baseline and a 24-hour CT-perfusion scan to assess reperfusion, as part of Project 2 (Lev). Other secondary analyses will include an assessment of post-therapy clinical function scores, brain hemorrhage rates, and lesion volume growth on CT scans. In year 1 we will exclude tPA-treated patients and investigate the safety and utility of combined NBO with tPA in embolic (clot-based) rodent stroke models. If the combined therapy appears safe in rodents, and if the year 1 human data raises no safety concerns, we will include tPA-treated patients in the clinical trial of NBO. From these studies we hope to collect preliminary data and gain pilot experience for a future multi-center trial of NBO intiated by EMS at the scene. From a public health standpoint, these studies are significant because they will assess whether breathing high-flow oxygen, a potentially simple, practical, widely accessible, portable, and cost-effective therapy, can improve stroke outcomes either independently or by extending the time window for IV tPA.