Monitoring Cerebral Autoregulation in Patients Undergoing Traumatic Hip Fracture Surgery to Improve Postoperative Outcomes

项目摘要/摘要 背景：髋部骨折的手术对老年人来说可能是毁灭性的，并发症包括 精神错乱，痴呆症风险增加，无法行走。作为一名麻醉师和临床科学家，我有 专注于减少术后精神错乱。在这份提案中，我将为自己的研究生涯奠定基础 重点关注减少老年人手术后神经认知和功能衰退的更广泛目标。我 由于试点数据的缘故，我将特别侧重于优化术中脑灌注的作用 这表明手术中脑血流灌注减少是导致神志不清的一个可改变的危险因素。 职业发展计划：我正在提出具体的教育目标，以解决我目前 知识。首先，我将在导师的指导下发展脑血管生理学和监测方面的专业知识 科勒博士是脑血流调节方面的专家。其次，我将发展神经认知方面的专业知识 在神经心理学家卡马斯博士和卡马特博士的指导下进行测试和痴呆症评估。 Gottesman说，他是研究环境中的痴呆症判决专家。第三，我将获得临床方面的专业知识 通过Sieber博士和Neuman博士的指导进行试验和测量功能状态( 老年人的围手术期临床试验)和沃尔斯顿博士(一位在功能状态方面有专长的老年病医生)。 最后，我将通过与我的导师、课程和领导机会的互动来发展成为一名领导者。 研究建议：在髋部骨折手术中，血压的极端变化在老年人中很常见 易受脑缺血和低血压后果影响的成年人。然而， 在手术中，什么是足够的血压并没有标准的护理。我们的团队已经 通过实时监测患者的血压来确定个体患者的最佳血压的方法 大脑自动调节。在心脏手术中使用这些方法，我们已经证明了平均动脉压 (MAP)低于脑自动调节极限与术后并发症有关，而且 在此基础上对术中MAP进行干预，可减少精神错乱。尽管前景看好， 心脏手术中的这些结果可能不适用于髋部骨折手术。为了解决这一知识差距，我将 将这些方法推广到髋部骨折手术患者。我将描述(A)风险因素的程度和(B)风险因素 髋部骨折患者术中MAP变化的脑自动调节功能 外科手术(目标1)。我还将研究地图变化与神经认知和功能的关系 成果(目标2)。根据这些结果，我将设计一项试点可行性/安全性试验，以确定是否 在自我调节的范围内以MAP为靶点可以改善神经认知/功能结果(目标3)。 摘要：这项提案的有希望的结果将支持最终的试验，这将有可能 从根本上改变广泛外科人群的麻醉策略。教育计划 这项提案将支持我的职业目标，即改善老年人手术后的结果。

PROJECT SUMMARY/ABSTRACT Background: Surgery for hip fracture can be devastating for older adults, with complications including delirium, increased risk of dementia, and inability to walk. As an anesthesiologist and clinician-scientist, I have focused on reducing delirium after surgery. In this proposal, I will build the foundation for a research career focused on the broader goals of reducing neurocognitive and functional decline after surgery in older adults. I will specifically focus on the role of optimizing intraoperative cerebral perfusion, because of pilot data suggesting that reduced cerebral perfusion during surgery is a modifiable risk factor for delirium. Career Development Plan: I am proposing specific educational goals that address gaps in my current knowledge. First, I will develop expertise in cerebrovascular physiology and monitoring under the mentorship of Dr. Koehler, an expert in cerebral blood flow regulation. Second, I will develop expertise in neurocognitive testing and dementia assessment under the mentorship of Dr. Kamath, a neuropsychologist, and Dr. Gottesman, an expert in dementia adjudication in the research setting. Third, I will gain expertise in clinical trials and measuring functional status through the mentorship of Drs. Sieber and Neuman (experts in perioperative clinical trials in older adults), and Dr. Walston (a geriatrician with expertise in functional status). Finally, I will develop as a leader through interactions with my mentors, courses, and leadership opportunities. Research Proposal: During hip fracture surgery, extreme variations in blood pressure are common in older adults, who are susceptible to cerebral ischemia and vulnerable to consequences of hypotension. However, there is no standard of care as to what constitutes adequate blood pressure during surgery. Our group has championed methodology to define optimal blood pressure in individual patients by real-time monitoring of cerebral autoregulation. Using these methods in cardiac surgery, we have shown that mean arterial pressure (MAP) below the limits of cerebral autoregulation is associated with postoperative morbidity, and that an intervention to target intraoperative MAP based on this monitoring may reduce delirium. Although promising, these results in cardiac surgery may not apply in hip fracture surgery. To address this gap in knowledge, I will extend these methods to hip fracture surgery patients. I will characterize (a) the extent of, and (b) risk factors for intraoperative MAP variation above and below the limits of cerebral autoregulation during hip fracture surgery (Aim 1). I will also examine associations of MAP variation with neurocognitive and functional outcomes (Aim 2). Based on these results, I will design a pilot feasibility/safety trial to determine whether targeting MAP within the limits of autoregulation could improve neurocognitive/functional outcomes (Aim 3). Summary: Promising results from this proposal would support a definitive trial, which would have the potential to fundamentally alter anesthetic strategies across a wide range of surgical populations. The educational plan in this proposal will support my career goal of improving outcomes for older adults after surgery.