Pterygopalatine Fossa (PPF) Block as an Opioid Sparing Treatment for AcuteHeadache in Aneurysmal Subarachnold Hemorrhage

翼腭窝 (PPF) 阻滞作为阿片类药物节省治疗动脉瘤性蛛网膜下腔出血的急性头痛

基本信息

批准号：
10584712
负责人：
Katharina Maria Busl
金额：
$ 351.45万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-15 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10584712
关键词：
Absence of pain sensation Activities of Daily Living Acute Acute Brain Injuries Acute Pain Address Adult Adverse event Affect Analgesics Anesthesiology Aneurysm Aneurysmal Subarachnoid Hemorrhages Bilateral Blinded Blood Vessels Caring Chronic Headaches Clinical Clinical Trials Common Data Element Complex Conscious Constipation Consumption Critical Care Dangerousness Data Data Coordinating Center Depressed Level of Consciousness Depressed mood Dexamethasone Disparity Double-Blind Method Enrollment Ethnic Origin Fiber Fossa Frequencies Functional disorder Funding Future Ganglia Gastrointestinal Transit Generations Goals Grant Headache Headache Disorders Hemorrhage High Prevalence Hospitalization Hospitals Hour Hyperalgesia Hypotension Individual Inflammatory Injections Intervention Intervention Studies Knowledge Lead Learning Literature Managed Care Massachusetts Measures Mediating Meningeal Migraine Minority Groups National Institute of Neurological Disorders and Stroke Nerve Block New York Numeric Rating Scale Opioid Oral Pain Pain Measurement Pain Research Pain intensity Pain management Patients Phase Placebo Effect Procedures Race Randomized Recovery Regimen Regulation Research Design Risk Safety Saline Sample Size Serious Adverse Event Severities Site Standardization Subarachnoid Hemorrhage Survivors Therapeutic Thunderclap Headaches Time Ultrasonography United States National Institutes of Health Universities Vasomotor Vasospasm Woman Work addiction adjudication blood product central pain central sensitization cerebrovascular clinically significant craniofacial cytokine design ethnic minority population experience follow-up hospital readmission improved innovation instrument irritation maxillary nerve morphine equivalent multimodality neglect neurosurgery novel strategies novel therapeutic intervention open label opioid epidemic opioid mortality opioid sparing opioid use pain perception pain reduction pain score phase III trial placebo controlled study prescription opioid racial disparity racial minority population recruit respiratory response ropivacaine sex sex disparity side effect sociodemographic factors socioeconomics theories ultrasound verbal

项目摘要

Severe headache is ubiquitous in subarachnoid hemorrhage (SAH), present in 90% of patients after ictus bleed. Despite steady consumption of analgesics, the degree of pain control in SAH patients is remarkably poor. In spite of this high prevalence, a dearth of data guides optimal management of post-SAH headache. Opioids are the most prescribed pain medication for severe post-SAH headache. However, opioid-based analgesia presents considerable risks: depressed level of consciousness and respiratory drive, hypotension, slow gastrointestinal transit, and high frequency of tolerance and addiction. Furthermore, it is urgent and critical to identify novel strategies to alleviate the excruciating and nearly universal headache post-SAH, while mitigating consequences of opioid use. This unmet therapeutic need reflects a key knowledge gap in a condition afflicting nearly 30,000 individuals each year in the US. We present an inexpensive, opioid-sparing strategy for post-SAH headache, using a nerve-block into the pterygopalatine fossa (PPF) to improve pain control and lessen opioid needs. A growing body of literature on the use of nerve-blocks in acute and chronic headache disorders supports our overarching hypothesis that PPF-block provides rapid, opioid-sparing analgesia, is safe and well-tolerated, and holds promise to adequately treat post-SAH headache. The pathophysiology of these headaches is complex and involves meningeal irritation from blood products, release of inflammatory cytokines, vasomotor instability, and central pain sensitization. Through selective modulation, PPF-blocks address pain mechanisms at their origin, targeting the maxillary nerve and sphenopalatine ganglion, including their branches. We propose a multicenter phase II, randomized, double-blinded, placebo-controlled study with sequential parallel comparison design of bilateral PPF-injections over 4 days at 12 centers. Following aneurysm treatment, 195 adults hospitalized with aneurysmal SAH, who are experiencing severe headaches and can verbalize pain scores, will be randomized to once daily active (ropivacaine + dexamethasone) or sham (saline) or PPF-injections during the first 2 consecutive days of the intervention period (Day 1/Stage 1, Day 2/Stage 2). The open-label phase spans the subsequent 2 days (Days 3-4), during which subjects may opt to receive an active PPF-block. This two-stage design leverages increased efficiency in data generation from the pooled sequential blinded stages (i.e., Stages 1 & 2) and reduced impact of sham responses, and thus, allows for smaller sample size without compromising statistical power. Our primary objective is to demonstrate the opioid-sparing analgesic effect of PPF-blocks vs sham. Our secondary objective is to assess the tolerability of PPF-injections as measured by rates of acceptance of second injection on Day 2, and their safety as measured by vasospasm rates at the end of the open-label period in patients with SAH. We will also explore the potential interplay of sex and racial disparities in pain experiences and both PPF- block tolerability and efficacy. This initiative merges our expertise in neurosurgery, neurocritical care, and acute- pain-anesthesiology to tackle a historically neglected aspect of the critical care management of SAH.

