背景:炎症与驱动与蛛网膜下腔出血(SAH)相关的发病率有关。尽管了解炎症在SAH后发病中的重要作用,目前没有有效的方法来调节这种有害反应。迫切需要一种安全的新型免疫调节方法,迅速,并有效地部署在SAH患者。迷走神经刺激(VNS)提供了一种非药物的免疫调节方法,先前的研究表明VNS可以减少全身炎症标志物,VNS早期成功治疗了关节炎等炎症性疾病,脓毒症,和炎症性肠病。非侵入性耳迷走神经刺激治疗蛛网膜下腔出血(NAVSaH)试验的目的是将非侵入性经皮耳廓VNS(taVNS)的使用转化为自发性SAH,我们的中心假设是在自发性SAH后的急性期实施taVNS减弱了预期的出血炎症反应,并降低了与炎症介导的临床终点相关的发病率.
方法:NAHSaH试验的总体目标是1)定义taVNS对血浆和脑脊液(CSF)中SAH诱导的炎症标志物的影响,2)确定SAH后taVNS是否减少放射学血管痉挛,和3)确定SAH后taVNS是否减少慢性脑积水。在向单个注册站点演示之后,纳入的SAH患者在重症监护病房住院期间,每天接受两次taVNS或假刺激治疗.在治疗开始前抽血和脑脊液,然后在病人住院期间每三天。主要终点包括第1天和第13天之间血浆和脑脊液中炎性细胞因子TNF-α的变化,放射学血管痉挛的发生率,以及通过心室分流进行长期脑脊液分流的需求率。次要结果包括一组其他细胞因子的探索性分析,住院获得性感染的数量和类型,以天为单位的外部心室引流的持续时间,血管痉挛所需的干预措施,之前的连续生理数据,during,治疗后,住院时间,重症监护室住院时间,和入院时修改的Rankin量表评分(mRS),放电,每个人都在SAH后随访长达两年。
结论:炎症在SAH后的发病中起重要作用。这项NAVSaH试验具有创新性,因为它通过利用新型非侵入性神经调节方法及其已知的抗炎作用来改变SAH的病理生理学,从而与药理学现状背道而驰。一个新的调查,有效,SAH的快速部署干预为改善SAH后的结局提供了新的途径。
背景:临床试验注册,NCT04557618。于2020年9月21日注册,第一位患者于2021年1月4日注册。
BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH) trial is to translate the use of non-invasive transcutaneous auricular VNS (taVNS) to spontaneous SAH, with our central hypothesis being that implementing taVNS in the acute period following spontaneous SAH attenuates the expected inflammatory response to hemorrhage and curtails morbidity associated with inflammatory-mediated clinical endpoints.
METHODS: The overall objectives for the NAHSaH trial are to 1) Define the impact that taVNS has on SAH-induced inflammatory markers in the plasma and cerebrospinal fluid (CSF), 2) Determine whether taVNS following SAH reduces radiographic vasospasm, and 3) Determine whether taVNS following SAH reduces chronic hydrocephalus. Following presentation to a single enrollment site, enrolled SAH patients are randomly assigned twice daily treatment with either taVNS or sham stimulation for the duration of their intensive care unit stay. Blood and CSF are drawn before initiation of treatment sessions, and then every three days during a patient\'s hospital stay. Primary endpoints include change in the inflammatory cytokine TNF-α in plasma and cerebrospinal fluid between day 1 and day 13, rate of radiographic vasospasm, and rate of requirement for long-term CSF diversion via a ventricular shunt. Secondary outcomes include exploratory analyses of a panel of additional cytokines, number and type of hospitalized acquired infections, duration of external ventricular drain in days, interventions required for vasospasm, continuous physiology data before, during, and after treatment sessions, hospital length of stay, intensive care unit length of stay, and modified Rankin Scale score (mRS) at admission, discharge, and each at follow-up appointment for up to two years following SAH.
CONCLUSIONS: Inflammation plays a central role in morbidity following SAH. This NAVSaH trial is innovative because it diverges from the pharmacologic status quo by harnessing a novel non-invasive neuromodulatory approach and its known anti-inflammatory effects to alter the pathophysiology of SAH. The investigation of a new, effective, and rapidly deployable intervention in SAH offers a new route to improve outcomes following SAH.
BACKGROUND: Clinical Trials Registered, NCT04557618. Registered on September 21, 2020, and the first patient was enrolled on January 4, 2021.