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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.

严重的头痛是普遍存在于蛛网膜下腔出血（SAH），目前在90%的患者后，发作性出血。尽管持续使用镇痛药，但SAH患者的疼痛控制程度非常差。尽管如此高的患病率，缺乏数据指导SAH后头痛的最佳管理。阿片类药物是严重SAH后头痛最常用的处方止痛药。然而，阿片类镇痛存在相当大的风险：意识和呼吸驱动水平降低，低血压，胃肠道传输缓慢，耐受和成瘾频率高。此外，迫切需要确定新的策略来缓解SAH后的痛苦和几乎普遍的头痛，同时减轻阿片类药物使用的后果。这种未得到满足的治疗需求反映了美国每年近3万人患有这种疾病的关键知识差距。我们提出了一个便宜的，阿片类药物节约战略后SAH头痛，使用神经阻滞到翼腭窝（PPF），以改善疼痛控制和减少阿片类药物的需求。越来越多的关于在急性和慢性头痛疾病中使用神经阻滞的文献支持我们的总体假设，即PPF阻滞提供快速、阿片类药物节省的镇痛，安全且耐受性良好，并有望充分治疗SAH后头痛。这些头痛的病理生理学是复杂的，涉及血液制品引起的脑膜刺激、炎性细胞因子的释放、血管不稳定和中枢疼痛敏感化。通过选择性调节，PPF阻滞剂在其起源处解决疼痛机制，靶向上颌神经和蝶腭神经节，包括其分支。我们提出了一项多中心II期、随机、双盲、安慰剂对照研究，采用序贯平行比较设计，在12个中心进行为期4天的双侧PPF注射。动脉瘤治疗后，195例因严重头痛住院治疗并能说出疼痛评分的蛛网膜下腔出血（SAH）成人患者将在干预期的前2个连续日（第1天/第1阶段，第2天/第2阶段）内随机接受活性药物（罗哌卡因+地塞米松）或假药物（生理盐水）或PPF注射，每日1次。开放标签期持续随后的2天（第3-4天），在此期间，受试者可选择接受活性PPF阻滞。这种两阶段设计利用了从合并的顺序盲化阶段（即，阶段1和2），并减少假反应的影响，因此，允许较小的样本量，而不影响统计功效。我们的主要目的是证明与假手术相比，PPF阻滞的阿片类药物保留镇痛作用。我们的次要目的是评估PPF注射的耐受性（通过第2天第二次注射的接受率测量）和安全性（通过开放标签期结束时SAH患者的血管痉挛率测量）。我们还将探讨疼痛体验中性别和种族差异的潜在相互作用以及PPF阻滞的耐受性和疗效。这项计划将我们在神经外科、神经重症监护和急性疼痛麻醉学方面的专业知识结合起来，以解决SAH重症监护管理中一个历史上被忽视的方面。