严重的头痛在蛛网膜下腔出血（SAH）中无处不在，在ICTUS出血后，有90％的患者存在于90％的患者中。尽管稳定食用了镇痛药，但SAH患者的疼痛控制程度非常差。尽管存在这种高流行，但数据的缺乏指导了SAH后头痛的最佳管理。阿片类药物是严重的SAH头痛的规定止痛药。但是，基于阿片类药物的镇痛呈现出很大的风险：意识和呼吸驱动水平降低，低血压，缓慢的胃肠道转移以及耐受性和成瘾的高频率。此外，确定减轻萨亚后令人发指和几乎普遍存在的新型策略是迫切和至关重要的，同时减轻阿片类药物使用的后果。这种未满足的治疗需求反映了在美国每年遭受近30,000个人的条件下的关键知识差距。我们提出了一种廉价的，分娩后的萨哈头痛策略，使用神经块进入翼状for骨窝（PPF），以改善疼痛控制并减轻阿片类药物的需求。关于在急性和慢性头痛障碍中使用神经阻滞剂的文献越来越多支持我们的总体假设，即PPF-Block提供了快速的，占阿片类药物的镇痛作用，安全且耐受性良好，并且有望充分地治疗萨哈之后的头痛。这些头痛的病理生理学很复杂，涉及血液产物的脑膜刺激，炎症细胞因子的释放，血管舒缩不稳定性和中枢疼痛敏感性。通过选择性调制，PPF块解决了其起源处的疼痛机制，以靶向上颌神经和蝶神经节（包括其分支）。我们提出了一个多中心II期，随机，双盲，安慰剂对照研究，在12个中心4天内双边PPF注射的顺序平行比较设计。经过动脉瘤治疗后，有195名成年人患有性动脉瘤SAH住院，患有严重的头痛并且可以口头上的疼痛评分，将随机分为每天活跃一次（Ropivacaine + dexamethasone）或Shame（盐水）或PPF注射，或在干预期间的前2天进行了两天的两天，第1阶段（第1阶段/阶段），第2阶段，第2阶段，第2阶段，第2阶段，第2阶段，第2阶段，2/阶段。开放标签相跨越随后的2天（第3-4天），在此期间，受试者可以选择接收活动的PPF块。这种两阶段的设计利用了汇总的顺序盲阶段（即第1和2阶段）的数据生成效率，并降低了假反应的影响，因此允许较小的样本量而不会损害统计能力。我们的主要目的是证明PPF-Blocks vs Sham的镇痛作用。我们的次要目标是评估通过在第2天接受第二次注射率来衡量的PPF注射剂的耐受性，以及在开放标签时期SAH患者中通过血管痉挛速率测量的安全性。我们还将探讨性别和种族差异在疼痛经历中的潜在相互作用以及PPF-阻止耐受性和功效。该计划将我们在神经外科，神经关怀和急性疼痛麻醉学方面的专业知识融合在一起，以应对SAH重症监护管理的历史忽视方面。